title: A simple method for screening assessment of acute toxicity of chemicals.
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.
authors.affiliation: Department of Hygiene, Tokyo Dental College, Chiba, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Yamanaka
authors.forename: M
authors.initials: M
authors.lastname: Hashimoto
authors.forename: M
authors.initials: M
authors.lastname: Tobe
authors.forename: K
authors.initials: K
authors.lastname: Kobayashi
authors.forename: J
authors.initials: J
authors.lastname: Sekizawa
authors.forename: M
authors.initials: M
authors.lastname: Nishimura
mesh_terms: D000645:Ammonium Sulfate / Q000633:toxicity; D000818:Animals; D004006:Dichlorvos / Q000633:toxicity; D004305:Dose-Response Relationship, Drug; D005260:Female; D005284:Fenthion / Q000633:toxicity; D007928:Lethal Dose 50; D008297:Male; D009055:Mouth / Q000187:drug effects; D011190:Potassium Cyanide / Q000633:toxicity; D051381:Rats; D011919:Rats, Inbred Strains; D012867:Skin / Q000187:drug effects; D014116:Toxicology / Q000379:methods*
chemical_list: D004006:Dichlorvos; D005284:Fenthion; D011190:Potassium Cyanide; D000645:Ammonium Sulfate