Evaluation of the reproductive and developmental toxicity of a fluoroalkylethanol mixture. 2005

Eve Mylchreest, and Gregory S Ladics, and Susan M Munley, and Robert C Buck, and Judith C Stadler
DuPont Haskell Laboratory for Health and Environmental Sciences, Newark, Delaware 19714, USA.

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 > or =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.

UI MeSH Term Description Entries
D008297 Male Males
D011247 Pregnancy The status during which female mammals carry their developing young (EMBRYOS or FETUSES) in utero before birth, beginning from FERTILIZATION to BIRTH. Gestation,Pregnancies
D011297 Prenatal Exposure Delayed Effects The consequences of exposing the FETUS in utero to certain factors, such as NUTRITION PHYSIOLOGICAL PHENOMENA; PHYSIOLOGICAL STRESS; DRUGS; RADIATION; and other physical or chemical factors. These consequences are observed later in the offspring after BIRTH. Delayed Effects, Prenatal Exposure,Late Effects, Prenatal Exposure
D012098 Reproduction The total process by which organisms produce offspring. (Stedman, 25th ed) Human Reproductive Index,Human Reproductive Indexes,Reproductive Period,Human Reproductive Indices,Index, Human Reproductive,Indexes, Human Reproductive,Indices, Human Reproductive,Period, Reproductive,Periods, Reproductive,Reproductive Index, Human,Reproductive Indices, Human,Reproductive Periods
D004305 Dose-Response Relationship, Drug The relationship between the dose of an administered drug and the response of the organism to the drug. Dose Response Relationship, Drug,Dose-Response Relationships, Drug,Drug Dose-Response Relationship,Drug Dose-Response Relationships,Relationship, Drug Dose-Response,Relationships, Drug Dose-Response
D005260 Female Females
D005865 Gestational Age The age of the conceptus, beginning from the time of FERTILIZATION. In clinical obstetrics, the gestational age is often estimated from the onset of the last MENSTRUATION which is about 2 weeks before OVULATION and fertilization. It is also estimated to begin from fertilization, estrus, coitus, or artificial insemination. Embryologic Age,Fetal Maturity, Chronologic,Chronologic Fetal Maturity,Fetal Age,Maturity, Chronologic Fetal,Age, Embryologic,Age, Fetal,Age, Gestational,Ages, Embryologic,Ages, Fetal,Ages, Gestational,Embryologic Ages,Fetal Ages,Gestational Ages
D000013 Congenital Abnormalities Malformations of organs or body parts during development in utero. Birth Defects,Congenital Defects,Deformities,Fetal Anomalies,Fetal Malformations,Abnormalities, Congenital,Defects, Congenital,Abnormality, Congenital,Anomaly, Fetal,Birth Defect,Congenital Abnormality,Congenital Defect,Defect, Birth,Defect, Congenital,Deformity,Fetal Anomaly,Fetal Malformation,Malformation, Fetal
D000284 Administration, Oral The giving of drugs, chemicals, or other substances by mouth. Drug Administration, Oral,Administration, Oral Drug,Oral Administration,Oral Drug Administration,Administrations, Oral,Administrations, Oral Drug,Drug Administrations, Oral,Oral Administrations,Oral Drug Administrations
D000431 Ethanol A clear, colorless liquid rapidly absorbed from the gastrointestinal tract and distributed throughout the body. It has bactericidal activity and is used often as a topical disinfectant. It is widely used as a solvent and preservative in pharmaceutical preparations as well as serving as the primary ingredient in ALCOHOLIC BEVERAGES. Alcohol, Ethyl,Absolute Alcohol,Grain Alcohol,Alcohol, Absolute,Alcohol, Grain,Ethyl Alcohol

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