Inhalation Toxicity Studies With 1,3-Butadiene 3 Two Year Toxicity/Carcinogenicity Study in Rats

Abstract

Groups of 110 male and 110 female CD (Sprague-Dawley) rats were exposed to atmospheres containing 0 (control), 1000 or 8000 ppm v/v butadiene for 6 hr/day and 5 days/week. Ten of each sex from each group were killed at 52 weeks. The study was terminated when it was predicted that survival would drop to 20% to 25% (105 weeks for females and 111 weeks for males). High dose rats had wet, ruffled fur and showed slight incoordination during the first exposure each week. During the second year, mortality in both treated female groups was increased because of humanitarian sacrifice of animals with large subcutaneous masses, while increased mortality in the high dose males was accompanied by an increase of the severity of nephropathy. Body weight was slightly lower than controls in both sexes at the high dose, but statistically significant only over the first 12 weeks. There were no effects in hematological analyses or tests of neuromuscular function that definitely could be associated with treatment. Liver weights at both doses were increased in both sexes with no associated pathological change. Kidney weight was increased in males at the high dose, together with an increase in the severity of nephrosis. There were increases in the incidences of pancreatic exocrine adenoma (high dose, male); uterine sarcoma (both doses, female); Zymbal gland carcinoma (high dose, female); mammary tumors (both doses, female); thyroid follicular cell tumors; and testis Leydig-cell tumors (high dose). These data suggest that butadiene is a weak oncogen to the rat under the conditions of exposure used in this study.

Reaction of 1,2,3,4-Diepoxybutane with 2‘-Deoxyguanosine: Initial Products and Their Stabilities and Decomposition Patterns under Physiological Conditions

“…Longterm inhalation exposure of mice and rats to BD caused development of tumors at multiple sites (1)(2)(3). BD is also considered a "Human Carcinogen" mostly because occupational exposure to BD has been associated with excess mortality from lymphatic and/or hematopoietic cancers (4)(5)(6)(7)(8).…”

Environmental Epidemiologic Investigations in the Styrene-Butadiene Rubber Production Industry

“…Since the completion ofthe Meinhardt et al report (5), two animal inhalation bioassays have found 1,3-butadiene to be carcinogenic in rats (10) and in mice (11). Additionally, the findings of McMichael et al (4) prompted a more detailed case-referent study of these cancer deaths by Spirtas et al (12); this evaluation revealed an estimated relative risk of 2.4 for fatal lymphatic and hematopoietic malignancies associated with employment in the SBR production plant.…”

A brief survey of butadiene health effects: a role for metabolic differences.

“…This study was first reported in 1981 (30) and in the peerreviewed literature in 1987 (31). Male and female SpragueDawley rats, 100/group, were exposed to concentrations of 0, 1000, and 8000 ppm butadiene for 2 years (6 hr/day, 5 days/week).…”