reaction mass of 2,2,3,3,5,5,6,6-octafluoro-4-(1,1,1,2,3,3,3-heptafluoropropan-2-yl)morpholine and 2,2,3,3,5,5,6,6-octafluoro-4-(heptafluoropropyl)morpholine

Endpoint summary

Description of key information

Two toxicokinetic studies have been conducted on FC-770 via oral gavage. The result of the studies are:

No quantifiable levels of FC-770, its isomers, ring-opened isomeric forms of the parent study compound, or other fluorochemical metabolite species of any kind derived from FC-770 were identified in serum, liver, or urine samples of FC-770-treated rats. The results of the studies indicate that FC-770 is not likely to be absorbed into the blood, does not undergo metabolic biotransformation, and has a very low potential to bioaccumulate in rats.

Additional information

The study was conducted to evaluate the serum uptake, liver distribution, and excretion profile of the test article. The study was no conducted under GLP conditions and the test method was based on an internal protocol. The test article (unchanged) was dosed via oral gavage to non-fasted male rats (3 doses) at 100, 300, or 1000 mg/kg body weight. Milli-Q water was dosed to negative control rats. Interim urine and feces were collected from 0-12 hours, 12-24 hours, and 24-48 hours post-dose from all animals. At 48 hours post-dose, all animals were euthanized via CO2 asphyxiation followed by gross necropsy. Blood (processed to serum) and liver were harvested during necropsy. Urine samples obtained from the 1000 mg/kg dose group were analyzed for potential test article metabolites. All animals appeared normal during the study and they all survived until the scheduled necropsy. There were no treatment-related findings or gross lesions noted in any animals. The test article was not quantifiable in either serum or liver samples at 48 hours post-dose; and the test article was not quantifiable in the urine samples collected throughout the study. No test article parent compound or its isomers, no ring-opened isomeric forms of the parent study compound, and no other fluorochemical metabolite species of any kind derived from the test article mixture are detected in the urine samples. The test article was quantifiable in most of the fecal samples collected and the overall test article recovery in the feces ranged from 19 -27%. Since the test article is highly volatile, in conjuncture with the fact that the fecal samples were left at room temperature for an extended period of time during collection (12 -24 hours), the low recovery in the feces likely reflects evaporative loss. Based on the results of the study, given that only fecal samples had quantifiable test article present after oral administration, these data suggest that the test article was not likely to be absorbed into the blood, does not undergo metabolic biotransformation, and has a very low potential to bioaccumulate in rats.

The potential serum uptake and elimination of the test article was evaluated in jugular-cannulated rats after a single oral dose. The study was not conducted under GLP conditions and the test method was based on an internal protocol. The test article was administered unchanged (no vehicle) to three fasted male rats at 1000 mg/kg body weight. Each animal was observed immediately following dosing and throughout the study for mortality and morbidity; body weights were recorded prior to treatment and necropsy. Interim blood samples (processed to serum) were collected via jugular vein at pre-dose, 0.25, 0.5, 1, 2, 4, 8, and 24 hours post-dose from all animals. At 24 hours post-dose, all animals were euthanized via CO2 asphyxiation followed by gross necropsies and terminal blood (processed to serum) and liver were harvested during necropsy. All animals appeared normal during the study and survived until the scheduled necropsy. No quantifiable levels of the test article were identified in the serum or liver tissue of test article-treated rats, indicating that the test article was not absorbed and therefore unlikely to bioaccumulate in rats.

The results of the studies indicate that FC-770 is not likely to be absorbed into the blood, does not undergo metabolic biotransformation, and has a very low potential to bioaccumulate in rats.