Comparison of the activity of topically applied pesticides and the herbicide 2,4-D in two short-term in vivo assays of genotoxicity in the mouse.
Genotoxicity of eight topically applied compounds was determined using the bone marrow micronucleus (MN) test and hair follicle nuclear aberration (NA) assay in CD1 mice. Twenty-four hours after a single treatment, cyclophosphamide (CY), applied at doses corresponding to 1/4, 1/8, 1/16, and 1/32 of the published dermal LD50, and N-methyl-N-nitrosourea (MNU), applied at 1/4, 1/8, and 1/16 of the published dermal LD50, were found to increase the incidence of NA in a dose-dependent manner. The frequency of MN was significantly increased only at the highest dose of CY. Using the same protocol, six pesticides applied in dimethyl sulfoxide (DMSO) at doses of 1/8, 1/16, and 1/32 of the dermal LD50 were investigated. Aminocarb and chlordane induced a dose-dependent increase in the frequency of NA, while there was an observed increase in NA incidence at only the highest doses of dichlorvos (DDVP), 4,4'-DDT (DDT), and 2,4-dichlorophenoxyacetic acid (2,4-D). No effect was observed with fenitrothion on nuclear aberrations in hair follicles. Except for the highest dose of chlordane, none of the pesticides tested positive in the bone marrow micronucleus test. Serum cholinesterase levels were reduced to 70 +/- 4.7% of the DMSO control level with DDVP, 57 +/- 8.2% with aminocarb, and 60.3 +/- 4.8% with fenitrothion, indicating some systemic activity with these topically applied agents. The data suggest that aminocarb, chlordane, DDVP, DDT, and 2,4-D are genotoxic as determined by the NA assay and that this assay may be more useful in detecting topically applied genotoxic agents than the more often used bone marrow micronucleus test.
Schop
R N
RN
Department of Biomedical Sciences, University of Guelph, Ontario, Canada.
Hardy
M H
MH
Goldberg
M T
MT
D015084:2,4-Dichlorophenoxyacetic Acid / Q000633:toxicity*; D000287:Administration, Topical; D000818:Animals; D001853:Bone Marrow / Q000187:drug effects / Q000648:ultrastructure; D002219:Carbamates / Q000633:toxicity; D002802:Cholinesterases / Q000097:blood; D003520:Cyclophosphamide / Q000633:toxicity; D004006:Dichlorvos / Q000633:toxicity; D004121:Dimethyl Sulfoxide / Q000633:toxicity; D005278:Fenitrothion / Q000633:toxicity; D006197:Hair / Q000187:drug effects; D008297:Male; D008770:Methylnitrosourea / Q000633:toxicity; D051379:Mice; D015162:Micronucleus Tests; D009153:Mutagens; D010575:Pesticides / Q000633:toxicity*; D048448:Phenylcarbamates
D002219:Carbamates; D009153:Mutagens; D010575:Pesticides; D048448:Phenylcarbamates; D015084:2,4-Dichlorophenoxyacetic Acid; D008770:Methylnitrosourea; C006511:aminocarb; D004006:Dichlorvos; D003520:Cyclophosphamide; D002802:Cholinesterases; D005278:Fenitrothion; D004121:Dimethyl Sulfoxide