Overview of reproductive and developmental toxicity studies of 1,3-butadiene in rodents.

Abstract

A series of studies to further evaluate the developmental and reproductive toxicity of inhaled 1,3-butadiene was sponsored by the National Toxicology Program. Pregnant Sprague-Dawley rats (24-28/group) and Swiss (CD-1) mice (18-22/group) were exposed to atmospheric concentrations of 0, 40, 200, or 1000 ppm 1,3-butadiene for 6 hr/day on days 6 through 15 of gestation (dg) and killed on dg 18 (mice) or dg 20 (rats). Subsequently, the uterine contents were evaluated; individual fetal body weights were recorded; and external, visceral, and skeletal examinations were performed. In rats, maternal toxicity was observed in the 1000-ppm group in the form of reduced extragestational weight gain and, during the first week oftreatment, decreased body weight gain. Under these conditions, there was no evidence ofdevelopmental toxicity in rats. In contrast, results of the mouse developmental toxicity study indicated that the fetus may be more susceptible than the dam to inhaled 1,3-butadiene. Maternal toxicity was observed in mice at the 200-and 1000-ppm 1,3-butadiene exposure levels, whereas 40 ppm and higher concentrations of 1,3-butadiene caused significant exposure-related reductions in the mean body weights of male fetuses. Mean body weights of female fetuses were also reduced at the 200-and 1000-ppm exposure levels. No increased incidence of malformations was observed in either study. Other studies addressing male reproductive and mutagenesis end points were performed with B6C3F, mice (sperm-head morphology) and Swiss (CD-1) mice (dominant lethal study). In both studies, groups of 20 male mice were exposed to atmospheric concentrations of 0, 200, 1000, or 5000 ppm 1,3-butadiene 6 hr/day for 5 consecutive days. There were small concentration-related increases in abnormal sperm morphology 5 weeks following exposure (the only time of examination). Sequential postexposure examinations to determine the effect of 1,3-butadiene on all stages of gamete development were not performed. In the dominant lethal study, there were indications that exposure of males to levels as low as 200 ppm 1,3-butadiene caused an increase in the percentage of females with two or more dead implants in the first week following exposure. In both the first and second weeks following exposure, there were increases in the number of dead implantations (early), although strict atmospheric concentration-response relationships were not observed. These results suggest that more mature cells (spermatozoa and spermatids) might be adversely affected in this strain of mouse.

The Toxicological Properties of Petroleum Gases

“…37 Acute toxicity per se was not assessed but LC 50 values could not be lower than the no effect levels in repeated exposure studies. c Critical values for 1,3-butadiene are taken from Owen and Glaister (repeated dose toxicity), 44 Morissey et al (developmental toxicity), 45 and WIL Research (reproductive toxicity). 008006-14-2 Natural gas Raw natural gas, as found in nature, or a gaseous combination of hydrocarbons having carbon numbers predominantly in the range of C 1 through C 4 separated from raw natural gas by the removal of natural gas condensate, natural gas liquid, and natural gas condensate/natural gas.…”

Reproductive and developmental toxicity of the components of gasoline

“…Butadiene was a clear developmental toxicant in mice, producing a reduction in mean fetal weight (59). These studies have been the subject of a recent, intensive review (60).…”

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

“…Studies conducted at Battelle Northwest Laboratories (15)(16)(17) have demonstrated that butadiene is maternally toxic to Sprague-Dawley rats at 1000 ppm. However, there is no developmental toxicity observed in the rat fetuses even at doses where maternal toxicity is observed.…”

“…A reduction in the weight of male mouse fetuses was also observed at 40 ppm, but no maternal toxicity was evident. After exposure to 200, 1000, or 5000 ppm for 5 days, there was a concentration-related increase in abnormal sperm in male B6C3F1 mice (17). The immunotoxicity of butadiene was examined in male B6C3F1 mice exposed to 1250 ppm (6 hr/day, 5 days/week) for 12 weeks (18).…”