Butenhoff John L, Kennedy Gerald L, Frame Steven R, O'Connor John C, York Raymond G
3M Medical Department, Corporate Toxicology, 3M Center 220-2E-02, Saint Paul, MN 55133, USA.
Toxicology. 2004 Mar 1;196(1-2):95-116. doi: 10.1016/j.tox.2003.11.005.
Ammonium perfluorooctanoate (APFO) is a surfactant used primarily as an aid in processing various fluoropolymers. Many toxicology and epidemiological studies have been conducted with APFO; however, no specific information regarding functional reproduction was previously available. Therefore, the potential reproductive toxicity of APFO across two generations of offspring was studied using current EPA OPPTS 870.3800 guidelines. Male and female Sprague-Dawley rats were dosed orally with 0, 1, 3, 10, or 30 mg/kg APFO. Parental (P) generation rats ( approximately 6 weeks old) were dosed at least 70 days prior to mating and until sacrificed (after mating for male rats; after weaning for female rats). F(1)-generation rats were dosed similarly, beginning at weaning. The F(2)-generation pups were maintained through 22 days of lactation. Reproductive parameters evaluated in P- and F(1)-generation rats included estrous cycling, sperm number and quality, mating, fertility, natural delivery, and litter viability and growth. Age at sexual maturation in F(1), anogenital distance in F(2), and presence of nipples (males) in F(2)-generation pups were also determined. Feed consumption, body-weight gain, selected organ-weights, gross pathology and appropriate histopathology were evaluated. Reproductive endpoints including mating, fertility, and natural delivery were not affected in either generation. P- and F(1)-generation male rats showed decreased body weight, and liver and kidney weight increases at all doses. The 30 mg/kg F(1)-generation pups had decreased birth weight. Viability was reduced in the 30 mg/kg F(1)-generation pups in apparent relationship to reduced body weight at birth and weaning; however, F(2)-generation pups at 30 mg/kg, although somewhat lighter, did not show a loss in viability. Preputial separation and vaginal opening were somewhat delayed at 30 mg/kg, but these rats went on to show normal reproductive performance. No-observed-adverse-effect-levels were >30 mg/kg for reproductive function of P- and F(1)-generation rats, 10 mg/kg for F(1)-generation pup mortality, birth weight, and sexual maturation, and less than 1mg/kg for male body-weight and organ-weight changes.
全氟辛酸铵（APFO）是一种表面活性剂，主要用于协助加工各种含氟聚合物。已经对APFO进行了许多毒理学和流行病学研究；然而，以前没有关于功能繁殖的具体信息。因此，使用美国环境保护局（EPA）OPPTS 870.3800现行指南研究了APFO对两代后代的潜在生殖毒性。将雄性和雌性斯普拉格-道利大鼠经口给予0、1、3、10或30mg/kg的APFO。亲代（P）代大鼠（约6周龄）在交配前至少70天给药，直至处死（雄性大鼠交配后；雌性大鼠断奶后）。F(1)代大鼠在断奶时开始进行类似给药。F(2)代幼崽维持哺乳22天。在P代和F(1)代大鼠中评估的生殖参数包括发情周期、精子数量和质量、交配、生育力、自然分娩以及窝仔的活力和生长。还测定了F(1)代的性成熟年龄、F(2)代的肛门生殖器距离以及F(2)代幼崽（雄性）乳头的存在情况。评估了饲料消耗量、体重增加、选定器官重量、大体病理学和适当的组织病理学。包括交配、生育力和自然分娩在内的生殖终点在两代中均未受到影响。P代和F(1)代雄性大鼠在所有剂量下体重均下降，肝脏和肾脏重量增加。30mg/kg F(1)代幼崽出生体重下降。30mg/kg F(1)代幼崽的活力降低，这显然与出生时和断奶时体重减轻有关；然而，30mg/kg F(2)代幼崽虽然体重稍轻，但并未出现活力丧失。30mg/kg时包皮分离和阴道开口有所延迟，但这些大鼠随后表现出正常的生殖性能。P代和F(1)代大鼠生殖功能的未观察到有害作用水平>30mg/kg，F(1)代幼崽死亡率、出生体重和性成熟的未观察到有害作用水平为10mg/kg，雄性体重和器官重量变化的未观察到有害作用水平小于1mg/kg。
