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

• Published in: Reproductive toxicology (Elmsford, N.Y.) Vol. 22; no. 1; pp. 30 - 36
• Main Authors: Ema, Makoto, Kimura, Eisuke, Matsumoto, Mariko, Hirose, Akihiko, Kamata, Eiichi
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 01.07.2006; Elsevier
• Subjects: Abnormalities, Drug-Induced - etiology; Animals; Animals, Newborn; Anticonvulsants - administration & dosage; Anticonvulsants - chemistry; Anticonvulsants - toxicity; Anus, Imperforate - chemically induced; Behavior, Animal - drug effects; Biological and medical sciences; Di- o-tolylguanidine; Dose-Response Relationship, Drug; Eating - drug effects; Embryology: invertebrates and vertebrates. Teratology; Embryonic Development - drug effects; Female; Fundamental and applied biological sciences. Psychology; Guanidines - administration & dosage; Guanidines - chemistry; Guanidines - toxicity; Intubation, Gastrointestinal; Litter Size - drug effects; Male; Malformation; Medical sciences; Pregnancy; Rat; Rats; Rats, Sprague-Dawley; Reproduction - drug effects; Reproductive and developmental toxicity; Rubber accelerator; Salivation - drug effects; Sex Ratio; Sigma ligand; Teratogenicity; Teratology. Teratogens; Toes - abnormalities; Toxicity Tests - methods; Toxicology; Weight Loss - drug effects; Rubber accelerator; Reproductive and developmental toxicity; Di- o-tolylguanidine; Rat; Malformation; Teratogenicity; Sigma ligand; Reproduction diseases; Ligand; Toxicity; Rodentia; Screening test; Teratogenesis; Vertebrata; Mammalia; Animal; Di-o-tolylguanidine; Teratogen; Rubber; Accelerator
• ISSN: 0890-6238; 1873-1708
• DOI: 10.1016/j.reprotox.2005.11.002

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.