Prenatal developmental toxicity study of the basic rubber accelerator, 1,3-di-o-tolylguanidine, in rats.
Pregnant rats were given 1,3-di-o-tolylguanidine (DTG) by gavage at 0, 10, 20 or 40mg/kgbw/day on days 6-19 of pregnancy and the pregnancy outcome was determined on day 20 of pregnancy. At 40mg/kgbw/day, deaths were observed in four out of 24 females. The incidences of females showing mydriasis at 20 and 40mg/kgbw/day and showing decreased locomotor activity at 40mg/kgbw/day were significantly increased. Alopecia, bradypnea, prone position and tremor were also observed at 40mg/kgbw/day. The maternal body weight gain at 20 and 40mg/kgbw/day and food consumption at 40mg/kgbw/day were significantly reduced. A significantly decreased weight of the gravid uterus, increased incidence of postimplantation loss, decreased number of live fetuses, and lowered weights of fetuses and placentae were found at 40mg/kgbw/day. The incidences of the total number of fetuses with external malformations at 40mg/kgbw/day and with skeletal malformations at 20 and 40mg/kgbw/day were significantly increased. Significantly higher incidences of fetuses with brachydactyly and short tail and defects of caudal vertebrae, phalanges and metacarpals were observed at 40mg/kgbw/day. Delayed ossification was also noted at 40mg/kgbw/day. The data indicate that DTG is teratogenic at maternal toxic doses and the NOAELs of DTG for maternal and developmental toxicity are 10mg/kgbw/day in rats.[1]References
- Prenatal developmental toxicity study of the basic rubber accelerator, 1,3-di-o-tolylguanidine, in rats. Ema, M., Fujii, S., Matsumoto, M., Hirose, A., Kamata, E. Reprod. Toxicol. (2006) [Pubmed]
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