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Research Article

Screening Study for Repeated Dose and Reproductive/Developmental Toxicity of Rubber Accelerator, N,N-Dicyclohexyl-2-benzothiazolesulfenamide, in Rats

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Pages 167-180 | Published online: 09 Oct 2008
 

Abstract

A screening study for a vulcanization accelerator N,N-dicyclohexyl-2-benzothiazolesulfenamide (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.

Notes

EA, MHW, and MITI (Environment Agency, Ministry of Health and Welfare, and Ministry of International Trade and Industry, Japan). (1988). Research of Designated Chemical Substances, Planning and Coordination Bureau. Tokyo: Environment Agency, No. 39, Environmental Health Bureau, Ministry of Health and Welfare, No. 229, Basic Industries Bureau, Ministry of International Trade and Industry, No. 85, March 31, 1984, and amendments, November 18, 1988.

OECD (Organization for Economic Co-operation and Development). (1981). OECD Principles on Good Laboratory Practice. OECD Series on Principles of Good Laboratory Practice and Compliance Monitoring, No. 1. Paris: OECD.

OECD (Organization for Economic Co-operation and Development). (1990). OECD Test Guideline for Testing of Chemicals. Extended Steering Group Document, No. 3, Combined Repeated Dose Toxicity Study with the Reproduction/Developmental Toxicity Screening Test. Paris: OECD.

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