2,2,3,3,5,5,6,6-octafluoro-4-(trifluoromethyl)morpholine

Endpoint summary

Additional information

Perfluoromethylmorpholine (PMM) is the most water soluble member of the Perfluorinated Organic Chemicals, C5-C18 category. Because these substances exhibit similarity in their physicochemical properties and toxicological properties in mammals, and because available data indicates that parent molecules are not reactive toward biological molecules and cannot undergo bioactivation by normal enzymatic processes, they can be considered members of a chemical category.

Recent, high-quality studies are available for toxicity to aquatic invertebrates of PMM and several other category members (perfluoroheptanes [PFHp], perfluorotributyl amines [PTBA], perfluorotripropyl amines [PTPA], and perfluoro-N-C1,3-alkyl morpholines [FC-770]). Loading rates were approximately 1000 mg/L except in the case of FC-770, which had a loading rate of 100 mg/L. In all cases, no toxicity was observed at the limit of solubility. Measured maximum achievable test concentrations ranged from 1.74 µg/L (PTBA) to 408 µg/L (PMM). In addition to the aquatic invertebrate tests noted above, PFHp and perfluoro-C6,8-furans, pyrans and acyclic ethers (FC-77) were not toxic to D. magna in limit tests conducted at loading rates of 1000 mg/L and 1500 mg/L, respectively (no analytical determination of concentrations). This lack of acute aquatic invertebrate toxicity across members of the category provides additional support for use of readacross to fill data gaps for other toxicological and ecotoxicological endpoints.

Data gaps for ecological toxicity can therefore be addressed by read-across and/or trend analysis between category members. Analytically determined concentrations for other category members are not reasonable to use for readacross because of divergent solubilities. Lack of toxicity at the limit of solubility is read across qualitatively to PMM. The solubility of PMM was determined to be 0.295 mg/L in organism-free Daphnia medium controls during the short-term toxicity test. This value is less than the measured PMM solubility in water (0.758 mg/L) and also less than the analytically determined concentrations in medium containing live daphnids. The organism-free medium solubility value is understood to be better representative of PMM solubility in natural waters, and avoids potential impacts on contamination of the analytical result by the action of living organisms. In accord with other category members, 0.295 mg/L is accepted as the basis for estimating the highest possible PMM concentration at media saturation. Category members FC-770 and FC-77 were not acutely toxic to fish. FC-770 was tested using D. rerio. After 96-hours, no toxicity was observed from a water-soluble fraction prepared at 100 mg/L. The mean measured concentration during the test was 0.096 mg/L. FC-77 was tested using P. promelas. In this case, test chambers were prepared at an initial loading rate of 1000 mg/L. Exposure concentrations were not measured, however, the test material could not be entirely dissolved and was observed in the test chambers throughout the experiment. Other category members including PMM showed no toxicity in limit tests with nominal concentrations ranging from 750 to 2700 mg/L. In algae tests, PMM and FC-770 were not toxic to P. subcapitata at measured maximum achievable test concentrations of 0.583 mg/L and 0.15 mg/L, respectively (loading rates of 1000 and 100 mg/L). PMM was not toxic to activated sludge respiration in limit tests conducted at 1000 mg/L.

A long-term study of aquatic invertebrate toxicity was conducted with category member PTBA with nominal concentrations only (no analytical determination of test substance). The study utilized a loading rate which assured that saturation of the water phase was stably maintained between media replacements, and no chronic toxicity was observed. Lack of toxicity at the limit of medium solubility is read across to PMM, and serves as the basis for PNEC calculations. We have proposed adaptation (waiving) of the long-term fish data requirement based on exposure considerations. No toxicity attributable to the test substance was observed in any of the available studies. This substance is not classified and therefore an exposure assessment is not required. However, for purposes of evaluating the need for chronic testing, aquatic PNECs were defined and exposure modeling was performed. PECs estimated for the freshwater and marine compartments are well below the PNECs, and RCRs are <1 (RCRs for the freshwater and marine water aquatic compartments are 6.68E-04 and 1.18E-03, respectively). Also, the PEC/water solubility ratios, 5.2E-06 and 4.6E-07, are considerably less than 1% of the water solubility limit of PMM. Further, based on use patterns, vapor pressure, water solubility, and Henry's Law constant, PMM would not be expected to attain significant concentrations in the aquatic compartment. Long-term testing of fish would provide no useful information.

Please see IUCLID section 13 for a matrix of aquatic toxicity data for members of the Perfluorinated Organic Chemicals C5-C18 category.