Document LpyeogyjKv41bd8b1GDvG0415

AR226-3388 Evaluation of the Subchronic Toxicity and One-Generation Reproductive Effects of a Fluoroalkylethyl Urethane Polymer G.T. Makovec, DA. Delker, E. Mylchreest, andJ.C. Stadler The DuPont Company, Haskell Laboratory for Health and Environmental Sciences, Newark, Delaware, USA ylllJSA,bstract A fluoroaikylethyi urethane polymer, used as a carpet protectant, was evaluated for its oral subchronic toxicity and reproductive effects when administered to male and female rats by gavage at dosages ofO, 50, 250, or iOOO mg/lcg/day. No compound-related mortality occurred in the study. No adverse clinicai signs of toxicity or neurobehavior changes were observed in male or female rats in any dose group. Hepatocelkilar hypertrophy was observed after 90 days of dosing in male rats at all dose levels. Nasal olfactory epithelium degeneration/necrosis was observed in maie and female rats at all dose levels and inflammation of we olfactory epithelium in male rals dosed with 250 and 1000 me/kg/day. Thyroid hypertrophy was seen in male and female rats in the 250 and 1000 ing/kg/day dose groups. After a 90-day recovery, hepatoceilular hypertrophy was stili present in male rats in the 250 and 1000 mg/kg/day dose groups. Nasal epithelial lesions were absent and evidence of reversibility of thyroid effects was observed after the recovery period. No test substance-related effects on reproductive parameters were observed. However, mean thyroid organ weight was significantly lower in the 250 and 1000 mg/kg/day dose groups in the F, generation- There were no histopathologicaf changes in the thyroid of the F, generation rats. Due to the presence of nasal lesions, a no-observedadverse-effect-level (NOEL) could not be determined for the subchronic toxicity evaluation. For reproductive assessments a NOEL of 50 mg/kg/day was determined based on decreased thyroid weights observed in both male and female F] adults. It could not be determined whether the nasal lesions observed are due to systemic loxicity or local toxicity as a result of gavage dosing. Based on the other systemic effects observed at 250 mg/kg/day and above, the potential risk of human health effects from exposure lo tilis product is very low. fllll Results Body Weights ami Food Efficiency Males After the 90-day exposure period, weight gain and food efficiency in male rats administered 1000 ing/hg/day was approximately 33 % and 20 % lower lhan control rais, Following aone-inontit recovery period weight gain and food efficiency values were K Histopathology Mates Host: DcgciisniAoafaKlcais. olfactory tpiilielium Thyroid elanil: Eiypatiopliy. folliculur riose: DcEtiiermion/netiDSis. olfactory cpiliieliuBi Thyroid eland: Hypcrttonliy, folliculnr Alteration, colloid Livm e prcseni in nose, thyroid gland and iiver niflflirMnv mciksfflav isstks/div/ mflkg/dw 8/10(0.9)'' 10/10(1.7) 10/10(2-1) 0/10 5/10(0.5) 6fl0(a,6) 1/10(0,1) 10/10 (l.B) 10/10(1.0) NA 10/10(1,0) 5f5(1.2) 4/5(1.2) 1/4(23) 515(2.6) USI Introduction The objective of this study was to evaluate the potential subchronic and reproductive toxicity of a fluorotelomer-based urethane polymer in male and female rats. The test substance is used as a textile proiectant and was administered as formulated product that contained approximately 23% active ingredient and 1.7% hydrocarbon surfactant in water. The test material was administered by gavage, the route selected as the most efficient way to deliver an accurate dosage. In a two-week range-finding study, there was no observable systemic toxicily in rats given a limit dosage of 1000 mg active ingredient/kg body weight/day. Dosages of 50,250, and 1000 mg/kg/day were selected for this study, based on this ability of rats to tolerate the limit dosage- | Study Design ^ : Liver Weights Males After ite 90-day exposure period, absolute and relative liver weights were increased, After 1-month and 3-inonlh recovery periods, absolute and relative liver weights remained elevated in male rats administered 1000 nig/kg/day compared to controls. After the 90-day exposure period, relative liver weights were statistically increased in _tiil;/kB/dny ninAis/jay mgfl:B/day nijJkE/dav Nose: DeEcneralion/necrosi 1, olfnclotyepillieliuni Thrrold gland: Hypciliophy. follicular AllnaUon. colloid Thyroid gland; Hypctiropliy.folliculiif Alteration, colloid ThrM-MonliiRci'iivi.rT (SMi-llilf Thyroid eland: Hypotiopliy. follicular Allenuioii, colloid 2/10(0.2)'' 4/10(0,5) 8/10(1.1] NA 5/10 (0-ti) Olfactory Epithelium Micrograpliofolfiictoryepitheliuinlromcc 1000 ing/kg/day lest substance <B). id from rat administered ^Summar I Conclusi Body weights, detailed clinicaf signs, and food consiimpiion were determined weekly througtiout the SO.day exposure and I-monlh recovery periods. Gross and microscopic pailiology evaluations were pcrfonned ai the end of the 90-day Reproductive evaiuniions were peribrnKd prior to mating and during the tnalinfi, gestation. and lactation periods. Developmental landmarks and gross padulogy was also