Toxicological Sciences 57, 61-74 (2000)
Copyright © 2000 by the Society of Toxicology
Endocrine Toxicology |
A 90-Day Drinking Water Toxicity Study in Rats of the Environmental Contaminant Ammonium Perchlorate
* Springborn Laboratories, Inc., 640 North Elizabeth Street, Spencerville, Ohio 45887;
AFRL/HEST, Wright-Patterson Air Force Base, Ohio;
ManTech Environmental Technology, Dayton, Ohio; and
§ Pathco, Inc., Ijamsville, Maryland
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 (T3), thyroxine (T4), 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 
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 1.0 mg/kg/day remains to be determined.
Key Words: perchlorate; water; contamination; toxicity; rat; thyroid; hypertrophy; risk.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  E. D. McLanahan, M. E. Andersen, and J. W. Fisher A Biologically Based Dose-Response Model for Dietary Iodide and the Hypothalamic-Pituitary-Thyroid Axis in the Adult Rat: Evaluation of Iodide Deficiency Toxicol. Sci., April 1, 2008; 102(2): 241 - 253. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Hu, B. Sharma, S. Mukhi, R. Patino, and J. A. Carr The Colloidal Thyroxine (T4) Ring as a Novel Biomarker of Perchlorate Exposure in the African Clawed Frog Xenopus laevis Toxicol. Sci., October 1, 2006; 93(2): 268 - 277. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Opitz, S. Hartmann, T. Blank, T. Braunbeck, I. Lutz, and W. Kloas Evaluation of Histological and Molecular Endpoints for Enhanced Detection of Thyroid System Disruption in Xenopus laevis Tadpoles Toxicol. Sci., April 1, 2006; 90(2): 337 - 348. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B D Beck An evaluation of the US Environmental Protection Agency definition of a risk assessment Human and Experimental Toxicology, January 1, 2006; 25(1): 3 - 5. [Abstract] [PDF]
|
|
|
|
 |
|
 M. A. Khan, S. E. Fenton, A. E. Swank, S. D. Hester, A. Williams, and D. C. Wolf A Mixture of Ammonium Perchlorate and Sodium Chlorate Enhances Alterations of the Pitutary-Thyroid Axis Caused by the Individual Chemicals in Adult Male F344 Rats Toxicol Pathol, December 1, 2005; 33(7): 776 - 783. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. G. York, J. Barnett Jr., W. R. Brown, R. H. Garman, D. R. Mattie, and D. Dodd A Rat Neurodevelopmental Evaluation of Offspring, Including Evaluation of Adult and Neonatal Thyroid, from Mothers Treated with Ammonium Perchlorate in Drinking Water International Journal of Toxicology, May 1, 2004; 23(3): 191 - 214. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. E. Stoker, S. C. Laws, K. M. Crofton, J. M. Hedge, J. M. Ferrell, and R. L. Cooper Assessment of DE-71, a Commercial Polybrominated Diphenyl Ether (PBDE) Mixture, in the EDSP Male and Female Pubertal Protocols Toxicol. Sci., March 1, 2004; 78(1): 144 - 155. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. G. York, K. A. Funk, M. F. Girard, D. Mattie, and J. E. Strawson Oral (Drinking Water) Developmental Toxicity Study of Ammonium Perchlorate in Sprague-Dawley Rats International Journal of Toxicology, November 1, 2003; 22(6): 453 - 464. [Abstract] [PDF]
|
|
|
|
|
|
E. A. Merrill, R. A. Clewell, J. M. Gearhart, P. J. Robinson, T. R. Sterner, K. O. Yu, D. R. Mattie, and J. W. Fisher PBPK Predictions of Perchlorate Distribution and Its Effect on Thyroid Uptake of Radioiodide in the Male Rat Toxicol. Sci., June 1, 2003; 73(2): 256 - 269. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. A. Mahle, K. O. Yu, L. Narayanan, D. R. Mattie, and J. W. Fisher Changes in Cross-Fostered Sprague-Dawley Rat Litters Exposed to Perchlorate International Journal of Toxicology, March 1, 2003; 22(2): 87 - 94. [Abstract] [PDF]
|
|