Two-generation reproductive toxicity study of the rubber accelerator N,N-dicyclohexyl-2-benzothiazolesulfenamide in rats.
Male and female Crl:CD(SD) rats were fed a diet containing rubber accelerator N,N-dicyclohexyl-2-benzothiazolesulfenamide (DCBS) at 0, 80, 600 or 4500ppm throughout the study beginning at the onset of a 10-week pre-mating period and continuing through the mating, gestation, and lactation periods for two generations. At 4500ppm, decreases in the body weight, body weight gain, and food consumption were found in F0 males and females. No changes in the estrous cyclicity, copulation index, fertility index, gestation index, delivery index, number of implantations, precoital interval, or gestation length were observed in any generation at any dose of DCBS. Delayed preputial separation at 4500ppm as well as delayed vaginal opening and higher body weight at the age of vaginal opening at 600 and 4500ppm were found in the F1 generation. A transient change in performance in a water-filled multiple T-maze was found at 600 and 4500ppm in F1 females. There were no compound-related changes in number of pups delivered, sex ratio of pups, viability of pups, anogenital distance, surface righting reflex, negative geotaxis reflex, mid-air righting reflex, pinna unfolding, incisor eruption, or eye opening in the F1 and F2 generations. The body weight of F1 and F2 male and female pups was lowered at 4500ppm. Reduced uterine weight of the weanlings was noted in the F1 generation at 4500ppm and in the F2 generation at 600 and 4500ppm. The data indicate that the NOAEL of DCBS for two-generation reproductive toxicity is 80ppm (5.2mg/kgbw per day) in rats.
Ema
Makoto
M
Division of Risk Assessment, Biological Safety Research Center, National Institute of Health Sciences, Tokyo 158-8501, Japan. ema@nihs.go.jp
Fujii
Sakiko
S
Matsumoto
Mariko
M
Hirata-Koizumi
Mutsuko
M
Hirose
Akihiko
A
Kamata
Eiichi
E
D000818:Animals; D000831:Animals, Newborn; D001522:Behavior, Animal / Q000187:drug effects; D052160:Benzothiazoles / Q000633:toxicity*; D001774:Blood Chemical Analysis; D001835:Body Weight / Q000187:drug effects; D001947:Breeding; D003510:Cyclohexanes / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D004435:Eating / Q000187:drug effects; D030762:Estrous Cycle / Q000187:drug effects; D005260:Female; D005835:Genitalia / Q000187:drug effects / Q000473:pathology; D012739:Gonadal Steroid Hormones / Q000097:blood; D006065:Gonadotropins, Pituitary / Q000097:blood; D048788:Growth and Development / Q000187:drug effects; D007774:Lactation; D008297:Male; D019055:No-Observed-Adverse-Effect Level; D009929:Organ Size; D051381:Rats; D017207:Rats, Sprague-Dawley; D012098:Reproduction / Q000187:drug effects*; D013094:Spermatozoa / Q000187:drug effects; D013997:Time Factors; D036401:Toxicity Tests, Chronic
D052160:Benzothiazoles; D003510:Cyclohexanes; D012739:Gonadal Steroid Hormones; D006065:Gonadotropins, Pituitary; C526935:N,N-dicyclohexyl-2-benzothiazolesulfenamide