risk assessment methodology for hazardous substances

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4.2. Risk Assessment Overview

Risk assessment, as defined by the National Academy of Sciences (NAS), is a systematic approach to organizing and analyzing scientific knowledge and information for potentially hazardous activities or for substances that might pose risks under specified conditions. 50 , 51  NAS describes the risk assessment paradigm as a process consisting of four major components: hazard identification, dose-response assessment, exposure assessment, and risk characterization. These components are described in more detail below. While the original NAS definition and paradigm reflect the risk assessment framework used today, risk assessment methodology has evolved to include new methods to reduce uncertainties and increase confidence in quantitative analyses.

It is important to recognize that risk assessment is not a single, fixed method of analysis. Risk assessment is an iterative process that involves identifying and filling data gaps in order to develop a more refined assessment of the risk. 52

The National Research Council proposed a three-phase system to ensure risk assessments are comprehensive and connected to the problems/decisions identified to render the best set of risk management options: Phase I: Enhanced Problem Formulation and Scoping; Phase II: Planning and Assessment; and Phase III: Risk Management. Phase I identifies risk management options, Phase II risks are determined using risk-assessment tools, and Phase III information gathered is used to inform risk management decisions. 53

Risk Assessment (Phase II), informs the Risk Management Process (Phase III), which integrates public health, political, social, economic, engineering, and other considerations into response decisions. The relationship between risk assessment and risk management is illustrated in the diagram below, first developed by the National Research Council (NRC) in 1994 54  (see Figure 5).

Prior to conducting a risk assessment, environmental data must be collected and analyzed. This requires planning and scoping to determine sampling and analytical needs. However, since characterization of an impacted area is an iterative process, these needs may be revisited as more information is obtained. The DHS Chemical and Security Analysis Center (CSAC) has the capacity to run risk and consequence modeling available to assist U.S. planning and response organizations.

The four components of risk assessment are described below, with hazard identification and dose- response assessment combined under the heading of toxicity assessment.

4.2.1. TOXICITY ASSESSMENT

Toxicity assessment integrates information from the hazard identification and dose-response assessment components of risk assessment.

4.2.1.1 Hazard Identification

Hazard identification is the process of determining whether an adverse health effect is likely to occur in humans and whether exposure to a particular chemical can cause an increase in the incidence of an adverse health effect in the near or long term (e.g., kidney failure, birth defects, cancer). Hazard identification involves characterizing the nature and strength of the evidence of causation. 55

4.2.1.2 Dose-Response Assessment

The purpose of the dose-response assessment is to determine the relationship between the magnitude of exposure (may be expressed as an environmental concentration or internal dose) to a substance and the resultant changes in body functions (response) or health. From this quantitative dose-response relationship, toxicity values are derived that can be used to estimate the incidence of adverse effects occurring in humans at different exposure levels. Chemical risk assessments have been conducted for some chemicals and the resulting toxicity values are available in published documents. Dose-response data are often used to derive these values. Chemicals may elicit different effects depending on the exposure route (oral, dermal, or inhalation), duration, and exposure concentration. Therefore, an appropriate evaluation of the dose-response relationship should consider the duration and exposure concentration for all relevant routes of exposure, when such data are available.

In the risk assessment, the dose to an exposed individual or group is compared to available toxicity values to estimate the potential for adverse health effects. Personal sampling for chemical exposures is the preferred method to estimate exposures; however, because it is not always possible to measure the actual dose on individual, concentrations in the environment are often used as a proxy for human exposure.

Just as exposure concentration is directly related to the dose an individual receives, the dose is directly related to the severity of injury. Besides severe injury and death, more subtle toxic effects are also considered adverse. Examples of these more subtle toxic effects include potential short-term effects such as impaired mobility or altered rates of basic physiological processes (e.g., respiration, heart rate), and potential longer-term effects such as decreased general or reproductive health, or the potential to develop cancer later in life.

Another important concept related to dose is the exposure rate . With some hazardous chemicals, the degree of damage is not simply dependent on the total dose received, but also on the rate at which the dose is received and the duration of exposure. This is especially true for chemicals that are metabolized relatively quickly into nontoxic metabolites. The type of adverse health effect associated with a hazardous chemical, the exposure rate, the duration of exposure, and the specific areas of the body exposed combine to determine the type and severity of injury.

4.2.2. EXPOSURE ASSESSMENT

The objective of the exposure assessment is to estimate the magnitude of actual or potential human exposures, the frequency and duration of these exposures, and the pathways by which humans may be exposed. Conducting an exposure assessment involves: 1) analyzing contaminant releases; 2) identifying exposed populations; 3) identifying all potential pathways of exposure; 4) estimating environmental concentrations for specific pathways; and 5) estimating contaminant intakes (i.e., doses) for each pathway. An exposure pathway is the course that a chemical takes from a source to an individual. Each exposure pathway includes a source or release from a source, an environmental concentration at the point of exposure, and an exposure route. If the point of exposure is some distance from the source, a transport medium (e.g., air) is also included. The exposure route is the way the individual encounters the chemical (i.e., through inhalation, ingestion and/or dermal contact). The route is important because the toxic effects of certain chemicals vary with different routes of exposure. For example, hydrofluoric acid can cause skin burns with dermal exposures and lung damage with inhalation exposure.

Physical and chemical properties influence the likelihood of human exposure. For example, volatile chemicals or gases that are readily dispersed can quickly affect relatively large areas and have the potential to impact a greater number of people. If a nonvolatile hazardous chemical is easily dispersible or readily forms an aerosol, it poses a risk of inhalation exposure in addition to the potential for direct contact exposure. Thus, managers need to be aware that measures taken to reduce inhalation exposures may not fully address the risks of exposure via other routes such as dermal contact or ingestion.

The distribution or pattern of hazardous chemical contamination in the impacted area is a crucial variable for exposure assessment. A sampling plan is executed to define the distribution of hazardous chemicals. If the distribution is understood, then the information can be used in risk management decision-making. Even though the distribution of a hazardous chemical is necessary information to understand the potential for exposure, such information does not constitute exposure assessment by itself; it is also necessary to identify the potentially exposed populations and characterize the frequency and duration of their exposures.

The mass of the chemical in the environment and the identification of the materials and surfaces that are contaminated will assist in estimating the magnitude of the problem and the potential routes of exposure. Unfortunately, it is possible that not all hazardous chemicals will be detectable in environmental samples. For example, some chemicals may degrade in the sample container so quickly that they are no longer present in a sample by the time the analysis is performed. Alternately, their presence might be masked by other environmental contaminants, or the methods for detection might not be sensitive enough to accurately quantify the chemical. The inability to detect a particular chemical that is known to have been released should not be interpreted as the absence of the chemical. Other sources of information, including epidemiologic and forensic evidence, should be evaluated in the context of what is known about the toxicant and specific nature of the incident in question to form a hypothesis of the distribution and intensity of contamination. Such information can then be used to inform the exposure assessment.

4.2.3. RISK CHARACTERIZATION

Risk characterization combines the information about toxicity and exposures to estimate the risk for developing adverse health effects. Risk characterization also serves as the bridge between risk assessment and risk management. Major assumptions, scientific judgments, and to the extent possible, the uncertainties associated with the risk assessment and the degree to which risks may be under- or over-estimated are discussed and communicated to the decision-makers and the public. 56  All information that will help inform the risk management decisions (including uncertainties and ranges for exposure and/or effect data) should be communicated clearly.

Risk assessments can be initiated at different phases of the response and can be tailored to quantify and evaluate risk to different groups for different purposes. Risk assessments for workers will incorporate regulatory occupational standards enforced by OSHA and worker focused guidelines for protective measures that are different than the standards and guidelines for protective measures used in the general population risk assessment. Although detailed, site-specific quantitative estimates of risk can be derived using data gathered during the response, qualitative risk assessments can also be developed through comparisons of measured environmental chemical concentrations to benchmarks of toxicity and exposure that have been developed by a variety of federal and state agencies: pre-calculated, health- based exposure guidelines (e.g., Acute Exposure Guideline Levels or AEGLs for short-term exposures; Regional Screening Levels for longer-term exposures; or Occupational Exposure Limits [OELs] and Immediately Dangerous to Life and Health [IDLH] values for occupational exposures). These health-based exposure guidelines are derived using equations that combine a toxicity value, a level of risk, and a set of exposure assumptions for a particular chemical, medium, and exposure scenario. Thus, the resulting health-based exposure guideline will be specific to a particular population and exposure scenario (Figure 6). For example, there are health-based exposure guidelines developed for workers that assume exposures lasting only 15 minutes and other exposure guidelines for exposures lasting 8 or 10 hours per day, 40 hours per week for a working lifetime. Likewise, there are exposure guidelines that are based on long-term/lifetime exposures to the general population that are meant to be protective of sensitive members of the population, such as children and the elderly. It should be recognized that all these approaches incorporate some degree of uncertainty in the estimated value. See Appendix A for more information.

In addition to the variables associated with the populations of concern, the exposure concentrations and the environmental persistence of the chemical contaminant may affect the magnitude of health risk associated with the exposure. One of the critical questions to be asked in performing a risk assessment associated with chemical remediation/cleanup is: “Will the hazardous chemical persist in the environment and pose a potential long-term health hazard?” The answer to this question will determine the duration of the potential exposure and the complexity and scope of the overall remediation operation. Therefore, integrating accurate information regarding persistence, total dose, toxicity, and exposure is critical to the formulation of a scientifically sound risk characterization and resultant remediation plan.

Although it may be preferred that technical staff supporting the IC develop scenario-specific remediation goals that include site- and situation-specific descriptors of exposure, in the absence of resources and site-specific information, pre-calculated, health-based exposure guidelines can provide a useful tool for risk assessors and decision-makers. However, it is important to clearly understand the basis for each exposure guideline to ensure that they are used appropriately in the response action. An overview and description of health-based exposure guidelines are presented in Appendix A.

EPA’s Risk Assessment Forum has identified four distinct time intervals that can be used to determine appropriate levels of concern for toxicity from chemical exposures. 57  These include exposures for acute (<24 hours), short-term (1 to 30 days), long-term (30 days to several years), and chronic (up to a lifetime of repeated exposure) durations. Acute exposure guidelines are often prescribed for use during emergency response decisions such as evacuation/sheltering-in-place, or for emergency drinking water guidance. In modeling and some planning activities, the lowest of the acute (one-time single exposure) exposure guidelines have sometimes been used to demarcate the edge of a hazard area. 58, 59   That is, these values delineate the level below which there is little to no immediate hazard to first responders for acute exposure durations. These acute exposure duration guidelines can also be used to inform decision- making regarding potential exposures to the general population during evacuation. Based on this approach, it is assumed that locations with exposure concentrations below the acute exposure guideline are less hazardous compared to those areas with concentrations above the exposure guideline. 60

Chronic or long-term exposure guidelines, which are based on long-term/lifetime exposures, reside at the other end of the exposure spectrum from the acute values. 61  Chronic exposure guidelines can be used as environmental screening levels or cleanup goals to evaluate chemical concentrations in different materials and surfaces and can assist in decisions regarding the extent of contamination or as a starting point for developing the ultimate clearance decision. In addition, a variety of risk assessment methods can be employed in developing risk-based, chemical-specific, site-specific radiation goals that can be used in conjunction with other site- and situation-specific information for making determinations concerning decontamination/remediation options.

Recommendations for the exposure guidelines that are most appropriate for any given situation should take into consideration the complexities and uncertainties of these determinations in order to use the available exposure guidelines most appropriately. Additionally, exposure guidelines can also be used to evaluate the adequacy of the detection limits of field- or laboratory-based analytical methods used to determine the extent and magnitude of contamination. Ideally, the full range of existing exposure guidelines should be evaluated in the context with the exposure range for the site-specific information (population exposed, duration of exposure, etc.), underlying assumptions, and other factors described in this section before determining the final cleanup goal(s).

In terms of available exposure guidelines, a wide array of quantitatively derived human toxicity and health-based exposure limits and guidelines exist for many substances. However, for certain chemicals

and certain types of environmental media, there simply may not be an existing value. In that situation, the decision-maker can consult with subject matter experts who may consider several options. 62   They can review available toxicity data from animal and human studies to determine if a human exposure value could be estimated using the same modeling procedures and principles used to develop the exposure guidelines described in Appendix A. 63  Another approach would be to use structural modeling, such as Quantitative Structure Activity Relationship (QSAR), or surrogate/relative potency chemical toxicity information to derive an alternative value. 64  These options may have several drawbacks and may not be practical in a large-scale incident. However, while QSAR modeling may be viewed as complex, it may yield useful risk assessment information. How it is managed is what's important.

Qualitative and Quantitative Risk Assessment of Hazardous Substances in the Workplace

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Original Research 22 November 2022 Improvements in protective measures in factories with acetylene hydrochlorination and ethylene oxychlorination techniques declined risk assessment levels and affected liver health status Yiwen Dong ,  7 more  and  Meng Ye 1,535 views 1 citations

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Original Research 16 November 2022 Evaluation of strategies for the occupational health risk assessment of chemical toxicants in the workplace based on a quantitative analysis model Qiuliang Xu ,  8 more  and  Yiyao Cao 1,826 views 1 citations

Original Research 14 November 2022 Impact of engineering renovation on dynamic health risk assessment of mercury in a thermometer enterprise Peihong Wu ,  6 more  and  Hengdong Zhang 942 views 3 citations

Original Research 25 October 2022 Exposure characteristics and risk assessment of air particles in a Chinese hotel kitchen Zanrong Zhou ,  3 more  and  Yulan Jin 1,135 views 0 citations

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Chemical Risk Assessment: Overview and Examples

In this article, we will give you an introduction to chemical risk assessment. We will focus on EU REACH regulation and industrial chemicals. However, the principles given in this article are consistent with risk assessment methodologies for other sector uses such as pesticides and cosmetics. 

If you have no chemistry, toxiclogy or eco-toxicology background, please start with following parts first.

• Chemical risk assessment basics part 1: Physico-chemical properties
• Chemical risk assessment basics part 2: Ecotoxicology and e-fate studies
• Chemical risk assessment basics part 3: Toxicology studies

Risk = Hazard x Exposure

When it comes to chemical management, a distinction must be made between hazard and risk. Hazard defines the inherent property of a chemical having the potential to cause adverse effects when an organism, system or population is exposed to that agent. Risk however, establishes the probability of the adverse effect occurring.

To be more specific, the risk of a chemical depends on the following 2 factors:

• The inherent toxicity of the chemical (hazard );
• How much of a chemical is present in an environmental medium (e.g., water, soil, air) and how much contact a person or ecological receptor has with the chemical substance ( exposure ).

A hazardous chemical substance poses no risk if there is no exposure . For example, sulfuric acid is very corrosive. It is of no or little risk to ordinary people who do not handle them. For some people who may be exposed to sulfuric acid (scientists, workers), risk management measures (i.e, wearing goggles and gloves) can be taken to minimize the risk.

Chemical Risk Assessment: Purpose, Procedure and Tasks

The goal of chemical risk assessment is to have a full understanding of the nature, magnitude and probability of a potential adverse health or environmental effect of a chemical. It takes into account of both hazard and exposure . Risk assessment forms the foundation of regulatory decisions for industrial chemicals, pesticides, pharmaceuticals, cosmetics, food additives and food contact substances in developed countries today.

In general, chemical risk assessment consists of the following three steps:

• Hazard characterization : Dose-response determination (LD50/LC50 , NOAEL , T25 , EC50 , NOEC , etc), determining the relationship between the magnitude of exposure to a hazard and the probability and severity of adverse effects.
• Exposure assessment : identifying the extent to which exposure actually occurs. Exposure levels are usually estimated or measured.
• Risk characterization : combining the information from the hazard characterization and the exposure assessment in order to form a conclusion about the nature and magnitude of risk, and, if indicated, implement additional risk management measures.

The picture below summarizes the complete procedure of chemical risk assessment under REACH.

The table below summarizes the detailed tasks of hazard characterization, exposure assessment and risk characterization for human health and the environment.

It shall be noted that risk characterization is an iterative process. If initial RCR>1, certain risk management measures can be taken to effectively reduce the RCR by reducing exposure. Such measures may include reducing the amount used, reducing the time or frequency of working, or reducing emissions.

How to Obtain Derived No- Effect Level (DNEL)?

Derived No- Effect Level (DNEL) is the level of exposure to the substance above which humans should not be exposed.  The DNELs are calculated by dividing the value of the health effect dose descriptor (NOAEL, NOAEC, LD50, LC50) by an assessment factor .Since dose descriptors are obtained from experimental data, an assessment factor is required to allow for extrapolation to real human exposure situations.

It may not always be possible to derive DNELs for each health effect. This may be the case, for example, for carcinogenicity , where no safe threshold level can be obtained. In these cases a semi-quantitative value, known as the DMEL or Derived Minimal Effect level may be developed

Read More : How to Derive DNELs?   How to Calculate DMELs?

DNEL and Human Healh Risk Assessment Example

In above case, the DNEL used for risk characterization will be 0.1mg/kg bw/day . If an adult (assuming weight is 60kgs ) intakes 12mg of a chemical substance per day, the estimated exposure (external dose per body weight) will be 0.2mg/kg bw/day . Since the exposure estimate is greater than DNEL, which will lead to a RCR>1, the risk will not be acceptable.

Note:  Assessment factors are not randomly chosen. For more info about how to choose appropriate assessment factors to obtain DNEL, please read how to derive DNEL .

How to Obtain Predicted No Effect Concentration (PNEC)?

The Predicted No Effect Concentration or PNEC is the concentration of a substance in any environment below which adverse effects will most likely not occur during long term or short term exposure. The PNEC needs to be determined for each environmental compartments (water, soil, sediment, etc.).

The PNEC for each environment is estimated by dividing the dose descriptor by the relevant assessment factor . Since dose descriptors are obtained from laboratory tests involving a limited number of species, the assessment factor is required to account for the uncertainties involved in the extrapolation to the real ecosystems.

Where several dose descriptors are available for an environment, all the possible PNECs will be derived.The lowest PNEC will later be used for risk characterization.

PNEC and Environmental Risk Assessment Example

In above case, PNEC-surface water is calculated as 1mg/L based on test data on the most sensitive species (Daphnia). Let's assume that we discharge waste water containing 20mg/L of a substance directly to river and the dilution factor is 10 , the Predicted Environmental Concentration (PEC-water) will be 2mg/L . Since the RCR(equal to PEC-water/PNEC-water) is 2, the risk is not acceptable. However, if we take some risk management measures (i.e, oxidization, neutralization) to remove >60% of the substance from waste water before discharging, we will get a RCR less than 1 and acceptable risks.

For other environmental compartments (sediment, soil, STP), we can do the same risk characterization. For more info about how to choose appropriate assessment factors to derive PNECs for various environmental compartments , please read how to derive Predicted No Effect Concentration (PNEC) . 

How to Estimate Exposure Level or PEC?

Under REACH, exposure estimation is only required for hazardous substances. When estimating exposure, all human populations liable to exposure and all environmental compartments for which exposure to the substance is known, need to be addressed.

Ideally, the process for estimating exposure should be based on measurement data. In practice, the availability of reliable measurement exposure data is scarce and mostly limited to the workplace.  In most cases, exposure estimation has to be based on exposure estimation models .

The most convenient models (also free) include:

• ECETOC TRA model for workers and consumer exposure estimation
• EUSES model for environmental exposure estimation

The reason that ECETOC TRA and EUSES are widely used is because they use standard parameters in a typical exposure scenario as input data . The standard parameters include the use descriptors, the concentration of a substance in a product, the applied amount, the duration of exposure or the presence of local exhaust ventilation or personal protection equipment. 

If you could gather all standard parameters for each exposure scenarios/use listed in the table below and input them to ECETOC TRA and EUSES,  you will get exposure estimates as output data. 

It should be noted that each of these models offers an initial estimation of exposure based on conservative or worst case exposure conditions . This estimation is usually defined as Tier 1 estimation. When the risk characterization shows that risks are not under control for these exposure conditions, additional estimation based on more detailed and specific data may be needed. This higher Tier estimation can be done using more sophisticated and detailed models or measured exposure data.

For more info about how to estimate exposure levels, please read the articles below.

• How to use ECETOC TRA to estimate worker exposure and consumer exposure (being developed);
• How to use EUSES to estimate environmental exposure  

References and More Readings

• ECHA Guidance on Chemical Safety Assessment (n a Nutshell)
• ECHA Guidance on Information Requirements and Chemical Safety Assessment
• ICCA Guidance on Chemical Risk Assessment

Good job. You have learned the difference between hazard and risk. You have also learned what are tasks of hazard characterization, exposure assessment and risk characterization. Please keep it going. This is part 4 of our chemical risk assessment basics.

"It does not matter how slowly you go as long as you do not stop. " – Confucius

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Hot Articles

Hazard Identification and Risk Assessment

Research laboratories are dynamic, fluid environments.  For the most part, no two days are alike; experiments change frequently and represent a variety of hazards.  Lab workers also represent a wide range of backgrounds and skills, from high school students to scientists with decades of experience. 

Hazard identification and evaluation, hazard controls, roles and responsibilities, and general chemical safety are all important parts of this assessment.

Steve Elwood Director for Research Safety 609-258-6271

Shaundree Davis Assistant Director, Environmental Health 609-258-6256

Stanley Howell Sr. Program Manager - Chemical Safety 609-258-2711

Hazard Identification and Evaluation

Before beginning the hazard evaluation and risk assessment process, a researcher must define the scope of work.  What are the tasks that must be evaluated?  A well-defined scope of work is a key starting point for all steps in the risk assessment and hazard analysis. 

The next step after identifying the scope of work is to identify the hazard.  A HAZARD IS A POTENTIAL FOR HARM .   Hazards can be identified as an agent, condition, or activity that has the potential to cause injury, illness, loss of property, or damage to the environment.  The table below has been adapted from Identifying and Evaluating Hazards in Research Laboratories , which you can find in the Resource tab to the right.

• Identifying and Evaluating Hazards in Research Laboratories.pdf

Steve Elwood Associate Director 609-258-6271

Hazard Controls

When evaluating the risks associated with specific hazards, the results of this evaluation should guide the researcher in the selection of risk management techniques including elimination, substitution, engineering controls, administrative controls, and personal protective equipment.  This is known as the Hierarchy of Controls.

Image courtesy of NIOSH . 

Elimination and Substitution

The most preferred method of controlling risk is to eliminate the hazard altogether. In most cases, elimination is not feasible and when possible, substitution is the best approach to hazard mitigation.  When possible, substitute less hazardous agents in place of their more hazardous counterparts.  This also applies to conditions and activities.  Examples include substituting toluene for benzene, non-lead-based paints for lead-based ones, or SawStop table saws for existing traditional table saws. 

Engineering Controls

Engineering controls consist of a variety of methods for minimizing hazards, including process control, enclosure and isolation, and ventilation.

• Process controls involve changing the way that a job activity is performed in order to reduce risk.  Examples of this include using wet methods when drilling or grinding or using temperature controls to minimize vapor generation.
• Enclosure and isolation are targeted at keeping the chemical in and the researcher out, or visa versa.  Glove boxes are a good example of enclosure and isolation.  Interlock systems for lasers and machinery are other good examples of isolating processes.
• The most common method for ventilation in research laboratories is localized exhaust systems.  Fume hoods, snorkels, and other ventilation systems are discussed at length in the Laboratory Equipment and Engineering Controls section of this site.

Administrative Controls

Administrative controls are controls which alter the way work is performed.  They may consists of policies, training, standard operating procedures/guidelines, personal hygiene practices, work scheduling, etc.  These controls are meant to minimize the exposure to the hazard and should only be used when the exposure cannot be completely mitigated through elimination/substitution or engineering controls.  

Personal Protective Equipment (PPE)

PPE should always be used as a last line of defense and is an acceptable control method when engineering or administrative controls cannot provide sufficient protection.  PPE may also be used on a temporary basis while engineering controls are being developed.  See the standalone PPE section of this site for more information.

Roles and Responsibilities

Laboratory worker.

• Attend laboratory safety training.
• Review the Chemical Hygiene Plan
• Follow procedures and laboratory practices outlined in the Chemical Hygiene Plan and EHS Website and as provided by supervisors and principal investigators.
• Use engineering controls and personal protective equipment, as appropriate.
• Report all incidents, accidents, potential chemical exposures and near miss situations to the principal investigator and the Chemical Hygiene Officer .
• Document specific operating procedures for work with particularly hazardous substances , including carcinogens, reproductive toxins and chemicals with high acute toxicity.

Principal Investigators

• Ensure laboratory workers attend laboratory safety training given by EHS.
• Ensure laboratory workers understand how to work with chemicals safely. Provide chemical and procedure-specific training, as needed.
• Provide laboratory workers with appropriate engineering controls and personal protective equipment needed to work safely with hazardous materials. Ensure such equipment is used correctly.
• Ensure laboratory workers complete and submit Particularly Hazardous Substance Use Approval forms and submit them for approval before using any particularly hazardous substance.
• Review and approve work with particularly hazardous substances .

Departmental Chemical Hygiene Officer

• Establish and implement a Chemical Hygiene Plan.
• Review and update the Chemical Hygiene Plan at least annually.
• Investigate accidents and chemical exposures within the department.
• Act as a liaison between the department and EHS for laboratory safety issues.
• Maintain records of training, exposure monitoring and medical examinations.
• Ensure laboratory workers receive chemical and procedure-specific training.
• Review and approve use of particularly hazardous substances .
• Approve laboratory worker's return to work following a chemical exposure requiring medical consultation.

Environmental Health and Safety (EHS)

• Conduct exposure monitoring, as needed.
• Provide general training.
• Audit the departmental program periodically.
• Provide safe working guidelines for laboratory workers through the EHS web page.
• Review the model Chemical Hygiene Plan at least annually.
• Inspect fume hoods annually.
• Provide consultation for safe work practices for hazardous chemicals.
• Conduct limited laboratory safety inspections annually.
• Develop and maintain the EHS Website.

Chemical Safety and Risk Assessments

General Chemical Safety

Physical health hazards of chemicals, routes of entry, and chemical exposures are all discussed at length in the Hazard Communication-Chemical Safety section of this site. 

For more specific chemical handling, storage, and waste considerations, please visit the Chemical Safety page located in the Laboratory & Research Safety section.   

Risk Assessments

There are a variety of methods for conducting risk assessments. For assistance in conducting a risk assessment for your laboratory, please contact EHS . 

Quick Guide to Risk Assessment for Hazardous Chemicals

The following outline provides a summary of the steps that laboratory workers should use to assess the risks of handling toxic chemicals.

• Identify chemicals to be used and circumstances of use. Identify the chemicals involved in the proposed experiment and determine the amounts that will be used. Is the experiment to be done once, or will the chemicals be handled repeatedly? Will the experiment be conducted in the open laboratory, in an enclosed apparatus, or in a fume hood? Is it possible that new or unknown substances will be generated in the experiment? Are any of the workers involved in the experiment pregnant or likely to become pregnant?
• Consult sources of information. Consult an up-to-date SDS for each chemical involved in the proposed experiment. Depending on the worker's level of experience and the degree of potential hazard associated with the proposed experiment, it may be necessary to obtain the assistance of supervisors and safety professionals before proceeding with risk assessment.
• Evaluate type of toxicity. Use the above sources of information to determine the type of toxicity associated with each chemical involved in the proposed experiment. Are any of the chemicals to be used acutely toxic or corrosive? Are any of the chemicals to be used irritants or sensitizers? Are any suspected to be reproductive toxins or neurotoxins?
• Consider possible routes of entry. Determine the potential routes of exposure for each chemical. Are the chemicals gases, or are they volatile enough to present a significant risk of exposure through inhalation? If liquid, can the substances be absorbed through the skin? Is it possible that dusts or aerosols will be formed in the experiment? Does the experiment involve a significant risk of inadvertent ingestion or injection of chemicals?
• Evaluate quantitative information on toxicity. Consult the information sources to determine the LD 50 for each chemical via the relevant routes of exposure. Determine the acute toxicity hazard level for each substance, classifying each chemical as highly toxic, moderately toxic, slightly toxic, and so forth.
• Select appropriate procedures to minimize exposure. Use basic prudent practices for handling chemicals. These include practicing good housekeeping, safe storage of chemicals, using personal protective equipment that is appropriate for the material and disposing of hazardous waste properly. In addition, determine whether if any of the chemicals meet the definition of a particularly hazardous substance due to high acute toxicity and/or reproductive toxicity. Use this information to determine whether it is appropriate to apply additional procedures for work with highly toxic substances, and whether additional consultation with safety professionals is warranted.
• Prepare for contingencies. Note the signs and symptoms of exposure to the chemicals to be used in the proposed experiment. Note appropriate measures to be taken in the event of exposure and accidental release of any of the chemicals.

Contact the WPI Office of Environmental Health and Safety at [email protected] for more information.

Control measures to prevent or limit exposure to hazardous substances

What is coshh for.

The objective of COSHH is to prevent, or to adequately control, exposure to substances hazardous to health, so as to prevent ill health.

You can do this by:

• using control equipment, eg total enclosure, partial enclosure, LEV ;
• controlling procedures, eg ways of working, supervision and training to reduce exposure, maintenance, examination and testing of control measures;
• worker behaviour, making sure employees follow the control measures.

Changing how often a task is undertaken, or when, or reducing the number of employees nearby, can make an improvement to exposure control.

See Working with substances hazardous to health: A brief guide to COSHH .

You should also look at the HSE REACH web pages for information about what the Regulations mean for users of chemicals.

Control equipment

Control equipment can be general ventilation, extraction systems such as local exhaust ventilation , enclosure, or where the air cannot be cleaned, refuges and respiratory protective equipment (RPE).

Other control equipment includes spillage capture, decontamination, clean-up procedures and personal protective equipment (PPE) .

Ways of working

Control through ways of working includes operating procedures, supervision and training.

It includes emergency procedures, decontamination and ' permits to work ' for tasks such as maintenance.

It also means testing all control measures regularly – equipment, ways of working and behaviour, to make sure that they work properly.

You should keep records of examinations, tests and repairs to equipment for at least five years. This helps to identify any trends or variations in equipment deterioration.

Worker behaviour

Where control measures are in place it is important to use them properly.

This includes:

• wearing any PPE necessary;
• using control equipment;
• following hygiene procedures;
• warning supervisors if anything appears to be wrong.
• Local exhaust ventilation
• Personal protective equipment (PPE)
• Permits to work

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Chemicals Risk Assessment

Almost all workplaces use chemicals which mean employees can be routinely exposed to paints, sprays, inks, toners and adhesives not to mention a wide range of materials used in cleaning and maintenance such as detergents and oils. Chemicals can be solids (e.g. dusts, fibres), liquids or mists (e.g. bleach) or gases / vapours (e.g. carbon monoxide, chlorine or ammonia). They can be individual substances like petrol or mixtures / products (e.g. paints, degreasers, ink and toners). Any chemical, in either gas, liquid or solid form, that has the potential to cause harm is referred to as a hazardous chemical. Chemicals include those that are brought into the workplace and used for processing (e.g. solvents and cleaning agents) and those that are generated by a process or work activity (such as fumes from welding / soldering) or generated as waste or residue (such as carbon monoxide from engine or exhausts).

How can chemicals cause harm to health?

Chemicals can cause harm to health ranging from mild skin irritation to cancer when they come in contact with the human body. The effects of hazardous chemicals may be seen immediately after contact e.g. chemical burn, or many years after contact e.g. lung cancer following exposure to asbestos. Harm can also occur following a single short exposure such as the use of a chemical for a couple of hours or longer-term exposures from the daily use of a chemical. Chemicals can come in contact with or enter the human body through inhalation (breathing in contaminated air), skin contact (splash, absorption through the skin), ingestion (swallowed accidentally e.g. not washing hands before eating) or injection (from sharp objects such as needles).

Examples of the effects of hazardous chemicals include:

• Skin irritation, dermatitis or skin cancer from frequent contact with oils
• Injuries to hands and eyes from contact with corrosive liquids such as acids / bases
• Asthma due to sensitisation to isocyanates in paints and adhesives
• Lung diseases following exposure to dusty environments such as respirable dust, wood dust or flour dust
• Death or injury from exposure to toxic gas, e.g. chlorine, ammonia, carbon monoxide

Some chemicals also present physical hazards such as the potential to ignite or support combustion of other chemical substances (an oxidiser).

Assessing the risk of chemicals

The Chemical Agent Regulations 2001 to 2021 point out the specific requirements necessary to complete a Chemical Agents risk assessment of the chemical agents used in the workplace. A generic assessment is unlikely to meet the requirements of the legislation. The Control of Substances Hazardous to Health (COSHH) Regulations are UK Regulations and do not apply in Ireland. COSHH assessments are UK requirements and do not meet the Irish legal requirements for risk assessments.

In the case of a new activity involving hazardous chemical agents, work shall not commence until after an assessment of the risk of that activity has been made and the preventive measures identified in the risk assessment have been implemented.

The risk assessments should be based on activities involving chemicals - the risk depends not only on the chemical or chemicals (many activities involve more than one) but also on how it is being stored, transported, used, generated or disposed of.

1. Make a list (inventory) Walk around your workplace, check your purchase orders and make a list of all the chemicals you bring in and those generated by work activities or waste (welding fume, dust, residues).

Organise the list by job roles / activities. Many jobs involve more than one chemical so employees can be exposed to several hazards.  Where there is exposure to several chemical agents, the risk shall be assessed on the basis of the risk presented by all such chemical agents in combination.

2. Identify chemical hazards The most important sources of information on the hazards of the chemicals brought into your workplace are the label and safety data sheet (SDS). Chemical containers should be supplied with a label which clearly identifies the chemical and its hazards. Where a chemical is hazardous, the label should contain a signal word (danger or warning) and may include an associated pictogram and a hazard statement giving more detailed information on the hazard (e.g. causes serious eye irritation, causes skin irritation). It should also contain precautionary statements giving advice on safety precautions to be taken (e.g. keep out of reach of children, wear protective gloves / protective clothing / eye protection / face protection). The safety data sheet is a document that should be provided by the supplier. The safety data sheet is a key tool for risk assessment as it includes detailed hazard information, advice on safe handling, use and storage, and the emergency measures to be followed in case of an accident.

For chemicals generated by work activities and chemicals which do not require a Safety Data Sheet (e.g. medicines, cosmetics), you can get information from:

• HSA Website (e.g. RCS, Welding fumes, Hazardous Medicinal Products)
• Professional organizations (e.g. BOHS, IOSH, OHSI, Roadmap on Carcinogens)
• Recognized Trade or representative Organizations

3. Assess exposure Once you have identified your chemical hazards you then need to assess what the potential exposure is to your employees. This involves looking at each chemical which you have identified as hazardous and considering the following questions:

• How is the chemical used (e.g. sprayed, poured) and how often is the chemical used?
• How will the user be exposed? (e.g. breathing it in, contact with skin?)
• How much is used /generated ?
• How long is each user exposed to the chemical? (e.g. full shift or a few minutes?)
• Who uses the chemical? (e.g. how many people?)
• Are any vulnerable groups potentially exposed? For example, identify if reprotoxins are in use.
• Is the chemical mixed with other chemicals or exposed to high temperatures or pressure?
• Can non-users be exposed? (e.g. people working nearby, visitors, cleaning or maintenance staff?)

4. Control your chemical risks Once you have assessed the risk associated with your chemicals, control measures must be put in place in order to keep your employees, your workplace, and the environment safe.

You should first consider if you can eliminate the hazard by changing the process or removing the hazardous chemical.

If you cannot eliminate the chemical(s), can you substitute the hazardous chemical with another, non-hazardous or less hazardous chemical? For example, you could replace isocyanate based paints with water based paints or you could use a less hazardous form of the same chemical (e.g. using a pellet rather than a powder form of the chemical could have a significant effect on reducing inhalable dust levels).

Where the above options are not possible, exposure to hazardous chemicals should be minimised and additional control measures must be put in place to remove or reduce the risks to employees:

• Engineering controls e.g. local exhaust ventilation (LEV), on tool extraction, isolation / containment hoods or booths
• Review of current work practices or procedures to reduce the frequency and length of exposure
• Training for employees on the chemicals currently used in the workplace, what the chemical hazards are and the potential risks to their health, and how to handle chemicals safely
• Hygiene arrangements e.g. separate meal and wash facilities, designated smoking areas or a no smoking policy
• Specific Storage arrangements so that chemicals are stored correctly, safely and securely. (Information on storage is available in section 7 of the SDS)
• Personal protective equipment (PPE), e.g. eye protection, gloves, masks and respiratory masks (RPE). As these are the last line of defence, PPE is used to control any residual risk after taking all the other measures. PPE only protects the user.    Information on the correct PPE and RPE is provided in section 8 of the SDS, but contact the supplier if unclear (Specify in your risk assessment the exact glove type, filter type etc.)
• A good level of housekeeping
• Correct disposal of waste
• Emergency procedures in case of an accident, incident or spillage, e.g. eyewashes, showers, spill kits

5. Record and review Write down your findings (this can be part of a work instructions) and discuss them with your employees. Consultation with your employees is necessary at every step and especially when implementing the findings of your chemicals risk assessment.

You may need to draw up an action plan, detailing who is responsible, for what action and when will it be carried out.

As no workplace remains the same, review your risk assessment at least once per year, and update if necessary. When changes such as new employees, machinery, equipment or materials occur in the workplace it is necessary to review the risk assessment. Change in work patterns such as overtime or shift work, the needs of pregnant/nursing employees and those with special needs must also be included.

Advice on Completing Chemical Risk Assessments

The following are examples of assessments that Inspectors have seen during inspections and investigations. They are in different formats because different formats suit different types of activities involving chemicals. The examples are varied as chemicals are varied. An approach/template/format that works in one situation will not work in another.

The formats presented below have been reviewed and comments included on how they should be improved. They illustrate how you can improve the compliance of your risk assessments. These are for interactive use and not for printing. If you print these then the pop-up directions disappear and the documents are invalid.

Example 1 Example 2 Example 3 Example 4

Quick Start questionnaire

Find and reduce the safety and health hazards associated with dangerous substances and chemical products in workplaces within your company - See EU OSHA Dangerous Substances e-tool (available in several languages).

This information sheet gives employers and employees practical advice on how to assess the risks from the chemicals in their workplace and how to manage chemicals safely.

Submission completed, thank you!

Related file(s).

Managing Hazards in the Workplace Information Pack

These information sheets will provide you with practical advice on how to manage the most common hazards in your workplace, and prevent them causing harm.

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Risk assessment for handling hazardous substances within the European industry: Available methodologies and research streams

Affiliations.

• 1 Department of Mechanical and Industrial Engineering, Norwegian University of Science and Technology, Trondheim, Norway.
• 2 Department of Mechanical, Chemical and Materials Engineering, University of Cagliari, Cagliari, Italy.
• 3 Occupational Safety and Health, CERIDES - Excellence in Innovation and Technology, European University Cyprus, Nicosia, Egkomi, Cyprus.
• PMID: 36109348
• DOI: 10.1111/risa.14010

After the Seveso disaster occurred more than 40 years ago, there has been an increasing awareness of the potential impacts that similar accident events can occur in a wide range of process establishments, where the handling and production of hazardous substances pose a real threat to society and the environment. In these industrial sites denominated "Seveso sites," the urgent need for an effective strategy emerged markedly to handle hazardous activities and to ensure safe conditions. Since then, the main challenging research issues have focused on how to prevent such accident events and how to mitigate their consequences leading to the development of many risk assessment methodologies. In recent years, researchers and practitioners have tried to provide useful overviews of the existing risk assessment methodologies proposing several reviews. However, these reviews are not exhaustive because they are either dated or focus only on one specific topic (e.g., liquefied natural gas, domino effect, etc.). This work aims to overcome the limitations of the current reviews by providing an up-to-date and comprehensive overview of the risk assessment methodologies for handling hazardous substances within the European industry. In particular, we have focused on the current techniques for hazards and accident scenarios identification, as well as probability and consequence analyses for both onshore and offshore installations. Thus, we have identified the research streams that have characterized the activities of researchers and practitioners over the years, and we have then presented and discussed the different risk assessment methodologies available concerning the research stream that they belong to.

Keywords: Seveso sites; literature review; risk analysis; risk assessment; systematic review.

© 2022 The Authors. Risk Analysis published by Wiley Periodicals LLC on behalf of Society for Risk Analysis.

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National Research Council (US) Committee on Prudent Practices in the Laboratory. Prudent Practices in the Laboratory: Handling and Management of Chemical Hazards: Updated Version. Washington (DC): National Academies Press (US); 2011.

Prudent Practices in the Laboratory: Handling and Management of Chemical Hazards: Updated Version.

• Hardcopy Version at National Academies Press

4 Evaluating Hazards and Assessing Risks in the Laboratory

4.a. introduction.

A key element of planning an experiment is assessing the hazards and potential risks associated with the chemicals and laboratory operations to be used. This chapter provides a practical guide for the trained laboratory personnel engaged in these activities. Section 4.B introduces the sources of information for data on toxic, flammable, reactive, and explosive chemical substances. Section 4.C discusses the toxic effects of laboratory chemicals by first presenting the basic principles that form the foundation for evaluating hazards for toxic substances. The remainder of this section describes how trained laboratory personnel can use this understanding and the sources of information to assess the risks associated with potential hazards of chemical substances and then to select the appropriate level of laboratory practice as discussed in Chapter 4 . Sections 4.D and 4.E present guidelines for evaluating hazards associated with the use of flammable, reactive, and explosive substances and physical hazards, respectively. Finally, nanomaterials, biohazards, and radioactivity hazards are discussed briefly in sections 4.F and 4.G , respectively.

The primary responsibility for proper hazard evaluations and risk assessments lies with the person performing the experiment. That being said, the responsibility is shared by the laboratory supervisor. The actual evaluations and assessments may be performed by trained laboratory personnel, but these should be checked and authorized by the supervisor. The supervisor is also responsible for ensuring that everyone involved in an experiment and those nearby understand the evaluations and assessments. For example, depending on the level of training and experience, the immediate laboratory supervisor may be involved in the experimental work itself. In addition, some organizations have environmental health and safety (EHS) offices, with industrial hygiene specialists to advise trained laboratory personnel and their supervisors in risk assessment. When required by federal regulation, Chemical Hygiene Officers (CHOs) play similar roles in many organizations. As part of a culture of safety, all of these groups work cooperatively to create a safe environment and to ensure that hazards are appropriately identified and assessed prior to beginning work.

4.B. SOURCES OF INFORMATION

4.b.1. chemical hygiene plan (chp).

Beginning in 1991, every laboratory in which hazardous chemicals are used has been required by federal regulations (Occupational Safety and Health Administration [OSHA] Occupational Exposure to Hazardous Chemicals in Laboratories, 29 CFR § 1910.1450) to have a written CHP, which includes provisions capable of protecting personnel from the “health hazards presented by hazardous chemicals used in that particular workplace.” All laboratory personnel should be familiar with and have ready access to their institution's CHP. In some laboratories, CHPs include standard operating procedures for work with specific chemical substances, and the CHP may be sufficient as the primary source of information used for risk assessment and experiment planning. However, most CHPs provide only general procedures for handling chemicals, and prudent experiment planning requires that laboratory personnel consult additional sources for information on the properties of the substances that will be encountered in the proposed experiment. Many laboratories require documentation of specific hazards and controls for a proposed experiment.

4.B.2. Material Safety Data Sheets (MSDSs)

Federal regulations (OSHA Hazard Communication Standard 29 CFR § 1910.1200) require that manufacturers and distributors of hazardous chemicals provide users with material safety data sheets (MSDSs), 1 which are designed to provide the information needed to protect users from any hazards that may be associated with the product. MSDSs have become the primary vehicle through which the potential hazards of materials obtained from commercial sources are communicated to trained laboratory personnel. Institutions are required by law (OSHA Hazard Communication Standard) to retain and make readily available the MSDSs provided by chemical suppliers. The MSDSs themselves may be electronic or on paper, as long as employees have unrestricted access to the documents. Be aware that some laboratories have been asked by local emergency personnel to print paper copies in the event of an emergency.

As the first step in risk assessment, trained laboratory personnel should examine any plan for a proposed experiment and identify the chemicals with toxicological properties they are not familiar with from previous experience. The MSDS for each unfamiliar chemical should be examined. Procedures for accessing MSDS files vary from institution to institution. In some cases, MSDS files are present in each laboratory, but often complete files of MSDSs are maintained only in a central location, such as the institution's EHS office. Many laboratories are able to access MSDSs electronically, either from CD-ROM disks, via the internet, or from other computer networks. Laboratory personnel can always contact the chemical supplier directly and request that an MSDS be sent by mail.

MSDSs are technical documents, several pages long, typically beginning with a compilation of data on the physical, chemical, and toxicological properties of the substance and providing concise suggestions for handling, storage, and disposal. Finally, emergency and first-aid procedures are usually outlined. At present, there is no required format for an MSDS; however, OSHA recommends the general 16-part format created by the American National Standards Institute (ANSI Z400.1). The information typically found in an MSDS follows:

• Supplier (with address and phone number) and date MSDS was prepared or revised. Toxicity data and exposure limits sometimes undergo revision, and for this reason MSDSs should be reviewed periodically to check that they contain up-to-date information. Phone numbers are provided so that, if necessary, users can contact the supplier to obtain additional information on hazards and emergency procedures.
• Chemical. For products that are mixtures, this section may include the identity of most but not every ingredient. Hazardous chemicals must be identified. Common synonyms are usually listed.
• Physical and chemical properties. Data such as melting point, boiling point, and molecular weight are included here.
• Physical hazards. This section provides data related to flammability, reactivity, and explosion hazards.
• Toxicity data. OSHA, the National Institute for Occupational Safety and Health (NIOSH), and the American Conference of Governmental Industrial Hygienists (ACGIH) exposure limits (as discussed in section 4.C.2.1 ) are listed. Many MSDSs provide lengthy and comprehensive compilations of toxicity data and even references to applicable federal standards and regulations.
• Health hazards. Acute and chronic health hazards are listed, together with the signs and symptoms of exposure. The primary routes of entry of the substance into the body are also described. In addition, potential carcinogens are explicitly identified. In some MSDSs, this list of toxic effects is quite lengthy and includes every possible harmful effect the substance has under the conditions of every conceivable use.
• Storage and handling procedures. This section usually consists of a list of precautions to be taken in handling and storing the material. Particular attention is devoted to listing appropriate control measures, such as the use of engineering controls and personal protective equipment necessary to prevent harmful exposures. Because an MSDS is written to address the largest scale at which the material could conceivably be used, the procedures recommended may involve more stringent precautions than are necessary in the context of laboratory use.
• Emergency and first-aid procedures. This section usually includes recommendations for firefighting procedures, first-aid treatment, and steps to be taken if the material is released or spilled. Again, the measures outlined here are chosen to encompass worst-case scenarios, including accidents on a larger scale than are likely to occur in a laboratory.
• Disposal considerations. Some MSDSs provide guidelines for the proper disposal of waste material. Others direct the users to dispose of the material in accordance with federal, state, and local guidelines.
• Transportation information. This chapter only evaluates the hazards and assesses the risks associated with chemicals in the context of laboratory use . MSDSs, in contrast, must address the hazards associated with chemicals in all possible situations, including industrial manufacturing operations and large-scale transportation accidents. For this reason, some of the information in an MSDS may not be relevant to the handling and use of that chemical in a laboratory. For example, most MSDSs stipulate that self-contained breathing apparatus and heavy rubber gloves and boots be worn in cleaning up spills, even of relatively nontoxic materials such as acetone. Such precautions, however, might be unnecessary in laboratory-scale spills of acetone and other substances of low toxicity.

Originally, the principal audience for MSDSs was constituted of health and safety professionals (who are responsible for formulating safe workplace practices), medical personnel (who direct medical surveillance programs and treat exposed workers), and emergency responders (e.g., fire department personnel). With the promulgation of federal regulations such as the OSHA Hazard Communication Standard (29 CFR § 1910.1200) and the OSHA Laboratory Standard (29 CFR § 1910.1450), the audience for MSDSs has expanded to include trained laboratory personnel in industrial and academic laboratories. However, not all MSDSs are written to meet the requirements of this new audience effectively.

In summary, among the currently available resources, MSDSs remain the best single source of information for the purpose of evaluating the hazards and assessing the risks of chemical substances. However, laboratory personnel should recognize the limitations of MSDSs as applied to laboratory-scale operations. If MSDSs are not adequate, specific laboratory operating procedures should be available for the specific laboratory manipulations to be employed:

• The quality of MSDSs produced by different chemical suppliers varies widely. The utility of some MSDSs is compromised by vague and unqualified generalizations and internal inconsistencies.
• Unique morphology of solid hazardous chemicals may not be addressed in MSDSs; for example, an MSDS for nano-size titanium dioxide may not present the unique toxicity considerations for these ultrafine particulates.
• MSDSs must describe control measures and precautions for work on a variety of scales, ranging from microscale laboratory experiments to large manufacturing operations. Some procedures outlined in an MSDS may therefore be unnecessary or inappropriate for laboratory-scale work. An unfortunate consequence of this problem is that it tends to breed a lack of confidence in the relevance of the MSDS to laboratory-scale work.
• Many MSDSs comprehensively list all conceivable health hazards associated with a substance without differentiating which are most significant and which are most likely to actually be encountered. As a result, trained laboratory personnel may not distinguish highly hazardous materials from moderately hazardous and relatively harmless ones.

4.B.3. Globally Harmonized System (GHS) for Hazard Communication

The GHS of Classification and Labeling of Chemicals is an internationally recognized system for hazard classification and communication. (Available at http://www.unece.org .) It was developed with support from the International Labour Organization (ILO), the Organisation for Economic Co-operation and Development, and the United Nations Sub-Committee of Experts on the Transport of Dangerous Goods with the goal of standardizing hazard communication to improve the safety of international trade and commerce. Within the United States, the responsibility for implementing the GHS falls to four agencies: OSHA, the Department of Transportation, the EPA, and the Consumer Product Safety Commission. At the time this book was written, the agencies had not yet provided final guidance on use of GHS. The revised Hazard Communication Standard (29 CFR § 1910.1200) is expected to be issued by OSHA in the near future.

GHS classifies substances by the physical, health, and environmental hazards that they pose, and provides signal words (e.g., Danger), hazard statements (e.g., may cause fire or explosion), and standard pictogram-based labels to indicate the hazards and their severity. When transporting hazardous chemicals, use the pictograms specified in the UN Recommendations on the Transport of Dangerous Goods, Model Regulations. For other purposes, the pictograms in Figure 4.1 should be used. Container labels should have a product identifier with hazardous ingredient disclosure, supplier information, a hazard pictogram, a signal word, a hazard statement, first-aid information, and supplemental information. Three of these elements—the pictograms, signal word, and hazard statements—are standardized under GHS. The signal words, either “Danger” or “Warning,” reflect the severity of hazard posed. Hazard statements are standard phrases that describe the nature of the hazard posed by the material (e.g., heating may cause explosion).

GHS placards for labeling containers of hazardous chemicals.

GHS recognizes 16 types of physical hazards, 10 types of health hazard, and an environmental hazard.

Physical hazards include

• explosives;
• flammable gases;
• flammable aerosols;
• oxidizing gases;
• gases under pressure;
• flammable liquids;
• flammable solids;
• self-reactive substances;
• pyrophoric liquids;
• pyrophoric solids;
• self-heating substances;
• substances which, in contact with water, emit flammable gases;
• oxidizing liquids;
• oxidizing solids;
• organic peroxides; and
• corrosive to metals.

Health hazards include

• acute toxicity,
• skin corrosion or irritation,
• serious eye damage or eye irritation,
• respiratory or skin sensitization,
• germ cell mutagenicity,
• carcinogenicity,
• reproductive toxicology,
• target organ systemic toxicity—single exposure,
• target organ systemic toxicity—repeated exposure, and
• aspiration hazard.

Environmental hazard includes

acute aquatic toxicity or

chronic aquatic toxicity with

• bioaccumulation potential
• rapid degradability.

In addition to the labeling requirements, GHS requires a standard format for Safety Data Sheets (SDS) that accompany hazardous chemicals. Note the change in terminology from MSDS. SDSs must contain a minimum of 16 elements:

• identification,
• hazard(s) identification,
• composition/information on ingredients,
• first-aid measures,
• firefighting measures,
• accidental release measures,
• handling and storage,
• exposure controls/personal protection,
• physical and chemical properties,
• stability and reactivity,
• toxicological information,
• ecological information,
• disposal considerations,
• transport information,
• regulatory information, and
• other information.

As with current MSDSs, these sheets are intended to inform employers and personnel of the hazards associated with the chemicals they are handling, and to act as a resource for management of the chemicals. Trained personnel should evaluate the information and use it to develop safety and emergency response policies, protocols, and procedures that are tailored to the workplace or laboratory.

4.B.4. Laboratory Chemical Safety Summaries (LCSSs)

As discussed above, although MSDSs are invaluable resources, they suffer some limitations as applied to risk assessment in the specific context of the laboratory. Committee-generated LCSSs, which are tailored to trained laboratory personnel, are on the CD accompanying this book. As indicated in their name, LCSSs provide information on chemicals in the context of laboratory use. These documents are summaries and are not intended to be comprehensive or to fulfill the needs of all conceivable users of a chemical. In conjunction with the guidelines described in this chapter, the LCSS gives essential information required to assess the risks associated with the use of a particular chemical in the laboratory.

The format, organization, and contents of LCSSs are described in detail in the introduction on the CD. Included in an LCSS are the key physical, chemical, and toxicological data necessary to evaluate the relative degree of hazard posed by a substance. LCSSs also contain a concise critical discussion, presented in a style readily understandable to trained laboratory personnel, of the toxicity, flammability, reactivity, and explosivity of the chemical; recommendations for the handling, storage, and disposal of the title substance; and first-aid and emergency response procedures.

The CD contains LCSSs for 91 chemical substances. Several criteria were used in selecting these chemicals, the most important consideration being whether the substance is commonly used in laboratories. Preference was also given to materials that pose relatively serious hazards. Finally, an effort was made to select chemicals representing a variety of classes of substances, so as to provide models for the future development of additional LCSSs. A blank copy of the form is provided for development of laboratory-specific LCSSs.

4.B.5. Labels

Commercial suppliers are required by law (OSHA Hazard Communication Standard) to provide their chemicals in containers with precautionary labels. Labels usually present concise and nontechnical summaries of the principal hazards associated with their contents. Note that precautionary labels do not replace MSDSs and LCSSs as the primary sources of information for risk assessment in the laboratory. However, labels serve as valuable reminders of the key hazards associated with the substance. As with the MSDS, the quality of information presented on a label can be inconsistent. Additionally, labeling is not always required for chemicals transferred between laboratories within the same building.

4.B.6. Additional Sources of Information

The resources described above provide the foundation for risk assessment of chemicals in the laboratory. This section highlights the sources that should be consulted for additional information on specific harmful effects of chemical substances. Although MSDSs and LCSSs include information on toxic effects, in some situations laboratory personnel should seek additional more detailed information. This step is particularly important when laboratory personnel are planning to use chemicals that have a high degree of acute or chronic toxicity or when it is anticipated that work will be conducted with a particular toxic substance frequently or over an extended period of time. Institutional CHPs include the requirement for CHOs, who are capable of providing information on hazards and controls. CHOs can assist laboratory personnel in obtaining and interpreting hazard information and in ensuring the availability of training and information for all laboratory personnel.

Sections 4.B.2 and 4.B.4 of this chapter provide explicit guidelines on how laboratory personnel use the information in an MSDS or LCSS, respectively, to recognize when it is necessary to seek such additional information.

The following annotated list provides references on the hazardous properties of chemicals and which are useful for assessing risks in the laboratory.

• International Chemical Safety Cards from the International Programme on Chemical Safety ( IPCS, 2009 ). The IPCS is a joint activity of the ILO, the United Nations Environment Programme, and the World Health Organization. The cards contain hazard and exposure information from recognized sources and undergo international peer review. They are designed to be understandable to employers and employees in factories, agriculture, industrial shops, and other areas, and can be considered complements to MSDSs. They are available in 18 languages and can be found online through the NIOSH Web site, www.cdc.gov/niosh , or through the ILO Web site, www.ilo.org .
• NIOSH Pocket Guide to Chemical Hazards ( HHS/ CDC/NIOSH, 2007 ). This volume is updated regularly and is found on the NIOSH Web site ( http://www.cdc.gov/niosh ). These charts are quick guides to chemical properties, reactivities, exposure routes and limits, and first-aid measures.
• A Comprehensive Guide to the Hazardous Properties of Chemical Substances , 3rd edition ( Patnaik, 2007 ). This particularly valuable guide is written at a level appropriate for typical laboratory personnel. It covers more than 1,500 substances; sections in each entry include uses and exposure risk, physical properties, health hazards, exposure limits, fire and explosion hazards, and disposal or destruction. Entries are organized into chapters according to functional group classes, and each chapter begins with a general discussion of the properties and hazards of the class.
• 2009 TLVs and BEIs: Based on the Documentation of the Threshold Limit Values for Chemical Substances and Physical Agents and Biological Exposure Indices ( ACGIH, 2009 ). A handy booklet listing ACGIH threshold limit values (TLVs) and short-term exposure limits (STELs). These values are under continuous review, and this booklet is updated annually. The multivolume publication Documentation of the Threshold Limit Values and Biological Exposure Indices ( ACGIH, 2008b ) reviews the data (with reference to literature sources) that were used to establish the TLVs. (For more information about TLVs, see section 4.C.2.1 of this chapter.)
• Fire Protection for Laboratories Using Chemicals ( NFPA, 2004 ). This is the national fire safety code pertaining to laboratory use of chemicals. It describes the basic requirements for fire protection of life and property in the laboratory. For example, the document outlines technical requirements for equipment such as fire suppression systems and ventilation systems for flammables and defines the maximum allowable quantities for flammable materials within the laboratory.
• Fire Protection Guide to Hazardous Materials , 13th edition ( NFPA, 2001 ). This resource contains hazard data on hundreds of chemicals and guidance on handling and storage of, and emergency procedures for, those chemicals.
• Bretherick's Handbook of Reactive Chemical Hazards , 7th edition ( Urben, 2007 ). This handbook is a comprehensive compilation of examples of violent reactions, fires, and explosions due to unstable chemicals, as well as reports on known incompatibility between reactive chemicals.
• Hazardous Chemicals Handbook , 2nd edition ( Carson and Mumford, 2002 ). This book is geared toward an industrial audience. It provides basic information about chemical hazards and synthesizes technical guidance from a number of authorities in chemical safety. The chapters are organized by hazard (e.g., “Toxic Chemicals,” “Reactive Chemicals,” and “Cryogens”).
• Sax's Dangerous Properties of Industrial Materials , 11th edition, three volumes ( Lewis, 2004 ). Also available on CD, this compilation of data for more than 26,000 chemical substances contains much of the information found in a typical MSDS, including physical and chemical properties; data on toxicity, flammability, reactivity, and explosivity; and a concise safety profile describing symptoms of exposure. It also contains immediately dangerous to life or health (IDLH) levels for approximately 1,000 chemicals, and for laboratory personnel it is a useful reference for checking the accuracy of an MSDS and a valuable resource in preparing a laboratory's own LCSSs.
• Patty's Industrial Toxicology , 5th edition ( Bingham et al., 2001 ). Also available on CD, this authoritative reference on the toxicology of different classes of organic and inorganic compounds focuses on health effects; hazards due to flammability, reactivity, and explosivity are not covered.
• Proctor and Hughes' Chemical Hazards of the Workplace , 5th edition ( Hathaway and Proctor, 2004 ). This resource provides an excellent summary of the toxicology of more than 600 chemicals. Most entries are one to two pages and include signs and symptoms of exposure with reference to specific clinical reports.
• Sittig's Handbook of Toxic and Hazardous Chemicals and Carcinogens , 5th edition, two volumes ( Pohanish, 2008 ). This very good reference, which is written with the industrial hygienists and first responder in mind, covers 2,100 substances.
• Clinical Toxicology , 1st edition ( Ford et al., 2001 ). This book is designed for clinicians and other health care providers. It describes the symptoms and treatment of poisoning from various sources.
• Casarett and Doull's Toxicology: The Basic Science of Poisons , 7th edition ( Klaassen, 2007 ). This complete and readable overview of toxicology is a good textbook but is not arranged as a ready reference for handling laboratory emergencies.
• Catalog of Teratogenic Agents , 11th edition ( Shepard and Lemire, 2004 ). This catalog is one of the best references available on the subject of reproductive and developmental toxins.
• Wiley Guide to Chemical Incompatibilities , 2nd edition ( Pohanish and Greene, 2003 ). Simple-to-use reference listing the incompatibilities of more than 11,000 chemicals. Includes information about chemical incompatibility, conditions that favor undesirable reactions, and corrosivity data.
• Occupational Health Guidelines for Chemical Hazards ( HHS/CDC/NIOSH, 1981 ) and a supplement ( HHS/CDC/NIOSH, 1995 ). The guidelines currently cover more than 400 substances and are based on the information assembled under the Standards Completion Program, which served as the basis for the promulgation of federal occupational health regulations (“substance-specific standards”). Typically five pages long and written clearly at a level readily understood by trained laboratory personnel, each set of guidelines includes information on physical, chemical, and toxicological properties; signs and symptoms of exposure; and considerable detail on control measures, medical surveillance practices, and emergency first-aid procedures. However, some guidelines date back to 1978 and may not be current, particularly with regard to chronic toxic effects. These guidelines are available on the NIOSH Web site ( http://www.cdc.gov/niosh/ ).

A number of Web-based resources also exist. Some of these are NIOSH Databases and Information Resources ( www.cdc.gov/niosh ) and TOXNET through the National Library of Medicine (NLM; www.nlm.nih.gov ).

4.B.7. Computer Services

In addition to computerized MSDSs, a number of computer databases are available that supply data for creating or supplementing MSDSs, for example, the NLM and Chemical Abstracts (CA) databases. These and other such databases are accessible through various online computer data services; also, most of this information is available as CD and computer updates. Many of these services can be accessed for up-to-date toxicity information.

Governmental sources of EHS information include

• NIOSH ( www.cdc.gov/niosh ),
• OSHA ( www.osha.gov ),
• Environmental Protection Agency (EPA; www.epa.gov ).

4.B.7.1. The National Library of Medicine Databases

The databases supplied by NLM are easy to use and free to access via the Web. TOXNET is an online collection of toxicological and environmental health databases. TOXLINE, for example, is an online database that accesses journals and other resources for current toxicological information on drugs and chemicals. It covers data published from 1900 to the present. Databases accessible through TOXNET include the Hazardous Substance Data Base (HSDB) Carcinogenic Potency Database (CPDB), the Developmental and Reproductive Toxicology Database (DART), the Genetic Toxicology Data Bank (GENE-TOX), the Integrated Risk Information System (IRIS), the Chemical Carcinogenesis Research Information System (CCRIS), and the International Toxicity Estimates for Risk (ITER). Other databases supplied by NLM that provide access to toxicological information are PubMed, which includes access to MEDLINE, PubChem, and ChemIDPlus. Free text searching is available on most of the databases.

4.B.7.2. Chemical Abstracts Databases

Another source of toxicity data is Chemical Abstracts Service (CAS). In addition to the NLM, several services provide CAS, including DIALOG, ORBIT, STN, and SciFinder. Searching procedures for CAS depend on the various services supplying the database. Searching costs are considerably higher than for NLM databases because CAS royalties must be paid. Telephone numbers for the above suppliers are as follows:

• DIALOG, 800-334-2564;
• Questel, 800-456-7248;
• STN, 800-734-4227;
• SciFinder, 800-753-4227.

Additional information can be found on the CAS Web site, www.cas.org .

Specialized databases also exist. One example is the ECOTOX database from EPA ( www.epa.gov/ecotox ). This database provides information on toxicity of chemicals to aquatic life, terrestrial plants, and wildlife.

Searching any database listed above is best done using the CAS registry number for the particular chemical.

4.B.7.3. Informal Forums

The “Letters to the Editor” column of Chemical & Engineering News (C&EN), published weekly by the American Chemical Society (ACS), was for many years an informal but widely accepted forum for reporting anecdotal information on chemical reactivity hazards and other safety-related information. Although less frequently updated, the ACS maintains an archive of all safety-related letters submitted to C&EN on the Web site of the Division of Chemical Health and Safety (CHAS) of ACS. CHAS also publishes the Journal of Chemical Health and Safety . Additional resources include the annual safety editorial called “Safety Notables: Information from the Literature” in the Organic Process Research and Development and community Listservs relating to laboratory safety.

4.B.8. Training

One important source of information for laboratory personnel is training sessions, and the critical place it holds in creating a safe environment should not be underestimated. Facts are only as useful as one's ability to interpret and apply them to a given problem, and training provides context for their use. Hands-on, scenario-based training is ideal because it provides the participants with the chance to practice activities and behaviors in a safe way. Such training is especially useful for learning emergency response procedures. Another effective tool, particularly when trying to build awareness of a given safety concern, is case studies. Prior to beginning any laboratory activity, it is important to ensure that personnel have enough training to safely perform required tasks. If new equipment, materials, or techniques are to be used, a risk assessment should be performed, and any knowledge gaps should be filled before beginning work. (More information about training programs can be found in Chapter 2 , section 2.G .)

4.C. TOXIC EFFECTS OF LABORATORY CHEMICALS

4.c.1. basic principles.

The chemicals encountered in the laboratory have a broad spectrum of physical, chemical, and toxicological properties and physiological effects. The risks associated with chemicals must be well understood prior to their use in an experiment. The risk of toxic effects is related to both the extent of exposure and the inherent toxicity of a chemical. As discussed in detail below, extent of exposure is determined by the dose, the duration and frequency of exposure, and the route of exposure. Exposure to even large doses of chemicals with little inherent toxicity, such as phosphate buffer, presents low risk. In contrast, even small quantities of chemicals with high inherent toxicity or corrosivity may cause significant adverse effects. The duration and frequency of exposure are also critical factors in determining whether a chemical will produce harmful effects. A single exposure to some chemicals is sufficient to produce an adverse health effect; for other chemicals repeated exposure is required to produce toxic effects. For most substances, the route of exposure (through the skin, the eyes, the gastrointestinal tract, or the respiratory tract) is also an important consideration in risk assessment. For chemicals that are systemic toxicants, the internal dose to the target organ is a critical factor. Exposure to acute toxicants can be guided by well-defined toxicity parameters based on animal studies and often human exposure from accidental poisoning. The analogous quantitative data needed to make decisions about the neurotoxicity and immunogenicity of various chemicals is often unavailable.

When considering possible toxicity hazards while planning an experiment, recognizing that the combination of the toxic effects of two substances may be significantly greater than the toxic effect of either substance alone is important. Because most chemical reactions produce mixtures of substances with combined toxicities that have never been evaluated, it is prudent to assume that mixtures of different substances (i.e., chemical reaction mixtures) will be more toxic than their most toxic ingredient. Furthermore, chemical reactions involving two or more substances may form reaction products that are significantly more toxic than the starting reactants. This possibility of generating toxic reaction products may not be anticipated by trained laboratory personnel in cases where the reactants are mixed unintentionally. For example, inadvertent mixing of formaldehyde (a common tissue fixative) and hydrogen chloride results in the generation of bis(chloromethyl)ether, a potent human carcinogen.

All laboratory personnel must understand certain basic principles of toxicology and recognize the major classes of toxic and corrosive chemicals. The next sections of this chapter summarize the key concepts involved in assessing the risks associated with the use of toxic chemicals in the laboratory. (Also see Chapter 6 , section 6.D .) Box 4.1 provides a quick guide for performing a toxicity-based risk assessment for laboratory chemicals.

Quick Guide for Toxicity Risk Assessment of Chemicals. The following outline provides a summary of the steps discussed in this chapter that trained laboratory personnel should use to assess the risks of handling toxic chemicals. Note that if a laboratory (more...)

4.C.1.1. Dose-Response Relationships

Toxicology is the study of the adverse effects of chemicals on living systems. The basic tenets of toxicology are that no substance is entirely safe and that all chemicals result in some toxic effects if a high enough amount (dose) of the substance comes in contact with a living system. As mentioned in Chapter 2 , Paracelsus noted that the dose makes the poison and is perhaps the most important concept for all trained laboratory personnel to know. For example, water, a vital substance for life, results in death if a sufficiently large amount (i.e., gallons) is ingested at one time. On the other hand, sodium cyanide, a highly lethal chemical, produces no permanent (acute) effects if a living system is exposed to a sufficiently low dose. The single most important factor that determines whether a substance is harmful (or, conversely, safe) to an individual is the relationship between the amount (and concentration) of the chemical reaching the target organ, and the toxic effect it produces. For all chemicals, there is a range of concentrations that result in a graded effect between the extremes of no effect and death. In toxicology, this range is referred to as the dose-response relationship for the chemical. The dose is the amount of the chemical and the response is the effect of the chemical. This relationship is unique for each chemical, although for similar types of chemicals, the dose-response relationships are often similar. (See Figure 4.2 .) Among the thousands of laboratory chemicals, a wide spectrum of doses exists that are required to produce toxic effects and even death. For most chemicals, a threshold dose has been established (by rule or by consensus) below which a chemical is not considered to be harmful to most individuals.

A simple representation of possible dose-response curves.

In these curves, dosage is plotted against the percent of the population affected by the dosage. Curve A represents a compound that has an effect on some percent of the population even at small doses. Curve B represents a compound that has an effect only above a dosage threshold.

Some chemicals (e.g., dioxin) produce death in laboratory animals exposed to microgram doses and therefore are extremely toxic. Other substances, however, have no harmful effects following doses in excess of several grams. One way to evaluate the acute toxicity (i.e., the toxicity occurring after a single exposure) of laboratory chemicals involves their lethal dose 50 (LD 50 ) or lethal concentration 50 (LC 50 ) value. The LD 50 is defined as the amount of a chemical that when ingested, injected, or applied to the skin of a test animal under controlled laboratory conditions kills one-half (50%) of the animals. The LD 50 is usually expressed in milligrams or grams per kilogram of body weight. For volatile chemicals (i.e., chemicals with sufficient vapor pressure that inhalation is an important route of chemical entry into the body), the LC 50 is often reported instead of the LD 50 . The LC 50 is the concentration of the chemical in air that will kill 50% of the test animals exposed to it. The LC 50 is given in parts per million, milligrams per liter, or milligrams per cubic meter. Also reported are LC LO and LD LO values, which are defined as the lowest concentration or dose that causes the death of test animals. In general, the larger the LD 50 or LC 50 , the more chemical it takes to kill the test animals and, therefore, the lower the toxicity of the chemical. Although lethal dose values may vary among animal species and between animals and humans, chemicals that are highly toxic to animals are generally highly toxic to humans.

4.C.1.2. Duration and Frequency of Exposure

Toxic effects of chemicals occur after single (acute), intermittent (repeated), or long-term repeated (chronic) exposure. An acutely toxic substance causes damage as the result of a single short-duration exposure. Hydrogen cyanide, hydrogen sulfide, and nitrogen dioxide are examples of acute toxins. In contrast, a chronically toxic substance causes damage after repeated or long-duration exposure or causes damage that becomes evident only after a long latency period. Chronic toxins include all carcinogens, reproductive toxins, and certain heavy metals and their compounds. Many chronic toxins are extremely dangerous because of their long latency periods: the cumulative effect of low exposures to such substances may not become apparent for many years. Many chemicals may be hazardous both acutely and chronically depending on exposure level and duration.

In a general sense, the longer the duration of exposure, that is, the longer the body (or tissues in the body) is in contact with a chemical, the greater the opportunity for toxic effects to occur. Frequency of exposure also has an important influence on the nature and extent of toxicity. The total amount of a chemical required to produce a toxic effect is generally less for a single exposure than for intermittent or repeated exposures because many chemicals are eliminated from the body over time, because injuries are often repaired, and because tissues may adapt in response to repeated low-dose exposures. Some toxic effects occur only after long-term exposure because sufficient amounts of chemical cannot be attained in the tissue by a single exposure. Sometimes a chemical has to be present in a tissue for a considerable time to produce injury. For example, the neurotoxic and carcinogenic effects from exposure to heavy metals usually require long-term, repeated exposure.

The time between exposure to a chemical and onset of toxic effects varies depending on the chemical and the exposure. For example, the toxic effects of carbon monoxide, sodium cyanide, and carbon disulfide are evident within minutes. The chemical reaches the target organ rapidly and the organ responds rapidly. For many chemicals, the toxic effect is most severe between one and a few days after exposure. However, some chemicals produce delayed toxicity; in fact, the neurotoxicity produced by some chemicals is not observed until a few weeks after exposure. Delayed toxic effects are produced by chemical carcinogens and some organ toxins that produce progressive diseases such as pulmonary fibrosis and emphysema: in humans, it usually takes 10 to 30 years between exposure to a known human carcinogen and the detection of a tumor, and pulmonary fibrosis may take 10 or more years to result in symptoms.

4.C.1.3. Routes of Exposure

Exposure to chemicals in the laboratory occurs by several routes: (1) inhalation, (2) contact with skin or eyes, (3) ingestion, and (4) injection. Important features of these different pathways are detailed below.

4.C.1.3.1. Inhalation

Toxic materials that enter the body via inhalation include gases, the vapors of volatile liquids, mists and sprays of both volatile and nonvolatile liquid substances, and solid chemicals in the form of particles, fibers, and dusts. Inhalation of toxic gases and vapors produces poisoning by absorption through the mucous membranes of the mouth, throat, and lungs and also damages these tissues seriously by local action. Inhaled gases and vapors pass into the capillaries of the lungs and are carried into the circulatory system, where absorption is extremely rapid. Because of the large surface area of the lungs in humans (approximately 75 m 2 ), they are the main site for absorption of many toxic materials.

The factors governing the absorption of gases and vapors from the respiratory tract differ significantly from those that govern the absorption of particulate substances. Factors controlling the absorption of inhaled gases and vapors include the solubility of the gas in body fluids and the reactivity of the gas with tissues and the fluid lining the respiratory tract. Gases or vapors that are highly water soluble, such as methanol, acetone, hydrogen chloride, and ammonia, dissolve predominantly in the lining of the nose and windpipe (trachea) and therefore tend to be absorbed from those regions. These sites of absorption are also potential sites of toxicity. Formaldehyde is an example of a reactive highly water-soluble vapor for which the nose is a major site of deposition. In contrast to water-soluble gases, reactive gases with low water solubility, such as ozone, phosgene, and nitrogen dioxide, penetrate farther into the respiratory tract and thus come into contact with the smaller tubes of the airways. Gases and vapors that are not water soluble but are more fat soluble, such as benzene, methylene chloride, and trichloroethylene, are not completely removed by interaction with the surfaces of the nose, trachea, and small airways. As a result, these gases penetrate the airways down into the deep lung, where they can diffuse across the thin alveoli lung tissue into the blood. The more soluble a gas is in the blood, the more it will be dissolved and transported to other organs.

For inhaled solid chemicals, an important factor in determining if and where a particle will be deposited in the respiratory tract is its size. One generalization is that the largest particles (>5 μm) are deposited primarily in the nose, smaller particles (1 to 5 μm) in the trachea and small airways, and the smallest particles in the alveoli region of the lungs. Thus, depending on the size of an inhaled particle, it will be deposited in different sections of the respiratory tract, and the location affects the local toxicity and the absorption of the material. In general, particles that are water soluble dissolve within minutes or days, and chemicals that are not water soluble but have a moderate degree of fat solubility also clear rapidly into the blood. Those that are not water soluble or highly fat soluble do not dissolve and are retained in the lungs for long periods of time. Metal oxides, asbestos, fiberglass, and silica are examples of water-insoluble inorganic particles that are retained in the lungs for years.

A number of factors affect the airborne concentrations of chemicals, but vapor pressure (the tendency of molecules to escape from the liquid or solid phase into the gaseous phase) is the most important characteristic. The higher the vapor pressure is, the greater the potential concentration of the chemical in the air. For example, acetone (with a vapor pressure of 180 mmHg at 20 °C) reaches an equilibrium concentration in air of 240,000 ppm, or approximately 24%. Fortunately, the ventilation system in most laboratories prevents an equilibrium concentration from developing in the breathing zone of laboratory personnel.

Even very low vapor pressure chemicals are dangerous if the material is highly toxic. A classic example is elemental mercury. Although the vapor pressure of mercury at room temperature is only 0.0012 mmHg, the resulting equilibrium concentration of mercury vapor is 1.58 ppm, or approximately 13 mg/m 3 . The TLV for mercury is 0.05 mg/m 3 , more than two orders of magnitude lower.

The vapor pressure of a chemical increases with temperature; therefore, heating solvents or reaction mixtures increases the potential for high airborne concentrations. Also, a spilled volatile chemical evaporates very quickly because of its large surface area, creating a significant exposure potential. Clearly, careful handling of volatile chemicals is very important; keeping containers tightly closed or covered and using volatiles in laboratory chemical hoods help avoid unnecessary exposure to inhaled chemicals.

Certain types of particulate materials also present potential for airborne exposure. If a material has a very low density or a very small particle size, it tends to remain airborne for a considerable time. For example, the very fine dust cloud generated by emptying a low-density particulate (e.g., vermiculite or nanomaterials) into a transfer vessel takes a long time to settle. Such operations should therefore be carried out in a laboratory chemical hood or in a glovebox.

Operations that generate aerosols (suspensions of microscopic droplets in air), such as vigorous boiling, high-speed blending, or bubbling gas through a liquid, increase the potential for exposure via inhalation. Consequently, these and other such operations on toxic chemicals should also be carried out in a laboratory chemical hood.

4.C.1.3.2. Contact with Skin or Eyes

Chemical contact with the skin is a frequent mode of injury in the laboratory. Many chemicals injure the skin directly by causing skin irritation and allergic skin reactions. Corrosive chemicals cause severe burns. In addition to causing local toxic effects, many chemicals are absorbed through the skin in sufficient quantity to produce systemic toxicity. The main avenues by which chemicals enter the body through the skin are the hair follicles, sebaceous glands, sweat glands, and cuts or abrasions of the outer layer. Absorption of chemicals through the skin depends on a number of factors, including chemical concentration, chemical reactivity, and the solubility of the chemical in fat and water. Absorption is also dependent on the condition of the skin, the part of the body exposed, and duration of contact. Differences in skin structure affect the degree to which chemicals are absorbed. In general, toxicants cross membranes and thin skin (e.g., scrotum) much more easily than thick skin (e.g., palms). Although an acid burn on the skin is felt immediately, an alkaline burn takes time to be felt and its damage goes deeper than the acid. When skin is damaged, penetration of chemicals increases. Acids and alkalis injure the skin and increase its permeability. Burns and skin diseases are the most common examples of skin damage that increase penetration. Also, hydrated skin absorbs chemicals better than dehydrated skin. Some chemicals such as dimethyl sulfoxide actually increase the penetration of other chemicals through the skin by increasing its permeability.

Contact of chemicals with the eyes is of particular concern because the eyes are sensitive to irritants. Few substances are innocuous in contact with the eyes; most are painful and irritating, and a considerable number are capable of causing burns and loss of vision. Alkaline materials, phenols, and acids are particularly corrosive and can cause permanent loss of vision. Because the eyes contain many blood vessels, they also are a route for the rapid absorption of many chemicals.

4.C.1.3.3. Ingestion

Many of the chemicals used in the laboratory are extremely hazardous if they enter the mouth and are swallowed. The gastrointestinal tract, which consists of the mouth, esophagus, stomach, and small and large intestines, can be thought of as a tube of variable diameter (approximately 5 m long) with a large surface area (approximately 200 m 2 ) for absorption. Toxicants that enter the gastrointestinal tract must be absorbed into the blood to produce a systemic injury, although some chemicals are caustic or irritating to the gastrointestinal tract tissue itself. Absorption of toxicants takes place along the entire gastrointestinal tract, even in the mouth, and depends on many factors, including the physical properties of the chemical and the speed at which it dissolves. Absorption increases with surface area, permeability, and residence time in various segments of the tract. Some chemicals increase intestinal permeability and thus increase the rate of absorption. More chemical will be absorbed if the chemical remains in the intestine for a long time. If a chemical is in a relatively insoluble solid form, it will have limited contact with gastrointestinal tissue, and its rate of absorption will be low. If it is an organic acid or base, it will be absorbed in that part of the gastrointestinal tract where it is most fat soluble. Fat-soluble chemicals are absorbed more rapidly and extensively than water-soluble chemicals.

4.C.1.3.4. Injection

Exposure to toxic chemicals by injection does not occur frequently in the laboratory, but it occurs inadvertently through mechanical injury from sharp objects such as glass or metal contaminated with chemicals or syringes used for handling chemicals. The intravenous route of administration is especially dangerous because it introduces the toxicant directly into the bloodstream, eliminating the process of absorption. Nonlaboratory personnel, such as custodial workers or waste handlers, must be protected from exposure by placing sharp objects in special trash containers and not ordinary scrap baskets. Hypodermic needles with blunt ends are available for laboratory use.

4.C.2. Assessing Risks of Exposure to Toxic Laboratory Chemicals

Exposure to a harmful chemical results in local toxic effects, systemic toxic effects, or both. Local effects involve injury at the site of first contact; the eyes, the skin, the nose and lungs, and the digestive tract are typical sites of local reactions. Examples of local effects include (1) inhalation of hazardous materials causing toxic effects in the nose and lungs; (2) contact with harmful materials on the skin or eyes leading to effects ranging from mild irritation to severe tissue damage; and (3) ingestion of caustic substances causing burns and ulcers in the mouth, esophagus, stomach, and intestines. Systemic effects, by contrast, occur after the toxicant has been absorbed from the site of contact into the bloodstream and distributed throughout the body. Some chemicals produce adverse effects on all tissues of the body, but others tend to selectively injure a particular tissue or organ without affecting others. The affected organ (e.g., liver, lungs, kidney, and central nervous system) is referred to as the target organ of toxicity, although it is not necessarily the organ where the highest concentration of the chemical is found. Hundreds of systemic toxic effects of chemicals are known; they result from single (acute) exposures or from repeated or long-duration (chronic) exposures that become evident only after a long latency period.

Toxic effects are classified as either reversible or irreversible. Reversible toxicity is possible when tissues have the capacity to repair toxic damage, and the damage disappears after cessation of exposure. Irreversible damage, in contrast, persists after cessation of exposure. Recovery from a burn is a good example of reversible toxicity; cancer is considered irreversible, although appropriate treatment may reduce the effects in this case.

Laboratory chemicals are grouped into several classes of toxic substances, and many chemicals display more than one type of toxicity. The first step in assessing the risks associated with a planned laboratory experiment involves identifying which chemicals in the proposed experiment are potentially hazardous substances. The OSHA Laboratory Standard (29 CFR § 1910.1450) defines a hazardous substance as a chemical for which there is statistically significant evidence based on at least one study conducted in accordance with established scientific principles that acute or chronic health effects may occur in exposed employees. The term “health hazard” includes chemicals that are carcinogens, toxic or highly toxic agents, reproductive toxins, irritants, corrosives, sensitizers, hepatotoxins, nephrotoxins, neurotoxins, agents that act on the hematopoietic systems, and agents that damage the lungs, skin, eyes, or mucous membranes.

The OSHA Laboratory Standard further requires that certain chemicals be identified as particularly hazardous substances (commonly known as PHSs) and handled using special additional procedures. PHSs include chemicals that are select carcinogens (those strongly implicated as a potential cause of cancer in humans), reproductive toxins, and compounds with a high degree of acute toxicity. When working with these substances for the first time, it is prudent to consult with a safety professional prior to beginning work. This will provide a second set of trained eyes to review the safety protocols in place and will help ensure that any special emergency response requirements can be met in the event of exposure of personnel to the material or accidental release.

Highly flammable and explosive substances make up another category of hazardous compounds, and the assessment of risk for these classes of chemicals is discussed in section 4.D . This section considers the assessment of risks associated with specific classes of toxic chemicals, including those that pose hazards due to acute toxicity and chronic toxicity.

The following are the most common classes of toxic substances encountered in laboratories.

4.C.2.1. Acute Toxicants

Acute toxicity is the ability of a chemical to cause a harmful effect after a single exposure. Acutely toxic agents cause local toxic effects, systemic toxic effects, or both, and this class of toxicants includes corrosive chemicals, irritants, and allergens (sensitizers).

In assessing the risks associated with acute toxicants, it is useful to classify a substance according to the acute toxicity hazard level as shown in Table 4.1 . LD 50 values can be found in the LCSS or MSDS for a given substance, and in references such as Sax's Dangerous Properties of Industrial Materials ( Lewis, 2004 ), A Comprehensive Guide to the Hazardous Properties of Chemical Substances, 3rd Edition ( Patnaik, 2007 ), and the Registry of Toxic Effects of Chemical Substances (RTECS) (NIOSH). Table 4.2 relates test animal LD 50 values expressed as milligrams or grams per kilogram of body weight to the probable human lethal dose, expressed in easily understood units, for a 70-kg person.

Acute Toxicity Hazard Level.

Probable Lethal Dose for Humans.

Special attention is given to any substance classified according to the above criteria as having a high level of acute toxicity hazard. Chemicals with a high level of acute toxicity make up one of the categories of PHSs defined by the OSHA Laboratory Standard. Any compound rated as highly toxic in Table 4.1 meets the OSHA criteria for handling as a PHS.

Table 4.3 lists some of the most common chemicals with a high level of acute toxicity that are encountered in the laboratory. These compounds are handled using the additional procedures outlined in Chapter 6 , section 6.D . In some circumstances, all these special precautions may not be necessary, such as when the total amount of an acutely toxic substance is a small fraction of the harmful dose. An essential part of prudent experiment planning is to determine whether a chemical with a high degree of acute toxicity should be treated as a PHS in the context of a specific planned use. This determination not only involves consideration of the total amount of the substance to be used but also requires a review of the physical properties of the substance (e.g., Is it volatile? Does it tend to form dusts?), its potential routes of exposure (e.g., Is it readily absorbed through the skin?), and the circumstances of its use in the proposed experiment (e.g., Will the substance be heated? Is there likelihood that aerosols may be generated?). Depending on the laboratory personnel's level of experience and the degree of potential hazard, this determination may require consultation with supervisors and safety professionals.

Examples of Compounds with a High Level of Acute Toxicity.

Because the greatest risk of exposure to many laboratory chemicals is by inhalation, trained laboratory personnel must understand the use of exposure limits that have been established by agencies such as OSHA and NIOSH and by an organization such as ACGIH.

The TLV assigned by the ACGIH, defines the concentration of a chemical in air to which nearly all individuals can be exposed without adverse effects. These limits reflect a view of an informed scientific community and are not legal standards. They are designed to be an aid to industrial hygienists. The TLV time-weighted average (TWA) refers to the concentration safe for exposure during an entire 8-hour workday; the TLV-STEL is a higher concentration to which workers may be exposed safely for a 15-minute period up to four times during an 8-hour shift and at least 60 minutes between these periods. TLVs are intended for use by professionals after they have read and understood the documentation of the TLV for the chemical or physical agent under study.

OSHA defines the permissible exposure limit (PEL) analogously to the ACGIH values, with corresponding 8-hour TWA and ceiling limits based on either a 15-minute TWA or an instantaneous reading, whichever is possible. In some cases, OSHA also defines a maximum peak concentration that cannot be exceeded beyond a given duration. Compliance with PELs is required, and the limits are enforceable by OSHA. PEL values allow trained laboratory personnel to quickly determine the relative inhalation hazards of chemicals. In general, substances with 8-hour TWA PELs of less than 50 ppm should be handled in a laboratory chemical hood. Comparison of these values to the odor threshold for a given substance often indicates whether the odor of the chemical provides sufficient warning of possible hazard. However, individual differences in ability to detect some odors as well as anosmia for ethylene oxide or olfactory fatigue for hydrogen sulfide can limit the usefulness of odors as warning signs of overexposure. LCSSs contain information on odor threshold ranges and whether a substance is known to cause olfactory fatigue.

Recommended exposure limits (RELs) are occupational exposure limits recommended by NIOSH to protect the health and safety of individuals over a working lifetime. Compliance with RELs is not required by law. RELs may also be expressed as a ceiling limit that should never be exceeded over a given time period, but the limit is usually expressed as a TWA exposure for up to 10 hours per day during a 40-hour workweek. As with TLVs, RELs are also expressed as STELs. One should not exceed the STEL for longer than 15 minutes at anytime throughout a workday.

A variety of devices are available for measuring the concentration of chemicals in laboratory air, so that the degree of hazard associated with the use of a chemical is assessed directly. Industrial hygiene offices of many institutions assist trained laboratory personnel in measuring the air concentrations of chemicals.

4.C.3. Types of Toxins

4.c.3.1. irritants, corrosive substances, allergens, and sensitizers.

Lethal dose and other quantitative toxicological parameters generally provide little guidance in assessing the risks associated with corrosives, irritants, allergens, and sensitizers because these toxic substances exert their harmful effects locally. It would be very useful for the chemical research community if a quantitative measure for such effects were developed. When planning an experiment that involves corrosive substances, basic prudent handling practices should be reviewed to ensure that the skin, face, and eyes are protected adequately by the proper choice of corrosion-resistant gloves and protective clothing and eyewear, including, in some cases, face shields. Similarly, LD 50 and LC 50 data are not indicators of the irritant effects of chemicals, and therefore special attention should be paid to the identification of irritant chemicals by consulting LCSSs, MSDSs, and other sources of information. Allergens and sensitizers are another class of acute toxicants with effects that are not included in LD 50 or LC 50 data.

4.C.3.1.1. Irritants

Irritants are noncorrosive chemicals that cause reversible inflammatory effects (swelling and redness) on living tissue by chemical action at the site of contact. A wide variety of organic and inorganic chemicals are irritants, and consequently, skin and eye contact with all reagent chemicals in the laboratory should be minimized. Examples include formaldehyde, iodine, and benzoyl chloride.

4.C.3.1.2. Corrosive Substances

Corrosive substances are those that cause destruction of living tissue by chemical action at the site of contact and are solids, liquids, or gases. Corrosive effects occur not only on the skin and eyes but also in the respiratory tract and, in the case of ingestion, in the gastrointestinal tract as well. Corrosive materials are probably the most common toxic substances encountered in the laboratory. Corrosive liquids are especially dangerous because their effect on tissue is rapid. Bromine, sulfuric acid, aqueous sodium hydroxide solution, and hydrogen peroxide are examples of highly corrosive liquids. Corrosive gases are also frequently encountered. Gases such as chlorine, ammonia, chloramine, and nitrogen dioxide damage the lining of the lungs, leading, after a delay of several hours, to the fatal buildup of fluid known as pulmonary edema. Finally, a number of solid chemicals have corrosive effects on living tissue. Examples of common corrosive solids include sodium hydroxide, phosphorus, and phenol. If dust from corrosive solids is inhaled, it causes serious damage to the respiratory tract.

There are several major classes of corrosive substances. Strong acids such as nitric, sulfuric, and hydrochloric acid cause serious damage to the skin and eyes. Hydrofluoric acid is particularly dangerous and produces slow-healing painful burns (see Chapter 6 , section 6.G.6 ). Strong bases, such as metal hydroxides and ammonia, are another class of corrosive chemicals. Strong dehydrating agents, such as phosphorus pentoxide and calcium oxide, have a powerful affinity for water and cause serious burns on contact with the skin. Finally, strong oxidizing agents, such as concentrated solutions of hydrogen peroxide, also have serious corrosive effects and should never come into contact with the skin or eyes.

4.C.3.1.3. Allergens and Sensitizers

A chemical allergy is an adverse reaction by the immune system to a chemical. Such allergic reactions result from previous sensitization to that chemical or a structurally similar chemical. Once sensitization occurs, allergic reactions result from exposure to extremely low doses of the chemical. Some allergic reactions are immediate, occurring within a few minutes after exposure. Anaphylactic shock is a severe immediate allergic reaction that results in death if not treated quickly. Delayed allergic reactions take hours or even days to develop, the skin is the usual site of such delayed reactions, becoming red, swollen, and itchy. Delayed chemical allergy occurs even after the chemical has been removed; contact with poison ivy is a familiar example of an exposure that causes a delayed allergic reaction due to uroshiol. Also, just as people vary widely in their susceptibility to sensitization by environmental allergens such as dust and pollen, individuals also exhibit wide differences in their sensitivity to laboratory chemicals.

Because individuals differ widely in their tendency to become sensitized to allergens, compounds with a proven ability to cause sensitization should be classified as highly toxic agents within the institution's CHP. When working with chemicals known to cause allergic sensitization, follow institutional policy on handling and containment of allergens and highly toxic agents. Once a person has become sensitized to an allergen, subsequent contact often leads to immediate or delayed allergic reactions.

Because an allergic response is triggered in a sensitized individual by an extremely small quantity of the allergen, it may occur despite personal protection measures that are adequate to protect against the acute effects of chemicals. Laboratory personnel should be alert for signs of allergic responses to chemicals. Examples of chemical substances that cause allergic reactions in some individuals include diazomethane; dicyclohexylcarbodiimide; formaldehyde and phenol derivatives; various isocyanates (e.g., methylene diphenyl diisocyanate (MDI) or toluene diisocyanate (TDI), used in adhesives, elastomers, and coatings); benzylic and allylic halides; metals including nickel, beryllium, platinum, cobalt, tin, and chromium; and acid anhydrides such as acetic anhydrides.

4.C.3.2. Asphyxiants

Asphyxiants are substances that interfere with the transport of an adequate supply of oxygen to vital organs of the body. The brain is the organ most easily affected by oxygen starvation, and exposure to asphyxiants leads to rapid collapse and death. Simple asphyxiants are substances that displace oxygen from the air being breathed to such an extent that adverse effects result. Acetylene, carbon dioxide, argon, helium, ethane, nitrogen, and methane are common asphyxiants. Certain other chemicals have the ability to combine with hemoglobin, thus reducing the capacity of the blood to transport oxygen. Carbon monoxide, hydrogen cyanide, and certain organic and inorganic cyanides are examples of such substances.

4.C.3.3. Neurotoxins

Neurotoxic chemicals induce an adverse effect on the structure or function of the central or peripheral nervous system, which can be permanent or reversible. The detection of neurotoxic effects may require specialized laboratory techniques, but often they are inferred from behavior such as slurred speech and staggered gait. Many neurotoxins are chronically toxic substances with adverse effects that are not immediately apparent. Some chemical neurotoxins that may be found in the laboratory are mercury (inorganic and organic), organophosphate pesticides, carbon disulfide, xylene, tricholoroethylene, and n -hexane. (For information about reducing the presence of mercury in laboratories, see Chapter 5 , section 5.B.8 .)

4.C.3.4. Reproductive and Developmental Toxins

Reproductive toxins are defined by the OSHA Laboratory Standard as substances that cause chromosomal damage (mutagens) and substances with lethal or teratogenic (malformation) effects on fetuses. These substances have adverse effects on various aspects of reproduction, including fertility, gestation, lactation, and general reproductive performance, and can affect both men and women. Many reproductive toxins are chronic toxins that cause damage after repeated or long-duration exposures with effects that become evident only after long latency periods. Developmental toxins act during pregnancy and cause adverse effects on the fetus; these effects include embryo lethality (death of the fertilized egg, embryo, or fetus), teratogenic effects, and postnatal functional defects. Male reproductive toxins in some cases lead to sterility.

When a pregnant woman is exposed to a chemical, generally the fetus is exposed as well because the placenta is an extremely poor barrier to chemicals. Embryotoxins have the greatest impact during the first trimester of pregnancy. Because a woman often does not know that she is pregnant during this period of high susceptibility, women of childbearing potential are advised to be especially cautious when working with chemicals, especially those rapidly absorbed through the skin (e.g., formamide). Pregnant women and women intending to become pregnant should seek advice from knowledgeable sources before working with substances that are suspected to be reproductive toxins. As minimal precautions, the general procedures outlined in Chapter 6 , section 6.D , should be followed, though in some cases it will be appropriate to handle the compounds as PHSs.

For example, among the numerous reproductive hazards to female laboratory scientists, gestational exposure to organic solvents should be of concern ( HHS/CDC/NIOSH, 1999 ; Khattak et al., 1999 ). Some common solvents in high doses have been shown to be teratogenic in laboratory animals, resulting in developmental defects. Although retrospective studies of the teratogenic risk in women of childbearing age of occupational exposure to common solvents have reached mixed conclusions, at least one such study of exposure during pregnancy to multiple solvents detected increased fetal malformations. Thus, inhalation exposure to organic solvents should be minimized during pregnancy. Also, exposure to lead or to anticancer drugs, such as methotrexate, or to ionizing radiation can cause infertility, miscarriage, birth defects, and low birth weight. Certain ethylene glycol ethers such as 2-ethoxyethanol and 2-methoxyethanol can cause miscarriages. Carbon disulfide can cause menstrual cycle changes. One cannot assume that any given substance is safe if no data on gestational exposure are available.

Specific hazards of chemical exposure are associated with the male reproductive system, including suppression of sperm production and survival, alteration in sperm shape and motility, and changes in sexual drive and performance. Various reproductive hazards have been noted in males following exposure to halogenated hydrocarbons, nitro aromatics, arylamines, ethylene glycol derivatives, mercury, bromine, carbon disulfide, and other chemical reagents ( HHS/CDC/ NIOSH, 1996 ).

Information on reproductive toxins can be obtained from LCSSs, MSDSs, and by consulting safety professionals in the environmental safety department, industrial hygiene office, or medical department. Literature sources of information on reproductive and developmental toxins include the Catalog of Teratogenic Agents ( Shepard and Lemire, 2007 ), Reproductively Active Chemicals: A Reference Guide ( Lewis, 1991 ), and “What Every Chemist Should Know About Teratogens” in the Journal of Chemical Education ( Beyler and Meyers, 1982 ). The State of California maintains a list of chemicals it considers reproductive toxins, and additional information can be found through the NLM TOXNET system. The study of reproductive toxins is an active area of research, and laboratory personnel should consult resources that are updated regularly for information.

4.C.3.5. Toxins Affecting Other Target Organs

Target organs outside the reproductive and neurological systems are also affected by toxic substances in the laboratory. Most of the chlorinated hydrocarbons, benzene, other aromatic hydrocarbons, some metals, carbon monoxide, and cyanides, among others, produce one or more effects in target organs. Such an effect may be the most probable result of exposure to the particular chemical. Although this chapter does not include specific sections on liver, kidney, lung, or blood toxins, many of the LCSSs mention those effects in the toxicology section.

4.C.3.6. Carcinogens

A carcinogen is a substance capable of causing cancer. Cancer, in the simplest sense, is the uncontrolled growth of cells and can occur in any organ. The mechanism by which cancer develops is not well understood, but the current thinking is that some chemicals interact directly with DNA, the genetic material in all cells, to result in permanent alterations. Other chemical carcinogens modify DNA indirectly by changing the way cells grow. Carcinogens are chronically toxic substances; that is, they cause damage after repeated or long-duration exposure, and their effects may become evident only after a long latency period. Carcinogens are particularly insidious toxins because they may have no immediate apparent harmful effects.

Because cancer is a widespread cause of human mortality, and because exposure to chemicals may play a significant role in the onset of cancer, a great deal of attention has been focused on evaluation of the carcinogenic potential of chemicals. However, a vast majority of substances involved in research, especially in laboratories concerned primarily with the synthesis of novel compounds, have not been tested for carcinogenicity. Compounds that are known to pose the greatest carcinogenic hazard are referred to as select carcinogens, and they constitute another category of substances that must be handled as PHSs according to the OSHA Laboratory Standard. A select carcinogen is defined in the OSHA Laboratory Standard as a substance that meets one of the following criteria:

• It is regulated by OSHA as a carcinogen.
• It is listed as known to be a carcinogen in the latest Annual Report on Carcinogens issued by the National Toxicology Program (NTP) ( HHS/ CDC/NTP, 2005 ).
• It is listed under Group 1 (carcinogenic to humans) by the International Agency for Research on Cancer (IARC).
• It is listed under IARC Group 2A (probably carcinogenic to humans) or 2B (possibly carcinogenic to humans), or under the category “reasonably anticipated to be a carcinogen by the NTP,” and causes statistically significant tumor incidence in experimental animals in accordance with any of the following criteria: (a) after inhalation exposure of 6 to 7 hours per day, 5 days per week, for a significant portion of a lifetime to dosages of less than 10 mg/m 3 ; (b) after repeated skin application of less than 300 mg/kg of body weight per week; or (c) after oral dosages of less than 50 mg/kg of body weight per day.

Chemicals that meet the criteria of a select carcinogen are classified as PHSs and should be handled using the basic prudent practices given in Chapter 6 , section 6.C , supplemented by the additional special practices outlined in Chapter 6 , section 6.D . Work with compounds that are possible human carcinogens may or may not require the additional precautions given in section 6.D . For these compounds, the LCSS should indicate whether the substance meets the additional criteria listed in category 4 and must therefore be treated as a select carcinogen. If an LCSS is not available, consultation with a safety professional such as a CHO may be necessary to determine whether a substance should be classified as PHS. Lists of known human carcinogens and compounds that are “reasonably anticipated to be carcinogens” based on animal tests can be found in the 11th Report on Carcinogens ( HHS/CDC/NTP, 2005 ). This report is updated periodically. Check the NTP Web site (ntp.niehs.nih.gov) for the most recent edition. Additional information can be found on the OSHA and IARC Web sites ( www.osha.gov and www.iarc.fr ).

In the laboratory many chemical substances are encountered for which there is no animal test or human epidemiological data on carcinogenicity. In these cases, trained laboratory personnel must evaluate the potential risk that the chemical in question is a carcinogenic substance. This determination is sometimes made on the basis of knowledge of the specific classes of compounds and functional group types that have previously been correlated with carcinogenic activity. For example, chloromethyl methyl ether is a known human carcinogen and therefore is regarded as an OSHA select carcinogen requiring the handling procedures outlined in section 6.D . On the other hand, the carcinogenicity of ethyl chloromethyl ether and certain other alkyl chloromethyl ethers is not established, and these substances do not necessarily have to be treated as select carcinogens. However, because of the chemical similarity of these compounds to chloromethyl methyl ether, these substances may have comparable carcinogenicity, and it is prudent to regard them as select carcinogens requiring the special handling procedures outlined in section 6.D .

Whether a suspected carcinogenic chemical is treated as a PHS in the context of a specific laboratory use is affected by the scale and circumstances associated with the intended experiment. Trained laboratory personnel must decide whether the amount and frequency of use, as well as other circumstances, require additional precautions beyond the basic prudent practices of section 6.C . For example, the large-scale or recurring use of such a chemical might suggest that the special precautions of section 6.D be followed to control exposure, whereas adequate protection from a single use of a small amount of such a substance may be obtained through the use of the basic procedures in section 6.C .

When evaluating the carcinogenic potential of chemicals, note that exposure to certain combinations of compounds (not necessarily simultaneously) causes cancer even at exposure levels where neither of the individual compounds would have been carcinogenic. 1,8,9-Trihydroxyanthracene and certain phorbol esters are examples of tumor promoters that are not carcinogenic themselves but dramatically amplify the carcinogenicity of other compounds. Understand that the response of an organism to a toxicant typically increases with the dose given, but the relationship is not always a linear one. Some carcinogenic alkylating agents exhibit a dose threshold above which the tendency to cause mutations increases markedly. At lower doses, natural protective systems prevent genetic damage, but when the capacity of these systems is overwhelmed, the organism becomes much more sensitive to the toxicant. However, individuals have differences in the levels of protection against genetic damage as well as in other defense systems. These differences are determined in part by genetic factors and in part by the aggregate exposure of the individual to all chemicals within and outside the laboratory.

4.C.3.7. Control Banding

Control banding is a qualitative risk assessment and management approach to assist in determining the appropriate handling of materials without occupational exposure limits (OELs) and to minimize the exposure of personnel to hazardous material. 2 It is not intended to be a replacement for OELs but as an additional tool. The system uses a range of exposure and hazard “bands” that, when mapped for a given material and application, help the user determine the appropriate safety controls that should be in place. The approach is built on two major premises: (1) there are a limited number of control approaches and (2) that many problems have been encountered and solved before. Control banding uses the solutions that experts have developed previously to control occupational chemical exposures and applies those solutions to other tasks with similar exposure concerns.

By considering the physical and chemical characteristics and hazards posed by the material (e.g., toxicity), the quantity used, the intended use or application, and the mode of exposure (e.g., inhalation), a graduated scale of controls can be applied, from general ventilation requirements to requiring containment of the material to recommending that the user seek expert advice. Because this approach is expected to provide simplified guidance for assessing hazards and applying controls, it is anticipated that control banding will have utility for small- and medium-size nonchemical businesses; however, larger companies may also find it useful for prioritizing chemical hazards and hazard communication.

Note that a number of control banding models exist, each with its own level of complexity and applicability to a variety of scenarios. Within the United States, questions about the utility of control banding for workplaces initiated a review by NIOSH on the critical issues and potential applications of the system. The resulting report, Qualitative Risk Characterization and Management of Occupational Hazards: Control Banding (CB) ( HHS/CDC/NIOSH, 2009b ), can be found on the NIOSH Web site. It provides an overview of the major concepts and methodologies and presents a critical analysis of control banding.

Control banding is of interest internationally, and variations on the methodology can be found in many countries. More information about control banding can be found by consulting these Web sites and articles.

• (UK Health and Safety Executive) Control of Substances Hazardous to Health Regulations, www.coshh-essentials.org.uk/
• ILO Programme on Safety and Health at Work and the Environment (SafeWork), www.ilo.org/
• NIOSH, www.cdc.gov/niosh/
• “Training Health and Safety Committees to Use Control Banding: Lessons Learned and Opportunities for the United States” ( Bracker et al., 2009 )
• “Evaluation of COSHH Essentials: Methylene Chloride, Isopropanol, and Acetone Exposures in a Small Printing Plant” ( Lee et al., 2009 )
• “Application of a Pilot Control Banding Tool for Risk Level Assessment and Control of Nanoparticle Exposures” ( Paik et al., 2008 )
• “‘Stoffenmanager,’ a Web-Based Control Banding Tool Using an Exposure Process Model” ( Marquart et al., 2008 )
• “History and Evolution of Control Banding: A Review” ( Zalk and Nelson, 2008 )
• “Control Banding: Issues and Opportunities.” A Report of the ACGIH Exposure Control Banding Task Force ( ACGIH, 2008a )
• “Evaluation of the Control Banding Method— Comparison with Measurement-Based Comprehensive Risk Assessment” ( Hashimoto et al., 2007 )
• Guidance for Conducting Control Banding Analyses (American Industrial Hygiene Association, 2008)

4.D. FLAMMABLE, REACTIVE, AND EXPLOSIVE HAZARDS

In addition to the hazards due to the toxic effects of chemicals, hazards due to flammability, explosivity, and reactivity need to be considered in risk assessment. These hazards are described in detail in the following sections. Further information can be found in Bretherick's Handbook of Reactive Chemical Hazards ( Urben, 2007 ), an extensive compendium that is the basis for lists of incompatible chemicals included in other reference works. The handbook describes computational protocols that consider thermodynamic and kinetic parameters of a system to arrive at quantitative measures such as the reaction hazard index. Reactive hazards arise when the release of energy from a chemical reaction occurs in quantities or at rates too great for the energy to be absorbed by the immediate environment of the reacting system, and material damage results. An additional resource is the Hazardous Chemical Handbook ( Carson and Mumford, 2002 ). The book is geared toward an industrial audience and contains basic descriptions of chemical hazards along with technical guidance.

Box 4.2 is a quick guide for assisting in the assessment of the physical, flammable, explosive, and reactive hazards in the laboratory.

Quick Guide to Risk Assessment for Physical, Flammable, Explosive, and Reactive Hazards in the Laboratory. The following outline provides a summary of the steps discussed in this chapter that laboratory personnel should use to assess the risks of managing (more...)

4.D.1. Flammable Hazards

4.d.1.1. flammable substances.

Flammable substances, those that readily catch fire and burn in air, may be solid, liquid, or gaseous. The most common fire hazard in the laboratory is a flammable liquid or the vapor produced from such a liquid. An additional hazard is that a compound can enflame so rapidly that it produces an explosion. Proper use of substances that cause fire requires knowledge of their tendencies to vaporize, ignite, or burn under the variety of conditions in the laboratory.

For a fire to occur, three conditions must exist simultaneously: an atmosphere containing oxygen, usually air; a fuel, such as a concentration of flammable gas or vapor that is within the flammable limits of the substance; and a source of ignition (see Figure 4.3 ). Prevention of the coexistence of flammable vapors and an ignition source is the optimal way to deal with the hazard. When the vapors of a flammable liquid cannot always be controlled, strict control of ignition sources is the principal approach to reduce the risk of flammability. The rates at which different liquids produce flammable vapors depend on their vapor pressures, which increase with increasing temperature. The degree of fire hazard of a substance depends also on its ability to form combustible or explosive mixtures with air and on the ease of ignition of these mixtures. Also important are the relative density and solubility of a liquid with respect to water and of a gas with respect to air. These characteristics can be evaluated and compared in terms of the following specific properties.

The fire triangle.

4.D.1.2. Flammability Characteristics

4.d.1.2.1. flash point.

The flash point is the lowest temperature at which a liquid has a sufficient vapor pressure to form an ignitable mixture with air near the surface of the liquid. Note that many common organic liquids have a flash point below room temperature: for example, acetone (-18 °C), benzene (-11.1 °C), diethyl ether (-45 °C), and methyl alcohol (11.1 °C). The degree of hazard associated with a flammable liquid also depends on other properties, such as its ignition point and boiling point. Commercially obtained chemicals are clearly labeled as to flammability and flash point. Consider the example of acetone given in section 4.C.1.3.1 . At ambient pressure and temperature, an acetone spill produces a concentration as high as 23.7% acetone in air. Although it is not particularly toxic, with a flash point of -18 °C and upper and lower flammable limits of 2.6% and 12.8% acetone in air, respectively (see Table 4.4 ), clearly an acetone spill produces an extreme fire hazard. Thus the major hazard given for acetone in the LCSS is flammability.

NFPA Fire Hazard Ratings, Flash Points (FP), Boiling Points (bp), Ignition Temperatures, and Flammable Limits of Some Common Laboratory Chemicals.

4.D.1.2.2. Ignition Temperature

The ignition temperature (autoignition temperature) of a substance, whether solid, liquid, or gaseous, is the minimum temperature required to initiate or cause self-sustained combustion independent of the heat source. The lower the ignition temperature, the greater the potential for a fire started by typical laboratory equipment. A spark is not necessary for ignition when the flammable vapor reaches its autoignition temperature. For instance, carbon disulfide has an ignition temperature of 90 °C, and it can be set off by a steam line or a glowing light bulb. Diethyl ether has an ignition temperature of 160 °C and can be ignited by a hot plate.

4.D.1.2.3. Limits of Flammability

Each flammable gas and liquid (as a vapor) has two fairly definite limits of flammability defining the range of concentrations in mixtures with air that will propagate a flame and cause an explosion. At the low extreme, the mixture is oxygen rich but contains insufficient fuel. The lower flammable limit (lower explosive limit [LEL]) is the minimum concentration (percent by volume) of the fuel (vapor) in air at which a flame is propagated when an ignition source is present. The upper flammable limit (upper explosive limit [UEL]) is the maximum concentration (percent by volume) of the vapor in air above which a flame is not propagated. The flammable range (explosive range) consists of all concentrations between the LEL and the UEL. This range becomes wider with increasing temperature and in oxygen-rich atmospheres and also changes depending on the presence of other components. The limitations of the flammability range, however, provide little margin of safety from the practical point of view because, when a solvent is spilled in the presence of an energy source, the LEL is reached very quickly and a fire or explosion ensues before the UEL is reached.

4.D.1.3. Classes of Flammability

Several systems are in use for classifying the flammability of materials. Some (e.g., Class I—flammable liquid, see Chapter 5 , section 5.E.5 , Table 5.2 ) apply to storage or transportation considerations. Another (Class A, B, C—paper, liquid, electrical fire) specifies the type of fire extinguisher to be used (see Chapter 7 , section 7.F.2 on emergency equipment). To assess risk quickly, the most direct indicator is the NFPA system, which classifies flammables according to the severity of the fire hazard with numbers 0 to 4 in order of increasing hazard: 0, will not burn; 1, must be preheated to burn; 2, ignites when moderately heated; 3, ignites at normal temperature; 4, extremely flammable ( Figure 4.4 ). Substances rated 3 or 4 under this system require particularly careful handling and storage in the laboratory. Some vendors include the NFPA hazard diamond on the labels of chemicals. The Fire Protection Guide on Hazardous Materials ( NFPA, 2001 ) contains a comprehensive listing of flammability data and ratings. Note that other symbols may be found in the Special Hazard quadrant of the diamond. These symbols (see Table 4.5 ) are not endorsed by NFPA.

National Fire Protection Association (NFPA) system for classification of hazards. SOURCE: Reproduced with permission from NFPA 704-2007. System for the Identification of the Hazards of Materials for Emergency Response, Copyright © 2007 National (more...)

Additional Symbols Seen in the NFPA Diamond.

The NFPA fire hazard ratings, flash points, boiling points, ignition temperatures, and flammability limits of a number of common laboratory chemicals are given in Table 4.4 and in the LCSSs (see accompanying CD). The data illustrate the range of flammability for liquids commonly used in laboratories. Dimethyl sulfoxide and glacial acetic acid (NFPA fire hazard ratings of 1 and 2, respectively) are handled in the laboratory without great concern about their fire hazards. By contrast, both acetone (NFPA rating 3) and diethyl ether (NFPA rating 4) have flash points well below room temperature.

Note that tabulations of properties of flammable substances are based on standard test methods, which have very different conditions from those encountered in practical laboratory use. Large safety factors should be applied. For example, the published flammability limits of vapors are for uniform mixtures with air. In a real situation, local concentrations that are much higher than the average may exist. Thus, it is good practice to set the maximum allowable concentration for safe working conditions at some fraction of the tabulated LEL; 10% is a commonly accepted value.

Among the most hazardous liquids are those that have flash points near or below 38 °C (100 °F) according to OSHA (29 CFR § 1910.106) and below 60.5 °C (140.9 °F) according to the U.S. Department of Transportation (49 CFR § 173.120). These materials can be hazardous in the common laboratory environment. There is particular risk if their range of flammability is broad. Note that some commonly used substances are potentially very hazardous, even under relatively cool conditions (see Table 4.4 ). Some flammable liquids maintain their flammability even at concentrations of 10% by weight in water. Methanol and isopropyl alcohol have flash points below 38 °C (100 °F) at concentrations as low as 30% by weight in water. High-performance liquid chromatography users generate acetonitrile-water mixtures that contain from 15-30% acetonitrile in water, a waste that is considered toxic and flammable and thus cannot be added to a sewer.

Because of its extreme flammability and tendency for peroxide formation, diethyl ether is available for laboratory use only in metal containers. Carbon disulfide is almost as hazardous.

4.D.1.4. Causes of Ignition

4.d.1.4.1. spontaneous combustion.

Spontaneous ignition (autoignition) or combustion takes place when a substance reaches its ignition temperature without the application of external heat. The possibility of spontaneous combustion should always be considered, especially when storing or disposing of materials. Examples of materials susceptible to spontaneous combustion include oily rags, dust accumulations, organic materials mixed with strong oxidizing agents (e.g., nitric acid, chlorates, permanganates, peroxides, and persulfates), alkali metals (e.g., sodium and potassium), finely divided pyrophoric metals, and phosphorus.

4.D.1.4.2. Ignition Sources

Potential ignition sources in the laboratory include the obvious torch and Bunsen burner, as well as a number of less obvious electrically powered sources ranging from refrigerators, stirring motors, and heat guns to microwave ovens (see Chapter 7 , section 7.C ). Whenever possible, open flames should be replaced by electrical heating. Because the vapors of most flammable liquids are heavier than air and capable of traveling considerable distances, special note should be taken of ignition sources situated at a lower level than that at which the substance is being used. Flammable vapors from massive sources such as spills have been known to descend into stairwells and elevator shafts and ignite on a lower story. If the path of vapor within the flammable range is continuous, as along a floor or benchtop, the flame propagates itself from the point of ignition back to its source.

Metal lines and vessels discharging flammable substances should be bonded and grounded properly to discharge static electricity. There are many sources of static electricity, particularly in cold dry atmospheres, and caution should be exercised.

4.D.1.4.3. Oxidants Other Than Oxygen

The most familiar fire involves a combustible material burning in air. However, the oxidant driving a fire or explosion need not be oxygen itself, depending on the nature of the reducing agent. All oxidants have the ability to accept electrons, and fuels are reducing agents or electron donors [see Young (1991) ].

Examples of nonoxygen oxidants are shown in Table 4.6 . When potassium ignites on addition to water, the metal is the reducing agent and water is the oxidant. If the hydrogen produced ignites, it becomes the fuel for a conventional fire, with oxygen as the oxidant. In ammonium nitrate explosions, the ammonium cation is oxidized by the nitrate anion. These hazardous combinations are treated further in section 4.D.2 . (See Chapter 6 , section 6.F , for a more detailed discussion on flammable substances.)

Examples of Oxidants.

4.D.1.5. Special Hazards

Compressed or liquefied gases present fire hazards because the heat causes the pressure to increase and the container may rupture ( Yaws and Braker, 2001 ). Leakage or escape of flammable gases produces an explosive atmosphere in the laboratory; acetylene, hydrogen, ammonia, hydrogen sulfide, propane, and carbon monoxide are especially hazardous.

Even if not under pressure, a liquefied gas is more concentrated than in the vapor phase and evaporates rapidly. Oxygen is an extreme hazard and liquefied air is almost as dangerous because nitrogen boils away first, leaving an increasing concentration of oxygen. Liquid nitrogen standing for a period of time may have condensed enough oxygen to require careful handling. When a liquefied gas is used in a closed system, pressure may build up and adequate venting is required. If the liquid is flammable (e.g., hydrogen and methane), explosive concentrations may develop without warning unless an odorant has been added. Flammability, toxicity, and pressure buildup become more serious on exposure of gases to heat.

(Also see Chapter 6 , section 6.G.2.5 , for more information.)

4.D.2. Reactive Hazards

4.d.2.1. water reactives.

Water-reactive materials are those that react violently with water. Alkali metals (e.g., lithium, sodium, and potassium), many organometallic compounds, and some hydrides react with water to produce heat and flammable hydrogen gas, which ignites or combines explosively with atmospheric oxygen. Some anhydrous metal halides (e.g., aluminum bromide), oxides (e.g., calcium oxide), and nonmetal oxides (e.g., sulfur trioxide), and halides (e.g., phosphorus pentachloride) react exothermically with water, resulting in a violent reaction if there is insufficient coolant water to dissipate the heat produced.

(See Chapter 6 , section 6.G , for further information.)

4.D.2.2. Pyrophorics

For pyrophoric materials, oxidation of the compound by oxygen or moisture in air proceeds so rapidly that ignition occurs. Many finely divided metals are pyrophoric, and their degree of reactivity depends on particle size, as well as factors such as the presence of moisture and the thermodynamics of metal oxide or metal nitride formation. Other reducing agents, such as metal hydrides, alloys of reactive metals, low-valent metal salts, and iron sulfides, are also pyrophoric.

4.D.2.3. Incompatible Chemicals

Accidental contact of incompatible substances results in a serious explosion or the formation of substances that are highly toxic or flammable or both. Although trained laboratory personnel question the necessity of following storage compatibility guidelines, the reasons for such guidelines are obvious after reading descriptions of laboratories following California earthquakes in recent decades [see Pine (1994) ]. Those who do not live in seismically active zones should take these accounts to heart, as well. Other natural disasters and chemical explosions themselves can set off shock waves that empty chemical shelves and result in inadvertent mixing of chemicals.

Some compounds pose either a reactive or a toxic hazard, depending on the conditions. Thus, hydro- cyanic acid (HCN), when used as a pure liquid or gas in industrial applications, is incompatible with bases because it is stabilized against (violent) polymerization by the addition of acid inhibitor. HCN can also be formed when cyanide salt is mixed with an acid. In this case, the toxicity of HCN gas, rather than the instability of the liquid, is the characteristic of concern.

Some general guidelines lessen the risks involved with these substances. Concentrated oxidizing agents are incompatible with concentrated reducing agents. Indeed, either may pose a reactive hazard even with chemicals that are not strongly oxidizing or reducing. For example, sodium or potassium, strong reducing agents frequently used to dry organic solvents, are extremely reactive toward halocarbon solvents (which are not strong oxidizing agents). Strong oxidizing agents are frequently used to clean glassware, but they should be used only on the last traces of contaminating material. Because the magnitude of risk depends on quantities, chemical incompatibilities will not usually pose much, if any, risk if the quantity of the substance is small (a solution in an NMR tube or a microscale synthesis). However, storage of commercially obtained chemicals (e.g., in 500-g jars or 1-L bottles) should be carefully managed from the standpoint of chemical compatibility.

(For more information about compatible and incompatible chemicals, see Chapter 5 , section 5.E.2 .)

4.D.3. Explosive Hazards

4.d.3.1. explosives.

An explosive is any chemical compound or mechanical mixture that, when subjected to heat, impact, friction, detonation, or other suitable initiation, undergoes rapid chemical change, evolving large volumes of gases that exert pressure on the surrounding medium. The term applies to materials that either detonate or deflagrate. Heat, light, mechanical shock, and certain catalysts initiate explosive reactions. Hydrogen and chlorine react explosively in the presence of light. Acids, bases, and other substances catalyze the explosive polymerization of acrolein, and many metal ions can catalyze the violent decomposition of hydrogen peroxide. Shock-sensitive materials include acetylides, azides, nitrogen triiodide, organic nitrates, nitro compounds, perchlorate salts (especially those of heavy metals such as ruthenium and osmium), many organic peroxides, and compounds containing diazo, halamine, nitroso, and ozonide functional groups.

Table 4.7 lists a number of explosive compounds. Some are set off by the action of a metal spatula on the solid; some are so sensitive that they are set off by the action of their own crystal formation. Diazomethane (CH 2 N 2 ) and organic azides, for example, may decompose explosively when exposed to a ground glass joint or other sharp surfaces ( Organic Syntheses, 1973 , 1961).

Functional Groups in Some Explosive Compounds.

4.D.3.2. Azos, Peroxides, and Peroxidizables

Organic azo compounds and peroxides are among the most hazardous substances handled in the chemical laboratory but are also common reagents that often are used as free radical sources and oxidants. They are generally low-power explosives that are sensitive to shock, sparks, or other accidental ignition. They are far more shock sensitive than most primary explosives such as TNT. Inventories of these chemicals should be limited and subject to routine inspection. Many require refrigerated storage. Liquids or solutions of these compounds should not be cooled to the point at which the material freezes or crystallizes from solution, however, because this significantly increases the risk of explosion. Refrigerators and freezers storing such compounds should have a backup power supply in the event of electricity loss. Users should be familiar with the hazards of these materials and trained in their proper handling.

Certain common laboratory chemicals form peroxides on exposure to oxygen in air (see Tables 4.8 and 4.9 ). Over time, some chemicals continue to build peroxides to potentially dangerous levels, whereas others accumulate a relatively low equilibrium concentration of peroxide, which becomes dangerous only after being concentrated by evaporation or distillation. (See Chapter 6 , section 6.G.3 .) The peroxide becomes concentrated because it is less volatile than the parent chemical. A related class of compounds includes inhibitor-free monomers prone to free radical polymerization that on exposure to air can form peroxides or other free radical sources capable of initiating violent polymerization. Note that care must be taken when storing and using these monomers—most of the inhibitors used to stabilize these compounds require the presence of oxygen to function properly, as described below. Always refer to the MSDS and supplier instructions for proper use and storage of polymerizable monomers.

Classes of Chemicals That Can Form Peroxides.

Types of Compounds Known to Autoxidize to Form Peroxides.

Essentially all compounds containing C—H bonds pose the risk of peroxide formation if contaminated with various radical initiators, photosensitizers, or catalysts. For instance, secondary alcohols such as isopropanol form peroxides when exposed to normal fluorescent lighting and contaminated with photosensitizers, such as benzophenone. Acetaldehyde, under normal conditions, autoxidizes to form acetic acid. Although this autoxidation proceeds through a peroxy acid intermediate, the steady-state concentrations of that intermediate are extremely low and pose no hazard. However, in the presence of catalysts (Co 2+ ) and under the proper conditions of ultraviolet light, temperature, and oxygen concentration, high concentrations of an explosive peroxide can be formed. The chemicals described in Table 4.9 represent only those materials that form peroxides in the absence of such contaminants or otherwise atypical circumstances.

Although not a requirement, it is prudent to discard old samples of organic compounds of unknown origin or history, or those prone to peroxidation if contaminated; secondary alcohols are a specific example.

Class A compounds are especially dangerous when peroxidized and should not be stored for long periods in the laboratory. Good practice requires they be discarded within 3 months of receipt. Inventories of Class B and C materials should be kept to a minimum and managed on a first-in, first-out basis. Class B and C materials should be stored in dark locations. If stored in glass bottles, the glass should be amber. Containers should be marked with their opening date and inspected every 6 months thereafter.

Class B materials are often sold with autoxidation inhibitors. If the inhibitor is removed, or if inhibitor-free material is purchased, particular care must be taken in their long-term storage because of the enhanced probability of peroxide formation. Purging the container headspace with nitrogen is recommended. Several procedures, including test strips, are available to check Class B materials for peroxide contamination. (For information about testing for peroxides, see Chapter 6 , section 6.G.3.2 .) No special disposal precautions are required for peroxide-contaminated Class B materials.

In most cases, commercial samples of Class C materials are provided with polymerization inhibitors that require the presence of oxygen to function and therefore are not to be stored under inert atmosphere. Inhibitor-free samples of Class C compounds (i.e., the compound has been synthesized in the laboratory or the inhibitor has been removed from the commercial sample) should be kept in the smallest quantities required and under inert atmosphere. Unused material should be properly disposed of immediately, or if long-term storage is necessary, an appropriate inhibitor should be added.

(For more information about handling of peroxides, see Chapter 6 , section 6.G.3 .)

4.D.3.3. Other Oxidizers

Oxidizing agents may react violently when they come into contact with reducing materials and sometimes with ordinary combustibles. Such oxidizing agents include halogens, oxyhalogens and organic peroxyhalogens, chromates, and persulfates as well as peroxides. Inorganic peroxides are generally stable. However, they may generate organic peroxides and hydroperoxides in contact with organic compounds, react violently with water (alkali metal peroxides), and form superoxides and ozonides (alkali metal peroxides). Perchloric acid is a powerful oxidizing agent with organic compounds and other reducing agents. Perchlorate salts are explosive and should be treated as potentially hazardous compounds.

Baths to clean glassware generally contain strong oxidizers and should be handled with care. For many years, sulfuric acid–dichromate mixtures were used to clean glassware. These solutions are corrosive and toxic and present difficulties for disposal. Their use should be avoided if at all possible. A common substitute is a sulfuric acid–peroxydisulfate solution, and commercial cleaning solutions that contain no chromium are readily available. Confusion about appropriate cleaning bath solutions has led to explosions due to mixing of incompatible chemicals such as potassium permanganate with sulfuric acid or nitric acid with alcohols. For information about how to clean glassware appropriately, consider contacting the manufacturer of the equipment.

4.D.3.4. Powders and Dusts

Suspensions of oxidizable particles (e.g., flour, coal dust, magnesium powder, zinc dust, carbon powder, and flowers of sulfur) in the air constitute a powerful explosive mixture. These materials should be used with adequate ventilation and should not be exposed to ignition sources. Some solid materials, when finely divided, spontaneously combust if allowed to dry while exposed to air. These materials include zirconium, titanium, Raney nickel, finely divided lead (such as prepared by pyrolysis of lead tartrate), and catalysts such as activated carbon containing active metals and hydrogen.

4.D.3.5. Explosive Boiling

Not all explosions result from chemical reactions; some are caused physically. A dangerous explosion can occur if a hot liquid or a collection of very hot particles comes into sudden contact with a lower boiling-point material. Sudden boiling eruptions occur when a nucleating agent (e.g., charcoal, “boiling chips”) is added to a liquid heated above its boiling point. Even if the material does not explode directly, the sudden formation of a mass of explosive or flammable vapor can be very dangerous.

4.D.3.6. Other Considerations

The hazards of running a new reaction should be considered especially carefully if the chemical species involved contain functional groups associated with explosions or are unstable near the reaction or work-up temperature, if the reaction is subject to an induction period, or if gases are byproducts. Modern analytical techniques (see Chapter 6 , section 6.G ) can be used to determine reaction exothermicity under suitable conditions.

Even a small sample may be dangerous. Furthermore, the hazard is associated not with the total energy released but with the remarkably high rate of a detonation reaction. A high-order explosion of even milligram quantities can drive small fragments of glass or other matter deep into the body; therefore, use minimum amounts of these hazardous materials with adequate shielding and personal protection. A compound is apt to be explosive if its heat of formation is more than 100 cal/g less than the sum of the heats of formation of its products. In making this calculation, a reasonable reaction should be used to yield the most exothermic products.

Scaling up reactions introduces several hazards. Unfortunately, the current use of microscale teaching methods in undergraduate laboratories increases the likelihood that graduate students and others are unprepared for problems that arise when a reaction is run on a larger scale. These problems include heat buildup and the serious hazard of explosion from incompatible materials. The rate of heat input and production must be weighed against that of heat removal. Bumping the solution or a runaway reaction can result when heat builds up too rapidly.

Exothermic reactions can run away if the heat evolved is not dissipated. When scaling up experiments, sufficient cooling and surface for heat exchange should be provided, and mixing and stirring rates should be considered. Detailed guidelines for circumstances that require a systematic hazard evaluation and thermal analysis are given in Chapter 6 , section 6.G .

Another situation that can lead to problems is a reaction susceptible to an induction period; particular care must be given to the rate of reagent addition versus its rate of consumption. Finally, the hazards of exothermic reactions or unstable or reactive chemicals are exacerbated under extreme conditions, such as high temperature or high pressure used for hydrogenations, oxygenations, or work with supercritical fluids.

4.E. PHYSICAL HAZARDS

4.e.1. compressed gases.

Compressed gases can expose the trained laboratory personnel to both mechanical and chemical hazards, depending on the gas. Hazards can result from the flammability, reactivity, or toxicity of the gas; from the possibility of asphyxiation; and from the gas compression itself, which could lead to a rupture of the tank or valve. (See Chapter 7 , section 7.D .)

4.E.2. Nonflammable Cryogens

Nonflammable cryogens (chiefly liquid nitrogen) can cause tissue damage from extreme cold because of contact with either liquid or boil-off gases. In poorly ventilated areas, inhalation of gas due to boil off or spills can result in asphyxiation. Another hazard is explosion from liquid oxygen condensation in vacuum traps or from ice plug formation or lack of functioning vent valves in storage Dewars. Because 1 volume of liquid nitrogen at atmospheric pressure vaporizes to 694 volumes of nitrogen gas at 20 °C, the warming of such a cryogenic liquid in a sealed container produces enormous pressure, which can rupture the vessel. (See Chapter 6 , section 6.G.4 , and Chapter 7 , section 7.E.2 , for detailed discussion.)

4.E.3. High-Pressure Reactions

Experiments that generate high pressures or are carried out at pressures above 1 atm can lead to explosion from equipment failure. For example, hydrogenation reactions are frequently carried out at elevated pressures, and a potential hazard is the formation of explosive O 2 /H 2 mixtures and the reactivity/pyrophoricity of the catalyst (see section 6.G.5 ). High pressures can also be associated with the use of supercritical fluids.

When evaluating whether a reaction generates high pressures, it is important to consider not just the initial reaction conditions, but the kinetics and thermodynamics of the reaction as a whole. Is any stage of the reaction exothermic? What are the characteristics of the reactants, products, intermediates, and synthetic byproducts (explosive, gaseous, etc.)? What are the temperature and pressure requirements for equipment used during the reaction? If scaling up a reaction, carefully calculate the expected temperatures and pressures that will be generated and the rates at which any pressures will be generated. Be sure to choose laboratory equipment that is appropriate for every stage of the reaction, and consult with the manufacturer if there are any questions or concerns about whether a given reactor or piece of equipment is appropriate for high-pressure work. (For more information about using high-pressure equipment, see Chapter 7 , section 7.E .)

In many cases, barricading is not necessary if the appropriate reaction vessel, fittings, and other equipment are used. However, the laboratory environment must be designed to accommodate the failure of the equipment: ventilation must be adequate to handle discharge from a high-pressure reaction to prevent asphyxiation, laboratory personnel may require hearing protection to guard against the sound of a rupture disc failure, and barricades are necessary if catastrophic failure could result in injury or death of laboratory personnel. For specific information regarding barricade design, see Porter et al. (1956) ; Smith (1964) ; and the Handbook of Chemical Health and Safety ( Alaimo, 2001 ).

4.E.4. Vacuum Work

Precautions to be taken when working with vacuum lines and other glassware used at subambient pressure are mainly concerned with the substantial danger of injury in the event of glass breakage. The degree of hazard does not depend significantly on the magnitude of the vacuum because the external pressure leading to implosion is always 1 atmosphere. Thus, evacuated systems using aspirators merit as much respect as high-vacuum systems. Injury due to flying glass is not the only hazard in vacuum work. Additional dangers can result from the possible toxicity of the chemicals contained in the vacuum system, as well as from fire following breakage of a flask (e.g., of a solvent stored over sodium or potassium). (For more information about working with equipment under vacuum, see Chapter 7 , section 7.E .)

Because vacuum lines typically require cold traps (generally liquid nitrogen) between the pumps and the vacuum line, precautions regarding the use of cryogens should be observed also. Health hazards associated with vacuum gauges have been reviewed ( Peacock, 1993 ). The hazards include the toxicity of mercury used in manometers and McLeod gauges, overpressure and underpressure situations arising with thermal conductivity gauges, electric shock with hot cathode ionization systems, and the radioactivity of the thorium dioxide used in some cathodes. (For information about reducing the presence of mercury in laboratories, see Chapter 5 , section 5.B.8 .)

4.E.5. Ultraviolet, Visible, and Near-Infrared Radiation

Ultraviolet, visible, and infrared radiation from lamps and lasers in the laboratory can produce a number of hazards. Medium-pressure Hanovia 450 Hg lamps are commonly used for ultraviolet irradiation in photochemical experiments. Ultraviolet lights used in biosafety cabinets, as decontamination devices, or in light boxes to visualize DNA can cause serious skin and corneal burns. Powerful arc lamps can cause eye damage and blindness within seconds. Some compounds (e.g., chlorine dioxide) are explosively photosensitive.

When incorrectly used, the light from lasers poses a hazard to the eyes of the operators and other people present in the room and is also a potential fire hazard. Depending on the type of laser, the associated hazards can include mutagenic, carcinogenic, or otherwise toxic laser dyes and solvents; flammable solvents; ultraviolet or visible radiation from the pump lamps; and electric shock from lamp power supplies.

At the time of this publication, two systems for classifying lasers are in use. Before 2002, lasers were classified as I, II, IIIA, IIIB, and IV. From 2002 forward, a revised system is being phased in which classifies lasers as 1, 1M, 2, 2M, 3R, 3B, and 4. Although they have different designations, both systems classify lasers based on their ability to cause damage to individuals. The older designation is given in the text with the new designation in parentheses. Class I (1) lasers are either completely enclosed or have such a low output of power that even a direct beam in the eye could not cause damage. Class II (2) lasers, can be a hazard if a person stares into the beam and resists the natural reaction to blink or turn away. Class IIIA (1M, 2M, or 3R, depending on power output) lasers can present an eye hazard if a person stares into the beam and resists the natural reaction to blink or turn away or views the beam with focusing optical instruments. Class IIIB (3B) lasers can produce eye injuries instantly from both direct and specularly reflected beams, although diffuse reflections are not hazardous. The highest class of lasers, Class IV (4), presents all the hazards of Class III (3B) lasers but because of their higher power output may also produce eye or skin damage from diffuse scattered light. In addition to these skin and eye hazards, Class IV (4) lasers are a potential fire hazard.

Select protective eyewear with the proper optical density for the specific type of laser in use. Dark lenses can be hazardous because of the risk of looking over the top of the glasses. Leave laser safety glasses in a bin outside the laboratory so that people entering use the appropriate laser safety glasses. When operating or adjusting a laser, remove or cover any reflective objects on hands and wrists to reduce the chance of reflections. Consider using beam blocks and containment walls to reduce the chance of stray reflections in the laboratory. When using a laser-based microscope, consider using a camera and computer display to view the sample rather than direct viewing through the eyepiece. Anyone who is not the authorized operator of a laser system should never enter a posted laser-controlled laboratory if the laser is in use. Visitors may be present when a laser is in use, but they must be authorized by the laboratory supervisor. Visitors must not operate the equipment and should be under the direct supervision of an approved operator.

4.E.6. Radio Frequency and Microwave Hazards

Radio frequency (rf) and microwaves occur within the range 10 kHz to 300,000 MHz and are used in rf ovens and furnaces, induction heaters, and microwave ovens. Extreme overexposure to microwaves can result in the development of cataracts or sterility or both. Microwave ovens are increasingly being used in laboratories for organic synthesis and digestion of analytical samples. Only microwave ovens designed for laboratory or industrial use should be used in a laboratory. Use of metal in microwave ovens can result in arcing and, if a flammable solvent is present, in fire or explosion. Superheating of liquids can occur. Capping of vials and other containers used in the oven can result in explosion from pressure buildup within the vial. Inappropriately selected plastic containers may melt.

4.E.7. Electrical Hazards

The electrocution hazards of electrically powered instruments, tools, and other equipment are almost eliminated by taking reasonable precautions, and the presence of electrically powered equipment in the laboratory need not pose a significant risk. Many electrically powered devices are used in homes and workplaces in the United States, often with little awareness of the safety features incorporated in their design and construction. But, in the laboratory these safety features should not be defeated by thoughtless or ill-informed modification. The possibility of serious injury or death by electrocution is very real if careful attention is not paid to engineering, maintenance, and personal work practices. Equipment malfunctions can lead to electrical fires. If there is a need to build, repair, or modify electrical equipment, the work should ideally be performed or, at a minimum, inspected by a trained and licensed electrician or electrical expert. All laboratory personnel should know the location of electrical shutoff switches and circuit breaker switches and should know how to turn off power to burning equipment by using these switches. Laboratory equipment should be correctly bonded and grounded to reduce the chances of electric shock if a fault occurs.

Some special concerns arise in laboratory settings. The insulation on wires can be eroded by corrosive chemicals, organic solvent vapors, or ozone (from ultraviolet lights, copying machines, and so forth). Eroded insulation on electrical equipment in wet locations such as cold rooms or cooling baths must be repaired immediately. In addition, sparks from electrical equipment can serve as an ignition source in the presence of flammable vapor. Operation of certain equipment (e.g., lasers, electrophoresis equipment) may involve high voltages and stored electrical energy. The large capacitors used in many flash lamps and other systems are capable of storing lethal amounts of electrical energy and should be regarded as live even if the power source has been disconnected.

Loss of electrical power can produce extremely hazardous situations. Flammable or toxic vapors may be released from freezers and refrigerators as chemicals stored there warm up; certain reactive materials may decompose energetically on warming. Laboratory chemical hoods may cease to function. Stirring (motor or magnetic) required for safe reagent mixing may cease. Return of power to an area containing flammable vapors may ignite them.

4.E.8. Magnetic Fields

Increasingly, instruments that generate large static magnetic fields (e.g., NMR spectrometers) are present in research laboratories. Such magnets typically have fields of 14,000 to 235,000 G (1.4 to 23.5 T), far above that of Earth's magnetic field, which is approximately 0.5 G. The magnitude of these large static magnetic fields falls off rapidly with distance. Many instruments now have internal shielding, which reduces the strength of the magnetic field outside of the instrument (see Chapter 7 , Table 7.1 ). Strong attraction occurs when the magnetic field is greater than 50 to 100 G and increases by the seventh power as the separation is reduced. However, this highly nonlinear falloff of magnetic field with distance results in an insidious hazard. Objects made of ferromagnetic materials such as ordinary steel may be scarcely affected beyond a certain distance, but at a slightly shorter distance may experience a significant attraction to the field. If the object is able to move closer, the attraction force increases rapidly, and the object can become a projectile aimed at the magnet. Objects ranging from scissors, knives, wrenches, and other tools, keys, steel gas cylinders, buffing machines, and wheelchairs have been pulled from a considerable distance to the magnet itself.

Superconducting magnets use liquid nitrogen and liquid helium coolants. Thus, the hazards associated with cryogenic liquids (see section 4.E.2 ) are of concern, as well.

The health effects of exposure to static magnetic fields is an area of active research. Currently, there is no clear evidence of a negative health impact from exposure to static magnetic fields, although biological effects have been observed ( Schenck, 2000 ), and recently, guidelines on limits of exposure to static magnetic fields have been issued by the International Commission on Non-ionizing Radiation ( ICNIRP, 2009 ), which is a collaborating organization with the World Health Organization's International Electromagnetic Field Project.

(For more information about magnetic fields, see Chapter 7 , section 7.C.8.4.1 .)

4.E.9. Sharp Edges

Among the most common injuries in laboratories are cuts from broken glass. Cuts can be minimized by the use of correct procedures (e.g., the procedure for inserting glass tubing into rubber stoppers and tubing, which is taught in introductory laboratories), through the appropriate use of protective equipment, and by careful attention to manipulation. Glassware should always be checked for chips and cracks before use and discarded if any are found. Never dispose of glass in the general laboratory trash. It should only be placed in specific glassware disposal bins. This will reduce the chance of anyone changing the trash receiving a cut.

Other cut hazards include razors, box cutters, knives, wire cutters, and any other sharp-edged tool. When working with these tools, it is important to wear appropriate eye protection and cut-resistant gloves. Follow basic safety procedures when using a cutting tool:

• Inspect the tool prior to use. Do not use it if it is damaged.
• When cutting, always use a tool with a sharp edge. Dull edges are more likely to slip and cause harm.
• Keep hands out of the line of the cut.
• Stand off-line from the direction of the cut.
• If using a box cutter or other tool with a mounted blade, ensure that the blade is well seated before use.
• Never use a cutting tool for a task for which it was not designed, for example, as a screwdriver or lever for opening a container.
• Never submerge a sharp object in soapy or dirty water. It can be difficult to see and poses a risk to the dishwasher.

4.E.10. Slips, Trips, and Falls

Other common injuries in the laboratory arise from slipping, tripping, or improper lifting. Spills resulting from dropping chemicals not stored in protective rubber buckets or laboratory carts can be serious because the laboratory worker can fall or slip into the spilled chemical, thereby risking injury from both the fall and exposure to the chemical. Chemical spills resulting from tripping over bottles of chemicals stored on laboratory floors are part of a general pattern of bad housekeeping that can also lead to serious accidents. Wet floors around ice, dry ice, or liquid nitrogen dispensers can be slippery if the areas are not carpeted and if drops or small puddles are not wiped up as soon as they form.

Attempts to retrieve 5-gallon bottles of distilled water, jars of bulk chemicals, and rarely used equipment stored on high shelves often lead to back injuries in laboratory environments. Careful planning of where to store difficult-to-handle equipment and containers (because of weight, shape, or overall size) reduces the incidence of back injuries.

4.E.11. Ergonomic Hazards in the Laboratory

General workplace hazards also apply in the laboratory. For example, laboratory personnel are often involved in actions such as pipetting and computer work that can result in repetitive-motion injuries. Working at a bench or at a microscope without considering posture can result in back strain, and some instruments require additional in-room ventilation that may raise the background noise level to uncomfortable or hazardous levels. With these and other issues such as high or low room temperatures and exposure to vibrations, it is important to be aware of and to control such issues to reduce occupational injuries. For example, microscope users may find that using a camera to view images on a screen, rather than direct viewing through the eyepiece, reduces back and eye strain.

The Centers for Disease Control and Prevention (CDC) and the National Institutes of Health have information on their Web sites ( www.cdc.gov and www.nih.gov , respectively) describing specific ergonomic concerns for laboratories and proposed solutions. The CDC provides a downloadable self-assessment form to aid in evaluating these hazards. NIOSH ( www.cdc.gov/niosh ) and OSHA ( www.osha.gov ) provide information about vibration, noise levels, and other workplace hazards.

4.F. NANOMATERIALS

Nanoscale materials are of considerable scientific interest because some chemical and physical properties can change at this scale. (See definition of engineered nanomaterials below.) These changes challenge the researcher's, manager's, and safety professional's understanding of hazards, and their ability to anticipate, recognize, evaluate, and control potential health, safety, and environmental risks. Essentially any solid may be formed in the nano size range, and in general, the term “nanomaterials” has been broadly accepted as including a number of nanometer-scale objects, including: nanoplates, nanofibers (including nanotubes); and nanoparticles. In addition to the conventional hazards posed by the material, hazard properties may also change.

Nanoparticles are dispersible particles that are between 1 and 100 nm in size that may or may not exhibit a size-related intensive property. The U.S. Department of Energy ( DOE, 2008 , 2009 ) states that engineered nanomaterials are intentionally created, in contrast with natural or incidentally formed, and engineered to be between 1 and 100 nm. This definition excludes biomolecules (proteins, nucleic acids, and carbohydrates). 3 Incidentally formed nanoparticles are often called “ultrafine” particles.

As with hazardous chemicals, exposures to these materials may occur through inhalation, dermal contact, accidental injection, and ingestion, and the risk increases with duration of exposure and the concentration of nanoparticles in the sample or air. Inhalation presents the greatest exposure hazard. Nanomaterials suspended in a solution or slurry pose a lesser hazard, but because the solutions can dry into a powder, they should be handled with care. Nanomaterials suspended in a solution or slurry present a hazard whenever mechanical energy is imparted to the suspension of slurry. Sonication, shaking, stirring, pouring, or spraying of a suspended nanomaterial can result in an inhalation exposure. Suspensions also represent a dermal exposure potential. Nanoparticles that are fixed within a matrix pose the least hazard as long as no mechanical disruption, such as grinding, cutting, or burning, occurs. (See Figure 4.5 .)

U.S. Department of Energy graded exposure risk for nanomaterials. This figure assumes that no disruptive force (e.g., sonication, grinding, burning) is applied to the matrix SOURCE: Adapted from Karn (2008).

Nanoparticles can enter the laboratory in a variety of ways. For example, the materials may be imported into the lab for characterizations or be incorporated into a study. Alternatively, they could be created (synthesized) in the lab as part of an experiment. In either case, it is important for laboratory personnel to know about the presence and physical state of the nanomaterial (i.e., powder, in solution, on a solid matrix, or in solid matrix) so they can manage the hazards accordingly.

Nanoparticles have significantly greater relative surface areas than larger particles of an equivalent mass, and animal studies have demonstrated a correlation between biological effects (toxic response) and surface area. Thus, nanoparticles represent a greater toxic hazard than an equivalent mass of the same material in larger form. In addition, the number of particles per unit mass is far greater than the number of particles in bulk material per unit mass, resulting in significantly different inhalational hazards between the two forms. Because of their size, nanoparticles can penetrate deep into the lungs, and with a large number of particles in a small volume, can overwhelm the organ and disrupt normal clearance processes. The greater surface reactivity also plays a role in this disruption. Once inside the lungs, nanoparticles may translocate to other organs via pathways not demonstrated in studies with larger particles. In addition, at the interface of the nanoparticle and human cell surface, bioactivity may occur. For example, nanometal particles have been demonstrated to produce reactive oxygen species, implicating the presence of free radicals, and causing the biological effects of inflammation and fibrosis.

The nanoparticulate forms of some materials show unusually high reactivity, especially for fire, explosion, and catalytic reactions. Engineered nanoparticles and nanostructured porous materials have been used effectively for many years as catalysts for increasing the rate of reactions or decreasing the temperature needed for reactions in liquids and gases. Depending on their composition and structure, some nanomaterials initiate catalytic reactions that would not otherwise be anticipated from their chemical composition. Note also that nanomaterials may be attached to the surface of larger particles. In those cases, the larger material may take on the higher reactivity features of the engineered nanoscale material, even though it is not in the form of a particle in the 1- to 100-nm size range.

As noted above, because material properties can change at the nanoscale, nanomaterials should not be assumed to present only those hazards known to be associated with bulk forms of material having the same composition. Instead, they must be handled as though toxic and reactive until credible evidence eliminates uncertainty. Hazard information is available on a limited number of nano-size materials. For example, NIOSH has proposed special exposure limits for nano-size titanium dioxide that are significantly more restrictive than for larger particles of titanium dioxide. Determination of EHS issues is an ongoing effort. The CHO assisting with protection from the EHS hazards will need special education and training to adequately assist in risk assessment and control of nanomaterial risks. Specialized monitoring equipment is required to evaluate potential exposures or release of nanomaterials.

Although there is limited specific guidance on evaluation and control of risks posed by nanomaterials, preliminary research suggests that a well-designed ventilation system with high-efficiency filtration is effective at capturing nanoparticles. However, recent studies ( Ellenbecker and Tsai, 2008 ) have demonstrated that conventional laboratory chemical hoods may create turbulence that can push the materials back into the laboratory space. Lower flow hoods with less turbulence may be more appropriate. (For more information about engineering controls for handling of nanoparticles, see Chapter 9 , section 9.E.5 . For further information on transportation, see Chapter 5 , section 5.F.2 and Chapter 6 , section 6.J for information about working with nanoparticles.)

4.G. BIOHAZARDS

Biohazards are a concern in laboratories in which microorganisms, or material contaminated with them, are handled. Anyone who is likely to come in contact with blood or potentially infectious materials at work is covered under OSHA's Bloodborne Pathogen Standard, 29 CFR § 1910.1030. These hazards are usually present in clinical and infectious disease research laboratories but may also be present in any laboratory in which bodily fluids, tissues, or primary or immortalized cell lines of human or animal origin are handled. Biohazards are also present in any laboratory that uses microorganisms, including replication-deficient viral vectors, for protein expression or other in vitro applications. Occasionally, biohazards are present in testing and quality control laboratories, particularly those associated with water and sewage treatment plants and facilities involved in the production of biological products and disinfectants. Teaching laboratories may introduce low-risk infectious agents as part of a course of study in microbiology.

Synthetic biology makes it possible to synthesize microorganisms from basic chemical building blocks, and these microorganisms may have different hazards from their naturally occurring relatives. If a microorganism identical or very similar to one found in nature is synthesized, the risks are assumed to be similar to those of the naturally occurring microorganism. If a novel microorganism is synthesized, however, extra caution must be used until the characteristics of the agent are well understood.

Risk assessment for biohazardous materials can be complicated because of the number of factors that must be considered. The things that must be accounted for are the organism being manipulated, any alterations made to the organism, and the activities that will be performed with the organism. Risk assessment for biological toxins is similar to that for chemical agents and is based primarily on the potency of the toxin, the amount used, and the procedures in which the toxin is used. An example of a risk assessment for a material with unknown biological risks can be found in Backus et al. (2001) . See Box 4.3 for a quick guide to assessing risks from biohazards in the laboratory.

Quick Guide to Risk Assessment for Biological Hazards in the Laboratory. The following steps are provided to assist trained laboratory personnel in performing a risk assessment of activities involving biohazardous materials. This is not intended as a (more...)

Certain biological toxins and agents are classified as select agents under 42 CFR Part 73 and have additional regulatory and security requirements that must be considered when receiving and working with these agents. For detailed information on risk assessment of biohazards, consult the fifth and most recent edition of Biosafety in Microbiological and Biomedical Laboratories (BMBL; HHS/CDC/NIH, 2007a) and the NIH Guidelines for Research Involving Recombinant DNA Molecules (NIH, 2009). BMBL is considered the consensus code of practice for identifying and controlling biohazards and was first produced by the CDC and the National Institutes of Health in 1984. (Also see Chapter 6 , section 6.E , and Chapter 11 .)

4.H. HAZARDS FROM RADIOACTIVITY

This section provides a brief primer on the potential hazards arising from the use of radioactivity in a laboratory setting. A comprehensive treatment of this topic is given in Radiation Protection: A Guide for Scientists, Regulators, and Physicians ( Shapiro, 2002 ). For an introduction to health physics, see Cember and Johnson (2008) . Note that the receipt, possession, use, transfer, and disposal of most radioactive materials is strictly regulated by the U.S. Nuclear Regulatory Commission (USNRC; see 10 CFR Part 20, Standards for Protection Against Radiation) and/or by state agencies who have “agreements” with the USNRC to regulate the users within their own states. Radioactive materials may be used only for purposes specifically described in licenses issued by this agency to licensees. Individuals working with radioactive materials should thus be aware of the restrictions and requirements of these licenses. Consult your radiation safety officer or other designated EHS professional for training, policies, and procedures specific to uses at your institution.

Unstable atomic nuclei eventually achieve a more stable form by emission of some type of radiation. These nuclei or isotopes are termed radioactive. The emitted radiation may be characterized as particulate (α, β, proton, or neutron) or electromagnetic (γ rays or X rays). Particulate radiations have both mass and electromagnetic radiations, which are sometimes referred to as photons. Radiation that has enough energy to ionize atoms and create ion pairs is referred to as ionizing radiation. Ionizing radiation not only comes from unstable nuclei, but can also be produced by machines such as particle accelerators, cyclotrons, and X-ray machines.

Alpha particles are charged particles containing two protons and two neutrons and are emitted from certain heavy atoms such as uranium and thorium. These particles are relatively large, slow, heavy, and easily stopped by a sheet of paper, a glove, a layer of clothing or even a dead layer of skin cells, and thus present virtually no external exposure hazard to people. However, because of the very large number of ionizations that α particles produce in short distances, α emitters can present a serious hazard when they come in contact with internal living cells and tissues. Special precautions are thus taken to ensure that α emitters are not inhaled, ingested, or injected. Care must be taken with unsealed α-emitting sources to control contamination and minimize the potential for internal uptakes.

A β particle (see Table 4.10 ) is an electron emitted from the nucleus of a radioactive atom. Positively charged counterparts of β particles are called positrons. Beta particles are much less massive and less charged than α particles and interact less intensely with atoms in the materials through which they pass, which gives them a longer range than α particles. Examples of β emitters commonly used in biological research are hydrogen-3 (tritium) ( 3 H), carbon-14 ( 14 C), phosphorus-32 ( 32 C), phosphorus-33 ( 33 P), and sulfur-35 ( 35 P). Although low-energy β particles are usually stopped by the dead layer of skin, higher energy β particles can penetrate more deeply and cause high exposures to the skin and eyes. The energy level of the β particle thus determines if shielding and exposure monitoring is required when working with these materials, as well as how contamination surveys are performed. Table 4.10 provides typical examples of high-energy, low-energy, and extremely low-energy β-particle handling precautions. When shielding is used to reduce external exposures from β emitters, a low-density shielding material such as Plexiglas, Lucite, or acrylic works best.

Examples of β Emitters.

Gamma rays, x rays, and photon radiations have no mass or charge. Gamma rays are generally emitted from the nucleus during nuclear decay, and x rays are emitted from the electron shells. Extremely dense material such as lead typically makes the best shields for these electromagnetic forms of radiation. Iodine-125 ( 125 I), indium-111 ( 111 In), and chromium-51 ( 51 Cr) are a few examples of radionuclides sometimes used in research laboratories.

Neutrons are emitted from the nucleus during decay, have no electrical charge, and are one-fourth the mass of an α particle. Exposure to neutrons can be hazardous because the interaction of neutrons with molecules in the body can cause disruption to molecules and atoms. Because of its lack of charge, the neutron is difficult to shield, can penetrate deeply into tissues, and can travel hundreds of yards in air depending on the kinetic energy of the neutron. A neutron is slowed when it collides with the nucleus of other atoms. This transfers kinetic energy of the neutron to the nucleus of the atom. As the mass of the nucleus approaches the mass of the neutron, this reaction becomes more effective in slowing the neutron. Therefore water and other hydrogen-rich materials, such as paraffin or concrete, are often used as shielding material.

Radioactive decay rates are reported in curies (1 curie [Ci] = 3.7 × 10 10 disintegrations per second [dps]) or in the International System of Units (SI) in becquerels (1 Bq = 1 dps). The decay rate provides a characterization of a given source but is not an absolute guide to the hazard of the material. The hazard depends on the nature, as well as the rate of production, of the ionizing radiation. In characterizing human exposure to ionizing radiation, it is assumed that the damage is proportional to the energy absorbed. The radiation absorbed dose (rad) is defined in terms of energy absorbed per unit mass: 1 rad = 100 ergs/g (SI: 1 Gy = 1 J/kg = 100 rads). For electromagnetic energy, the roentgen (R) produces 1.61 × 10 12 ion pairs per gram of air (SI: 1 C/kg = 3.876 R).

Acceptable limits for occupational exposure to ionizing radiation are set by the USNRC based on the potential amount of tissue damage that can be caused by the exposure. This damage is expressed as a dose equivalent; the common unit for dose equivalent is the roentgen equivalent man (rem). The dose equivalent is determined by the rad multiplied by a weighting factor, called a quality factor, to account for the differences in the nature of the ionizing radiation from different types of radiation. Table 4.11 shows the quality factors for different types of radiation. For γ rays and X rays, rad and rem are virtually equivalent.

Radiation Quality Factors.

Damage may occur directly as a result of the radiation interacting with a part of the cell or indirectly by the formation of toxic substances within the cell. The extent of damage incurred depends on many factors, including the dose rate, the size of the dose, and the site of exposure. Effects may be short term or long term. Acute short-term effects associated with large doses and high dose rates—for example, 100,000 mrad (100 rad) in less than 1 week—may include nausea, diarrhea, fatigue, hair loss, sterility, and easy bruising. In appropriately managed workplaces, such exposures are impossible unless various barriers, alarms, and other safety systems are deliberately destroyed or bypassed. Single-dose exposures higher than 500 rem are probably fatal. A single dose of ~100 rem may cause a person to experience nausea or skin reddening, although recovery is likely. However, if these doses are cumulative over a period of time rather than a single dose, the effects are less severe. Long-term effects, which develop years after a high-dose exposure, are primarily cancer. Exposure of the fetus in utero to radiation is of concern, and the risk of damage to the fetus increases significantly when doses exceed 15,000 mrem. The USNRC has set limits for whole-body occupational exposure at 5,000 mrem/year, with minors and declared pregnant workers allowed only 500 mrem/ year (or 9-month gestation period), and members of the public allowed only 100 mrem/year (see Table 4.12 ). Exposure limits are lower in facilities operated by the U.S. Department of Energy and other agencies. Note that properly managed work with radioactive materials in the vast majority of laboratory research settings can be performed without any increase in a worker's exposure to radiation.

U.S. Nuclear Regulatory Commission Dose Limits.

As with all laboratory work, protection of laboratory personnel against the hazard consists of good facility design, operation, and monitoring, as well as good work practices. The ALARA (as low as reasonably achievable) exposure philosophy is central to both levels of protection. The amount of radiation or radioactive material used should be minimized. Exposures should be minimized by shielding radiation sources, laboratory personnel, and visitors and by use of emergency alarm and evacuation procedures. The amount of time spent working with radioactive materials should be minimized. Physical distance between personnel and radiation sources should be maximized, and whenever possible, robotic or other remote operations should be used to reduce exposure of personnel. (Also see Chapter 6 , section 6.E .)

In the Globally Harmonized System for Hazard Communication, the term “material safety data sheet” has been shortened to “safety data sheet (SDS).” This book will continue to use the term MSDS as it is more recognizable at the time of writing than SDS.

For information on how OELs are determined, see Alaimo (2001).

Note that this definition is slightly different from the definition of the International Organization for Standardization, where “ nanoobject is defined as material with one, two, or three external dimensions in the size range of approximately 1–100 nm. Subc ategories of nano-object are (1) nanoplate , a nano-object with one external dimension at the nanoscale; (2) nanofiber , a nano-object with two external dimensions at the nanoscale with a nanotube defined as a hollow nanofiber and a nanorod as a solid nanofiber; and (3) nanoparticle , a nano-object with all three external dimensions at the nanoscale. Nano-objects are commonly incorporated in a larger matrix or substrate referred to as a nanomaterial ” ( HHS/CDC/NIOSH, 2009a ).

• Cite this Page National Research Council (US) Committee on Prudent Practices in the Laboratory. Prudent Practices in the Laboratory: Handling and Management of Chemical Hazards: Updated Version. Washington (DC): National Academies Press (US); 2011. 4, Evaluating Hazards and Assessing Risks in the Laboratory.
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• FLAMMABLE, REACTIVE, AND EXPLOSIVE HAZARDS
• PHYSICAL HAZARDS
• NANOMATERIALS
• HAZARDS FROM RADIOACTIVITY

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• Published: 16 September 2024

Development a risk assessment method for dimensional stone quarries

• Mojtaba Yari 1 ,
• Saeed Jamali 2 , 3 ,
• Gamil M. S. Abdullah 4 , 5 ,
• Mahmood Ahmad 6 , 7 ,
• Muhammad Usman Badshah 8 &
• Taoufik Najeh 9  

Scientific Reports volume  14 , Article number:  21582 ( 2024 ) Cite this article

Metrics details

• Engineering
• Materials science

Over the last 20 years, the global production of dimension stones has grown rapidly. Today, seven countries—China, India, Turkey, Iran, Italy, Brazil, and Spain—account for around two-thirds of the world's output of dimension stones. Each one has annual production levels of nine to over twenty-two million tons. Mining operation in general is one of the most hazardous fields of engineering. A large amount of dimensional stone quarries require a special scheme of risk assessment. Risk Breakdown Structure is one of the major stages of risk assessment. In this paper, a detailed structure of risks of the dimension stone quarrying is formed, and divided into 17 main levels and 128 sublevels. The complexity of identifying different parameters made it requisite to use multi-attribute decision-making methods for prioritizing associated risks. As a case study, the main risks of the Ghasre Dasht marble mine are evaluated using the VIKOR method considering 10 major parameters under a Fuzzy environment. The results showed that the economic, Management, and Schedule risks are the most threatening risks of dimensional stone quarrying.

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Introduction.

Investment decisions in dimension stone projects are highly susceptible to risks, making effective risk management essential. As the Project Management Institute's (PMI) Guide to the Project Management Body of Knowledge (PMBOK) defines, risk is inherently uncertain, potentially leading to adverse impacts like safety hazards and financial losses 1 . Additionally, risk encompasses any event or condition, positive or negative, that can affect project goals, including both threats and opportunities 2 , 3 .

Therefore, robust risk management practices are crucial for maximizing the impact of positive events while minimizing the likelihood and severity of detrimental occurrences. Following the PMBOK standard, risk management involves six key steps: planning, identification, qualitative analysis, quantitative analysis, response planning, and monitoring 4 .

The global production of dimension stone, particularly for building projects, has witnessed significant growth over the past two decades. Architects increasingly leverage the diverse colors, textures, and finishes natural stone offers. Consequently, seven countries—China, India, Turkey, Iran, Italy, Brazil, and Spain—now contribute approximately two-thirds of global dimension stone output, with individual annual production exceeding 9 million and reaching up to 22 million tons. Mining operations, in general, represent some of the most risk-intensive engineering projects throughout both the design and implementation stages, demanding meticulous attention to risk management. The high volume of dimensional stone quarrying necessitates a specific risk analysis approach. Identifying risk factors, understanding their potential impact, and prioritizing them are fundamental steps. Doing so allows for timely decision-making, implementation of appropriate responses to potential risks, and ultimately, the reduction of negative consequences. Notably, various studies have explored risk assessment and management in the context of open-pit and underground mining operations 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 . Machine learning algorithms have shown promising results in risk assessment modeling e.g. 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 .

In 2011, Careddu and Siotto, by implementing 3-dimensional topographic models, analyzed environmental effects and consequent challenges of these factors such as noise, vibration, fumes, dust, and vehicle traffic on a Marble quarrying in Orosei industrial area 29 .

Yarahmadi et al. 30 selected risks of dimensional quarries are considered for calculating safety risks in this field. Machinery or man falls from bench crest and rock falls were the most influential incidents reported by researchers.

Yari et al. 31 presented a comprehensive method for evaluating 19 active mines of the Pyrtak Company in Lorestan province, Iran, considering safety parameters.

The efficiency of dimensional stone quarries was processed by Esmailzadeh et al. 32 . Based on this research selected factors of gross income, safety, desirability, reduction of environmental impacts, waste and reduction of extracting time are implemented for determining a suitable method to extract the dimensional stone to achieve a more efficiency. As a result, extraction of dimensional stone using diamond wire presented as more efficient method considering the mentioned factors.

Khalilabad et al. 33 provided a model to analyze the safety risk of dimension stone mines. In the mentioned study, fault tree analysis under the fuzzy environment was used to analyze hazards related to the wire-cutting machine in a quarry mine in Iran.

Marras and Careddu 34 studied the work-related injuries and fatal accidents in the dimension stone mines of the Italian industry from 2012 to 2019. The role of human behavioral factors, the competence of safety measures, and the identification of unambiguous regulations are reported as the most important factors in preventing quarry accidents.

Yari et al. 35 determined and ranked the main hazards of decorative stone quarrying by implementing the ‘Preference Ranking Organization Method for Enrichment Evaluation’ (PROMETHEE) technique.

Melodi et al. 36 studied the risk management analysis for labor and equipment in quarry mines in three states of Nigeria. In this study, the level of risks and the likelihood of occurrence of potential hazards were identified and analyzed.

Rasti et al. 37 investigated research for decreasing financial risk by considering all affecting factors on extraction direction. They recommended determining discontinuities and rock blocks and evaluating the typical geometry of a rock block, counting the shape and size, before mining the benches to maximize mining exploitation efficiency and minimize waste ore production.

The study was presented by Wangela and Shah 38 which processed quarrying operations in the Ndarugo area of Kiambu County and concluded that these activities both positive and negative impacts. This study indicates that quarrying companies should consider all environmental, health, and education safety factors to approach sustainable mining.

Esmaeilzadeh et al. 39 used the failure modes and effect analysis (FMEA) method for the safety risk assessment of quarry mines. In this research, the main causes of risks in the West Azerbaijan quarry mines of Iran were identified and studied.

A user-friendly decision-making program was developed by Hazrathosseini 40 using a combination of the AHP and Folchi methods to select the most appropriate method for the identification and assessment of hazards. The suggested model was evaluated in two decorative quarries.

Mikaeil et al. 41 identified the safety and economic hazards of 10 dimensional stone mines in West Azerbaijan province in Iran. Then, the risk severity, probability of occurrence, and probability of risk were assessed by completing a questionnaire. Finally, the risk scores of each risk were determined using the FMEA risk assessment method.

Rahimdel 42 , evaluated the safety risk of incidents in dimension stone mines in Iran using the fuzzy inference system. The fuzzy analytical hierarchy process is used to identify the importance degree of each incidence and then, the overall risk priority number is calculated based on the fuzzy inference process.

The background of research in the field of the risks of the dimensional stone quarries is summarized in Table 1 . As seen, there is extensive research on risk assessment and management in dimension stone quarrying, primarily focusing on safety but also addressing efficiency and environmental sustainability. Different methodologies are employed, with FMEA and fuzzy logic being popular choices. The previous research often employs comprehensive methods that fail to capture the full spectrum of potential risks. Typically, specific risks are addressed through case-by-case analyses, neglecting a holistic approach. Moreover, most studies rely solely on "consequence" and "probability" as key risk assessment factors, leading to concerns about the reliability of these methods 17 , 43 . A critical limitation is the equal weighting given to risks with low probability but high consequence and those with high probability but low consequence 44 .

A grading system for water inrush risk is developed based on the amount of simultaneous anomalous data instances found inside a borehole group 45 . A study conducted by Xiao et al. 46 provides a theoretical foundation for policymakers and engineers to develop hot dry rock resources utilizing closed-loop geothermal systems. Guo et al. 47 developed mathematical model to provide theoretical direction for the investigation of stress wave energy transformation and fracture propagation during rock blasting and mineral mining. The influence of cyclic weak disturbance on the stress relaxation of rock under different confining pressures was studied by Yu et al. 48 . For effective risk prioritization and ranking, the multi-attribute decision-making (MADM) method based on expert opinions offers a valuable approach 49 , 50 . This method has been successfully implemented in previous studies about risk assessment for example in the tunnel projects, as demonstrated in Sayadi Anari, et al. 17 . There are many MADM methods; selecting the appropriate methods depend on matching methods with the problems.

This study aims to rank various risks associated with dimensional stone quarries based on their non-commensurable and conflicting nature. Given these characteristics, the VIKOR method emerges as the appropriate choice for this research. For this purpose, in the first stage, all influencing factors of risks are determined considering the published research on this topic and the authors’ expertise in Risk Breakdown Structure (RBS) in Dimensional Stone Quarries in 17 major levels and 128 sublevels. In the next step, the weights of assessment factors are evaluated using Fuzzy-Analytical Hierarchy Processes (Fuzzy-AHP), Finally, all defined risks are prioritized using the Fuzzy-VIKOR method, and the most threatening risks are determined associated with the Ghasre Dasht Mine.

Risk breakdown structure

Since this definition of Risk Breakdown Structure (RBS) by Hillson 51 , this structure has been used as an efficient and effective tool for risk management in prominent standards such as PMBOK. The definition of RBS generally is similar to the Work Breakdown Structure (WBS). RBS is a hierarchy structure of potential risks that can help managers determine further risks of the project. In the sublevel of the risk breakdown structure, more detailed risk factors are presented.

A comprehensive RBS can be useful for the identification of risks of a Project but does not necessarily comprise all risks of every project. Therefore, an appropriate RBS should be prepared for each project according to its specific characteristics. The risks associated with mining projects generally divided into internal and external risks. Internal risks are about storage and mine conditions and external risks are caused by external conditions such as business and market conditions 52 .

Fuentes classifies risks in the mining industry as follows: geological risks, geotechnical risks, project risks, operational risks, environmental risks, marketing risks, macroeconomic risks, political risks, and transaction risks 15 . Critical risks of mining industry in Mongolia have been expressed by Chinbat and Takakuwa as follows 53 : Owners' financial problems, Poor management, Technical problems, Government bureaucracy certificate, Wrong evaluation of reserve, Workers irresponsibility, Rail transport delays, Shortage of experts (skilled worker), Delivery delay of machines, Government inspectors’ pressure, Changes in laws and regulations, Fuel shortage in the country, Unexpected environmental accidents, Insufficient investment, Organization/Human Resistance, Accidents during production operations.

Evaluating attributes for risk assessment

Due to the disadvantages of the conventional method mentioned in the introduction for risk assessment and ranking (using only two parameters: probability and consequence), in this research, after comprehensive analysis, 10 attributes were identified for risk assessment (Table 2 ).

Multi-attribute decision-making methods

Multi-Attribute Decision Making (MADM) presents a process for decision making such as evaluation, prioritization, and selection of the best available alternatives. In MADM problems, some alternatives should be ranked. Every problem has also several attributes that would specify alternatives and decision-making to define problems accurately 54 . The attributes in a decision matrix are different from each other in terms of scale and units. Sometimes, attributes have a positive aspect and sometimes, they have negative features. Therefore, proper alternatives will provide the best state of each attribute 54 .

Fuzzy-AHP method

Decision-making problems have several attributes with different degrees of importance. Therefore, each attribute is given weight, and the preference for each index over other attributes is determined using these “weights”. There are different methods for measuring the weights of the attributes. In this study, considering the broad application, the Fuzzy-AHP method has been used.

Fuzzy-AHP methods are applied in the calculation of attributes with comparative priority. Comparative priority is obtained from taking pairs of comparison matrices while overall priorities are the final rank of alternatives. Here, only the calculation of the weights of the attributes is the main goal of using the AHP method 55 .

The Fuzzy-AHP technique can be viewed as an advanced analytical method developed from the traditional AHP. The process, depending on this hierarchy, using the method of Chang’s 56 analysis, consists of the following steps:

Step 1 . Break down the complex problem into a hierarchical structure form.

Step 2 . Form a pair of comparisons of matrices (with n rows and m columns):

Step 3. Calculating fuzzy synthetic extent value \(S_{i}\) for rows of pair-wise comparison matrix as follows:

where \(M_{{g_{i} }}^{j}\) are Triangular Fuzzy Numbers (TFNs). To obtain \(\sum\nolimits_{j = 1}^{m} {M_{{g_{i} }}^{j} }\) perform the “fuzzy addition operation” of m extent analysis values for a particular matrix given below:

where l is the lower limit value, m is the most promising value and u is the upper limit value. To obtain \(\sum\nolimits_{i = 1}^{n} {\sum\nolimits_{j = 1}^{m} {M_{{g_{i} }}^{j} } }\) perform the “fuzzy addition operation” of \(M_{{g_{i} }}^{j}\) ( \(j \, = \, 1, \, 2, \ldots , \, m\) ) values give as:

and then compute the inverse of the vector:

Step 4. The degree of possibility of \(M_{2} = \left( {l_{2} ,m_{2} ,u_{2} } \right) \ge \,M_{1} = \left( {l_{1} ,m_{1} ,u_{1} } \right)\) is defined as 57 (see Fig.  1 ):

The degree of possibility of two fuzzy numbers.

The degree of possibility for a convex fuzzy number to be greater than k convex fuzzy numbers \(M_{i}\) ( \(i \, = \, 1, \, 2,..., \, k\) ) can be defined as follows:

Step 5 . Calculating the weights of attributes in pair-wise comparisons matrix:

Then the weight vector is given by:

where \(A_{i} \,(i = 1,2, \ldots ...,n)\) are n attributes.

Step 6. Via normalization, the normalized weight vectors are given:

where \(W\) is a non-fuzzy number. To evaluate the risks, experts only select the related linguistic variable, then for calculations, they are converted into the scale including triangular fuzzy numbers developed 58 and are specified as given in Table 3 .

Fuzzy VIKOR Method

VIKOR is an abbreviation of the Serbian name ‘VlseKriterijumska Optimizacija I Kompromisno Resenje’, which means multi-criteria optimization and compromise solution. This method was developed by Opricovic in late 1998 59 . The VIKOR method which is a multi-conflicting criteria decision-making method concentrates on ranking and selecting the best alternative from a set of alternatives, by finding the compromise solution (closest to the ideal) of a problem. The basic principle of VIKOR is defining the positive-ideal solution and the negative-ideal solution in the first step 60 . The positive and negative-ideal solutions are respectively the best value and the worst value of alternatives under the measurement criteria. In the end, the alternatives are arranged based on the proximity to the calculated ideal value. Therefore, the VIKOR method is generally known as a multi-attribute decision-making method based on the ideal point technique 61 .

VIKOR uses the following adopted form of LP-metric aggregate function for compromise ranking of multi-criteria measurement 62 :

where, \(1 \le P \le \infty\) ; \(j = 1, \, ... \, ,\,n\) , is the number of the attributes; \(i = 1, \, ... \, ,\,m\) , respect to alternatives such as \(A_{1} ,\,A_{2} ,...,A_{m}\) ; \(f_{ij}\) is the evaluated value of the \(jth\) criterion for the alternative \(A_{i}\) ; \(n\) is the number of criteria.

The measured \(L_{Pi}\) shows the distance between the alternative \(A_{i}\) and the positive-ideal solution. Within the VIKOR method \(L_{1i}\) (as \(S_{i}\) in Eq.  20 ) and \(L_{\infty i}\) (as \(R_{i}\) in Eq.  21 ) have been used to formulate the ranking calculation.

In this paper, the fuzzy-VIKOR method has been used to evaluate the most threatening risk under the group multi-criteria decision-making based on the concept of fuzzy set theory and VIKOR method. Generally, decision-making problems deal with some alternatives which can be ranked, concerning different criteria. Ratings of the alternatives and the weights of each criterion are the two most important factors that can affect the results of decision-making problems. Therefore, this methodology has been used in this research, to calculate the weights of criteria and prioritize the risks. In this paper, the important weights of various criteria and ratings of qualitative criteria are measured as linguistic variables. Linear triangular fuzzy numbers are considered for capturing the vagueness of these linguistic assessments because linguistic assessment can only have the capability to approximate the subjective judgment through a decision maker’s opinion. It should be supposed, that there are k experts with different weights of opinions who are responsible for judging m alternatives ( \(A_{i}\) , \(i = 1, \, ... \, ,\,m\) ), regarding the importance of each of the \(n\) criteria, ( \(C_{j}\) , \(j = 1, \, ... \, ,\,n\) ) 63 .

The compromise ranking algorithm of the fuzzy VIKOR method consists of the following steps 64 :

Step 1. Defining appropriate linguistic variables and their positive triangular fuzzy numbers and forming Experts’ opinions-criteria matrix:

where, for example, \(\tilde{x}_{12}\) is a fuzzy number that shows the importance of \(1th\) criterion with respect to \(2th\) expert opinion and \(\tilde{W}_{j}\) is the average fuzzy weighted of each criterion. If \(\omega_{t} \in \left[ {0,1} \right]\) be expert’s opinion weights (where \(\sum\nolimits_{t = 1}^{k} {\omega_{t} } = 1\) ), then \(\tilde{W}_{j}\) can be calculated as:

Linguistic variables are used to calculate the important weights of criteria and the ratings of the alternatives concerning criteria. In this paper, linguistic variables are defined by a triangular fuzzy number as presented in Table 2 .

Step 2. Forming a fuzzy alternatives-criteria matrix for each decision maker:

Step 3. Forming a fuzzy decision matrix by pulling all of the experts’ opinions.

where \(\tilde{z}_{ij}\) is calculated by the following equation:

Step 4. Defuzzification of the fuzzy decision matrix and fuzzy weight of each criterion:

Step 5. Computing the positive-ideal solutions value ( \(f_{j}^{ * }\) ) and negative-ideal solutions value ( \(f_{j}^{ - }\) ) for all criterion ratings:

where, \(j = 1, \, ... \, ,\,n\) and \(C_{1}\) is a benefit type criteria set, \(C_{2}\) is a cost type criteria set.

Step 6. Computing the values of \(S_{i}\) , \(R_{i}\) , ( \(i = 1,2, \ldots ,m\) ), by using the relations:

where, \(S_{i}\) is the aggregated value of \(ith\) alternatives with a maximum group utility, and \(R_{i}\) is the aggregated value of \(ith\) alternatives with a minimum individual regret of ‘opponent’. \(W_{j}\) is the average weight of each criterion.

Step 7. Computing \(Q_{i}\) by using the following equation:

where, \(S^{*} = \min_{i = 1,2, \ldots ,m} S_{i}\) , \(S^{ - } = \max_{i = 1,2, \ldots ,m} S_{i}\) , \(R^{*} = \min_{i = 1,2, \ldots ,m} R_{i}\) , \(R^{ - } = \max_{i = 1,2, \ldots ,m} R_{i}\) and \(v\) is a weight for the strategy of maximum group utility, and \(v = 0.5\) whereas \(1 - v\) is the weight of individual regret. The compromise can be selected with ‘voting by the majority’ ( \(v > 0.5\) ), with ‘consensus’ ( \(v = 0.5\) ), with ‘veto’ ( \(v < 0.5\) ).

Step 8. Ranking of the alternatives by sorting each \(S\) , \(R\) and \(Q\) values in ascending order.

Step 9. Selecting the best alternative by choosing \(Q\left( {A^{\left( m \right)} } \right)\) as the best compromise solution with the minimum value of \(Q_{i}\) and must have to satisfy the below conditions 64 :

Condition 1

The alternative \(Q\left( {A^{\left( 1 \right)} } \right)\) has an acceptable benefit; in other words,

where \(A^{\left( 2 \right)}\) is the alternative with the second position in the ranking list by and \(m\) is the number of alternatives.

Condition 2

The alternative \(Q\left( {A^{\left( 1 \right)} } \right)\) is stable within the decision-making process ; in other words, it is also best ranked in \(S_{i}\) and \(R_{i}\) .

If condition 1 is not satisfied, that means \(Q\left( {A^{\left( m \right)} } \right) - Q\left( {A^{\left( 1 \right)} } \right) \ge {1 \mathord{\left/ {\vphantom {1 {\left( {m - 1} \right)}}} \right. \kern-0pt} {\left( {m - 1} \right)}}\) , then alternatives \(A^{\left( 1 \right)} ,A^{\left( 2 \right)} , \cdots ,A^{\left( m \right)}\) all are the same compromise solution and there is no comparative advantage of \(A^{\left( 1 \right)}\) from others. But for the case of maximum value, the corresponding alternative is the compromise (proximity) solution. If condition 2 is not satisfied, the stability in decision-making is deficient while it has \(A^{\left( 1 \right)}\) a comparative advantage. Therefore, \(A^{\left( 1 \right)}\) and \(A^{\left( 2 \right)}\) has the same compromise solution.

Results and discussion

The mentioned studies indicate that the classifications of risk factors in mines have not enough integrity and only some of the risk factors are considered by authors. The large variety of risks that can occur in the mining process, without any systematic procedure for identifying and managing risks, makes quarrying projects more hazardous. RBS presents an effective and targeted tool for the identification and classification of risks 17 , 65 . The present study provides a comprehensive structure of risks for Dimensional Stone Quarries in the two general categories of internal risks (11 main categories and 79 sublevels) and external risks (6 main categories and 49 sublevels).

Figures  2 and 3 show Risk Breakdown Structures for internal and external sources of risk in Dimensional stone quarries respectively.

Risk Breakdown Structure for internal risks in dimensional stone quarries.

Risk Breakdown Structure for external risks in dimensional stone quarries.

The Ghasre Dasht Marble Quarry is a building stone quarry with a high production rate. This quarry is located in the northeast of Fars Province, Iran. The quarry primarily extracts marble, characterized by its northwest-southeast orientation and association with the Bangestan Group marls. Figure  4 provide a general overview of the Ghasre Dasht quarry.

The Ghasre Dasht quarry.

This case study presents risk assessment at Ghasre Dasht, leveraging the insights of 18 experts. These 18 experts included 14 PhDs, 3 MSc holders, and 1 BSc graduate person spanning diverse fields of mining engineering and geology. The group of experts possesses an average of 15 years of academic experience as a teacher, and 10 years of industry expertise. Two questionnaires were distributed: The first questionnaire for determining the important weights of 10 attributes using Fuzzy-AHP; and another questionnaire to form a decision matrix to evaluate and rank the risks using the Fuzzy-VIKOR method. The decision matrix has 17 rows and 10 columns: the rows are risks, and the columns are attributes. In this research, in the first stage, the opinions of the 18 experts are collected as linguistic variables for the weight of attributes and risk scores in relation to each attribute. In the next stage, the weights of attributes are calculated using the Fuzzy-AHP method based on experts’ opinions. Fuzzy weights of attributes are presented in Table 4 and fuzziness weights of them are shown in Fig.  5 .

The fuzziness weights of attributes.

After evaluating the weight of attributes and applying all mentioned stages of the Fuzzy-VIKOR method, the ranking process of risks is conducted according to section “ Conclusions ”. The hierarchical structure of the problem is shown in Fig.  6 . The presented results in Table 5 showed that social risks fall as the lowest-threat risks. Located quarry far from the city, with limited community connection and a small workforce, social risks naturally rank lowest. Conversely, economic risk is the most threatening risk for the Ghasre Dasht quarry, and management and Schedule risks are ranked next.

The hierarchical structure of the problem.

Economic risks, identified in the RBS of external risks of the Ghasre Dasht quarry (Fig.  3 ), encompass more than ten sublevel risks, including Marketing Conditions, Price fluctuations, Interest rates, Inflation rate, Economic policies of the government, Financing terms, Taxes, tolls and customs duties, and more. These risks can significantly impact various project aspects, such as time, quality, cost, and overall performance.

Economic downturns, inflation, or currency fluctuations can lead to material shortages, resource limitations, and funding delays, potentially slowing down or stalling project activities and extending the timeline. Consequently, the economic risks negatively affect project time (with a relative weight of 16%). Furthermore, economic risks can significantly increase project costs due to inflation, higher material costs, and resource scarcity. Additionally, economic instability can drive up financing costs and interest rates. Economic fluctuations can lead to unpredictable costs, such as currency exchange rate variations or higher insurance premiums. Therefore, economic risks also negatively affect project costs (with a relative weight of 11%). In response to economic pressure, project managers may implement cost-cutting measures that compromise on materials, labor, or quality control. This can lead to reduced functionality, durability, or safety in the final product. Furthermore, project scope might be reduced to stay within budget, potentially sacrificing desired features or functionalities. The economic risks likewise have a negative effect on the project quality (with a relative weight of 10%). Project performance (with a relative weight of 8%) is also impacted by economic risks. Delays, reduced quality, and cost overruns lead to reduced stakeholder satisfaction. Failure to meet deadlines and budgets can damage the project's reputation and credibility, potentially affecting future funding opportunities.

On the other hand, the economic risks for the Ghasre Dasht quarry have high values in terms of probability of occurrence, proximity, and repeatability. The nature of these economic risks in the mentioned mine makes them difficult to manage and predict. Considering these factors, it is understandable why economic risks is ranked as the most threatening risk of the Ghasre Dasht quarry.

A more comprehensive analysis of risk classification results reveals a significant trend: 70% of the top ten most threatening risks plaguing Ghasre Dasht quarry stem from internal sources. While external risks present greater challenges in identification and management, mining experts prioritize controlling internal risks due to their greater influence. Many of these top internal risks are human-made and labor-related, such as management risks, Schedule risks, planning risks, that leading to operational problems causing low productivity, low efficiency, more delays and safety hazards. The results resembles the results presented in regard to the previous studies in the field of risks assessment of dimensional stone quarries as reported in 34 , 35 , 38 , 39 , 41 . Considering the importance of personnel's role in these risks, owners of Ghasre Dasht quarry can control and limit the resulting risks by employing an experienced and skilled team for management and technical positions.

Conclusions

The mining process as one of the hazardous fields of engineering requires additional consideration of risk assessment. Risk Breakdown Structure as one of the major stages of risk assessment is formed for dimension stone quarrying and divided into 17 main levels and 128 sublevels. In the next, the main risks of the Ghasre Dasht marble quarry are evaluated using the ‘VlseKriterijumska Optimizacija I Kompromisno Resenje’ (VIKOR) method considering 10 major parameters under a fuzzy environment. Finally, after analyzing 18 experts’ opinions and sorting the main risks, the economic, management, and schedule risks are presented as the most threatening risks of dimensional stone quarrying.

It should be noted that this research focuses on the initial steps of risk management, specifically the identification and qualitative analysis of risks associated with dimensional stone quarries, to uncover the most threatening risks. The next stages of the research will involve the quantitative analysis, management, and control of consequences, as well as the monitoring of risks associated with dimensional stone quarries. Additionally, the authors are currently developing the same procedure for identification, qualitative analysis, and ranking of risks of other types of mines, including coal mines, open-cast metallic mines, underground mines, and more.

Data availability 

The datasets used and/or analyzed during the current study available from the corresponding author on reasonable request.

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Acknowledgements

The authors are thankful to the Deanship of Graduate Studies and Scientific Research at Najran University for funding this work under the Growth Funding Program grant code (NU/GP/SERC/13/34-1).

This work is funded and supported by the Deanship of Graduate Studies and Scientific Research at Najran University under the Growth Funding Program grant code (NU/GP/SERC/13/34-1). Furthermore, the open access funding provided by Luleå University of Technology Sweden.

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Mojtaba Yari

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Department of Civil Engineering, College of Engineering, Najran University, P.O. 1988, Najran, Kingdom of Saudi Arabia

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Mojtaba Yari: Conceptualization, Methodology, Software, Validation, Writing the original draft, Writing, editing and review. Saeed Jamali: Data curation, Writing the original draft, Analysis, editing and review. Gamil M. S. Abdullah, Mahmood Ahmad, Muhammad Usman Badshah, and Taoufik Najeh: Investigation, Analysis, Validation, Writing, editing and review.

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Yari, M., Jamali, S., Abdullah, G.M.S. et al. Development a risk assessment method for dimensional stone quarries. Sci Rep 14 , 21582 (2024). https://doi.org/10.1038/s41598-024-64276-1

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Risk assessment of pulegone in foods based on benchmark dose–response modeling.

1. Introduction

2. materials and methods, 3.1. multiple hepatocellular adenoma, 3.2. hepatocellular adenoma (including multiple), 3.3. hepatocellular adenoma or carcinoma or hepatoblastoma (combined), 4. discussion, 4.1. calculated bmdl values, 4.2. risk assessment of pulegone, 4.3. calculation of adi, 4.4. relevance of neoplastic lesion findings in humans, 5. conclusions, supplementary materials, author contributions, institutional review board statement, informed consent statement, data availability statement, acknowledgments, conflicts of interest.

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Voigt, V.; Franke, H.; Lachenmeier, D.W. Risk Assessment of Pulegone in Foods Based on Benchmark Dose–Response Modeling. Foods 2024 , 13 , 2906. https://doi.org/10.3390/foods13182906

Voigt V, Franke H, Lachenmeier DW. Risk Assessment of Pulegone in Foods Based on Benchmark Dose–Response Modeling. Foods . 2024; 13(18):2906. https://doi.org/10.3390/foods13182906

Voigt, Verena, Heike Franke, and Dirk W. Lachenmeier. 2024. "Risk Assessment of Pulegone in Foods Based on Benchmark Dose–Response Modeling" Foods 13, no. 18: 2906. https://doi.org/10.3390/foods13182906

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