Loveless Scott E, Slezak Brian, Serex Tessa, Lewis Joseph, Mukerji Pushkor, O'Connor John C, Donner E Maria, Frame Steven R, Korzeniowski Stephen H, Buck Robert C
DuPont Haskell Global Centers for Health and Environmental Sciences, Elkton Rd, Newark, DE 19714-0050, USA.
Toxicology. 2009 Oct 1;264(1-2):32-44. doi: 10.1016/j.tox.2009.07.011. Epub 2009 Jul 24.
Sodium perfluorohexanoate [NaPFHx, F(CF(2))(5)CO(2)Na, CAS#2923-26-4] was evaluated in acute, 90-day subchronic, one-generation reproduction, developmental and in vitro genetic toxicity studies. In the subchronic/one-generation reproduction study, four groups of young adult male and female Crl:CD(SD) rats were administered NaPFHx daily for approximately 90 days by gavage at dosages of 0, 20, 100, or 500 mg/kg. Selected groups of rats were evaluated after 1- and 3-month recovery periods. Rats selected for reproductive evaluations were dosed for approximately 70 days prior to cohabitation, through gestation and lactation, for a total of about 4 months. The subchronic toxicity no observed adverse effect level (NOAEL) was 20mg/(kg day), based on nasal lesions observed at 100 and 500 mg/(kg day). No effects were observed for neurobehavioral endpoints. NaPFHx was a moderate inducer of hepatic peroxisomal beta-oxidation with a no observed effect level (NOEL) of 20 (male rats) and 100mg/(kg day) (female rats). Elevated hepatic beta-oxidation levels were observed following 1-month recovery in male and female rats at 500 mg/(kg day). No NaPFHx-related effects were observed on any reproductive parameters. The P(1) adult rat NOAEL was 20mg/(kg day), based on reduced body weight parameters, whereas the NOAEL for reproductive toxicity was 100 mg/(kg day), based on effects limited to reduced F(1) pup weights. In the developmental study, female rats were dosed via gavage on gestation day (GD) 6-20 with the same doses of NaPFHx administered in the subchronic study. The maternal and developmental toxicity NOAEL was 100 mg/(kg day), based on maternal and fetal body weight effects at 500 mg/(kg day). NaPFHx is therefore concluded not to present a reproductive or developmental hazard. NaPFHx genotoxicity studies showed no mutations in the bacterial reverse mutation (Ames) assay or chromosome aberrations in human lymphocytes treated with NaPFHx in vitro. The lowest NOAEL from all of the studies was 20mg/(kg day) in the subchronic study based on nasal lesions. Benchmark doses (BMDL10) for nasal lesions were 13 and 21 mg/(kg day) for male and female rats, respectively. The relevance of the nasal lesions to humans is not known.
全氟己酸钠[NaPFHx，F(CF(2))(5)CO(2)Na，化学物质登记号#2923 - 26 - 4]在急性、90天亚慢性、一代繁殖、发育及体外遗传毒性研究中进行了评估。在亚慢性/一代繁殖研究中，将四组年轻成年雄性和雌性Crl:CD(SD)大鼠每日经口灌胃给予NaPFHx，持续约90天，剂量分别为0、20、100或500 mg/kg。在1个月和3个月恢复期后对选定的大鼠组进行评估。选择用于生殖评估的大鼠在同居前、整个妊娠期和哺乳期给药约70天，共计约4个月。基于在100和500 mg/(kg·天)剂量下观察到的鼻部病变，亚慢性毒性未观察到有害作用水平(NOAEL)为20mg/(kg·天)。未观察到对神经行为终点的影响。NaPFHx是肝过氧化物酶体β - 氧化的中度诱导剂，无观察到影响水平(NOEL)在雄性大鼠中为20，在雌性大鼠中为100mg/(kg·天)。在500 mg/(kg·天)剂量下，雄性和雌性大鼠在1个月恢复期后观察到肝β - 氧化水平升高。未观察到与NaPFHx相关的对任何生殖参数的影响。基于体重参数降低，P(1)成年大鼠的NOAEL为20mg/(kg·天)，而基于仅限于F(1)幼崽体重降低的影响，生殖毒性的NOAEL为100 mg/(kg·天)。在发育研究中，雌性大鼠在妊娠第6 - 20天经口灌胃给予与亚慢性研究相同剂量的NaPFHx。基于在500 mg/(kg·天)剂量下对母体和胎儿体重的影响，母体和发育毒性NOAEL为100 mg/(kg·天)。因此得出结论，NaPFHx不存在生殖或发育危害。NaPFHx遗传毒性研究表明，在细菌回复突变(Ames)试验中未出现突变，体外给予NaPFHx处理的人淋巴细胞中也未出现染色体畸变。基于鼻部病变，所有研究中的最低NOAEL在亚慢性研究中为20mg/(kg·天)。雄性和雌性大鼠鼻部病变的基准剂量(BMDL10)分别为13和21 mg/(kg·天)。鼻部病变与人类的相关性尚不清楚。
