Exposure Assessment

Workers’ exposure levels can be estimated either by occupational hygiene sampling or by biological monitoring. Since inhalation is usually the most im­portant exposure route, occupational hygiene surveys generally include the measurements of airborne concentrations of many impurities in workroom air. However, dermal exposure is also important for many substances* It can be assessed by analyzing hand-wash and patch samples. In biological monitor­ing, the concentration of a substance or its metabolite is determined from bio­logical samples. Urine, blood, and exhaled air are the most common biological samples. Furthermore, molecular dosimetry, or target-dose monitoring, usu­ally based on the analysis of DNA or protein adducts in lymphocytes or hemo­globin adducts in erythrocytes in exposed individuals, has become popular and holds great promise in the assessment of the association between exposure and the effects of carcinogens. Determination of Airborne Concentrations

Major time variation is typical for occupational inhalation exposure. It is not unusual if a worker’s daily average exposure levels varies by a factor of ten within a single week. The concentration distribution is usually close to lognormal (the logarithms of concentrations are distributed normally). In fact, the distribution may be slightly skewed so that its right side is less steep than its left. The concentration distributions can be characterized by their geometric mean (mg) and geometric standard deviation (sg). However, the geometric mean should never be used to describe exposure because the exposure dose depends on the arithmetic mean. The geometric standard deviation is typically 1.5-2.5. In industries with continuous processes,

May be lower (1.1-1.5), whereas sg may exceed 2.5 in some manual occu­pations. The lognormal distribution becomes a straight line on logarithmic probability paper. The concentration corresponding to the probability of 50% is mg (also the median) and s is obtained from the ratio c50/cls.) or (<:X41/e50) as shown in Fig. 5.52.19-

A European standard (EN 689/95) has been set for occupational ex­posure assessment. However, this is primarily intended to be used to guarantee that the concentrations of air impurities are in compliance with OELs. According to the standard, exposures exceeding 10% of OEL level should be followed with repeated measurements, the interval of which depends on the concentration observed. The interval decreases as the concentration approaches the OEL.193 The standard also includes the concept that workers should be divided into homogeneous exposure groups (HEGs). These consist of workers who have similar jobs and are exposed to the same agents. This is practical because it would be unnec­essarily laborious to investigate every worker. On the other hand, the prerequisite of the standard that the exposure levels of the members of a HEG remain within the range 0.5-2 times the mean exposure level is un­practically tight. In addition, airborne concentrations usually fluctuate greatly with time. The within — and between-worker components of expo­sure variability can be calculated by using the random-effects analysis of variance.194 However, this would require extensive sampling. Even though repeated random personal sampling is, in principle, the most ac­curate method for exposure assessment, it has the serious limitation that it does not provide information on the reasons for the exposure. Without this basic knowledge, it may be difficult to institute effective remedial measures.52

It is appropriate to consider the differences between manual tasks and process industries (see Section while assessing the exposure, and to perform air sampling so that it also can support planning of engineering control. Because of steep concentration gradients, breathing zone sampling must be performed when investigating manual tasks. A worker often per­forms several tasks, and the exposure may be very different during differ­ent tasks. Therefore, all major tasks done by the worker should be studied under various conditions. If the position of the local exhaust is not fixed, its influence should also be examined. The time-weighted average (TWA) concentration is obtained using the lengths of various tasks as the weights. It is common practice to determine the TWA of a working day (shift). Since the health effects usually depend on long-term average exposure level, this should also be estimated. Past exposures are often very difficult to assess because working conditions and methods may have been changed. How­ever, the present (e. g., annual) average exposure level can be estimated by asking the worker how much time he/she spends on average (e. g., during the past year) for various tasks and use these as weights. For example, if we want to assess a construction painter’s exposure to organic solvents, we must first list all tasks in which solvent-based paints are used. The expo­sure during painting depends mainly on the size of the surface painted (or on paint consumption rate), the room volume, and the ventilation. Since

*Sbji 300 ppm/200 pзrv

Local exhausts cannot be used generally, the ventilation may depend oo the possibility of keeping the doors and windows open. Breathing zone sam­ples are collected during painting of doors, window frames, floors, walls, etc. in rooms of different size (e. g., small, medium, and large), both with doors and windows open and with them closed. The time use distribution can be obtained with a questionnaire.

In process industries, the areal distribution of airborne pollutant con­centrations becomes important. Thus, workers’ exposure levels depend on their movement patterns during the working day. Ideally, the pro­cesses are closed, but, in practice, in-plant emissions occur from openings needed for material flows and sampling. Sometimes, in-plant emissions are intentionally allowed to be discharged into workroom air in areas where workers do not spend any time. In addition, fugitive emissions commonly take place due to leaking seals in flanges, valves, pumps, and fans. For continuous processes, the time variation of airborne concentra­tion often depends predominantly on relatively few process parameters, such as production rate, temperature, and pressure. These are also im­portant for batch processes, but there are usually certain process phases during which the emissions are heaviest. Batch processes generally also include several manual tasks, such as emptying sacks and barrels.

Since the concentration gradients are not very steep at the actual working areas, it is more convenient to use stationary monitoring instead of personal sampling, and ask how much time, on average, each worker spends in various areas. Direct reading instruments provided with a multi-point sampling system are especially useful because they permit long-term concentration follow-up without excessive costs. Even though accurate information on time use cannot be obtained with questionnaires or interviews, and the coverage of stationary sampling points remains in­complete, the error due to these inadequacies is, nevertheless, usually much smaller than that caused by too brief a sampling time in personal monitoring. In addition, relationships between process parameters and airborne concentrations may be identified. This allows the assessment of long-term exposure because long-term statistics of the important process parameters are usually available. In industries using batch processes, the concentration variation during various process phases should also taken into consideration. Figure 5.53 shows the linear relationship between air­borne toluene concentration and toluene concentration observed at sta­tionary sampling sites in a printing plant. The annual average concentration is now obtained for each monitoring site simply from the

Point on the line corresponding to the average use of toluene during the

‘! <-) ^ year.1 Biological Monitoring

While occupational hygiene measurements always measure only the con­centrations of chemical compounds present in the occupational environment, i. e., the potential dose, the analysis of biological specimens predominantly re­flects the body burden. Furthermore, biological monitoring is always limited to assessment of individual exposure. Personal occupational hygiene sampling takes into consideration only some of the individual factors, e. g., working

Exposure Assessment

Toluene consumption [kg/h]

FIGURE 5.53 Relationship between the concentration of toluene in front of a gravure press and the consumption of toluene.1’5

Habits and height, which can affect exposure. In biological monitoring, factors such as physical activity, i. e., cardiac output and minute volume of ventilation, metabolism, and the mass of depot tissues (e. g., adipose tissue) may also be considered.66’67 Figure 5.54 depicts the difference between occupational hy­giene and biological monitoring.

Exposure Assessment

FIGURE 5.54 The idea of biomonitoring compared to the concept of occupational/ environmental hygienic monitoring. Hygienic monitoring (I) means measurement of concentration of a compound or a fac­tor (e. g., fungal spores) outside the organism, e. g., air monitoring. Biomonitoring (2) means measurement of a compound or its metabolites within the organism, for example in the blood, urine, or exhaled air; measure­ment of binding products in the blood or urine or assessment of an existing effect such as chromosomal or DNA damage in white blood cells.151

Biological monitoring provides integrated information on exposure via all routes, including dermal and oral routes. ’2 It also includes exposure that takes place outside the workplace. These are benefits in individual risk assessment; on the other hand, they can also be considered disadvantages in occupational health because its aim is to provide safe working conditions for everybody, ir­respective of individual characteristics. Biological monitoring can also be used to ascertain effectiveness of personal protective equipment. It also has inherent benefits for substances with long half-lives. The accumulation of substances with very long biological half-lives, such as cadmium, is suitable for biological monitoring because a single sample can provide valuable information pro­vided that a steady-state situation in the body has been reached. In addition, the variation of exposure with time will be attenuated for biological indicators with long half-lives. Therefore, fewer biological monitoring samples are needed for long-term exposure assessment than with conventional occupa­tional hygiene monitoring. However, even this advantage is occasionally ne­gated by the large individual variability typical of biological indicators.

Biological monitoring has several other limitations, in addition to those presented above. Biological monitoring is not suitable for agents which do not need to enter blood, such as irritating gases and many dusts. Neither is it very useful for substances with high acute toxicity (in fact occupational hygiene surveys are not very practical in such cases, but the working area should be provided with some kind of continuous monitoring equipped with an auto­matic alarm system). Another limitation is the small number of compounds for which there are biological exposure limits or indices (BE1) compared to those for occupational exposure limits (only ca. 10%). However, it should be noted that biological monitoring of exposure to a certain agent is often useful even if no BE! has been established for it. Biological monitoring is especially beneficial for substances with significant skin penetration. Urine sampling may well represent the most convenient means for exposure trend analysis.196 Blood sampling may be slightly more difficult due to the analytical procedures and unpleasantness of blood sampling. The main limitation is, however, that biological monitoring as such does not provide any information on the causes of exposure. New technologies have become available in which cell samples can be collected, e. g., from the oral cavity, and possible protein or DNA ad — ducts (reaction products between a reactive compound and proteins or DNA) can be quantitated, e. g., with high-pressure-liquid-chromatography. Examples of such compounds are formaldehyde and isocyanates. Biomarkers

Extensive research is currently underway to use biological markers (biomarkers) in exposure and risk assessment. Biomarkers include the reaction products of chemi­cals or their metabolic products with biological macromolecules, especially with DNA. They also involve indicators of effect, such as chromosomal damage, and indi­cators of individual genetic susceptibility.

Formation of DNA adducts has been demonstrated for many carcinogens. DNA bases are nucleophilic and react with electrophilic compounds. Guanine seems to be especially reactive. Several studies have described how adduct formation can increase with exposure. However, the individual variability is larger than with conventional biological monitoring. Very high interindividual variation has been

Observed with compounds that require metabolic activation (e. g., polycyclic aro­matic compounds). Even though the formation of the adducts is an expression of an interaction of a carcinogen with DNA, the significance of these adducts in chemical carcinogenesis is not yet known. DNA repair and cell proliferation mechanisms re­move damage caused by adducts. Peripheral white blood cells are often used in DNA adduct studies; T cells are especially popular because they are long-lived (half­life is about three years) and therefore they do not solely reflect current exposure. Peripheral white blood cells have also been frequently used for studies of chromo­somal changes. Individuals who have high enzyme activity for formation of reactive metabolites and/or abnormally low metabolic activity of detoxifying enzymes are probably especially susceptible to toxicity.197-199 The use of biomarkers in biomoni­toring is likely to provide a valuable tool for this purpose in the future. This technol­ogy can also be used for molecular dosimetry, or target dose monitoring, in exposed individuals. The goal is to assess the dose at a critical organ or site, such as DNA or a protein.187’1981200 Figure 5.55 depicts some essential features and prerequisites of biomonitoring.64 Table 5.23 indicates the main purposes of biological monitoring of exposure to chemical compounds in the workplace.