title: 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.
authors.affiliation: Charles River Laboratories, Preclinical Services, 905 Sheehy Drive, Horsham, PA 19044, USA. raymond.york@us.crl.com
authors.forename: Raymond G
authors.initials: RG
authors.lastname: York
authors.forename: Elise
authors.initials: E
authors.lastname: Lewis
authors.forename: W Ray
authors.initials: WR
authors.lastname: Brown
authors.forename: Michael F
authors.initials: MF
authors.lastname: Girard
authors.forename: David R
authors.initials: DR
authors.lastname: Mattie
authors.forename: Kathleen A
authors.initials: KA
authors.lastname: Funk
authors.forename: Joan S
authors.initials: JS
authors.lastname: Strawson
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000831:Animals, Newborn; D001522:Behavior, Animal / Q000187:drug effects; D001921:Brain / Q000187:drug effects / Q000254:growth & development; D004305:Dose-Response Relationship, Drug; D005260:Female; D007774:Lactation; D008297:Male; D018811:Maternal Exposure; D019055:No-Observed-Adverse-Effect Level; D009929:Organ Size / Q000187:drug effects; D010472:Perchlorates / Q000008:administration & dosage / Q000633:toxicity*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D000644:Quaternary Ammonium Compounds / Q000008:administration & dosage / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012098:Reproduction / Q000187:drug effects*; D013961:Thyroid Gland / Q000187:drug effects* / Q000254:growth & development / Q000473:pathology; D013972:Thyrotropin / Q000097:blood; D013974:Thyroxine / Q000097:blood; D014284:Triiodothyronine / Q000097:blood; D014874:Water Pollutants, Chemical / Q000008:administration & dosage / Q000633:toxicity*
chemical_list: D010472:Perchlorates; D000644:Quaternary Ammonium Compounds; D014874:Water Pollutants, Chemical; D014284:Triiodothyronine; D013972:Thyrotropin; D013974:Thyroxine; C053506:ammonium perchlorate