title: A 90-day drinking water toxicity study in rats of the environmental contaminant ammonium perchlorate.
abstract: Perchlorate (ClO(4)(-)), the dissociated anion of perchlorate salts such as ammonium, potassium, and sodium perchlorate, has been recently recognized as a persistent and pervasive contaminant of drinking water supplies in a number of metropolitan areas. Perchlorate is of concern because of uncertainties in the toxicological database available to address the potential human health effects of low-level exposure. The purpose of this study was to evaluate the subchronic toxicity of perchlorate when administered to Sprague-Dawley rats as ammonium perchlorate (AP) for 14 or 90 days. The study consisted of an untreated control group and five treatment groups that received continuous exposure to AP via the drinking water at dosage levels of 0.01, 0.05, 0.2, 1.0, and 10.0 mg/kg/day. The study design included a nontreatment recovery period of 30 days to evaluate the reversibility of any AP-induced effects at the 0.05, 1.0, and 10.0 mg/kg/day levels. The study also investigated the potential effects of AP on male sperm parameters, female estrous cyclicity, bone marrow micronucleus formation, and serum hormone levels, i.e., triiodothyronine (T(3)), thyroxine (T(4)), and thyroid stimulating hormone (TSH). No toxicologically meaningful differences were observed between the control and AP-treated groups with respect to survival, clinical observations, body weights, food consumption, water consumption, ophthalmology, hematology, clinical chemistry, estrous cycling, sperm parameters, or bone marrow micronucleus formation. A target organ effect was produced by AP in the thyroids of male and female rats at the 10 mg/kg/day level after 14 and 90 days of exposure. The effect was characterized by significantly increased thyroid weights and thyroid histopathology consisting primarily of follicular cell hypertrophy with microfollicle formation and colloid depletion. These changes were reversible after a nontreatment recovery period of 30 days. Statistically significant changes in TSH and thyroid hormones were observed at all AP dosage levels tested; however, no thyroid organ weight or histopathological effects were observed at AP dosage levels < or = 1.0 mg/kg/day. In the absence of thyroid organ weight and histopathological effects, the toxicological significance of TSH and thyroid hormone changes at AP dosage levels < or = 1.0 mg/kg/day remains to be determined.
authors.affiliation: Springborn Laboratories, Inc., 640 North Elizabeth Street, Spencerville, Ohio 45887, USA. jsiglin@springborn.com
authors.forename: J C
authors.initials: JC
authors.lastname: Siglin
authors.forename: D R
authors.initials: DR
authors.lastname: Mattie
authors.forename: D E
authors.initials: DE
authors.lastname: Dodd
authors.forename: P K
authors.initials: PK
authors.lastname: Hildebrandt
authors.forename: W H
authors.initials: WH
authors.lastname: Baker
mesh_terms: D000818:Animals; D001835:Body Weight / Q000187:drug effects; D004326:Drinking / Q000187:drug effects; D004435:Eating / Q000187:drug effects; D004971:Estrus / Q000187:drug effects; D005128:Eye Diseases / Q000139:chemically induced; D005260:Female; D008297:Male; D015162:Micronucleus Tests; D009929:Organ Size / Q000187:drug effects; D010472:Perchlorates / Q000633:toxicity*; D000644:Quaternary Ammonium Compounds / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012727:Sex Characteristics; D013094:Spermatozoa / Q000187:drug effects; D013972:Thyrotropin / Q000097:blood; D013974:Thyroxine / Q000097:blood; D014284:Triiodothyronine / Q000097:blood; D014874:Water Pollutants, Chemical / Q000633:toxicity*; D014881:Water Supply / Q000032:analysis*
chemical_list: D010472:Perchlorates; D000644:Quaternary Ammonium Compounds; D014874:Water Pollutants, Chemical; D014284:Triiodothyronine; D013972:Thyrotropin; D013974:Thyroxine; C053506:ammonium perchlorate