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

York, Raymond G.; Funk, Kathleen A.; Girard, M; Mattie, David R.; Strawson, Joan

doi:10.1080/725310726

Cited by 6 publications

(8 citation statements)

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“…No effects of perchlorate exposure were observed on any cesarean-sectioning or litter parameters, and there were no fetal alterations observed at gross external examination. These findings are in agreement with the results of previously published rat and rabbit developmental toxicity studies (York et al 2001b, 2003) using similar exposure parameters that concluded ammonium perchlorate should not be identified as a specific rat or rabbit developmental toxicant. Reproductive parameters of gestational length, number of implants, litter size, and pup viability and lactation indices for the rat were also comparable and did not differ significantly.…”

Section: Discussionsupporting

confidence: 92%

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Refining the Effects Observed in a Developmental Neurobehavioral Study of Ammonium Perchlorate Administered Orally in Drinking Water to Rats. I. Thyroid and Reproductive Effects

York

Lewis

Brown³

et al. 2005

Int J Toxicol

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A recent study further investigated the potential effects of maternal thyroid function and morphology on fetal development upon maternal exposure to ammonium perchlorate during gestation and lactation. Female Sprague-Dawley rats (25/group) were given continual access to 0 (carrier), 0.01, 0.1, 1.0, and 30.0 mg/kg-day perchlorate in drinking water beginning 2 weeks prior to cohabitation through lactation day 10. Maternal, fetal, and pup serum thyroid hormone (thyroid-stimulating hormone [TSH], triiodo thyronine [T(3)], thyroxine [T(4)]) levels and thyroid histopathology were evaluated on gestation day 21, and lactation days 5, 10, and 22. No effects of exposure were observed on cesarean-sectioning, litter parameters, or fetal alterations. Reproductive parameters, including gestation length, number of implants, litter size, pup viability, and lactation indices, were comparable among all groups. Thyroid weights of dams sacrificed on gestation day 21, and lactation days 10 and 22 were significantly increased at 30.0 mg/kg-day. Increased thyroid weights were observed in male and female pups as early as postpartum days 5 and 10, respectively. Changes in maternal and neonatal thyroid histopathology were detectable at 1.0 mg/kg-day exposure. The maternal no-observable-effect level (NOEL) was 0.1 mg/kg-day (follicular cell hyperplasia was present at 1.0 and 30.0 mg/kg-day). The developmental NOEL was less than 0.01 mg/kg-day; thyroid weights of postpartum day 10 pups were increased at all exposures. Colloid depletion at 1.0 and 30.0 mg/kg-day exposures and changes of hormone levels at all exposures were considered an adaptive effect and appeared reversible in the rodent.

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Section: Discussionsupporting

confidence: 92%

“…Blood (pooled by sex and litter), thyroid, and brain samples were collected from culled pups on PPD 5 and from the remaining PPD 22 pups. The last subset of the study was a standard rat developmental toxicity study that has been previously reported (York et al 2003).…”

Section: Methodsmentioning

confidence: 99%

Refining the Effects Observed in a Developmental Neurobehavioral Study of Ammonium Perchlorate Administered Orally in Drinking Water to Rats. I. Thyroid and Reproductive Effects

York

Lewis

Brown³

et al. 2005

Int J Toxicol

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“…The effects of ammonium perchlorate were investigated in a developmental toxicity study by York et al (2003) in Sprague-Dawley rats (25 mated rats/group). Doses of 0, 0.01, 0.1, 1.0 and 30 mg/kg b.w.…”

Section: Reproductive and Developmental Toxicitymentioning

confidence: 99%

Scientific Opinion on the risks to public health related to the presence of perchlorate in food, in particular fruits and vegetables

2014

EFSA Journal

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The European Food Safety Authority (EFSA) received a request from the European Commission for a scientific opinion on perchlorate in food, in particular fruits and vegetables. Perchlorate is a contaminant released into the environment from both natural and anthropogenic sources. The use of natural fertilisers and perchlorate contaminated irrigation water may lead to substantial concentrations in leafy vegetables. Water disinfection with chlorinated substances that potentially degrade to perchlorate could be another potential source of contamination. EFSA received analytical results for 11 675 samples submitted by eight Member States, mainly for fruits, vegetables, and fruit and vegetable products. The EFSA Panel on Contaminants in the Food Chain (CONTAM Panel) performed estimates of both chronic and 'short-term' exposure considering the available dataset, and data from the literature on the levels of perchlorate in fruit juices, alcoholic beverages, milk, infant formulae and breast milk. The CONTAM Panel established a tolerable daily intake of 0.3 µg/kg body weight per day, based on the inhibition of thyroid iodine uptake in healthy adults. Amongst the vulnerable subpopulations, potential acute effects of perchlorate have been suggested for fetuses and infants. The CONTAM Panel noted that a single acute exposure to perchlorate at levels found in food and water is unlikely to cause adverse effects on human health, including the more vulnerable groups of the population, and concluded that the establishment of an acute reference dose for perchlorate is not warranted. Overall, the

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“…Perchlorate is an inorganic anion that is used for a variety of purposes, including the manufacturing of solid rocket fuel propellants, fireworks and munitions components (EPA 2002(EPA & 2005Urbansky 2002;York et al 2003). Perchlorate competes with iodide for uptake into the thyroid gland, disrupting normal thyroid hormone production (Wolff 1998;Motzer 2001).…”

mentioning

confidence: 99%

“…Environmental contaminants capable of reducing maternal thyroid hormone concentrations require careful consideration when exposure demographics include women considering conception or women who have already conceived (Miculan et al 1993;Kooistra et al 1994;Haddow et al 1999;Anderson 2001). Indeed, perchlorate has been reported to cross the placental barrier (Wolff 1998), alter ovarian follicle maturation (Baldridge et al 2004), reduce thyroid hormone concentrations and produce a compensatory increase in thyroid-stimulating hormone in gestating dams (York et al 2003), and to reduce thyroxine concentrations in both the rat dam and in the foetus when exposure occurs during the gestational period (Mahle et al 2003). The destructive effects of another environmental contaminant, ethanol, have been well documented when consumption occurs during pregnancy.…”

mentioning

confidence: 99%

The Effect of Oral Consumption of Perchlorate, Alone and in Combination with Ethanol, on Plasma Thyroid Hormone and Brain Catecholamine Concentrations in the Rat

James-Walke

Williams

Taylor

et al. 2006

Basic Clin Pharma Tox

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Literature has reported a controversy concerning the effects of the environmental pollutant perchlorate on pertinent physiological systems. However, no research to date has evaluated the effect of concomitant consumption of perchlorate and an additional environmental contaminant on physiological systems. The present preliminary investigation served to assess the effects of oral consumption of perchlorate, alone and in combination with ethanol, on thyroid hormone and brain catecholamine concentrations in female rats of gestational age. Forty, female Myers' high ethanolpreferring rats were randomly assigned to 1 of 7 groups that received: (1) deionized water, both bottles (2) deionized water and 10% ethanol (v/v), two separate bottles (3) 300 mg/l perchlorate solution in deionized water, both bottles (4) 300 mg/l perchlorate in deionized water and in 10% ethanol (v/v), two separate bottles (5) 3000 mg/l perchlorate solution in deionized water, both bottles (6) 3000 mg/l perchlorate in deionized water and in 10% ethanol (v/v), two separate bottles (7) 0.01% propylthiouracil solution in deionized water, both bottles. At cessation of the treatment period, plasma triiodothyronine (T3) and thyroxine (T4) levels were measured by radioimmunoassay and brain area concentrations of dopamine, 3,4-dihydroxyphenylacetic acid (DOPAC), and norepinephrine were measured by high performance liquid chromatography. Perchlorate consumption, alone and/or in combination with ethanol consumption, failed to produce significant alterations from control values for triiodothyronine, thyroxine, dopamine, DOPAC, or norepinephrine. The data suggest that the noobserved effect level of perchlorate consumption on thyroid hormone and brain catecholamine concentrations is above the 3000 mg/l concentration in the adult female rat.

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

Cited by 6 publications

References 0 publications

Refining the Effects Observed in a Developmental Neurobehavioral Study of Ammonium Perchlorate Administered Orally in Drinking Water to Rats. I. Thyroid and Reproductive Effects

Refining the Effects Observed in a Developmental Neurobehavioral Study of Ammonium Perchlorate Administered Orally in Drinking Water to Rats. I. Thyroid and Reproductive Effects

Scientific Opinion on the risks to public health related to the presence of perchlorate in food, in particular fruits and vegetables

The Effect of Oral Consumption of Perchlorate, Alone and in Combination with Ethanol, on Plasma Thyroid Hormone and Brain Catecholamine Concentrations in the Rat

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