Mutagenicity to bacteria, cultured cells, and rodents of the human carcinogen chlornaphazine.
The human carcinogen and nitrogen mustard chlornaphazine (CN) has been confirmed to be mutagenic to Salmonella and, unexpectedly, the more so when evaluated in the presence of liver S9 mix. It also has been established as clastogenic to Chinese hamster lung cells exposed in vitro to dose levels greater than 2.5 micrograms/ml. Chlornaphazine subdued mice at doses of 5 g/kg, but only the occasional death occurred during the 4 days following oral administration of this dose in corn oil. Consequently, a median lethal dose level was not established. Nonetheless, dose levels of 500 mg/kg or greater gave a clear positive response in both the mouse and the rat bone marrow micronucleus assay. Although depression of erythropoeisis was observed in mice, a clastogenic response still was observed in the bone marrow 24 hr after dosing. The positive response in the rat was greater than that observed in the mouse. The present data provide a further instance of an established human carcinogen being readily detected by standard in vitro and in vivo mutagenicity assays.
Ashby
J
J
ICI PLC, Central Toxicology Laboratory, Cheshire, England.
Loquet
C
C
Ishidate
M
M
Callander
R D
RD
Albanese
R
R
D000818:Animals; D001853:Bone Marrow / Q000187:drug effects; D002460:Cell Line; D055598:Chemical Phenomena; D002621:Chemistry; D002869:Chromosome Aberrations; D004920:Erythropoiesis / Q000187:drug effects; D005260:Female; D008297:Male; D051379:Mice; D008808:Mice, Inbred CBA; D009152:Mutagenicity Tests; D009154:Mutation; D009588:Nitrogen Mustard Compounds / Q000633:toxicity*; D051381:Rats; D012486:Salmonella typhimurium / Q000187:drug effects*
D009588:Nitrogen Mustard Compounds; C010406:chlornaphazin