Biological monitoring

Biological monitoring – the measurement of a substance or its metabolites in body fluids such as urine or blood – provides a complementary approach to air monitoring for estimating exposure to workplace contaminants. BEI (Biological Exposure Indices) are guidance values for assessing biological monitoring results.

Biological exposure monitoring should not be confused with health monitoring. Exposure monitoring means the measurement and evaluation of exposure to a health hazard experienced by a person; and includes biological monitoring of the people.

Health monitoring, in relation to an individual, means monitoring of the individual to identify any changes in his or her health status because of exposure to certain health hazards. More information on health monitoring can be found in the Exposure monitoring and health monitoring - Good practice guidelines

Biological monitoring provides a better indication than does air monitoring of the bodily uptake of a chemical, as the monitored parameter is a reflection of not only the air level but also the breathing rate and depth, practice regarding respiratory protection, the absorption from other routes (such as skin and/or inadvertent hand to mouth ingestion), and the efficiency or otherwise of elimination. As such it reveals more about a specific individual’s uptake of the chemical and hence their risk. It also reflects any additional non-workplace exposures to the chemical, which can add to risk. (The latter though can serve to complicate assessment of workplace exposure to the chemical.)

The monitoring result is compared to a standard established for the specific substance, termed its biological exposure index (BEI). However there have been fewer BEIs than WESs set, as there is less data directly correlating adverse health effects to blood or urine levels than to air levels. Indeed most BEIs have been set indirectly from the chemical’s WES.

Thus a BEI is considered by the American Conference of Governmental Industrial Hygienists (ACGIH) as a value often corresponding to the WES. That is, if a worker is exposed solely through inhalation, and that exposure is equal to the WES, and they are engaged in moderate work, then the BEI represents the expected level of the biological determinant.

This applies where (as in most cases), the BEI has been derived from the observed relationship between the measured air levels and measured biological (for example, blood or urine) levels as this knowledge enables extrapolation from a WES to a BEI. However, in some cases (such as with lead), the relationship between the biological level and the potential health effects has been approached more directly (for example, by identifying adverse effects as a function of blood lead levels, not air levels).

Other exceptions can be where a WES is set to protect against non-systemic effects such as tissue irritation or respiratory disorders, while a BEI is designed to avoid the risk of systemic effects.

Exposure periods

Depending on the toxicokinetics of the substance (for example its half life), the results from the biological determination may reflect very recent exposure, the average exposure over the last day(s), or long-term cumulative exposure.

The BEIs listed in this document assume that exposure has been reasonably steady and that an eight-hour day, five-day week has been worked. Extrapolation to other exposures can be made, but only with a clear understanding of the relationship between absorption, metabolism, and elimination.

Effectiveness

Biological monitoring has been widely used to monitor the uptake of cumulative toxins; for example lead, mercury, and organophosphates. (However for the latter the term biological effect monitoring is also used, as the test monitors the cumulative effect of organophosphate insecticides by measuring the level of cholinesterase inhibition.)

It also may be employed effectively where there is a significant potential for increased uptake as a result of skin absorption, increased respiratory rate, or exposure outside the workplace (even if there is no change in workplace air levels).

The effectiveness of hazard control measures taken to limit uptake may also in some cases be assessed with follow-up biological monitoring tests. As with air monitoring, the design of the monitoring protocol and interpretation of results should only be done by a person with the appropriate qualifications and experience.

The fact that a BEI has been listed for a particular substance does not imply that biological monitoring is necessary. An appraisal of the exposure should be made before considering monitoring requirements.

Biological assays

Several conditions must be satisfied for a biological assay to be a reliable indicator of exposure to a substance. The fate of the substance in the human body must have been adequately researched, and a time/concentration relationship must exist. It is not essential for the concentration of the determinant to be zero in cases where there is no occupational exposure, as long as the increase is measurably observable above the background level.

The biological assay must be as sensitive and specific as possible. While the concentration of the major metabolite may be high, and therefore easily detected, if it is a metabolite that is common to several substances, the determination of the unaltered substance, or minor metabolite, may be preferable.

The biological assay is often performed at a remote laboratory, therefore the determinant must be stable in the biological fluid.

Issues with biological monitoring

Generally a BEI as assessed by only one specific assay method is given for each substance, even though there may be several ways of estimating exposure. Preference has been given to urinary assays over more invasive blood tests, but factors such as the stability of the sample and the possibility of sample interference should be considered.

Cultural sensitivity of the worker towards submitting a particular type of sample may also influence the selection of the biological monitoring procedure. Alternative methods may be available, especially for monitoring exposure to solvents.^{1, 2}

For the routine surveillance of exposure to some substances, biological monitoring may be preferred over air sampling. For example, if the substance has a long half-life in the body, the biological monitoring assay will give a result that reflects an integrated exposure, with little variation no matter when the sample is taken. In other cases, the corresponding air sampling procedure may, because of the typical work practices or sampling difficulties encountered, give less reliable results than biological monitoring.

Quantitative interpretation of biological monitoring results is often difficult. The overall value of the information may be improved if measurements are obtained from several workers with similar exposure, and/or serial determinations on an individual worker are conducted.

Information prior to monitoring

Before undertaking a biological monitoring exercise, it is essential that background information be obtained, including data on the pharmacokinetics of the substances, interferences, and ‘background’ levels of the determinant arising from non- workplace exposures. The following two references are recommended as a source of the relevant background material:

1. ACGIH Documentation of the Threshold Limit Values and Biological Exposure Indices.³
2. Industrial Chemical Exposure, Guidelines for Biological Monitoring.⁴

Sample collection

It is important to observe the timing of the sample collection for each determination. The level of a substance, or its metabolic products, will vary with the time elapsed since the last exposure, and the BEI for some substances is only applicable if the recommended timing of sample collection is closely adhered to.

Assuming that there has been continual exposure over the working day, the following potential sample periods (causing minimal disturbance of working routines) have received most attention: 

• Prior to (next) shift
• End of shift
• End of work week.

For definitions see Sample collection time definitions.

The most appropriate sample period for any given substance depends on how quickly it (or its measured metabolite) is eliminated from the body.

However, if the exposure has been confined to a portion of the working day, it may be necessary to adjust the timing, but it must be recognised that the estimation of exposure may be compromised.

Other factors may also compromise test results. Contamination of the sample could take place during collection as a result of inadequate cleaning of the skin prior to taking a blood sample, or on other inadvertent contamination of a specimen.

Loss of sample integrity on storage and transport may occur through the use of an inappropriate container or storage conditions. Further details of the procedure to be followed for sample collection should be obtained from the laboratory carrying out the analysis.

Interpretation of results

Biological monitoring data must be interpreted with some caution. Especially useful is to compare any individual’s result with their previous results (if any).

There are several reasons why the levels of the determinant may vary between individuals, even under seemingly identical exposure situations. Workers may differ in size, physical fitness and work practices, resulting in differing uptakes, such as through variations in respiration rate/volume and skin contact (and absorption). Further, there may be inter-individual differences in metabolism and elimination rates of the absorbed substance or contaminant.

Further advice on the application of biological monitoring.

Endnotes

1. Paustenbach, D.J. ‘The History and Biological Basis of Occupational Exposure Limits for Chemical Agents’, Patty’s Industrial Hygiene and Toxicology, 5th Edition, volume 3. John Wiley and Sons (2000).

2. Lauwerys R.R. and Hoet P. Industrial Chemical Exposure, Guidelines for Biological Monitoring. 2nd Edition. ISBN: 0-87371-650-7, (1993).

3. American Conference of Governmental Industrial Hygienists (ACGIH). Documentation of the Threshold Limit Values and Biological Exposure Indices. 7th Edition, ACGIH, Cincinnati, Ohio (2015).

4. Industrial Chemical Exposure – Guidelines for Biological Monitoring, 3rd edition, R.R. Lauwerys, P. Hoet (2001).