For definition of Groups, see Preamble Evaluation.
VOL.: 71 (1999) (p. 1189)
Chem. Abstr. Name: Dimethylbenzene
Chem. Abstr. Name: 1,2-Dimethylbenzene
Chem. Abstr. Name: 1,4-Dimethylbenzene
N.B. - Summary (but not the evaluation) prepared by the Secretariat after the meeting.
5.1 Exposure data
Exposure to xylenes may occur during their production and in the production of aviation gasoline and protective coatings, and during their use in petroleum products, e.g., solvents, and as intermediates in organic synthesis. Natural sources include petroleum, forest fires and volatile substances in plants.
5.2 Human carcinogenicity data
Xylene was mentioned as an exposure in four studies. Two were community-based case–control studies, one of which involved brain cancer and one involved several types of cancer. The two industry-based studies were configured as nested case–control studies, one of central nervous system tumours and one of several sites. In none of these studies was xylene the sole or predominant exposure. Cancers at most sites were not significantly associated with xylene exposure in any study. Incidence of colorectal cancer was significantly elevated in the Canadian case–control study, but no other study reported colorectal cancer results. Hodgkin’s disease was elevated in one study; non-Hodgkin lymphoma was elevated in one study, but not in another. Most results were based on small numbers. In view of the multiple exposure circumstances in most studies, the multiple inference context of these studies, and the weak consistency of the findings, these results are not strong enough to establish whether there is an association with xylene exposure.
5.3 Animal carcinogenicity data
Xylene (technical grade or mixed xylenes) was tested for carcinogenicity in one strain of mice and in two strains of rats by gavage. One study in rats with mixed xylenes was considered inadequate for evaluation. No increase in the incidence of tumours was observed in either mice or rats following the administration of a technical-grade xylene.
No data were available on the indidivual isomers.
5.4 Other relevant data
Xylenes are absorbed after inhalation and dermal exposure. Elimination after human exposure is rapid and mostly as urinary metabolites after oxidation to the methylbenzyl alcohols, methylbenzoic acids and their glycine and glucuronic acid conjugates. In mice inhaling para-xylene, methylhippurate accumulated in the nasal mucosa and olfactory bulb.
Renal and hepatic toxicity has been described following human accidental poisonings and experimental exposure of rats and mice. In rats, hepatic cytochrome P450 content, particularly of CYP2B1, and the activities of certain conjugation enzymes are increased upon inhalation exposure to meta-xylene. Although xylenes have been studied extensively, there is no confirmed evidence of genetic activity for any of the isomers.
There is inadequate evidence in humans for the carcinogenicity of xylenes.
There is inadequate evidence in experimental animals for the carcinogenicity of xylenes.
Xylenes are not classifiable as to their carcinogenicity to humans (Group 3).For definition of the italicized terms, see Preamble Evaluation.
Previous evaluation: Vol. 47 (1989)
See Also: Toxicological Abbreviations Xylenes (EHC 190, 1997)