York Raymond G, Funk Kathleen A, Girard Michael F, Mattie David, Strawson Joan E
Argus Research, Charles River Laboratories, Inc., Horsham, Pennsylvania 19044, USA.
Int J Toxicol. 2003 Nov-Dec;22(6):453-64. doi: 10.1177/109158180302200606.
A developmental toxicity study was conducted with ammonium perchlorate (AP) in the drinking water at doses of 0.0, 0.01, 0.1, 1.0, and 30.0 mg/kg-day beginning 14 days before cohabitation and continuing through sacrifice. Twenty-four rats/group were cesarean-sectioned on day of gestation (DG) 21 and fetuses examined for visceral and skeletal alterations. An additional 16 litters/group were sacrificed on DG 21 for maternal and fetal serum TSH, T(3), and T(4) (thyroid-stimulating hormone, triiodothyronine, and thyroxine) levels and thyroid histopathology. Clinical and necropsy observations, body weights, feed and water consumption, and cesarean-sectioning parameters were comparable among the groups with only delays in ossification observed in the 30 mg/kg-day group. Maternal thyroid weights were increased in the 30.0 mg/kg-day group. Decreased colloid was present in male and female fetal thyroids in the 1.0 and 30.0 mg/kg-day groups. Maternal TSH was increased and T(4) was decreased at all levels, and T(3) was reduced at 30.0 mg/kg-day. Fetal TSH was increased at 1.0 and 30.0 mg/kg-day, T(4) was reduced at 30.0 mg/kg-day, and T(3) was decreased at all levels. The maternal no-observable-adverse-effect level (NOAEL) was 1.0 mg/kg-day; exposures of 30.0 mg/kg-day increased absolute and relative maternal thyroid weights and histopathology findings. The developmental NOAEL was 1.0 mg/kg-day; developmental delays in ossification occurred in the 30.0 mg/kg-day group. The colloid depletion in the thyroids and increased TSH and decreased T(3) and T(4) levels at lower exposures were considered adaptive and not adverse. No adverse effects on development at occurred levels that did not cause maternal toxicity. AP is not a selective developmental toxicant.
对高氯酸铵（AP）进行了一项发育毒性研究，在交配前14天开始，以0.0、0.01、0.1、1.0和30.0mg/kg-天的剂量添加到饮用水中，并持续至处死。每组24只大鼠在妊娠第21天进行剖腹产，检查胎儿的内脏和骨骼改变。每组额外选取16窝在妊娠第21天处死，检测母鼠和胎儿血清促甲状腺激素（TSH）、三碘甲状腺原氨酸（T3）和甲状腺素（T4）水平以及甲状腺组织病理学。各实验组间的临床和尸检观察、体重、饲料和水消耗量以及剖腹产参数具有可比性，仅在30mg/kg-天组观察到骨化延迟。30.0mg/kg-天组母鼠甲状腺重量增加。1.0和30.0mg/kg-天组的雄性和雌性胎儿甲状腺中胶体减少。所有剂量下母鼠TSH升高、T4降低，30.0mg/kg-天组T3降低。1.0和30.0mg/kg-天组胎儿TSH升高，30.0mg/kg-天组T4降低，所有剂量下T3均降低。母鼠未观察到有害作用的剂量水平（NOAEL）为1.0mg/kg-天；30.0mg/kg-天的暴露增加了母鼠甲状腺的绝对重量和相对重量以及组织病理学发现。发育NOAEL为1.0mg/kg-天；30.0mg/kg-天组出现骨化发育延迟。较低暴露水平下甲状腺胶体减少以及TSH升高、T3和T4水平降低被认为是适应性变化而非有害作用。在未引起母鼠毒性的暴露水平下未观察到对发育的有害影响。AP不是一种选择性发育毒物。
