A Reproductive and Developmental Toxicity Screening Study of 1,3-Butadiene in Sprague-Dawley Rats.

1,3 Butadiene (BD) is an industrial intermediate used primarily in product manufacturing with the greatest exposure potential via inhalation. BD was evaluated for reproductive and developmental effects in a Good Laboratory Practice (GLP)-compliant, extended OECD 421 guideline study (completed 2003). Twelve-week old rats (12/sex/dose) were exposed via whole-body inhalation to BD vapor (0, 300, 1500, 6000 ppm) for 6 h/day, 7 days/week, starting 14 days prior to mating through the day prior to euthanasia (total exposures: 83-84 days for F0 males 60-70 days for F0 females). Select F1 offspring (1/sex/litter) were dosed 7 days (postnatal days 21-27 or 28-34), then necropsied. At 1500 and 6000 ppm, treatment-related facial soiling was seen in F0 males and females with decreased body weights/gains in F0 males. F1 males and females exhibited similar effects at 1500 and 6000 ppm. Importantly, the F0 generation had no evidence of altered sperm production, testicular effects, or ovarian atrophy, which were sensitive responses in mice. The no-observed-adverse-effect-level (NOAEL) is 300 ppm due to decreased body weight/gain and facial soiling at 1500 ppm, whereas 6000 ppm serves as a NOAEL for reproductive and developmental endpoints. This study contributes to the weight-of-evidence of differential BD reproductive toxicity in rats and mice.