The Effect of Sodium Perchlorate and Ionizing Irradiation on the Thyroid Parenchymal and Pituitary Thyrotropic Cells

Pajer, Zdenka; Kališnik, Miroslav

doi:10.1159/000226950

Cited by 11 publications

(4 citation statements)

References 2 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Ammonium perchlorate has been tested in a battery of in vitro and in vivo genotoxicity tests; perchlorate does not appear to be mutagenic or clastogenic ( OEHHA 2004 ). A number of animal studies have shown that perchlorate at high doses (> 1,300 mg/kg/day) causes thyroid tumors in rodents ( Gauss 1972 ; Kessler and Kruskemper 1966 ; Pajer and Kalisnik 1991 ). Because the occurrence of the tumors was preceded mostly by signs of thyroid hormone disruption and thyroid enlargement, these tumors are generally interpreted as being secondary to the anti-thyroid effects of perchlorate [ OEHHA 2004 ; U.S. Environmental Protection Agency (U.S. EPA) 2002 ].…”

Section: Animal Toxicity Datamentioning

confidence: 99%

Development of a Health-Protective Drinking Water Level for Perchlorate

Ting

Howd

Fan

et al. 2006

Environ Health Perspect

View full text Add to dashboard Cite

We evaluated animal and human toxicity data for perchlorate and identified reduction of thyroidal iodide uptake as the critical end point in the development of a health-protective drinking water level [also known as the public health goal (PHG)] for the chemical. This work was performed under the drinking water program of the Office of Environmental Health Hazard Assessment of the California Environmental Protection Agency. For dose–response characterization, we applied benchmark-dose modeling to human data and determined a point of departure (the 95% lower confidence limit for 5% inhibition of iodide uptake) of 0.0037 mg/kg/day. A PHG of 6 ppb was calculated by using an uncertainty factor of 10, a relative source contribution of 60%, and exposure assumptions specific to pregnant women. The California Department of Health Services will use the PHG, together with other considerations such as economic impact and engineering feasibility, to develop a California maximum contaminant level for perchlorate. We consider the PHG to be adequately protective of sensitive subpopulations, including pregnant women, their fetuses, infants, and people with hypothyroidism.

show abstract

Section: Animal Toxicity Datamentioning

confidence: 99%

Development of a Health-Protective Drinking Water Level for Perchlorate

Ting

Howd

Fan

et al. 2006

Environ Health Perspect

View full text Add to dashboard Cite

show abstract

“…The primary target tissue for perchlorate toxicity is the thyroid gland as indicated by perturbations of T 3 , T 4 , and TSH hormones and by thyroid histopathology. Benign tumors and follicular cell carcinomas have been reported in the thyroid of male Wistar rats and female BALB/c mice treated with repeated, high dose exposures (2 years at 1,339 and 46 weeks at 2,147 mg/kg/day, respectively) of potassium perchlorate in drinking water (24,37). The majority of human data are clinical reports of patients treated with potassium perchlorate for hyperthyroidism resulting from Graves disease, an autoimmune condition.…”

Section: Histopathologymentioning

confidence: 99%

Subchronic Sodium Chlorate Exposure in Drinking Water Results in a Concentration-Dependent Increase in Rat Thyroid Follicular Cell Hyperplasia

et al. 2001

View full text Add to dashboard Cite

Chlorine dioxide (ClO 2 ) is an effective drinking water disinfectant, but sodium chlorate (NaClO 3 ) has been identi ed as a potentially harmful disinfection by-product . Studies were performed to describe the developmen t of thyroid lesions in animals exposed to NaClO 3 in the drinking water. Male and female F344 rats and B6C3F 1 mice were exposed to 0, 0.125, 0.25, 0.5, 1.0, or 2.0 g/L NaClO 3 for 21 days. Additional male F344 rats were exposed to 0, 0.001, 0.01, 0.1, 1.0, or 2.0 g/L NaClO 3 for 90 days. Female F344 rats were exposed to 0, 0.5, 1.0, 2.0, 4.0, or 6.0 g/L of NaClO 3 for 105 days. Thyroid tissues were processed by routine methods for light microscopi c examination, and follicular cell hyperplasia was diagnosed using a novel method. Thyroid hormone levels were altered signi cantly after 4 and 21 days. NaClO 3 treatment induced a concentration-dependen t increase in the incidence and severity of thyroid follicular cell hyperplasia. Male rats are more sensitive to the effects of NaClO 3 treatment than females. Follicular cell hyperplasi a was not present in male or female B6C3F 1 mice. These data can be used to estimate the human health risk that would be associated with using ClO 2 , rather than chlorine, to disinfect drinking water.

show abstract

“…not evaluate the effects of long-term exposures to perchlorate on reproduction or behavior. In animals, long-term studies clearly show thyroid toxicity at high doses (1% potassium or sodium perchlorate in drinking water), but these studies generally did not examine targets other than the thyroid (Kessler and Krunkemper 1966;Pajer and Kalisnik 1991). No adequate developmental toxicity study in rats has been conducted to date.…”

mentioning

confidence: 99%

Oral (Drinking Water) Developmental Toxicity Study of Ammonium Perchlorate in Sprague-Dawley Rats

York

Funk

Girard³

et al. 2003

Int J Toxicol

View full text Add to dashboard Cite

A developmental toxicity study was conducted with ammonium perchlorate (AP) in the drinking water at doses of 0.0, 0.01, 0.1, 1.0, and 30.0 mg/kg-day beginning 14 days before cohabitation and continuing through sacrifice. Twenty-four rats/group were cesarean-sectioned on day of gestation (DG) 21 and fetuses examined for visceral and skeletal alterations. An additional 16 litters/group were sacrificed on DG 21 for maternal and fetal serum TSH, T(3), and T(4) (thyroid-stimulating hormone, triiodothyronine, and thyroxine) levels and thyroid histopathology. Clinical and necropsy observations, body weights, feed and water consumption, and cesarean-sectioning parameters were comparable among the groups with only delays in ossification observed in the 30 mg/kg-day group. Maternal thyroid weights were increased in the 30.0 mg/kg-day group. Decreased colloid was present in male and female fetal thyroids in the 1.0 and 30.0 mg/kg-day groups. Maternal TSH was increased and T(4) was decreased at all levels, and T(3) was reduced at 30.0 mg/kg-day. Fetal TSH was increased at 1.0 and 30.0 mg/kg-day, T(4) was reduced at 30.0 mg/kg-day, and T(3) was decreased at all levels. The maternal no-observable-adverse-effect level (NOAEL) was 1.0 mg/kg-day; exposures of 30.0 mg/kg-day increased absolute and relative maternal thyroid weights and histopathology findings. The developmental NOAEL was 1.0 mg/kg-day; developmental delays in ossification occurred in the 30.0 mg/kg-day group. The colloid depletion in the thyroids and increased TSH and decreased T(3) and T(4) levels at lower exposures were considered adaptive and not adverse. No adverse effects on development at occurred levels that did not cause maternal toxicity. AP is not a selective developmental toxicant.

show abstract

The Effect of Sodium Perchlorate and Ionizing Irradiation on the Thyroid Parenchymal and Pituitary Thyrotropic Cells

Cited by 11 publications

References 2 publications

Development of a Health-Protective Drinking Water Level for Perchlorate

Development of a Health-Protective Drinking Water Level for Perchlorate

Subchronic Sodium Chlorate Exposure in Drinking Water Results in a Concentration-Dependent Increase in Rat Thyroid Follicular Cell Hyperplasia

Oral (Drinking Water) Developmental Toxicity Study of Ammonium Perchlorate in Sprague-Dawley Rats

Contact Info

Product

Resources

About