Screening study for repeated dose and reproductive/developmental toxicity of rubber accelerator, N,N-dicyclohexyl-2-benzothiazolesulfenamide, in rats.
A screening study for a vulcanization accelerator N,N-dicyclohexyl-2-benzothiazole-sulfenamide (DCBS) was performed in rats. Rats were given DCBS by gavage daily at 0, 6, 25, 100, or 400 mg/kg. Males were dosed for a total of 44 days beginning 14 days before mating. Females were dosed for a total of 40-51 days beginning 14 days before mating to day 3 of lactation. Toxicologic changes were significantly noted only at 400 mg/kg. Three females died. An increased incidence of females showing decreased locomotor activity, soil of the lower abdominal fur, and reddish tears was observed. A lowered body weight was found in males and females. Increased urinary ketones and serum inorganic phosphorus and decreased serum glutamate pyruvate transaminase in males were found. Increased absolute and relative weights of the kidneys in males and decreased absolute weight of the thymus in both sexes were noted. Significant fatty degeneration of the renal tubular epithelia, vacuolation of the adrenocortical cells, and atrophy of the spleen were observed in females. Significant decreases in the gestation index, numbers of corpura lutea, implantations, pups born and pups born alive, live birth index, and viability index were detected. It is concluded that the No Observed Adverse Effect Levels (NOAELs) for repeat dose and reproductive/developmental toxicity are 100 mg kg-1 day-1 in this screening study.
Ema
Makoto
M
Division of Risk Assessment, Biological Safety Research Center, National Institute of Health Sciences, Tokyo, Japan. ema@nihs.go.jp
Ito
Yoshihiko
Y
Matsumoto
Mariko
M
Hirose
Akihiko
A
Kamata
Eiichi
E
D000311:Adrenal Glands / Q000187:drug effects / Q000473:pathology; D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D052160:Benzothiazoles / Q000633:toxicity*; D001835:Body Weight / Q000187:drug effects; D003338:Corpus Luteum / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D010064:Embryo Implantation / Q000187:drug effects; D047108:Embryonic Development / Q000187:drug effects*; D005260:Female; D005313:Fetal Death / Q000139:chemically induced; D005328:Fetal Viability / Q000187:drug effects; D005865:Gestational Age; D007659:Ketones / Q000652:urine; D007668:Kidney / Q000187:drug effects / Q000473:pathology; D008098:Litter Size / Q000187:drug effects; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D019055:No-Observed-Adverse-Effect Level; D009929:Organ Size / Q000187:drug effects; D010758:Phosphorus / Q000097:blood; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D012098:Reproduction / Q000187:drug effects*; D013154:Spleen / Q000187:drug effects / Q000473:pathology; D013666:Tears / Q000187:drug effects; D013950:Thymus Gland / Q000187:drug effects / Q000473:pathology
D052160:Benzothiazoles; D007659:Ketones; D010758:Phosphorus; D000410:Alanine Transaminase; C044169:thiohexam