Perfluamine

Endpoint summary

Key value for chemical safety assessment

Effects on fertility

Description of key information

Two studies investigating the reproductive or developmental toxicity potential of perfluoropropylamine (PTPA) have been conducted. The results of the studies are:

The No Observed Adverse Effect Level (NOAEL) is 1,000 mg/kg/day when tested according to OECD 421.

The No Observed Adverse Effect Level (NOAEL) is 1,000 mg/kg/day when tested according to OECD 414.

Additional information

Discussion:

The reproductive/developmental and repeated dose toxicity of the test article was evaluated in male and female Wistar Han rats.  The study was conducted according to OECD 421 in compliance with OECD GLP regulations.  Rats (10/sex/dose) were dosed with 0 (control), 100, 300, or 1000 mg/kg/day via oral gavage for a minimum of 28 days.  The following parameters and end points were evaluated in this study: mortality/moribundity, clinical signs, body weight and food consumption, estrous cycle determination, measurement of thyroid hormone T4 (F0-males), gross necropsy findings, organ weights and histopathologic examinations.  In addition, the following reproduction/developmental parameters were determined: mating and fertility indices, precoital time, number of implantation sites, gestation index and duration, parturition, maternal care, sex ratio and early postnatal pup development, mortality, clinical signs, body weights, sex, anogenital distance, areola/nipple retention and macroscopy, measurement of thyroid hormone T4 (PND 14-16 pups)).  Due to a dosing error occurring during the pre-mating period of the study, the animals of low and mid dose groups had received at least five 5 times less than intended. The results of these two groups were, therefore, excluded from interpretation. No parental toxicity was observed at the highest dose tested (1000 mg/kg/day).  No adverse treatment-related changes were noted in any of the parameters investigated in this study (clinical appearance, body weight, food consumption, T4 thyroid hormone levels (in males only), macroscopic examination, organ weights, and microscopic examination.  No treatment-related changes were noted in any of the reproductive parameters investigated (mating and fertility indices, precoital time, number of implantations, estrous cycle, spermatogenic profiling, and histopathological examination of reproductive organs).  No treatment-related changes were noted in any of the developmental parameters investigated in this study (gestation, viability and lactation indices, duration of gestation, parturition, sex ratio, maternal care and early postnatal pup development consisting of mortality, clinical signs, body weight, anogenital distance, areola/nipple retention, T4 thyroid hormone levels and macroscopic examination).  Based on the results of the study, the parental and reproductive/developmental No Observed Adverse Effect Level (NOAEL) is 1000 mg/kg/day.

 

The prenatal developmental toxicity potential of the test article was evaluated in female Wistar Han rats. The study was conducted according to OECD 414 in compliance with OECD GLP regulations. Time-mated female rats (22/dose) were exposed from Day 6 to Day 20 post-coitum, inclusive, via oral gavage to 0 (control), 100, 300, or 1000 mg/kg/day test article. The following parameters and end points were evaluated in this study for the F0-generation: mortality/moribundity, clinical signs, body weights, food consumption, thyroid hormone levels (T3, T4, TSH), gross necropsy findings, number of corpora lutea, organ weights ((gravid) uterus and thyroid gland), uterine contents and histopathologic examination (thyroid gland). In addition, the following parameters were determined for the F1-generation: the number of live and dead fetuses, early and late resorptions, total implantations, fetal body weights, sex ratio, ano-genital distance, external, visceral and skeletal malformations and developmental variations. No maternal toxicity was observed in any dose group. No developmental toxicity was observed in any dose group. Based on the results of the study, the prenatal developmental No Observed Adverse Effect Level (NOAEL) is 1000 mg/kg/day.

 Reproductive and developmental studies conducted on structural analogs indicate that the repro/dev profile is similar across the chemical category.

 

Effects on developmental toxicity

Description of key information

Two studies investigating the reproductive or developmental toxicity potential of perfluoropropylamine (PTPA) have been conducted. The results of the studies are:

The No Observed Adverse Effect Level (NOAEL) is 1,000 mg/kg/day when tested according to OECD 421.

The No Observed Adverse Effect Level (NOAEL) is 1,000 mg/kg/day when tested according to OECD 414.

Additional information

Discussion:

The reproductive/developmental and repeated dose toxicity of the test article was evaluated in male and female Wistar Han rats.  The study was conducted according to OECD 421 in compliance with OECD GLP regulations.  Rats (10/sex/dose) were dosed with 0 (control), 100, 300, or 1000 mg/kg/day via oral gavage for a minimum of 28 days.  The following parameters and end points were evaluated in this study: mortality/moribundity, clinical signs, body weight and food consumption, estrous cycle determination, measurement of thyroid hormone T4 (F0-males), gross necropsy findings, organ weights and histopathologic examinations.  In addition, the following reproduction/developmental parameters were determined: mating and fertility indices, precoital time, number of implantation sites, gestation index and duration, parturition, maternal care, sex ratio and early postnatal pup development, mortality, clinical signs, body weights, sex, anogenital distance, areola/nipple retention and macroscopy, measurement of thyroid hormone T4 (PND 14-16 pups)).  Due to a dosing error occurring during the pre-mating period of the study, the animals of low and mid dose groups had received at least five 5 times less than intended. The results of these two groups were, therefore, excluded from interpretation. No parental toxicity was observed at the highest dose tested (1000 mg/kg/day).  No adverse treatment-related changes were noted in any of the parameters investigated in this study (clinical appearance, body weight, food consumption, T4 thyroid hormone levels (in males only), macroscopic examination, organ weights, and microscopic examination.  No treatment-related changes were noted in any of the reproductive parameters investigated (mating and fertility indices, precoital time, number of implantations, estrous cycle, spermatogenic profiling, and histopathological examination of reproductive organs).  No treatment-related changes were noted in any of the developmental parameters investigated in this study (gestation, viability and lactation indices, duration of gestation, parturition, sex ratio, maternal care and early postnatal pup development consisting of mortality, clinical signs, body weight, anogenital distance, areola/nipple retention, T4 thyroid hormone levels and macroscopic examination).  Based on the results of the study, the parental and reproductive/developmental No Observed Adverse Effect Level (NOAEL) is 1000 mg/kg/day.

 

The prenatal developmental toxicity potential of the test article was evaluated in female Wistar Han rats. The study was conducted according to OECD 414 in compliance with OECD GLP regulations. Time-mated female rats (22/dose) were exposed from Day 6 to Day 20 post-coitum, inclusive, via oral gavage to 0 (control), 100, 300, or 1000 mg/kg/day test article. The following parameters and end points were evaluated in this study for the F0-generation: mortality/moribundity, clinical signs, body weights, food consumption, thyroid hormone levels (T3, T4, TSH), gross necropsy findings, number of corpora lutea, organ weights ((gravid) uterus and thyroid gland), uterine contents and histopathologic examination (thyroid gland). In addition, the following parameters were determined for the F1-generation: the number of live and dead fetuses, early and late resorptions, total implantations, fetal body weights, sex ratio, ano-genital distance, external, visceral and skeletal malformations and developmental variations. No maternal toxicity was observed in any dose group. No developmental toxicity was observed in any dose group. Based on the results of the study, the prenatal developmental No Observed Adverse Effect Level (NOAEL) is 1000 mg/kg/day.

 Reproductive and developmental studies conducted on structural analogs indicate that the repro/dev profile is similar across the chemical category.

 

Justification for classification or non-classification

The results of these studies indicate that perfluorotripropylamine (PTPA) does not meet the requirements to be classified for reproductive or developmental toxicity.