Potassium 1,1,2,2,3,3,4,4,4-nonafluorobutane-1-sulphonate

Endpoint summary

Key value for chemical safety assessment

Effects on fertility

Description of key information

A two-generation reproductive and developmental toxicity study (US EPA OPPTS 870.3800 and US EPA TSCA 799.9380) was conducted on PFBSK+. The results of the study was:

 

A reproductive No Observed Adverse Effect Level (NOAEL) of 1,000 mg/kg/day, was determined when tested according to US EPA OPPTS 870.3800 and US EPA TSCA 799.9380. 

Additional information

The reproductive and developmental toxicity of T-7485 was evaluated in Sprague Dawley rats in a 2-generation study. This study was performed in compliance with OECD GLP (1997) and US EPA GLP 40 CFR 160 and 792. The study design was based on US EPA OPPTS 870.3800 (1998), and US EPA TSCA Test Guideline 799.9380 (1997). The test material was prepared in 0.1% carboxymethylcellulose in deionized water (vehicle). P generation rats (30/sex/dose) received 0 (vehicle), 30, 100, 300, or 1000 mg/kg/day of T-7485 via oral gavage at a dose volume of 10 mL/kg beginning at approximately 6 weeks of age (at least 70 days before cohabitation) and continuing until the day before sacrifice (males: after completion of cohabitation period; females: DL 22). All F1 pups were weaned on DL 22 and were randomly selected for continued evaluation. F1 pups (30/sex/dose) received 0 (vehicle), 30, 100, 300, or 1000 mg/kg/day of T-7485 via oral gavage beginning at weaning (approximately 70 days before cohabitation) and continuing until the day before sacrifice (males: after completion of cohabitation period; females: DL 22). 

Parameters evaluated in P and F1 generations: clinical observations (daily), body weights and food consumption (males: weekly; females: weekly; DGs 0, 7, 10, 14, 18, 21, and 25; and DLs 1, 5, 8, 11, 15, and 22), estrous cycling, duration of gestation, fertility index, gestation index, number and sex of offspring per litter, number of implantation sites, general condition of dam and litter during postpartum period, litter size and viability, viability indices, lactation index, percent survival, sex ratio, maternal behavior, gross necropsy, sperm count and motility, organ weights of select organs, and histopathology of select organs and tissues. F1 females and males were also evaluated for age of vaginal patency and age of preputial separation, respectively. Parameters evaluated in F2 generation: number and sex of pups, stillbirths, live births, pup body weights, and gross external alterations.

P generation: One male treated at 1000 mg/kg/day was found dead on Day 55 as a result of an intubation accident. All other P generation animals survived until scheduled termination. Males treated at 1000 mg/kg/day exhibited significant increases in the incidences of excess salivation, perioral substance, chromorhinorrea, and urine-stained abdominal fur. One or two males treated at 300 mg/kg/day exhibited excess salivation and perioral substance that were considered treatment-related. Females treated at 1000 mg/kg/day exhibited a significant increase in the incidence of dried or wet red perioral substance and excess salivation during precohabitation and gestation. At 1000 mg/kg/day, male body weight gains were significantly reduced on Days 43 to 50 and 50 to 57, and significant body weight loss occurred on Days 105 to 112. Body weights and body weight gains of females during precohabitation, gestation, and lactation were unaffected by T-7485 doses as high as 300 mg/kg/day. Terminal body weights of males and females were unaffected by test article administration. There were no abnormal changes in absolute or relative food consumption values. All mating and fertility parameters were unaffected by T-7485 doses as high as 300 mg/kg/day in females and 1000 mg/kg/day in males. The average numbers of estrous stages per 21 days for F1 females were comparable among the dosage groups. There were no test article-related gross necropsy findings in males or females. Absolute and relative liver weights were significantly increased in males treated at 300 or 1000 mg/kg/day. Absolute brain weight was significantly reduced in 1000 mg/kg/day-treated females. Treatment-related microscopic changes were observed in the liver of males treated at 300 or 1000 mg/kg/day and in the kidneys of males and females treated at 300 or 1000 mg/kg/day. No test article-related microscopic changes were observed in the reproductive organs of males and females treated at 1000 mg/kg/day. Sperm parameters in males were unaffected by test material administration. Natural delivery observations were unaffected by test article administration. Terminal body weights of F1 pups were comparable among the dose groups. There were no test article-related clinical or necropsy observations in F1 pups at any dose. 

F1 generation: All F1 animals survived. Animals treated at 1000 mg/kg/day exhibited a significant increase in the incidence of excess salivation. There were no abnormal body weights and body weight gains for F1 females. Body weight gains for F1 males treated at 1000 mg/kg/day were significantly reduced for the entire precohabitation period and on the day cohabitation started. There were no abnormal changes in absolute or relative food consumption values. Preputial separation of F1males was slightly delayed (approximately 2 days later than control group value) in the 1000 mg/kg/day dose group. This observation was considered to be associated with the significantly reduced body weights at the time of sexual maturation. The age of vaginal patency and average numbers of estrous stages per 21 days for F1 females were comparable among the dosage groups. All female and male mating and fertility parameters were unaffected by test article administration. All necropsy observations were considered unrelated to test article administration. Terminal body weights and absolute weights of the seminal vesicles (with and without fluid) of F1 males were significantly reduced in the 1000 mg/kg/day dose group. Terminal body weights were significantly increased in F1 females treated at any T-7485 dose. Relative liver weights were increased in F1 males treated at 1000 mg/kg/day. Microscopic examination of the liver of F1 males and the kidneys of F1 males and females revealed test article-related effects similar to those in P males and females. No test article-related microscopic changes were observed in the reproductive organs of F1 males and females treated at 1000 mg/kg/day. Sperm parameters in F1 males were unaffected by test material administration. Natural delivery observations were unaffected by test material administration. The number of surviving pups per litter, the percentage of male pups, litter size, and average pup body weight per litter were comparable among the dose groups. There were no test article-related clinical or necropsy observations in F2 pups at any dose. No test article-related differences in F2 pup absolute and relative organ weights or terminal body weights among the dose groups.

 

Based on the results of this study, no male or female reproductive toxicity was observed in P or F1 generation rats following ingestion of T-7485 at up to 1000 mg/kg/day. The reproductive NOAEL is 1000 mg/kg/day. Developmental toxicity at 1000 mg/kg/day cannot be evaluated due to presence of maternal and paternal toxicity. The NOAEL for developmental effects is 300 mg/kg/day.

Effects on developmental toxicity

Description of key information

A two-generation reproductive and developmental toxicity study (US EPA OPPTS 870.3800 and US EPA TSCA 799.9380) and developmental toxicity study (OECD 414) were conducted on PFBSK+. The results of the studies were:

 

Developmental toxicity at 1000 mg/kg/day cannot be evaluated due to presence of maternal and paternal toxicity. The NOAEL for developmental effects is 300 mg/kg/day. When tested according to US EPA OPPTS 870.3800 and US EPA TSCA 799.9380

 

Developmental toxicity at 1000 mg/kg/day cannot be evaluated due to presence of maternal toxicity (significant decrease in maternal body weight gain at 1000 mg/kg/day). The No Observed Adverse Effect Level (NOAEL) for developmental effects is 300 mg/kg/day when tested according to OECD 414.

Additional information

The reproductive and developmental toxicity of T-7485 was evaluated in Sprague Dawley rats in a 2-generation study. This study was performed in compliance with OECD GLP (1997) and US EPA GLP 40 CFR 160 and 792. The study design was based on US EPA OPPTS 870.3800 (1998), and US EPA TSCA Test Guideline 799.9380 (1997). The test material was prepared in 0.1% carboxymethylcellulose in deionized water (vehicle). P generation rats (30/sex/dose) received 0 (vehicle), 30, 100, 300, or 1000 mg/kg/day of T-7485 via oral gavage at a dose volume of 10 mL/kg beginning at approximately 6 weeks of age (at least 70 days before cohabitation) and continuing until the day before sacrifice (males: after completion of cohabitation period; females: DL 22). All F1 pups were weaned on DL 22 and were randomly selected for continued evaluation. F1 pups (30/sex/dose) received 0 (vehicle), 30, 100, 300, or 1000 mg/kg/day of T-7485 via oral gavage beginning at weaning (approximately 70 days before cohabitation) and continuing until the day before sacrifice (males: after completion of cohabitation period; females: DL 22). 

Parameters evaluated in P and F1 generations: clinical observations (daily), body weights and food consumption (males: weekly; females: weekly; DGs 0, 7, 10, 14, 18, 21, and 25; and DLs 1, 5, 8, 11, 15, and 22), estrous cycling, duration of gestation, fertility index, gestation index, number and sex of offspring per litter, number of implantation sites, general condition of dam and litter during postpartum period, litter size and viability, viability indices, lactation index, percent survival, sex ratio, maternal behavior, gross necropsy, sperm count and motility, organ weights of select organs, and histopathology of select organs and tissues. F1 females and males were also evaluated for age of vaginal patency and age of preputial separation, respectively. Parameters evaluated in F2 generation: number and sex of pups, stillbirths, live births, pup body weights, and gross external alterations.

P generation: One male treated at 1000 mg/kg/day was found dead on Day 55 as a result of an intubation accident. All other P generation animals survived until scheduled termination. Males treated at 1000 mg/kg/day exhibited significant increases in the incidences of excess salivation, perioral substance, chromorhinorrea, and urine-stained abdominal fur. One or two males treated at 300 mg/kg/day exhibited excess salivation and perioral substance that were considered treatment-related. Females treated at 1000 mg/kg/day exhibited a significant increase in the incidence of dried or wet red perioral substance and excess salivation during precohabitation and gestation. At 1000 mg/kg/day, male body weight gains were significantly reduced on Days 43 to 50 and 50 to 57, and significant body weight loss occurred on Days 105 to 112. Body weights and body weight gains of females during precohabitation, gestation, and lactation were unaffected by T-7485 doses as high as 300 mg/kg/day. Terminal body weights of males and females were unaffected by test article administration. There were no abnormal changes in absolute or relative food consumption values. All mating and fertility parameters were unaffected by T-7485 doses as high as 300 mg/kg/day in females and 1000 mg/kg/day in males. The average numbers of estrous stages per 21 days for F1 females were comparable among the dosage groups. There were no test article-related gross necropsy findings in males or females. Absolute and relative liver weights were significantly increased in males treated at 300 or 1000 mg/kg/day. Absolute brain weight was significantly reduced in 1000 mg/kg/day-treated females. Treatment-related microscopic changes were observed in the liver of males treated at 300 or 1000 mg/kg/day and in the kidneys of males and females treated at 300 or 1000 mg/kg/day. No test article-related microscopic changes were observed in the reproductive organs of males and females treated at 1000 mg/kg/day. Sperm parameters in males were unaffected by test material administration. Natural delivery observations were unaffected by test article administration. Terminal body weights of F1 pups were comparable among the dose groups. There were no test article-related clinical or necropsy observations in F1 pups at any dose. 

F1 generation: All F1 animals survived. Animals treated at 1000 mg/kg/day exhibited a significant increase in the incidence of excess salivation. There were no abnormal body weights and body weight gains for F1 females. Body weight gains for F1 males treated at 1000 mg/kg/day were significantly reduced for the entire precohabitation period and on the day cohabitation started. There were no abnormal changes in absolute or relative food consumption values. Preputial separation of F1males was slightly delayed (approximately 2 days later than control group value) in the 1000 mg/kg/day dose group. This observation was considered to be associated with the significantly reduced body weights at the time of sexual maturation. The age of vaginal patency and average numbers of estrous stages per 21 days for F1 females were comparable among the dosage groups. All female and male mating and fertility parameters were unaffected by test article administration. All necropsy observations were considered unrelated to test article administration. Terminal body weights and absolute weights of the seminal vesicles (with and without fluid) of F1 males were significantly reduced in the 1000 mg/kg/day dose group. Terminal body weights were significantly increased in F1 females treated at any T-7485 dose. Relative liver weights were increased in F1 males treated at 1000 mg/kg/day. Microscopic examination of the liver of F1 males and the kidneys of F1 males and females revealed test article-related effects similar to those in P males and females. No test article-related microscopic changes were observed in the reproductive organs of F1 males and females treated at 1000 mg/kg/day. Sperm parameters in F1 males were unaffected by test material administration. Natural delivery observations were unaffected by test material administration. The number of surviving pups per litter, the percentage of male pups, litter size, and average pup body weight per litter were comparable among the dose groups. There were no test article-related clinical or necropsy observations in F2 pups at any dose. No test article-related differences in F2 pup absolute and relative organ weights or terminal body weights among the dose groups.

 

Based on the results of this study, no male or female reproductive toxicity was observed in P or F1 generation rats following ingestion of T-7485 at up to 1000 mg/kg/day. The reproductive NOAEL is 1000 mg/kg/day. Developmental toxicity at 1000 mg/kg/day cannot be evaluated due to presence of maternal and paternal toxicity. The NOAEL for developmental effects is 300 mg/kg/day.

 

The reproductive and developmental toxicity of T-7485 was evaluated in Sprague Dawley rats. This study was performed in compliance with OECD GLP (1997), Japanese MAFF GLP Standards (1984), and US EPA GLP 40 CFR 160 and 792. The study design was based on OECD 414 (1981), US EPA OPPTS 870.3700 (1998), and US EPA TSCA Test Guideline 799.9370 (1997). The test material was prepared in 0.1% carboxymethylcellulose in deionized water (vehicle). Female rats were placed into cohabitation with male rats at a ratio of 1:1. Pregnancy was confirmed by vaginal smear and/or absence of copulatory plug (DG 0). Female rats (25/dose) received 0, 100, 300, or 1000 mg/kg/day of T-7485 via oral gavage at a dose volume of 10 mL/kg on DGs 6 through 20. Clinical observations and body weights were recorded daily. Feed consumption values were recorded on DGs 0, 6, 9, 12, 5, 18, 20, and 21. All surviving rats were euthanized on DG 21. Caesarean-section and gross necropsy was performed. The uterus of each animal was excited and examined for pregnancy, number and distribution of implantations, live and dead fetuses, and early and late resorptions. Fetuses were weighed and examined for sex, gross external alterations, soft tissue alterations, and skeletal alterations. 

 

Two females treated at 1000 mg/kg/day were found dead on DG 17 and 18, respectively. One of the deaths was attributed to an intubation accident. No cause of death was determined for the other animal, but the death was considered unrelated to test article administration because it was a single event. There were no test article-related, abnormal clinical observations. In the 1000 mg/kg/day dose group, maternal body weight gains were significantly reduced on DGs 6 to 9 and 18 to 21, and thus were also significantly reduced for the entire gestation period (DGs 0 to 21). Gravid uterine weights were slightly reduced in the 1000 mg/kg/day dose group. Food consumption values were significantly reduced in the 1000 mg/kg/day dose group. Body weights, body weight gains, gravid uterine weights, and food consumption were not affected by test article administration in the 100 and 300 mg/kg/day dose groups. Fetal body weights (total, male and female) were significantly reduced in the 1000 mg/kg/day dose group when compared to the control group value. No other litter parameters were affected by test article administration. No gross external, soft tissue, or skeletal fetal alterations were attributed to test article administration.

 

Developmental toxicity at 1000 mg/kg/day cannot be evaluated due to presence of maternal toxicity (significant decrease in maternal body weight gain at 1000 mg/kg/day). The NOAEL for developmental effects is 300 mg/kg/day.

Justification for classification or non-classification

The results of the test do not meet the requirements to classify PFBSK+ as a reproductive or developmental toxicant.