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

Abstract

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.

Developmental toxicity of thyroid-active compounds in a zebrafish embryotoxicity test

“…In another study with volunteers given perchlorate in drinking water the administered dose was negatively correlated with thyroidal iodide uptake but even a 70% decrease in iodide transport did not result in altered t4 levels (Greer et al, 2002;Strawson et al, 2004). the relatively low developmental toxicity of perchlorate is supported by animal studies showing that pregnant rats and rabbits exposed to a perchlorate dose as high as 30 mg/kg bw/ day do not give birth to offspring with signs of developmental toxicity and changes in thyroid hormone levels were seen as adaptive and reversible (York et al, 2003(York et al, , 2005.…”

A method for the analysis of six thyroid hormones in thyroid gland by liquid chromatography–tandem mass spectrometry

“…A recent study reported that perchlorate exposure in women with low iodide intake caused changes in TH levels [19]. In experimental studies using rats, perchlorate exposure decreased serum levels of T 4 and T 3 and increased thyroid stimulating hormone (TSH) levels [27,28]. High doses of perchlorate in rodents during fetal development resulted in permanent detriment to the brain function of the pup [29].…”

Iodine Uptake and Prostate Cancer in the TRAMP Mouse Model

“…The pathological grading system used was that proposed by Kaplan-Lefko, which considers several criteria such as epithelial cytoarchitecture and the presence of mitosis, apoptosis and inflammation (28). The percentages of normal and pathological acini were registered.…”

“…The TRAMP mice were obtained from The Jackson Laboratory (Bar Harbor, ME, USA 4 -inhibits >80% of iodide uptake in thyroid gland (positive control) (28). Thyroid, prostate and liver were collected, and the radiolabel was measured in counts per minute (cpm) in a γ-counter (Packard, Palo Alto, CA, USA).…”