Mechanistic data indicate that 1,3-butadiene is a human carcinogen

Area of Science:

• Toxicology
• Carcinogenesis
• Molecular Biology

Background:

• 1,3-Butadiene is identified as a human carcinogen.
• Epidemiological studies link occupational exposure to increased lymphatic and hematopoietic cancer mortality.
• Laboratory animal studies demonstrate butadiene's carcinogenicity across multiple organ sites.

Purpose of the Study:

• To review epidemiological and mechanistic data on 1,3-butadiene.
• To establish the mouse as an appropriate model for assessing human cancer risk from 1,3-butadiene.
• To explore the molecular mechanisms of butadiene-induced carcinogenesis and compare them to ethylene oxide.

Main Methods:

• Review of epidemiological data on occupational butadiene exposure.
• Analysis of mechanistic data from animal studies on butadiene metabolism and genotoxicity.
• Comparison of mutational spectra and molecular alterations in butadiene-induced tumors with human cancers and ethylene oxide effects.

Main Results:

• 1,3-Butadiene induces lymphomas in mice and is associated with lymphatic/hematopoietic cancers in humans.
• Butadiene is metabolized to mutagenic epoxides in mammals, forming DNA adducts (N7-alkylguanine) and increasing hprt mutations.
• Genetic alterations in butadiene-induced tumors resemble those in human cancers; mutational spectra are similar to ethylene oxide.

Conclusions:

• The mouse is a suitable model for evaluating human cancer risk from 1,3-butadiene.
• Similarities in genetic alterations and mutational spectra suggest shared molecular mechanisms between ethylene oxide and 1,3-butadiene in cancer induction.
• 1,3-Butadiene is a human carcinogen with significant implications for occupational health and risk assessment.