A simple method for screening assessment of acute toxicity of chemicals |
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Authors: | Sumie Yamanaka Masanori Hashimoto Masuo Tobe Kazuo Kobayashi Jun Sekizawa Masao Nishimura |
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Institution: | (1) Department of Hygiene, Tokyo Dental College, 1-2-2 Masago, 260 Chiba, Japan;(2) Division of Toxicology, National Institute of Hygienic Science, 1-18-1 Yoga, Setagaya, 158 Tokyo, Japan;(3) Division of Information on Chemical Safety, National Institute of Hygienic Science, 1-18-1 Yoga, Setagaya, 158 Tokyo, Japan;(4) Present address: Pathology Research Department, Biosafety Research Center, Foods, Drugs and Pesticides, 582-2 Arahama, Shioshinden, Fukude-cho, Iwata-gun, Shizuoka, Japan |
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Abstract: | We proposed a simple method for screening assessment of acute oral and dermal toxicity using only three rats and mice of each sex at each dose level. Animals were first treated with chemicals at a dose of 2000 mg/kg and were carefully observed for compound-related morbidity and mortality. If none of the animals died, the following toxicity tests were suspended. If some of the animals died, toxicity tests at doses of 200 and 20 mg/kg were performed. The approximate LD50 values calculated by this method showed little difference between two separate laboratories and were in good agreement with LD50 values reported in the literature. Our toxicological data also showed that LD50 values were about 2–2.5 times the MNLD (maximum non lethal dose) in acute oral and dermal toxicity. This meant that a chemical could be regarded as having an LD50 of about 4000 mg/kg or higher when there was no mortality at the dose of 2000 mg/kg. A chemical with such low toxicity would not require further testing for lethal effects. Therefore, this simple method combining the fixed-dose procedure with the limit test is suitable for determination of approximate LD50 values of chemicals and for screening for necessity for classical full LD50 test using many animals.This work was supported by a grant from Ministry of Health and Welfare in Japan (No. 467 and 511) |
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Keywords: | Acute toxicity Approximate LD50 Screening assessment |
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