Evaluation of the Reproductive and Developmental Toxicity of a Fluoroalkylethanol Mixture

Abstract

The objective of these studies was to evaluate the reproductive and developmental toxicity of a commercial fluoroalkylethanol mixture, which is an intermediate in the production of fluorotelomers. The test substance was administered daily by gavage to Sprague–Dawley rats as a suspension in 0.5% aqueous methylcellulose. In a one-generation reproductive toxicity study, rats (20 per sex per group) were given dosages of 0, 25, 100, or 250 mg kg^{− 1} day^{− 1} for a period of 74 days prior to cohabitation, and during mating, gestation, and lactation. Body weights, feed consumption, clinical signs, gross pathology, sperm parameters, estrous cyclicity, and reproductive performance were evaluated for the P₁ generation. The F₁ offspring were evaluated during the lactation period for growth and survival and given a gross pathology examination at weaning. A subset of the offspring were retained; body weights, feed consumption, clinical signs, and age at onset of vaginal opening and preputial separation were evaluated, and gross pathology was performed on postnatal day 60. In the developmental toxicity study, groups of time-mated Sprague–Dawley female rats were given the test substance as a suspension in 0.5% aqueous methylcellulose at daily dosages of 0, 50, 200, or 500 mg kg^{− 1} day^{− 1} by gavage on gestation days 6–20. During the in-life portion of the study, growth parameters and clinical observations were made. On gestation day 21, dams were euthanized, and the thoracic and abdominal viscera were examined. The uterine contents were removed and examined, and fetuses were evaluated for any alterations. In the reproduction study, litter size at birth, number of live pups per litter on day 0 and 4 of lactation, and pup weights during lactation were reduced in groups administered ≥ 100 mg kg^{− 1} day^{− 1}. No other reproductive parameters were affected. There were no adverse reproductive effects observed at 25 mg kg^{− 1} day^{− 1}. In the developmental toxicity study, reduced maternal body weight parameters, increased perineal fur staining, and increased fetal skeletal alterations were observed at 500 mg kg^{− 1} day^{− 1}. There was no maternal or developmental toxicity at 50 or 200 mg kg^{− 1} day^{− 1}. Under the conditions of the studies, the no-observed adverse effect levels for this mixture were 25 mg kg^{− 1} day^{− 1} for subchronic toxicity and reproductive parameters and 200 mg kg^{− 1} day^{− 1} for developmental toxicity end points. No functional reproductive or developmental effects were observed at dose levels that did not adversely affect adult animals.

Key Words: :

• Reproductive toxicity
• Developmental toxicity
• Fluoroalkylethanol
• Fluorotelomer