title: A review of the genotoxicity of ethylbenzene.
abstract: Ethylbenzene is an important industrial chemical that has recently been classified as a possible human carcinogen (IARC class 2B). It induces tumours in rats and mice, but neither the relevance of these tumours to humans nor their mechanism of induction is clear. Considering the carcinogenic potential of ethylbenzene, it is of interest to determine whether there is sufficient data to characterize its mode of action as either genotoxic or non-genotoxic. A review of the currently available genotoxicity data is assessed. Ethylbenzene is not a bacterial mutagen, does not induce gene conversion or mutations in yeast and does not induce sister chromatid exchanges in CHO cells. Ethylbenzene is not clastogenic in CHO or rat liver cell lines but was reported to induce micronuclei in SHE cells in vitro. No evidence for genotoxicity has been seen in humans exposed to relatively high levels of ethylbenzene. Mouse lymphoma gene mutation studies produced a mixed series of responses that have proved difficult to interpret. An increase in morphological transformation of SHE cells was also found. Results from a more relevant series of in vivo genotoxicity studies, including acute and sub-chronic micronucleus tests and the mouse liver UDS assay, indicate a lack of in vivo genotoxic activity. The composite set of results from both in vitro and in vivo tests known to assess direct damage to DNA have been predominantly negative in the absence of excessive toxicity. The available data from the standard battery of genotoxicity assays do not support a genotoxic mechanism for ethylbenzene-induced kidney, liver or lung tumors in rats and mice.
authors.affiliation: Henderson Scientific Consultancy, Cuddington, Cheshire CW82UT, UK. Electronic address: leigh.m.henderson@btopenworld.com.
authors.forename: Leigh
authors.initials: L
authors.lastname: Henderson
authors.affiliation: Brusick Consultancy, Bumpass, VA 23024, USA.
authors.forename: David
authors.initials: D
authors.lastname: Brusick
authors.affiliation: NOVA Chemicals, Inc. 1300 Wilson Blvd., Arlington, VA 22209, USA. Electronic address: ratpanf@novachem.com.
authors.forename: Flora
authors.initials: F
authors.lastname: Ratpan
authors.affiliation: Shell International BV, The Hague, The Netherlands. Electronic address: gauke.veenstra@shell.com.
authors.forename: Gauke
authors.initials: G
authors.lastname: Veenstra
mesh_terms: D000818:Animals; D001555:Benzene Derivatives / Q000633:toxicity*; D006801:Humans; D009152:Mutagenicity Tests / Q000379:methods; D009153:Mutagens / Q000633:toxicity*
chemical_list: D001555:Benzene Derivatives; D009153:Mutagens; C004912:ethylbenzene