Activity of the human carcinogens benzidine and 2-naphthylamine in triple- and single-dose mouse bone marrow micronucleus assays: results for a combined test protocol.
The activities of the human bladder carcinogens benzidine and 2-naphthylamine in the mouse bone marrow micronucleus assays using a limited test protocol (oral dosing to male mice, sampling 24 h later) have recently been established. As a contribution to the International Collaborative Study on the evaluation of the sensitivity of the triple-dose micronucleus test protocol it was decided to re-evaluate benzidine and 2-naphthylamine using a combined triple- and single-dose test protocol. Benzidine gave a clear positive response in male mice 24 h after 3 daily doses of 150 and 300 mg/kg. A single dose of 900 mg/kg of benzidine gave a weaker response 24 h after dosing. In the case of 2-naphthylamine a stronger positive response was observed 24 h after a single dose of 600 mg/kg as compared to 3 daily doses of 200 or 400 mg/kg. There was no significant difference in the increased positive response observed for a single dose of 30 mg/kg of cyclophosphamide compared with 3 successive daily doses of 10 mg/kg. Based on the present data the combined triple/single-dose micronucleus test protocol is strongly supported.
Mirkova
E
E
Institute of Hygiene and Occupational Health, Medical Academy, Sofia, Bulgaria.
D015081:2-Naphthylamine / Q000494:pharmacology*; D000818:Animals; D001560:Benzidines / Q000008:administration & dosage / Q000494:pharmacology*; D001853:Bone Marrow / Q000187:drug effects*; D001854:Bone Marrow Cells; D002273:Carcinogens / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004912:Erythrocytes / Q000187:drug effects* / Q000648:ultrastructure; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D048629:Micronuclei, Chromosome-Defective / Q000187:drug effects*; D015162:Micronucleus Tests / Q000379:methods; D009281:Naphthalenes / Q000494:pharmacology*; D001749:Urinary Bladder Neoplasms / Q000139:chemically induced
D001560:Benzidines; D002273:Carcinogens; D009281:Naphthalenes; C029876:benzidine; D015081:2-Naphthylamine