Reproductive and developmental toxicity screening test of basic rubber accelerator, 1,3-di-o-tolylguanidine, in rats

Reprod Toxicol. 2006 Jul;22(1):30-6. doi: 10.1016/j.reprotox.2005.11.002. Epub 2005 Dec 27.

Abstract

Twelve male and female rats per group were exposed to the rubber accelerator 1,3-di-o-tolylguanidine (DTG) by gavage at 0, 8, 20 or 50 mg/kg bw/day. Males were dosed for a total of 49 days beginning 14 days before mating. Females were dosed for a total of 40-49 days beginning 14 days before mating to day 3 of lactation throughout the mating and gestation period. At 50 mg/kg bw/day, deaths were observed in two males and three females. Lowered body weight gain and food consumption were noted in males at 50 mg/kg bw/day and females at 20 and 50 mg/kg bw/day. Mydriasis, decreased locomotor activity, bradypnea, prone position, tremor and/or salivation were observed in males and females at 20 and 50 mg/kg bw/day. No effects of DTG were found on the estrous cyclicity, precoital interval, copulation, fertility and gestational indices, numbers of corpora lutea and implantations, or gestation length. A significant decrease in the number, body weight and viability of offspring and increase in the incidence of fetuses with external malformations were found at 50 mg/kg bw/day. Oligodactyly, anal atresia and tail anomalies were observed. These data suggest that DTG may be teratogenic. The NOAELs of DTG for general and developmental toxicity in rats are 8 and 20 mg/kg bw/day, respectively.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Abnormalities, Drug-Induced / etiology
  • Animals
  • Animals, Newborn
  • Anticonvulsants / administration & dosage
  • Anticonvulsants / chemistry
  • Anticonvulsants / toxicity
  • Anus, Imperforate / chemically induced
  • Behavior, Animal / drug effects
  • Dose-Response Relationship, Drug
  • Eating / drug effects
  • Embryonic Development / drug effects*
  • Female
  • Guanidines / administration & dosage
  • Guanidines / chemistry
  • Guanidines / toxicity*
  • Intubation, Gastrointestinal
  • Litter Size / drug effects
  • Male
  • Pregnancy
  • Rats
  • Rats, Sprague-Dawley
  • Reproduction / drug effects*
  • Salivation / drug effects
  • Sex Ratio
  • Toes / abnormalities
  • Toxicity Tests / methods*
  • Weight Loss / drug effects

Substances

  • Anticonvulsants
  • Guanidines
  • 1,3-ditolylguanidine