title: An evaluation of the feasibility of using cytogenetic damage as a biomarker for alachlor exposure.
abstract: Alachlor is a widely used herbicide for which there is significant human exposure, principally through groundwater contamination and inhalation. Because alachlor is purported to be carcinogenic and mutagenic, we initiated studies to determine if induced cytogenetic damage could be used as a biomarker for exposure to this herbicide. Both isolated and whole blood human lymphocytes were exposed to alachlor using several protocols. The lymphocytes were cultured for analysis of sister chromatid exchange (SCE), chromosome aberrations (CAs), micronuclei (MN) in cytochalasin B-induced binucleated cells, and proliferation kinetics using the replicative index (RI). In addition, CD rats were injected with either 10 or 50 mg kg-1 of alachlor, 2-chloro-N-(2,6-diethylphenyl) acetamide (CDEPA) or 2, 6-diethylanaline (DEA). After 24 h, the peripheral blood lymphocytes were removed and cultured for SCE and RI analysis. Alachlor did induce a concentration-related increase in SCE in vitro, but neither it nor its metabolites (CDEPA or DEA) induced a significant increase in SCEs or an alteration of RI in vivo. At the highest in vitro concentration tested, alachlor induced a statistically-significant increase in MN, but no concomitant increase in CAs was seen. From analyses of our data and the literature on alachlor clastogenicity and exposure levels, we concluded that cytogenetic damage may not be an adequately sensitive marker for evaluating human exposure to alachlor.
authors.affiliation: Genetics and Cellular Toxicology Branch, Environmental Carcinogenesis Division, U.S. Environmental Protection Agency, Mail Drop 68, Research Triangle Park, NC 27711, USA. kligerman.andrew@epa.gov
authors.forename: A D
authors.initials: AD
authors.lastname: Kligerman
authors.forename: G L
authors.initials: GL
authors.lastname: Erexson
mesh_terms: D000081:Acetamides / Q000633:toxicity*; D000083:Acetanilides / Q000633:toxicity; D000328:Adult; D000814:Aniline Compounds / Q000633:toxicity; D000818:Animals; D015415:Biomarkers; D002453:Cell Cycle / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D002869:Chromosome Aberrations; D003571:Cytochalasin B / Q000633:toxicity; D004261:DNA Replication / Q000187:drug effects; D005240:Feasibility Studies; D005260:Female; D006540:Herbicides / Q000633:toxicity*; D006801:Humans; D008214:Lymphocytes / Q000166:cytology / Q000187:drug effects*; D008297:Male; D015162:Micronucleus Tests; D009152:Mutagenicity Tests / Q000379:methods*; D051381:Rats; D012854:Sister Chromatid Exchange
chemical_list: D000081:Acetamides; D000083:Acetanilides; D000814:Aniline Compounds; D015415:Biomarkers; D006540:Herbicides; C000188:alachlor; D003571:Cytochalasin B; C093872:2-chloro-N-(2,6-diethylphenyl)acetamide; C085691:2,6-diethylaniline