Vol.: 77 (2000) (p. 227)CAS No.:
5. Summary of Data Reported and Evaluation
5.1 Exposure data
Ethylbenzene is a major industrial chemical produced by alkylation of benzene. The pure chemical is used almost exclusively for styrene production. It is also present at up to 25% in technical grades of mixed xylenes and up to 15% in gasoline.
Occupational exposure to ethylbenzene may occur by inhalation during its production and use. Most occupational exposures are related to technical grades of mixed xylenes used as solvents in various paints and coatings, inks, insecticides and in rubber and plastic production, as well as from the production and handling of gasoline and bitumen. Ethylbenzene from these sources as well as from vehicle emissions is ubiquitous at mg/m3 levels in ambient air. It is a component of tobacco smoke and of several household products. These various sources contribute to indoor air levels that are often higher than adjacent outdoor levels. Ethylbenzene is only rarely found in drinking-water but is found at mg/kg levels in a variety of foodstuffs.
5.2 Human carcinogenicity data
Two studies of workers potentially exposed to ethylbenzene in a production plant and a styrene polymerization plant were available. In the first study, no excess of cancer incidence was found but the description of methods was insufficient to allow proper evaluation of this finding. In the second study, no cancer mortality excess was observed during the follow-up of 15 years.
5.3 Animal carcinogenicity data
Ethylbenzene was tested by inhalation exposure in single experiments in mice and rats. In mice, it increased the incidence of lung adenomas in males and of liver adenomas in females. In male rats, it increased the incidence of renal tubule adenomas and carcinomas. An increase in the incidence of renal adenomas was seen in females only after step-sectioning. A study in rats by oral administration could not be evaluated. A metabolite of ethylbenzene, 1-phenylethanol, increased the incidence of renal tubule adenomas in male rats.
5.4 Other relevant data
Ethylbenzene is well absorbed from the skin, lungs and gastrointestinal tract. It is virtually completely metabolized, the primary pathways being hydroxylation of the two carbons of the side-chain, followed by further oxidation to a range of metabolites that are excreted principally in the urine. The fate of ethylbenzene is similar in animals and humans.
Limited data were available to evaluate the toxic effects of ethylbenzene in humans. Liver and kidney weights were increased in rats following exposure to ethylbenzene with no signs of hepatic necrosis. Cytochrome P450 enzymes were induced in both liver and kidney of ethylbenzene-exposed rats. Ethylbenzene caused changes in dopamine levels in brain and prolactin secretion in rats exposed for three to seven days. In rat brain cell cultures, ethylbenzene decreased the activity of several integral membrane enzymes.
No data on reproductive or developmental effects of ethylbenzene in humans were available. In rats and mice, developmental retardation and an increased incidence of variations were reported after inhalation exposure during pregnancy. Reduced numbers of live pups per litter or abortions were reported in rabbits exposed during pregnancy. No changes in sperm motility or oestrous cyclicity were found in rats or mice exposed to ethylbenzene for 13 weeks.
Ethylbenzene was non-mutagenic in bacteria, yeast and insects. In mammalian cells, it was inactive in inducing sister chromatid exchanges in Chinese hamster embryo cells but very weakly positive in cultured human lymphocytes. It did not induce micronuclei in vivo, although it was positive in Syrian hamster embryo cells in vitro. It also caused cell transformation in these cells. Ethylbenzene induced mutations in the mouse lymphoma assay, but only at the highest non-lethal concentration tested.
There is inadequate evidence in humans for the carcinogenicity of ethylbenzene.
There is sufficient evidence in experimental animals for the carcinogenicity of ethylbenzene.
Ethylbenzene is possibly carcinogenic to humans (Group 2B).For definition of the italicized terms, see Preamble Evaluation.
See Also: Toxicological Abbreviations Ethylbenzene (EHC 186, 1996) Ethylbenzene (ICSC)