Changes in cross-fostered Sprague-Dawley rat litters exposed to perchlorate.
Ammonium perchlorate is used as an oxidizer in rocket fuel. It has become a groundwater contaminant, dissociating to ammonium cation and perchlorate anion. The perchlorate ion competes with iodide for uptake into the thyroid, reducing thyroid hormone production. Pregnant Sprague-Dawley rats were given either untreated or perchlorate (1 mg/kg-day) treated drinking water beginning on gestation day 2. One set of control and exposed dams was sacrificed on gestation day 20. The litters from the second set of control and exposed dams were crossed immediately after parturition and were sacrificed at postnatal day 10. Dam serum and thyroid, pooled fetal sera, and male and female pup sera were collected and analyzed for perchlorate, thyroid-stimulating hormone (TSH), triiodothyronine (T(3)), and thyroxine (T(4)). Control pups receiving perchlorate through lactation had serum levels at postnatal day 10 of 0.54 microg/ml and 0.56 microg/ml for male and female pups, respectively, whereas exposed fetuses had serum perchlorate levels of 0.38 +/- 0.04 microg/ml. Female pups receiving perchlorate lactationally had significantly lower levels of serum T(4) than control pups and prenatally exposed pups. Serum T(4) levels in male pups were not affected by perchlorate. Serum thyroid hormone levels from gestational perchlorate exposure were restored to control values by postnatal day 10. In utero perchlorate-exposure decreased serum T(4) levels in the fetus. Gestational studies in conjunction with a cross-fostering study design helped discern thyroid hormonal changes caused by perchlorate exposure during the perinatal period.
ManTech Environmental Technology, Inc, Human Effectiveness Directorate, Wright-Patterson Air Force Base, Ohio, USA. deidre.mahle@wpafb.af.mil
Deirdre A
DA
Mahle
Kyung O
KO
Yu
Latha
L
Narayanan
David R
DR
Mattie
Jeffrey W
JW
Fisher
D000014:Abnormalities, Drug-Induced; D000822:Animal Husbandry / Q000379:methods*; D000818:Animals; D000831:Animals, Newborn; D000833:Animals, Suckling; D013956:Antithyroid Agents / Q000633:toxicity*; D005314:Embryonic and Fetal Development / Q000187:drug effects; D005260:Female; D005312:Fetal Blood / Q000737:chemistry; D005333:Fetus / Q000187:drug effects; D007774:Lactation / Q000187:drug effects; D008297:Male; D008431:Maternal-Fetal Exchange; D010472:Perchlorates / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000633:toxicity*; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D017670:Sodium Compounds / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000633:toxicity*; D013961:Thyroid Gland / Q000002:abnormalities / Q000187:drug effects* / Q000473:pathology; D013963:Thyroid Hormones / Q000097:blood; D013972:Thyrotropin / Q000097:blood; D014873:Water Pollutants / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000633:toxicity*; D014881:Water Supply
D013956:Antithyroid Agents; D010472:Perchlorates; D017670:Sodium Compounds; D013963:Thyroid Hormones; D014873:Water Pollutants; D013972:Thyrotropin; C031068:sodium perchlorate