Evaluation of the reproductive and developmental toxicity of 6:2 fluorotelomer alcohol in rats

Abstract

6:2 Fluorotelomer alcohol (6:2 FTOH) was evaluated for potential developmental and reproductive toxicity. 6:2 FTOH was administered by oral gavage to Sprague-Dawley rats as a suspension in 0.5% aqueous methylcellulose at dosages of 5, 25, 125, or 250 mg/kg/day. The developmental toxicity study was performed in accordance with the Organization for Economic Development (OECD) Test Guideline 414, and the one-generation reproductive toxicity study was performed in accordance with the OECD Test Guideline 415. For the developmental toxicity study, adverse maternal toxicity observed at 250 mg/kg/day included reductions in body weight parameters and food consumption. Evidence of developmental toxicity was limited to increases in skeletal variations (ossification delays in the skull and rib alterations) at 250 mg/kg/day. There were no adverse maternal or developmental effects observed at 5, 25, or 125 mg/kg/day and there were no effects on reproductive outcome or quantitative litter data at any dose level. For the one-generation reproduction toxicity study, systemic parental and developmental toxicity were observed at 125 and 250 mg/kg/day. At 250 mg/kg/day, there was increased mortality among male and female parental rats, effects on body weight parameters, food consumption, and clinical signs, and there were effects on offspring survival indices and body weights. At 125 mg/kg/day, there was an increase in mortality in parental males only, and parental toxicity was limited to effects on body weight gain, food consumption (lactation), and clinical signs. Uterine weights were decreased at 125 and 250 mg/kg/day, although there were no corroborative histopathological changes. At 125 mg/kg/day, pup mortality was increased on lactation day 1, and body weights of the offspring were decreased during the second half of lactation. There was no evidence of either parental or developmental toxicity at 5 or 25mg/kg/day, and there were no effects on reproductive outcome at any dose level. Based on these data, 6:2 FTOH is not a selective reproductive or developmental toxicant at dosages that induce clear maternal/parental toxicity. Therefore, 6:2 FTOH would not be classified for reproductive/developmental toxicity under the United Nations' Globally Harmonized System of Classification and Labeling of Chemicals.

Keywords: 6:2 fluorotelomer alcohol; Developmental toxicity; Reproductive toxicity.