N-chloropiperidine and calcium hypochlorite: possible examples of toxicity-dependent clastogenicity in vitro.
N-Chloropiperidine (NCP) has been reported to be both toxic and mutagenic in a wide range of in vitro and in vivo genotoxicity assays, however, few experimental details or numerical data have been presented to support these claims. The latter facts, together with the lack of any clear structural precedent for the mutagenicity of this agent, led us to re-evaluate it using the Salmonella mutation assay and the mouse bone marrow micronucleus test. The absence of mutagenic activity observed in both of these systems indicates that the genotoxicity of NCP and related chloramines remains to be unequivocally established. In particular, the potent clastogenicity to CHO cells reported for NCP may be related solely to oxidative denaturation of cellular proteins induced by hypochlorous acid, a hydrolysis product of NCP. Separate reports indicate that calcium hypochlorite (bleaching powder) is also clastogenic in vitro but not in vivo. We therefore suggest that N-chloropiperidine may prove of value as a model compound for studies designed to distinguish genotoxic clastogenicity (specifically DNA-reactive) from general toxicity-mediated clastogenicity.
Ashby
J
J
Mohammed
R
R
Callander
R D
RD
D000818:Animals; D001853:Bone Marrow / Q000648:ultrastructure; D002118:Calcium / Q000633:toxicity*; D017610:Calcium Compounds; D002470:Cell Survival / Q000187:drug effects*; D002869:Chromosome Aberrations; D003520:Cyclophosphamide / Q000633:toxicity; D051379:Mice; D009154:Mutation / Q000187:drug effects*; D010880:Piperidines / Q000633:toxicity*; D012486:Salmonella typhimurium / Q000187:drug effects; D008941:Spindle Apparatus / Q000187:drug effects
D017610:Calcium Compounds; D010880:Piperidines; C004488:calcium hypochlorite; C028563:N-chloropiperidine; D003520:Cyclophosphamide; D002118:Calcium