Benzene estimating exposures

Estimates of daily exposure to benzene from urban or suburban air range from 180 to 1300 /ig/person/day.1112 Urban air concentrations of the other aromatic hydrocarbons are similar to those of benzene and the vast majority of exposure of the general population to these other aromatic hydrocarbons will be due to road transport or solvent-containing products rather than food. A 1995 survey of these compounds in samples from the UK Total Diet Study showed that average dietary exposures to benzene and related compounds from food in the UK are low, and very much lower than estimated exposure from active smoking of tobacco or intakes from air by urban dwellers.13 The mean dietary exposure to benzene was estimated to be in the range 0.9-2.4 /ig/person/day. 

For completeness, we must mention that benzene also occurs naturally in foods such as fruits, fish, vegetables, nuts, meats, dairy products, eggs, and alcoholic beverages. Exposures are estimated by multiplying measured concentrations by usage of the food product. 

In the SRI report (2) the release information on benzene was used with atmospheric dispersion models and data on geographic distribution of population to obtain aggregate exposure estimates (shown in Table IV). 

Although several figures in Table IV are significant, the estimates are probably accurate to the first digit at best. However, they do suggest that widespread but low-level exposures from automobiles and service stations provide the majority of benzene molecules that enter human bodies. Whether these are the most biologically significant emissions depends on the behavior of dose-response relationships at low dose levels. 

Table I illustrates the estimation of ambient exposures to benzene associated with various categories of atmospheric emission sources. Since benzene is a suspected carcinogen, annual exposure is an appropriate measure for assessing long-term effects.

Let us assume that enough information is available regarding the levels of benzene in Mr. Z s well, the number of years he consumed the water, and even his water consumption rate, to derive a reasonably accurate estimate of his cumulative exposure from this source. The epidemiologists and biostatisticians carefully evaluate the dose-response data from the published epidemiology studies used as the basis for classifying benzene as a cause of leukemia. Further assume that we learn from this evaluation that Mr. Z incurred a cumulative benzene exposure approximately equivalent to the cumulative exposure that was found to cause a three-fold excess risk of leukemia in the occupational studies of benzene exposure. A relative risk of three. 

Paxton MB, Chinchilli VM, Brett SM, et al Leukemia risk associated with benzene exposure in the pliofilm cohort. II. Risk estimates. Risk Analysis 14 155-161, 1994... 

Crump KS Risk of benzene-induced leukemia a sensitivity analysis of the pliofilm cohort with additional follow-up and new exposure estimates. J Toxicol Environ Health 42 219-242, 1994... 

This estimate is similar to the 1.2 /rg/person/day for the exposure to benzene by Canadian adults from food.14 These exposures to benzene from food are up to three orders of magnitude smaller than the estimated daily exposure to benzene from active smoking of tobacco, or exposures from air by urban dwellers. 

The environmental effects from the emission of these chlorinated benzenes are estimated to be insigificant because of the low levels and the further dilution by factors of 103 to 105 in the atmosphere before any hunan or plant exposure. 

EPA has set the maximum permissible level of benzene in drinking water at 5 parts per billion (ppb). Because benzene can cause leukemia, EPA has set a goal of 0 ppb for benzene in drinking water and in water such as rivers and lakes. EPA estimates that 10 ppb benzene in drinking water that is consumed regularly or exposure to 0.4 ppb benzene in air over a lifetime could cause a risk of one additional cancer case for every 100,000 exposed persons. EPA recommends a maximum permissible level of benzene in water of 200 ppb for short-term exposures (10 days) for children. 

Levels of exposure associated with the carcinogenic effects (Cancer Effect Levels, CELs) of benzene are indicated in Figures 2-1 and 2-2. Because cancer effects could occur at lower exposure levels, the figures also show a range for the upper bound of estimated excess risks, ranging from a risk of 1 in 10,000 to 1 in 10,000,000 (10 4 to 10 7), as developed by EPA. 

Estimates of exposure levels posing minimal risk to humans (Minimal Risk Levels or MRLs) have been made for benzene. An MRL is defined as an estimate of daily human exposure to a substance that is likely to be without an appreciable risk of adverse effects (noncarcinogenic) over a specified duration of exposure. MRLs are derived when reliable and sufficient data exist to identify the target organ(s) of effect or the most sensitive health effect(s) for a specific duration within a given route of exposure. MRLs are based on noncancerous health effects only and do not consider carcinogenic effects. MRLs can be derived for acute, intermediate, and chronic duration exposures for inhalation and oral routes. Appropriate methodology does not exist to develop MRLs for dermal exposure. 

The same group reported that between 1979 and 1981, Chinese workers using benzene or benzene-containing mixtures were examined. Nine cases of leukemia were found out of4,602 exposed workers. Presumably, some of these may have been included in the study discussed above. Although one worker was exposed for only 2 years, the others were exposed for between 7 and 25 years. No estimate of exposure levels was given for the leukemia cases, but exposure estimates for aplastic anemia cases found in the same study were 29-362 ppm (Yin et al. 1987c). 

EPA has used cancer risk data from human epidemiological studies to derive risk factors associated with oral exposure to benzene. Oral dose levels associated with specific carcinogenic risks have been extrapolated the risk value of 2.7x 10"2 for lifetime inhalation exposure to 1 ppm was converted to a slope factor of 2.9/10"2 for oral exposure of 1 mg/kg/day, assuming identical levels of absorption of benzene following both routes of exposure. Using the method described by EPA (IRIS 1996), the drinking water levels associated with individual upper-bound estimates of 10"4, 10"5, 10"6, and 10"7 have been calculated to be lxlO 1, lxlO"2, lxlO"3, and lxlO"4 mg/L, respectively, which are equivalent to dose levels of 3x 10"3,... 

Dermal exposure to benzene did not induce skin tumors in mice (Bull et al. 1986). No papillomas developed in mice that were given a 2-week, 800 mg/kg/day topical application of benzene as the initiator and a 1 pg topical application of 12-o-tetradecanoylphorbol-13-acetate 3 times a week for 20 weeks and observed for 52 weeks (Bull et al. 1986). The authors concluded that it is difficult to estimate benzene-induced tumor incidence after dermal exposure, and that mouse skin may not be the optimal study system. This is because of the high rate of false-negative responses to chemicals, like benzene, with recognized carcinogenic activity. 

In vivo experiments on 4 human volunteers, to whom 0.0026 mg/cm2 of 14C-benzene was applied to forearm skin, indicated that approximately 0.05% of the applied dose was absorbed (Franz 1984). Absorption was rapid, with more than 80% of the total excretion of the absorbed dose occurring in the first 8 hours after application. Calculations were based on urinary excretion data and no correction was made for the amount of benzene that evaporated from the applied site before absorption occurred. In addition, the percentage of absorbed dose excreted in urine that was used in the calculation was based only on data from rhesus monkeys and may not be accurate for humans. In another study, 35-43 cm2 of the forearm was exposed to approximately 0.06 g/cm2 of liquid benzene for 1.25-2 hours (Hanke et al. 1961). The absorption was estimated from the amount of phenol eliminated in the urine. The absorption rate of liquid benzene by the skin (under the conditions of complete saturation) was calculated to be low, approximately 0.4 mg/cm2/hour. The absorption due to vapors in the same experiment was negligible. The results indicate that dermal absorption of liquid benzene is of concern, while dermal absorption from vapor exposure may not be of concern because of the low concentration of benzene in vapor form at the point of contact with the skin. No signs of acute intoxication due to liquid benzene dermally absorbed were noted. These results confirm that benzene can be absorbed through skin. However, non-benzene-derived phenol in the urine was not accounted for. 

Based on data for skin absorption of benzene vapors in mice and occupational exposure data, Tsuruta (1989) estimated the ratio of skin absorption rate to pulmonary uptake to be 0.037 for humans. Dermal absorption could account for a relatively higher percentage of total benzene uptake in occupational settings where personnel, using respirators but not protective clothing, are exposed to high concentrations of benzene vapor. 

---