title: Refining the effects observed in a developmental neurobehavioral study of ammonium perchlorate administered orally in drinking water to rats. II. Behavioral and neurodevelopment effects.
abstract: A developmental neurotoxicity study was conducted to generate additional data on the potential functional and morphological hazard to the central nervous system caused by ammonium perchlorate in offspring from in utero and lactation exposure. Female Sprague-Dawley rats (23 to 25/group) were given continuous access to 0 (carrier), 0.1, 1.0, 3.0, and 10.0 mg/kg-day perchlorate in the drinking water beginning 2 weeks prior to mating and continuing through day 10 of lactation for the behavioral function assessment or given continuous access to 0 (carrier), 0.1, 1.0, 3.0, and 30.0 mg/kg-day beginning on gestation day 0 and continuing through day 10 of lactation for neurodevelopment assessments. Motor activity was conducted on postpartum days 14, 18, and 22 and juvenile brain weights, neurohistopathological examinations, and regional brain morphometry were conducted on postpartum days 10 and 22. This research revealed a sexually dimorphic response, with some brain regions being larger in perchlorate-treated male rats than in comparable controls. Even so, there was no evidence of any obvious exposure-related effects on male rat brain weights or neuropathology. The most consistent exposure-related effect in the male pups was on the thickness of the corpus callosum, with both the right- and left-sided measures of the thickness of this white matter tract being significantly greater for the male pups in the 0.1 and 1.0 mg/kg-day exposure groups. The behavioral testing suggests prenatal exposure to ammonium perchlorate does not affect the development of gross motor movements in the pups.
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: John
authors.initials: J
authors.lastname: Barnett
authors.forename: Michael F
authors.initials: MF
authors.lastname: Girard
authors.forename: David R
authors.initials: DR
authors.lastname: Mattie
authors.forename: Marni V K
authors.initials: MV
authors.lastname: Bekkedal
authors.forename: Robert H
authors.initials: RH
authors.lastname: Garman
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 / Q000473:pathology; D005260:Female; D007774:Lactation; D008297:Male; D018811:Maternal Exposure; D009043:Motor Activity / 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; D012737:Sex Factors; D013997:Time Factors; D014874:Water Pollutants, Chemical / Q000633:toxicity*
chemical_list: D010472:Perchlorates; D000644:Quaternary Ammonium Compounds; D014874:Water Pollutants, Chemical; C053506:ammonium perchlorate