Introduction to the Biological Exposure Indices (BEIs)

Biological monitoring provides an important means to assess exposure and health risk to workers. It entails measurement of a chemical determinant in the biological media of those exposed and is an indicator of the uptake of a substance. Biological Exposure Indices (BEIs) are guidance values for evaluating biological monitoring results. BEIs generally represent the levels of determinants that are most likely to be observed in specimens collected from healthy workers who have been exposed to chemicals to the same extent as workers with inhalation exposure at the Threshold Limit Value–Time Weighted Average (TLV–TWA). However, there are BEIs for chemicals for which the TLVs are based on protection against nonsystemic effects (e.g., irritation or respiratory impairment) where biological monitoring is desirable because of the potential for significant absorption via an additional route of entry (usually the skin). There are also BEIs that better predict health effects than air levels and finally, BEIs that are based on the levels in the environmentally exposed population. The BEI^® generally indicates a concentration below which nearly all workers should not experience adverse health effects. The BEI^® determinant can be the chemical itself; one or more metabolites; or a characteristic, reversible biochemical change induced by the chemical. The specimens used for BEIs are urine, blood, or exhaled air. The BEIs are not intended for use as a measure of adverse effects or for diagnosis of occupational illness.

Biological monitoring can assist the occupational health professional (occupational and industrial hygienists, occupational physicians and nurses, etc.) to determine absorption via the skin or gastrointestinal system, in addition to that by inhalation; assess body burden; reconstruct past exposure; detect nonoccupational exposures among workers; test the efficacy of personal protective equipment and engineering controls; and monitor work practices.

Biological monitoring serves as a complement to exposure assessment by air sampling and medical surveillance. The existence of a BEI^® does not indicate a need to conduct biological monitoring. Conducting, designing, and interpreting biological monitoring protocols and the application of the BEI^® require professional experience in occupational health and reference to the current edition of the Documentation of the Threshold Limit Values and Biological Exposure Indices (ACGIH^®).

Editor’s note: The approximate year that the current Documentation was last substantially reviewed and, where necessary, updated may be found following the CAS number for each of the adopted entries in the alphabetical listing, e.g., Acetone [67-64-1] (2014). The reader is advised to refer to the “BEI^® Chronology” section in each Documentation for a brief history of the BEI^® recommendations and notations.

Documentation

It is essential that the user consult the specific BEI^® Documentation before designing biological monitoring protocols and interpreting BEIs for a specific agent. The Documentation for each compound contains the explicit information that is only discussed in general in this Introduction. In addition, each BEI^® Documentation now provides a chronology that traces all BEI^® recommended actions for the chemical substance in question.

BEIs are developed by Committee consensus through an analysis and evaluation process. The detailed scientific criteria and justification for each BEI^® can be found in the Documentation of the Threshold Limit Values and Biological Exposure Indices. The principal material evaluated by the BEI^® Committee includes peer-reviewed published data taken from the workplace (i.e., field studies), data from controlled exposure studies, and from appropriate toxicokinetic modeling when available. The results of animal research are also considered when relevant. The Documentation provides essential background information and the scientific reasoning used in establishing each BEI^®. Information given includes the analytical methods, possible potential for confounding exposures, specimen collection recommendations, limitations, as well as other essential information, specific for each compound and analyte.

In recommending a BEI^®, ACGIH^® considers whether published data are of reasonable quality and may also consider unpublished data if a complete copy of the data/report is provided to ACGIH^®. However, unpublished data are never used as the primary basis for a BEI^®, although it may provide a secondary support. There are numerous instances when analytical techniques are available for the measurement of a biological determinant, but published information is unavailable or inadequate to determine a BEI^®. The data needed to establish a BEI^® include comprehensive assessment of total exposure and/or health effects. Therefore, occupational health professionals are encouraged to accumulate and report biological monitoring data together with exposure and health data.

Relationship of BEIs to TLVs

BEI^® determinants are an index of an individual’s uptake of a chemical by all routes. In some cases they correspond to the TLV^® as a “safe” level without reported health effects. In other cases they may reflect the highest 5% of levels seen in the general population. In addition, some BEIs are without a numerical value and/or provide only qualitative estimates of exposure. These indices are useful to confirm that an exposure to a specific agent is occurring. The basis of each BEI^® is provided in the Documentation. Air monitoring to determine the TLV^® indicates the potential inhalation exposure of an individual or group. The internal dose for individuals within a workgroup may be different for a variety of reasons, some of which are indicated below:

• Exposure by routes other than inhalation, usually dermal, is often a major reason why there is less than perfect concordance between air sampling and biological monitoring. This is often the strongest argument for doing biological monitoring.
• Physiological makeup and health status of the worker, such as body build, diet (water and fat intake), metabolism, body fluid composition, age, gender, pregnancy, medication, and disease state.
• Occupational exposure factors, such as the work-rate intensity and duration, temperature and humidity, co-exposure to other chemicals, and other work factors.
• Nonoccupational exposure factors, such as community and home air pollution, water and food components, personal hygiene, smoking, alcohol and drug intake, exposure to household products, or exposure to chemicals from hobbies or from another workplace.
• Methodological factors, which include specimen contamination or deterioration during collection and storage and bias of the selected analytical method.
• Location of the air monitoring device in relation to the worker’s breathing zone.
• Particle size distribution and bioavailability.
• Variable effectiveness of personal protective devices.

It is important that the reader consult the Documentation of the TLVs and BEIs to understand the importance of each of these factors for each particular agent.

Specimen Collection

Because the concentration of some determinants can change rapidly, the specimen collection time (sampling time) is very important and must be observed and recorded carefully. The sampling time is specified in the BEI^® and is determined by the duration of retention of the determinant, modified in some cases by practicality (for example, if the peak level is expected several hours after the end of a shift). Substances and determinants that accumulate may not require a specific sampling time. An explanation of the BEI^® sampling time is as follows:

*These determinants have long half-lives and their levels may take weeks, months or years after a worker first begins their job to approach steady state and be comparable to the BEI^®. Health professionals should note that if sequential samples taken early in a worker’s exposure career show a marked increase, an overexposure situation might be developing and must be addressed despite the values being below the BEI^®.

Urine Specimen Acceptability

Urine specimens that are highly dilute or highly concentrated are generally not suitable for biomonitoring. The World Health Organization has adopted guidelines (without reference) for acceptable limits on urine specimens as follows:

Creatinine concentration: > 0.3 g/L and < 3.0 g/L

or
Specific gravity: > 1.010 and < 1.030

Specimens falling outside either of these ranges should be discarded and another specimen should be collected when possible.

Some BEIs for determinants whose concentration is dependent on urine output are expressed relative to creatinine concentration. For other determinants such as those excreted by diffusion into the renal tubules, correction for urine output is not appropriate. In general, the best correction method is chemical-specific, but research data sufficient to identify the best method may not be available. When the field data are only available as adjusted for creatinine, the BEI^® will continue to be expressed relative to creatinine; in other circumstances, no correction is recommended, and the BEI^® will be expressed as concentration in urine (e.g., μg/L).
Notations

“B” = background

The determinant may be present in biological specimens collected from subjects who have not been occupationally exposed, at a concentration that could affect interpretation of the result. A “B” notation is assigned to a determinant when the observed 95th percentile value of a random sample, from  national population studies, such as the NHANES surveys, is more than 20% of the BEI^®. When general population data are not available to make this assessment, the BEI^® Committee may assign a “B” notation based on its interpretation of the available data in the scientific literature. In this case, the rationale for the notation is provided in the Documentation for the particular Index. Such background concentrations are incorporated in the BEI^® value.

“Nq” = Nonquantitative

Biological monitoring should be considered for this compound based on the review; however, a specific BEI^® could not be determined due to insufficient data.

“Ns”  = Nonspecific

The determinant is nonspecific, since it is also observed after exposure to other chemicals.

“Sq”  = Semi-quantitative

The biological determinant is an indicator of exposure to the chemical, but the quantitative interpretation of the measurement is ambiguous. These determinants should be used as a screening test if a quantitative test is not practical or as a confirmatory test if the quantitative test is not specific and the origin of the determinant is in question.

“Pop”  = Population based

“Pop” indices are assigned when there are insufficient data to establish a numerical BEI^® but where there are sufficient data on background levels in the general population. “Pop” values can be based on the 95th percentile of large studies of the general population, like the NHANES surveys by the CDC, or they can be based on nonoccupationally exposed populations from the scientific literature.
“Pop” values are not health-based and are intended to give the health professional guidance regarding exposures that are likely to be occupational and not from the general environment. A measurement at or above a “Pop” level will have a high probability of resulting from an occupational exposure.

Quality Assurance

Each aspect of biological monitoring should be conducted within an effective quality assurance (QA) program. The appropriate specimen must be collected at the proper time, without contamination or loss, utilizing a suitable container. Donor identification, time of exposure, source of exposure, and the sampling time must be recorded. The analytical method used by the laboratory must have the accuracy, sensitivity, and specificity needed to produce results consistent with the BEI^®. Appropriate quality control specimens should be included in the analysis, and the laboratory must follow routine quality control rules. Whenever possible, the laboratory should participate in an external proficiency program.

The occupational health professional may also provide known challenge samples to the laboratory along with worker specimens (e.g., blanks, purchased specimens containing the determinant, or split specimens). These challenges will enable the occupational health professional to assess the ability to process, analyze, and report results properly, and to have confidence in their ability to estimate exposure.

The most effective means for controlling laboratory quality is through an external QA/QC program.

Application of BEIs

BEIs are intended as guidelines to be used in the evaluation of potential health hazards in the practice of occupational hygiene. BEIs do not indicate a sharp distinction between hazardous and nonhazardous exposures. For example, it is possible for an individual’s determinant concentration to exceed the BEI^® without incurring an increased health risk. If measurements in specimens obtained from a worker on different occasions exceed the BEI^®, the cause of the excessive value should be investigated and action taken to reduce the exposure. An investigation is also warranted if measurements in specimens obtained from a group of workers at the same workplace and workshift exceed the BEI^®. It is desirable that relevant information on related operations in the workplace be recorded.

Due to the variable nature of concentrations in biological specimens, administrative action should not be normally based on a single result, but on measurements of multiple samplings, or an analysis of a repeat specimen. However, it may be appropriate to remove the worker from exposure following a single high result if there is reason to believe that significant exposure may have occurred.

BEIs apply to 8-hour exposures, 5 days per week. Although modified work schedules are sometimes used in various occupations, the BEI^® Committee does not recommend that any adjustment or correction factor be applied to the BEIs (i.e., the BEIs should be used as listed, regardless of the work schedule).

Use of the BEI^® should be applied by a knowledgeable occupational health professional. Toxicokinetic and toxicodynamic information is taken into account when establishing the BEI^®; thus, some knowledge of the metabolism, distribution, accumulation, excretion, and effect(s) is helpful in using the BEI^® effectively. ACGIH^® may be contacted for technical assistance on any BEI^® issue. The BEI^® is a guideline for the control of potential health hazards to the worker and should not be used for other purposes. The values are inappropriate to use for the general population or for nonoccupational exposures. The BEI^® values are neither rigid lines between safe and dangerous concentrations nor are they an index of toxicity.

Note:

It is essential to consult the BEI^® Documentation before designing biological monitoring protocols and interpreting BEIs. In addition, each BEI^® Documentation now provides a chronology that traces all BEI^® actions for the chemical substance in question.