Toxicological evaluation of fluproquazone.
The toxicological characteristics of 4-(p-fluorophenyl-1-isopropyl-7-methyl-2-(1H)quinazolinone (fluproquazone), an analgesic with distinct antiinflammatory properties, were evaluated in acute and chronic toxicity studies as well as in reproduction toxicity, carcinogenicity and mutagenicity studies. The following overall results were obtained: The acute oral toxicity in mice, rats, and rabbits is of low order. In the chronic oral studies fluproquazone was generally well tolerated when given to rats and dogs for 13 weeks, to dogs and monkeys for 52 weeks, to mice for 78 weeks and to rats for 104 weeks. In particular, there was no indication of gastrointestinal irritations or lesions in any of these studies. The results of the studies in dogs and rats showed the major target organs for the toxicity of fluproquazone to be the liver and kidney, where mild, reversible changes were observed. These findings were considerably less severe than those found with several other antiphlogistic-analgesic compounds. In the reproduction toxicity studies, the only drug-related effects seen in experiments on female fertility or peri- and postnatal development in rats were a prolongation of pregnancy and an impairment of delivery leading to an increased perinatal mortality. These findings may be related to an inhibition of prostaglandin synthesis by fluproquazone. Similar effects are known to occur after administration of other inhibitors of prostaglandin synthesis. The oral teratological studies in rats and rabbits did not reveal any embryolethal or teratogenic effects. The drug had no mutagenic effects in either the micronucleus test and the dominant-lethal test using mice, or in the Ames-Test using Salmonella typhimurium. The carcinogenicity studies showed that fluproquazone has no carcinogenic potential in rats and mice.
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000633:toxicity*; D002273:Carcinogens; D005260:Female; D005298:Fertility / Q000187:drug effects; D007928:Lethal Dose 50; D008252:Macaca fascicularis; D008297:Male; D051379:Mice; D009153:Mutagens; D011247:Pregnancy; D011799:Quinazolines / Q000633:toxicity*; D052999:Quinazolinones; D011817:Rabbits; D051381:Rats; D013723:Teratogens; D013997:Time Factors
D000894:Anti-Inflammatory Agents, Non-Steroidal; D002273:Carcinogens; D009153:Mutagens; D011799:Quinazolines; D052999:Quinazolinones; D013723:Teratogens; C023491:fluproquazone