title: Assessment of the reproductive and developmental toxicity of pesticide/fertilizer mixtures based on confirmed pesticide contamination in California and Iowa groundwater.
abstract: Pesticides and fertilizers, as used in modern agriculture, contribute to the overall low-level contamination of groundwater sources. In order to determine the potential of pesticide and fertilizer mixtures to produce reproductive or developmental toxicity at concentrations up to 100 x the median level found in groundwater, we prepared and studied two mixtures of pesticides and a fertilizer (ammonium nitrate). One mixture containing aldicarb, atrazine, dibromochloropropane, 1,2-dichloropropane, ethylene dibromide, and simazine plus ammonium nitrate was considered to be a representative of groundwater contamination in California (CAL). The other, containing alachlor, atrazine, cyanazine, metolachlor, metribuzin, and ammonium nitrate, simulated groundwater contamination in Iowa (IOWA). Each mixture was administered in the drinking water of either Swiss CD-1 mice during a Reproductive Assessment by Continuous Breeding study or pregnant Sprague-Dawley rats (gd 6-20) at three dose levels (1x, 10x, and 100x) where 1x was the median concentration of each pesticide component as determined in the groundwater surveys in California or Iowa. Unlike conventional toxicology studies, the purpose of this study was to evaluate the health effects of realistic human concentrations. Thus, the testing concentrations are probably well below the maximally tolerated dose. Propylene glycol was used as the solubilizer for the pesticides in drinking water formulations in both studies. In the reproductive study, neither mixture caused any clinical signs of toxicity, changes in food or water consumption, or body weight in either F0 or F1 mice at doses up to 100x the median groundwater concentrations. There were no treatment-related effects on fertility or any measures of reproductive performance of either the F0 or the F1 generation mice exposed to either CAL or IOWA at up to 100x. Similarly, measures of spermatogenesis, epididymal sperm concentration, percentage motile sperm, percentage abnormal sperm, and testicular and epididymal histology were normal. In the developmental study, CAL- or IOWA-exposed females did not exhibit any significant treatment-related clinical signs of toxicity. No adverse effects of CAL or IOWA were observed for measures of embryo/fetal toxicity, including resorptions per litter, live litter size, or fetal body weight. CAL or IOWA did not cause an increased incidence of fetal malformations or variations. In summary, administration of these pesticide/fertilizer mixtures at levels up to 100-fold greater than the median concentrations in groundwater supplies in California or Iowa did not cause any detectable reproductive (mice), general, or developmental toxicity (rats).
authors.affiliation: National Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709.
authors.forename: J J
authors.initials: JJ
authors.lastname: Heindel
authors.forename: R E
authors.initials: RE
authors.lastname: Chapin
authors.forename: D K
authors.initials: DK
authors.lastname: Gulati
authors.forename: J D
authors.initials: JD
authors.lastname: George
authors.forename: C J
authors.initials: CJ
authors.lastname: Price
authors.forename: M C
authors.initials: MC
authors.lastname: Marr
authors.forename: C B
authors.initials: CB
authors.lastname: Myers
authors.forename: L H
authors.initials: LH
authors.lastname: Barnes
authors.forename: P A
authors.initials: PA
authors.lastname: Fail
authors.forename: T B
authors.initials: TB
authors.lastname: Grizzle
mesh_terms: D000818:Animals; D001724:Birth Weight / Q000187:drug effects; D002140:California; D005314:Embryonic and Fetal Development / Q000187:drug effects*; D005260:Female; D005308:Fertilizers / Q000633:toxicity*; D007484:Iowa; D008098:Litter Size / Q000187:drug effects; D008297:Male; D051379:Mice; D010575:Pesticides / Q000633:toxicity*; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D012098:Reproduction / Q000187:drug effects*; D013094:Spermatozoa / Q000187:drug effects; D014874:Water Pollutants, Chemical / Q000633:toxicity*
chemical_list: D005308:Fertilizers; D010575:Pesticides; D014874:Water Pollutants, Chemical