For definition of Groups, see Preamble Evaluation.
VOL.: 71 (1999) (p. 1015)
CAS No.:
Chem. Abstr. Name: 2-Methyl-1,3-butadiene
5.1 Exposure data
Exposure to isoprene occurs in the production of the monomer and in the production of synthetic rubbers. Isoprene occurs in the environment due to emissions from vegetation and the production of ethylene by naphtha cracking.
5.2 Human carcinogenicity data
No data were available to the Working Group.
5.3 Animal carcinogenicity data
Isoprene was tested for carcinogenicity in mice and rats by inhalation exposure. In two studies in mice, exposure to isoprene resulted in increased combined incidences of benign and malignant tumours of the lung and liver and of Harderian gland adenomas. In one study, haemangiosarcomas of the heart and spleen and histiocytic sarcomas were also found in male mice, as well as increased incidences of pituitary adenomas and Harderian gland adenomas in female mice. In one adequate study with rats, increased incidences were observed for benign neoplasms in the mammary gland in males and females and in the kidney and testis in males.
5.4 Other relevant data
Both rats and mice exhibited saturation kinetics when exposed to concentrations above 300 ppm [840 mg/m3]. The maximal rate of metabolism in vivo, which occurs via monoepoxides and diepoxide and subsequent epoxide hydration, is more than three times greater in mice than in rats. In-vitro studies and a physiological toxicokinetic model suggest that the rates of metabolism in humans is lower.
At high inhalation exposures, proliferative lesions in olfactory epithelium and lung were observed. Forestomach epithelial hyperplasia was detected at lower exposure levels in rats and mice. Adverse effects in reproductive organs of male and female mice were detected after high inhalation doses.
Isoprene did not induce mutations in bacteria or sister chromatid exchanges or chromosomal aberrations in animal cells in vitro. Isoprene induced sister chromatid exchanges and micronuclei in bone-marrow cells after inhalation exposure of mice.
Isoprene binds covalently to haemoglobin in vivo.
5.5 Evaluation
No epidemiological data relevant to the carcinogenicity of isoprene were available.
There is sufficient evidence in experimental animals for the carcinogenicity of isoprene.
Overall evaluation
Isoprene is possibly carcinogenic to humans (Group 2B).
For definition of the italicized terms, see Preamble Evaluation.
Previous evaluation: Vol. 60 (1994)
Synonym
See Also:
Toxicological Abbreviations
Isoprene (ICSC)