Perfluamine

Endpoint summary

Description of key information

Short Description of Key Information:

Two repeated dose studies have been conducted on perfluorotripropylamine (PTPA). 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 1,200 mg/kg/day when tested according to OECD 408.

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 repeated dose toxicity of the test article (MTDID 42916) was evaluated in male and female Wistar Rats. The study was conducted according to OECD 408, in compliance with OECD GLP regulations. Four groups of Rats (n= 10/sex) received 0 (control), 75, 300, and 1200 mg/kg bw/day MTDID 42916 in corn oil via oral gavage for 13-weeks. Two recovery groups (n= 5/sex) received 0 (control) or 1200mg/kg bw/day MTDID 42916 in corn oil via oral gavage for 13-weeks, after which they were kept untreated for another 4-weeks. There was no mortality and there were no test substance-related clinical signs of toxicity. Neurobehavioral observations and motor activity assessment did not indicate any neurotoxic potential of MTDID 42916. Ophthalmoscopic examination did not reveal any treatment-related ocular changes. There were no relevant changes in body weights, food intake or water intake. Urinalysis was conducted in week 12 of the study and did not reveal changes in urinary volume, specific gravity, or semi-quantitative (dipstick) urinary measurements. Hematology, clinical chemistry, macroscopic examination, and microscopic examination were conducted in all rats at necropsy at the end of treatment and the recovery period. The following organs were weighed (paired organs together) as soon as possible after dissection: adrenals, brain, epididymides, heart, kidneys, ovaries, prostrate, seminal vesicles, spleen, testes, thymus, thyroid, and uterus. For histopathological examination, the following tissues and organs of all animals were preserved: adrenals, aorta, axillary lymph nodes, brain, cecum, colon, duodenum, epididymides, esophagus, exorbital lachrymal glands, eyes, femur with joint, gut associated lymphoid tissue (GALT), heart, ileum, jejunum, kidneys, liver, lungs, mammary glands (females), mandibular lymph nodes, mesenteric lymph nodes, nerve-peripheral (sciatic), nose including incisor teeth, molars in upper jaw, ovaries, oviducts, pancreas, parathyroid, parotid salivary glands, pituitary, prostate, rectum, seminal vesicles + coagulating glands, skeletal muscle (thigh), skin (flank), spinal cord, spleen, sternum with bone marrow, stomach, sublingual salivary glands, submaxillary salivary glands, testes, thymus, thyroid, trachea/bronchi, urinary bladder, uterus (with cervix), vagina, and all gross lesions. Hematology indicated that no treatment-related changes occurred in red blood cells, coagulation parameters, and differential white blood cell counts. Clinical chemistry revealed that at the end of the treatment period glucose was lower in males of the mid- and high-dose groups than in controls. These clinical chemistry findings were not considered adverse. Macroscopic examination did not reveal any treatment-related abnormalities. Microscopic examination at the end of the treatment period showed treatment-related changes in the liver of male rats. Minimal centrilobular hepatocellular hypertrophy was observed in 9/10 low-dose males, 9/10 mid-dose males, and 10/10 high dose males, whereas none of the control males showed this microscopic change. Additionally, hepatocellular vacuolation was increased in males of all dose groups (incidence: 1/10 controls, 8/10 low-dose males, 6/10 mid-dose males, and 5/10 high-dose males). None of the female rats showed centrilobular hepatocellular hypertrophy or hepatocellular vacuolation. These hepatic changes were considered to be non-adverse. Additionally, microscopic examination of nose level 1 showed granulocytic inflammation, epithelial hyperplasia, and erosion in treatment groups as well as in controls. These lesions were ascribed to be specific to the gavage procedure rather than a direct or indirect nasal tissue reaction to the test substance. The remaining microscopic findings were considered unremarkable and part of the background pathology of rats of this strain and age. Under the conditions of this study, the no-observed-adverse-effect level (NOAEL) of MTDID 42916 was considered to be 1200 mg/kg bw/day, due to the lack of any test substance-specific adverse findings.  

Repeated dose studies conducted on structural analogs indicate that the repeated dose toxicity profile is similar across the chemical category.

Justification for classification or non-classification

The results of these tests do not meet the requirement to classify perfluorotripropylamine as dangerous.