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Description of key information

An acute oral toxicity study has been conducted on Perfluoro-N-methylmorpholine, an acute oral study has been conducted on Fluorinert Category member perfluorotripropylamine, an acute inhalation toxicity study and an acute oral toxicity study have been conducted on Fluoroinert Category member FC-770, an acute oral study was conducted on Fluoroinert Category member perfluorohexane, an acute oral study was conducted on Fluoroinert Category member perfluoroheptane and five acute studies have been conducted on Fluoroinert Category member perfluorotributylamine. Classification for category members is based on experimental results for certain members of the class.  Since one of the defining characteristics of the class is a lack of biological effects based on chemical and electronic properties, the results from tests (mammalian toxicity, environmental and ecotoxicity) are applicable to all members of the category.  
Perfluoro-N-methylmorpholine results:
Oral LD50>5000 mg/kg
Perfluorotripropylamine results:
Oral LD50>5000 mg/kg
FC-770 results:
Inhalation 4 hour LC50>20 mg/l
Acute Oral LD50>5000 mg/kg
Perfluorohexane result
Oral LD50>5 g/kg
Perfluoroheptane result
Oral LD50>5000 mg/kg
Perfluorotributylamine results:
Oral LD50> 5000 mg/kg
Oral LD50>10000 mg/kg
Inhalation LC50>41 mg/l
Inhalation LC50>17 mg/l
IP LD50>34.6 g/kg
The studies on Fluoroinert Category members are considered to be applicable to perfluoro-N-methylmorpholine.

Key value for chemical safety assessment

Additional information

Perfluoro-N-methylmorpholine results

The acute oral toxicity of the test article was evaluated in male and female Hsd: Sprague Dawley SD rats when administered as a single oral gavage dose at a level of 5.0 g/kg of body weight (2.98 mL/kg body weight dose volume). Clinical observations and mortality checks were conducted at approximately 1, 2.5, and 4 hours after test material administration. Additional clinical observations and twice daily mortality checks (a.m. and p.m.) were conducted daily thereafter for 14 days. Body weights were determined before test material administration (Day 0), at Day 7, and at termination of the experimental phase (Day 14). At termination of the experimental phase, all animals were euthanized, subjected to gross necropsy examination. All animals appeared normal throughout the study with the exception of two male animals which exhibited soft stool on the day of treatment. All animals exhibited body weight gain throughout the study. The estimated oral LD50 for male and females was determined to be greater that 5000 mg/kg body weight.

Perfluorotripropylamine results

The acute oral toxicity of Perfluorotripropylamine (FC-3283) in albino rats was assessed using OECD 401 guidelines. Young animals were treated with 5000 mg/kg bodyweight of the undiluted test article via oral gavage. Mortality, clinical observations, body weight and gross pathology was observed. There was no mortality and bodyweights and clinical observations were normal during the study. In one female animal, an increased size of mandibular lymph nodes was observed. Those effects were considered not related to the treatment of the test article. The estimated oral LD50 for male and female albino rats is greater than 5000 mg/kg of body weight.

FC-770 Results

In the FC-770 acute inhalation study, animals were exposed to 20.6 mg/l for four hours. No mortality occurred and no clinical signs were noted. Macroscopic evaluation did not show any abnormalities and body weight gain was normal.

The acute oral toxicity of FC-770 (liquid, batch 142072-43) was assessed in female 9 week old Wistar rats following OECD guideline No. 423 (2001), “Acute Toxicity-Oral, Acute Toxic Class Method.” Five animals were given a single undiluted oral gavage dose of 2000 mg/kg body weight. One additional animal was inadvertently dosed at 1875 mg/kg body weight. The results from this inadvertent dose were consistent with the 2000 mg/kg dose group and for the purposes of this study that animal was considered as receiving the 2000 mg/kg dose. Animals were observed daily for 15 days. Body weights were recorded on day 1, 8 and 15. A necropsy was performed on day 15. Hunched posture and piloerection were observed on day 1 after dose administration. There were no abnormalities in remaining clinical observations, body weight and macroscopic post mortem examination. The oral LD50 of FC-770 in Wistar rats was >2000 mg/kg body weight. According to the OECD 423 test guideline the LD50 cut-off value was considered to exceed 5000 mg/kg body weight.

Perfluoroheptane Result

An acute oral toxicity screen with perfluoroheptane was conducted using male and female albino rats. Animals were given a single dose (5000 mg/kg body weight) of the test article via oral gavage. The animals were observed for 14 days after dosing and mortality, behavioral abnormalities were observed throughout out the study. The animals were necropsied after euthanasia and examined for visible lesions. No mortality or other abnormalities were observed during the study. The approximate acute oral LD50 of perfluoroheptane is greater than 5000 mg/kg in fasted male and female albino rats.

Perfluorohexane Result

An acute oral toxicity study was conducted according to OECD guideline 420. 5 male and 5 female acclimated albino rats were selected and maintained during the study in the same manner. Each test animal was administered an individual dose of the undiluted test article based upon its fasted body weight and administered by gavage. The test material was administered at a dose of 5.0 g/kg of body weight. Clinical signs and mortality checks were conducted at 1, 2.5, and 4 hours after test material administration. The animals were observed daily thereafter for 14 days for clinical signs and twice a day (morning and afternoon) for mortality. body weights were determined before test material administration (Day 0), at Day 7, and at termination of the experimental phase (Day 14). All animals appeared clinically normal throughout the study after administration of the test article. Gross necropsy of all animals revealed no visible lesions or abnormalities. All animals exhibited normal weight gain throughout the study. The estimated oral LD50 for perfluorohexane for males and females was determined to be greater than 5.0 g/kg. The test article is considered practically nontoxic by oral exposure at the does administered (5.0 g/kg bw)

 

Perfluorotributylamine Results

In the first oral study, an acute oral toxicity study was conducted on the test article using rats. One group of ten albino rats (5 male 5 female) were fasted for 24 hours previous receiving the test article by oral gavage. All rats were dosed at 10 g/kg bw. Following administration the rats were allowed food and water ad libitum for a 14 day observation period after which necropsy was performed on the survivors. No mortality or abnormal pathological findings were observed. The test article has an acute oral LD50 of greater than 10 grams per kilogram body weight in rats.

In the second oral study, an acute oral toxicity screen with the test article was conducted using male and female albino rats ranging in body weight from 183 to 217 grams. The test article was administered by gastric intubation at a dosage level of 5000 mg/kg body weight with no mortalities noted. No untoward behavioral reactions occurred during the 14 day observation period and body weight gains were noted for all animals which survived the test period. Necropsies performed at termination of the study revealed no visible lesions. The approximate oral LD50 of the test article is greater than 5000 mg/kg in fasted male and female albino rats.

In the first inhalation study, fourteen health albino rats (7 male, 7 female) were exposed to a nominal concentration of the test article at 41 mg per liter of air in a 70 liter Liter Plexiglas chamber for a period of four hours. During exposure the animals were observed for mortality and pharmacotoxic signs. Upon removal from the chamber 2 males and 2 females were sacrificed. Sections of their lungs, spleen, liver and kidneys were taken and placed in 10% formalin. The lung tissues were processed for histological evaluation. The remaining ten rats were observed for a period of 2 weeks, weighed, sacrificed and grossly examined. Results show that there were no deaths in the study. Weight gains were normal. At necropsy no grossly observable lesions were noted. The lung tissues examined microscopically, were normal. The test article can be considered practically non-toxic by inhalation.

In the second inhalation study, an acute inhalation study was conducted on the test article utilizing albino rats, guinea pigs, and Swiss white mice. All animals were acclimated for seven days and were not fasted prior to exposure to the test article. Five groups of two rats each, five groups of two mice each and five groups of two guinea pigs each were employed in the study. The inhalation exposures were conducted in a multiple inhalation chamber designed for simultaneous exposure to atmospheres saturated and fractionally saturated with vapors of the test material at room temperature (26 degrees C). Each test was designed to run for four hours. At the end of the exposure periods, surviving animals were returned to their stock cages and observed for the succeeding 14 days. No untoward reactions were noted in any of the animals species tested at the vapor concentration employed (17.0 mg/L) as a result of a four hour inhalation exposure of the test article.

In the intraperitoneal study, undiluted test article was administered by injection into the peritoneal cavity to three groups consisting of four albino rats (2 male, 2 female) each. The dose groups were 15.4, 23.1, and 34.6 grams per kilogram body weight. The rats were observed for pharmacotoxic signs, weight gains and mortality. Results show that the test article elicited abnormal stance, hypoactivity, and muscular weakness at all doses within 2 hours of compound administration. Ruffled fur was also observed at the high dose level. There were no deaths in the study. Weight gains were normal. No lesions were observed at necropsy. The test article can be considered practically non-toxic by intraperitoneal injection.

Since one of the defining characteristics of the class is a lack of biological effects based on chemical and electronic properties, the results from tests (mammalian toxicity, environmental and ecotoxicity) are applicable to all members of the category. Please see IUCLID section 13 for the category justification and a matrix of acute toxicity data for members of the Perfluorinated Organic Chemicals C5-C18 category.

Justification for classification or non-classification

The results of the acute oral and inhalation studies do not meet the criteria for classification of perfluoro-N-methylmorpholine as toxic.