For definition of Groups, see Preamble Evaluation.
VOL.: 60 (1994) (p. 321)
Chem. Abstr. Name: Phenyloxirane
Styrene-7,8-oxide is produced by cyclization of styrene chlorohydrin and by epoxidation of styrene with peroxyacetic acid. It is used mainly in the preparation of fragrances and as a reactive diluent in epoxy resin formulations. Few data are available on levels of occupational exposure to styrene-7,8-oxide. It has been detected in association with styrene, but at much lower levels, in industries where unsaturated polyester resins are used.
No data were available to the Working Group.
Styrene-7,8-oxide was tested for carcinogenicity in one experiment in mice and in two experiments in rats by oral gavage. It produced benign and malignant tumours of the forestomach in animals of each species and sex and induced hepatocellular tumours in male mice. It was also tested in one strain of rats by prenatal exposure followed by postnatal gastric intubation, producing benign and malignant tumours of the forestomach.
Styrene-7,8-oxide is absorbed by rabbits and rats following its oral administration. In mice, the highest tissue concentrations are found in kidney, adipose tissue and blood. Styrene-7,8-oxide is hydrolysed rapidly in the acid environment of the stomach. Almost all of an administered dose of styrene-7,8-oxide is excreted in the urine of experimental animals. Styrene-7,8-oxide can be metabolized by epoxide hydrolase to the glycol or by glutathione S-transferase to glutathione conjugates. A small amount may be reduced to styrene. Styrene glycol is further metabolized to mandelic, phenyl glyoxylic and hippuric acids.
Styrene-7,8-oxide bound to histidine in haemoglobin and to cysteine in plasma proteins in vitro. Low levels of covalent binding to DNA were observed in the stomachs of orally dosed rats. In rat brain, it can decrease the activity of some neurotransmitters and monoamine oxidase, and it increases the availability of dopamine receptors. Glutathione S-transferase from human erythrocytes was inhibited by low concentrations of styrene-7,8-oxide.
No teratogenic effect was observed in rats or rabbits treated with doses of styrene-7,8-oxide up to the lethal level.
No data were available on the genetic and related effects of styrene-7,8-oxide in humans.
Both positive and negative results have been obtained with styrene-7,8-oxide for a variety of genetic end-points in vivo. Chromosomal aberrations and sister chromatid exchange were induced in mouse bone marrow only after treatment with the S enantiomer and not with the R enantiomer. DNA damage, mutations and chromosomal aberrations have been observed consistently in mammalian and nonmammalian systems in vitro.
There is inadequate evidence in humans for the carcinogenicity of styrene-7,8-oxide.
There is sufficient evidence in experimental animals for the carcinogenicity of styrene-7,8-oxide.
In making the overall evaluation, the Working Group took into consideration the following supporting evidence. Styrene-7,8-oxide:
(i) forms covalent adducts with DNA in humans, rats and mice;
(ii) induces gene mutation in bacteria and rodent cells in vitro;
(iii) induces chromosomal aberrations, micronuclei and sister chromatid exchange in human cells in vitro; and
(iv) induces chromosomal aberrations and sister chromatid exchange in mice in vivo.
Styrene-7,8-oxide is probably carcinogenic to humans (Group 2A).
Previous evaluation: Suppl. 7 (1987) (p. 72)
For definition of the italicized terms, see Preamble Evaluation.
See Also: Toxicological Abbreviations