Fluoroethylene

Endpoint summary

Key value for chemical safety assessment

Repeated dose toxicity: inhalation - systemic effects

Endpoint conclusion

Dose descriptor:

LOAEC

47 mg/m³

Additional information

Male and female rats were exposed to 0, 25, 250, or 2500 ppm test substance for 6 hours per day, 5 days per week, for two years. Slight decreases in mean body weight gain were noted among rats of the 25 and 250 ppm groups, but not the 2500 ppm group, when evaluated through final sacrifice. Survival was decreased in male rats of the 250 and 2500 ppm groups and female rats of all test substance-exposed groups compared to controls. There were no biologically significant effects on haematological, clinical chemical, or urinalysis parameters measured in rats at any of the evaluations. There were no unique or unusual incidences of clinical signs that were associated with test substance toxicity. The only possible exception was an increased incidence of "weak" and "coloured discharge eye(s)" among 25 ppm female rats compared to controls. There were no ophthalmoscopic observations that occurred with an incidence suggestive of a compound-related effect. Urinary fluoride excretion was concentration- and time-dependent. At necropsy, the following main gross observations were made in rats that were related to test substance exposure: masses, nodules, discoloration and haemorrhage of the liver; mass/nodules and discoloration of the lungs, and fluid of the peritoneal cavity; and masses of the head, face and periaural area; and abscesses of the face. Microscopically, these lesions were correlated with hepatic hemangiosarcoma, hepatocellular adenoma and carcinoma, foci of clear cell and basophilic alteration, and sinusoidal dilatation, metastatic lung tumours, and Zymbal's gland tumours. The incidences of these lesions were concentration-related in all exposed groups. Hepatic hemangiosarcoma appeared to be the sentinel lesion in rats. The first hepatic hemangiosarcoma appeared on test day 362. Early mortality was primarily related to haemorrhage from hepatic hemangiosarcoma. There were no increases in cell proliferation of the organs examined that were consistent and could be related to test substance exposure. The spectrum of test substance-induced tumours is similar to that induced by other similar test substances, such as vinyl chloride, in rats.

 

Male and female (Crl:CD^®-1(ICR)BR) mice were exposed to 0, 25, 250, or 2500 ppm of test substance for 18 months. No NOAEL was determined in the study. The LOAEL was 25 ppm based on test substance-related mortality, gross pathology (increases in the incidences of gross observations in lung, peritoneum and subperitoneum, liver, and mammary gland), and non-neoplastic lesions considered precursors to test substance-induced neoplasms (bronchioalveolar hyperplasia in the lung, hypertrophy/hyperplasia/angiectasis and basophilic foci in the liver, mammary gland hyperplasia, and acinar hypertrophy/hyperplasia in the Harderian gland). Under the conditions of this study, a no-observable adverse effect level was not determined. The lowest observable adverse level was determined to be 25 ppm (47 mg/m³).

 

This substance is a gas, and tests to evaluate dermal and oral systemic toxicity were not feasible.

 

Dose Descriptor: LOAEL for significant systemic effects resulting from repeated inhalation exposure was 25 ppm (47 mg/m³).

Justification for classification or non-classification

Based on results of repeated inhalation studies, the substance is classified criteria for repeated dose toxicity as Xn, R48/20 (Harmful: danger of serious damage to health by prolonged exposure through inhalation) according the EU Directive 67/548/EEC. Based on the results of repeated inhalation studies, the substance is classified as Specific Target Organ Toxicity Repeated Exposure Category 2 (Liver) according to the EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008.