Toxicological evaluation of sodium perfluorohexanoate.
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.
Loveless
Scott E
SE
DuPont Haskell Global Centers for Health and Environmental Sciences, Elkton Rd, Newark, DE 19714-0050, USA. scott.e.loveless@usa.dupont.com
Slezak
Brian
B
Serex
Tessa
T
Lewis
Joseph
J
Mukerji
Pushkor
P
O'Connor
John C
JC
Donner
E Maria
EM
Frame
Steven R
SR
Korzeniowski
Stephen H
SH
Buck
Robert C
RC
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001772:Blood Cell Count; D001835:Body Weight / Q000187:drug effects; D002208:Caproates / Q000633:toxicity*; D004435:Eating / Q000187:drug effects; D005128:Eye Diseases / Q000139:chemically induced / Q000473:pathology; D005260:Female; D047109:Fetal Development / Q000187:drug effects; D005466:Fluorocarbons / Q000633:toxicity*; D006801:Humans; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D009152:Mutagenicity Tests; D009153:Mutagens / Q000633:toxicity*; D009929:Organ Size / Q000187:drug effects; D010084:Oxidation-Reduction; D020675:Peroxisomes / Q000187:drug effects / Q000378:metabolism; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D012098:Reproduction; D013997:Time Factors
D002208:Caproates; D005466:Fluorocarbons; D009153:Mutagens; C479228:perfluorohexanoic acid