Evaluation of potential reproductive and developmental toxicity of potassium perfluorohexanesulfonate in Sprague Dawley rats.
This study evaluates the potential reproductive and developmental toxicity of perfluorohexanesulfonate (PFHxS), a surfactant found in sera of the general population. In a modified OECD 422 guideline-based design, 15 rats per sex and treatment group (control, 0.3, 1, 3, and 10mg/kg-d) were dosed by gavage with potassium PFHxS (K(+)PFHxS) or vehicle (0.5% carboxymethylcellulose) 14 days prior to cohabitation, during cohabitation, and until the day before sacrifice (21 days of lactation or presumed gestation day 25 (if not pregnant) for females and minimum of 42 days of treatment for males). Offspring were not dosed by gavage but were exposed by placental transfer in utero and potentially exposed via milk. Evaluations were made for reproductive success, clinical signs, body weight, food consumption, estrous cycling, neurobehavioral effects, gross and microscopic anatomy of selected organs, sperm, hematology, clinical pathology, and concentration of PFHxS in serum and liver. Additional three rats per sex per group were added to obtain sera and liver samples for PFHxS concentration determinations during the study. No reproductive or developmental effects were observed. There were no treatment-related effects in dams or offspring. K(+)PFHxS-induced effects noted in parental males included: (1) at all doses, reductions in serum total cholesterol; (2) at 0.3, 3, and 10mg/kg-d, decreased prothrombin time; (3) at 3 and 10mg/kg-d, increased liver-to-body weight and liver-to-brain weight ratios, centrilobular hepatocellular hypertrophy, hyperplasia of thyroid follicular cells, and decreased hematocrit; (4) at 10mg/kg-d, decreased triglycerides and increased albumin, BUN, ALP, Ca(2+), and A/G ratio. Serum and liver concentrations of PFHxS are reported for parents, fetuses, and pups. PFHxS was not a reproductive or developmental toxicant under study conditions.
Butenhoff
John L
JL
3M Company, Medical Department, 3M Center 220-6W-08, St. Paul, MN 55144, United States. Electronic address: jlbutenhoff@mmm.com.
Chang
Shu-Ching
SC
3M Company, Medical Department, 3M Center 220-6W-08, St. Paul, MN 55144, United States.
Ehresman
David J
DJ
3M Company, Medical Department, 3M Center 220-6W-08, St. Paul, MN 55144, United States.
York
Raymond G
RG
Charles River Preclinical Services, Horsham, PA 13104, United States; RG York and Associates, LLC 7598 Ashlind Circle, Manlius, New York 13104, United States.
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical; D004435:Eating / Q000187:drug effects; D004785:Environmental Pollutants / Q000633:toxicity*; D005260:Female; D005465:Fluorocarbon Polymers / Q000633:toxicity*; D017408:Guidelines as Topic; D007774:Lactation / Q000187:drug effects; D008099:Liver / Q000187:drug effects / Q000473:pathology; D008297:Male; D009929:Organ Size / Q000187:drug effects; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D012098:Reproduction / Q000187:drug effects*; D013961:Thyroid Gland / Q000187:drug effects / Q000473:pathology; D018675:Toxicity Tests
D004785:Environmental Pollutants; D005465:Fluorocarbon Polymers; C040402:perfluorosulfonic acid