Distribution benzene exposure

Paxton MB, Chinchilli VM, Breet SM, et al. 1994a. Leukemia risk associated with benzene exposure in the pliofilm cohort I. mortality update and exposure distribution. Risk Analysis 14(2) 147-154. 

Rushton L. 1996. Benzene exposure in the petroleum distribution industry associated with leukemia in the United Kingdom Overview of the methodology of a case-control study. Environ Health Perspect 104 (Suppl 6) 1371-1374. 

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). 

No information was found on the placental transfer and distribution of phenol, however, Ghantous and Danielsson (1986) examined this question for benzene, the principal metabolite of which is phenol. Mice at gestation day 11, 14, and 17, were exposed by inhalation to 14C benzene and the distribution of benzene and its volatile and non-volatile metabolites examined using whole body autoradiaography and assessment of tissue concentrations of 14C (day 17 only). The authors indicated that the exposure regimen (50 Ci of 14C benzene in maize oil, volatilized by gentle heating) would theoretically produce 2,000 ppm in the inhalation chamber. Measurements of the difference between the amount added to the... 

The toxicokinetics of benzene has been extensively studied. Inhalation exposure is probably the major route of human exposure to benzene, although oral and dermal exposure are also important. Absorption, distribution, metabolism, and elimination have been studied in both humans and animals. Investigations of the metabolism of benzene have led to the identification of toxic metabolites, and to hypotheses about the mechanism of toxicity. 

Animal data confirm that benzene is rapidly absorbed through the lungs. Inhalation studies with laboratory dogs indicate that distribution of benzene throughout the animal s body is rapid, with tissue values dependent on blood supply. A linear relationship existed between the concentration of benzene in air (200-1,300 ppm) and the equilibrium concentration in blood (Schrenk et al. 1941). At these exposures, the concentrations of benzene in the blood of dogs exposed to benzene reached a steady state within 30 minutes. 

Benzene was also distributed to the kidney, lung, liver, brain, and spleen. The benzene metabolites phenol, catechol, and hydroquinone were detected in blood and bone marrow following 6 hours of exposure to benzene, with levels in bone marrow exceeding the respective levels in blood. The levels of phenol in blood and bone marrow decreased much more rapidly after exposure ceased than did those of catechol or hydroquinone, suggesting the possibility of accumulation of the latter two compounds. 

Benzene was rapidly distributed throughout the bodies of dogs exposed via inhalation to concentrations of 800 ppm for up to 8 hours per day for 8-22 days (Schrenk et al. 1941). Fat, bone marrow, and urine contained about 20 times the concentration of benzene in blood benzene levels in muscles and organs were 1-3 times that in blood and erythrocytes contained about twice the amount of benzene found in plasma. During inhalation exposure of rats to 1,000 ppm (2 hours per/day, for 12 weeks), benzene was stored longer (and eliminated more slowly) in female and male rats with higher body fat content than in leaner animals (Sato et al. 1975). 

No studies were located regarding distribution in humans after oral exposure to benzene. 

The bioavailability of pure as opposed to soil-adsorbed benzene was conducted in adult male rats (Turkall et al. 1988). Animals were gavaged with an aqueous suspension of 14C-benzene alone, or adsorbed to clay or sandy soil. Two hours after exposure, stomach tissue contained the highest amount of radioactivity, followed by fat in all treatment groups. No differences in tissue distribution patterns were detected for the three treatments. 

Description of the Model. Bois and Paxman (1992) produced a model that they used to explore the effect of exposure rate on the production of benzene metabolites. The model had three components, which described the pharmacokinetics of benzene and the formation of metabolites, using the rat as a model. Distribution and elimination of benzene from a five-compartment model, comprised of liver, bone marrow, fat, poorly perfused tissues, and well perfused tissues, made up the first component of the model. The five-compartment model included two sites for metabolism of benzene, liver and bone marrow. The bone marrow component was included for its relevance to human leukemia. Parameter values for this component were derived from the literature and from the previously published work of Rickert et al. 

Comparative Toxicokinetics. Qualitatively, absorption, distribution, metabolism, and excretion appear to be similar in humans and laboratory animals. However, quantitative variations in the absorption, distribution, metabolism, and excretion of benzene have been observed with respect to exposure routes, sex, nutritional status, and species. Further studies that focus on these differences and their implications for human health would be useful. Additionally, in vitro studies using human tissue and further research into PBPK modeling in animals would contribute significantly to the understanding of the kinetics of benzene and would aid in the development of pharmacokinetic models of exposure in humans. These topics are being addressed in ongoing studies (see Section 2.10.3). 

Gilli G, Scursatone E, Bono R. 1994. Benzene, toluene and xylenes in air, geographical distribution in the piedmont region (Italy) and personal exposure. Sci Total Environ 148(l) 49-56. 

The exposure route partly determines the distribution of the chemiccil in tlie body. Like tlie chemical benzene, a single clieniiciil may follow multiple routes of exposure. The liver, like the skin, acts as a filter. The liver is the primary detoxification site. Toxicants that arc absorbed into the lungs, skin, mouth, and esophagus may temporarily bypass the liver however, toxicants absorbed tlirougli the stomach and intestines follow the blood s direct path to tlie liver. 

Ethyl benzene distributes to the adipose tissues. It is metabolized to mandelic acid (64%) and phenyl-glyoxylic acid (25%). The percentage of metabolites may vary according to the route of exposure with mandelic acid formation being favored with inhalation. The primary route of excretion is via the urine. Experimental evidence indicates that the percutaneous absorption rate of ethyl benzene is 37 pgcm... 

Absorption, Distribution, Metabolism, and Excretion. There are no quantitative data available on the rates and extent of absorption, distribution, metabolism, or excretion of gasoline in humans or animals following inhalation, oral, or dermal exposure. Although data are available on these parameters for many of the individual components of gasoline (i.e., benzene, toluene, xylene) that may be used to predict the toxicokinetics of gasoline, it is possible that interactions between these components may influence the toxicokinetics of the mixture as a whole. Quantitative data on the toxicokinetics of gasoline following inhalation, oral, and dermal exposure would be useful to predict the behavior of this mixture in the body. 

Aromatic EC5-EC9 Fraction. Studies with humans and animals exposed predominately to vapors of individual BTEXs (there are fewer data for oral and dermal exposure) indicate that, following absorption, compounds in this fraction are widely distributed, especially to lipid-rich and highly perfused tissues (see ATSDR 1994, 1995d, 1997a, 1999a). Studies of rats exposed by inhalation to single hydrocarbons at 100 ppm, 12 hours/day, for 3 days found that C6-C10 aromatics (benzene, toluene, xylene, trimethylbenzene, and f-buty I benzene), compared with C6-C10 -alkanes ( -hexane... 

Lewis, S. J., Bell, G. M., Cordingley, N., Pearlman, E. D., and Rushton, L. (1997). Retrospective estimation of exposure to benzene in a leukaemia case-control smdy of petroleum marketing and distribution workers in the United Kingdom. Occup Environ Med 54, 167-175. 

The subcommittee also recommends that toxicokinetic studies be conducted so that existing human studies on JP-8 and related fuels can be better interpreted. Those studies should provide quantitative information on the relationship of blood and tissue concentrations of JP-8 components after vapor and aerosol exposures to JP-8. Traditional compartmental and physiologically-based toxicokinetic models that take into account absorption, distribution, metabolism, and elimination should include studies on JP-8 and on longer-chain -alkancs, naphthalene, benzene, and other components of JP-8. With improved dosimetry, available human data from a recently com-... 

---