A colourless gas produced as a co-product in the manufacture of ethylene, 1,3-butadiene is used largely as a starting material in the manufacture of synthetic rubber (e.g., styrene-butadiene rubber (SBR) and polybutadiene rubber) and thermoplastic resins.
Animal studies. Inhaled butadiene is carcinogenic at multiple organ sites in rats and mice. In rats exposed to 0, 1,000, or 8,000 ppm butadiene for 2 years, increased tumour incidences and/or dose-response trends were observed in the exocrine pancreas, testis and brain of males and in the mammary gland, thyroid gland, uterus and Zymbal gland of females. Inhalation studies of butadiene in mice were conducted at exposures ranging from 6.25 to 1,250 ppm. Particularly noteworthy in mice were the induction of early malignant lymphomas and uncommon haemangiosarcomas of the heart. Malignant lung tumours were induced at all exposure concentrations. Other sites of tumour induction in mice included the liver, forestomach, Harderian gland, ovary, mammary gland and preputial gland. Non-neoplastic effects of butadiene exposure in mice included bone marrow toxicity, testicular atrophy, ovarian atrophy and developmental toxicity.
Butadiene is genotoxic to bone marrow cells of mice, but not rats, producing increases in sister chromatid exchanges, micronuclei and chromosomal aberrations. Butadiene is also mutagenic to Salmonella typhimurium in the presence of metabolic activation systems. The mutagenic activity of butadiene has been attributed to its metabolism to mutagenic (and carcinogenic) epoxide intermediates.
Human studies. Epidemiological studies have consistently found excess mortality from lymphatic and haematopoietic cancers associated with occupational exposure to butadiene. In the butadiene production industry, increases in lymphosarcomas in production workers were concentrated among men who were first employed before 1946. A case-control study of lymphatic and haematopoietic cancers in eight SBR facilities identified a strong association between leukaemia mortality and exposure to butadiene. Important characteristics of the leukaemia cases were that most were hired before 1960, worked in three of the plants and had been employed for at least 10 years in the industry. The International Agency for Research on Cancer (IARC) has classified as 1,3-butadiene probably carcinogenic to humans (IARC 1992).
A recent epidemiological study has provided data that confirm the excess in leukaemia mortality among SBR workers exposed to butadiene (Delzell et al. 1996). The site correspondence between lymphomas induced in mice exposed to butadiene and lymphatic and haematopoietic cancers associated with occupational exposure to butadiene is especially noteworthy. Furthermore, estimates of human cancer risk derived from data of butadiene-induced lymphomas in mice are similar to estimates of leukaemia risk determined from the new epidemiological data.
Industrial Exposure and Control
Surveys of exposure in industries where butadiene is produced and utilized were conducted by the US National Institute for Occupational Safety and Health (NIOSH) in the mid-1980s. Exposures were greater than 10 ppm in 4% of the samples and less than 1 ppm in 81% of the samples. Exposures were not homogeneous within specific job categories, and excursions as high as 370 ppm were measured. Exposures to butadiene were probably much higher during the Second World War, when the synthetic rubber industry was undergoing rapid growth. Limited sampling from rubber tyre and hose manufacture plants were below the limit of detection (0.005 ppm) (Fajen, Lunsford and Roberts 1993).
Exposures to butadiene can be reduced by ensuring that fittings on closed-loop systems are not worn or incorrectly connected. Further measures to control potential exposures include: use of closed-loop systems for cylinder sampling, use of dual mechanical seals to control release from leaking pumps, use of magnetic gauges to monitor rail-car filling operations and use of a laboratory hood for cylinder voiding.