Fluoroethylene

Carcinogenicity

Description of key information

LOAEC = 47 mg/m3

Key value for chemical safety assessment

Carcinogenicity: via inhalation route

Endpoint conclusion

Dose descriptor:

LOAEC

47 mg/m³

Justification for classification or non-classification

Based on results of repeated inhalation studies, the substance meets Category 2 classification criteria for carcinogenicity according the EU Directive 67/548/EEC and Category 1B classification criteria for EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008.

Additional information

Groups of 95 male and 95 female Crl:CD^®BR rats were exposed to 0, 25, 250, or 2500 ppm substance for 6 hours per day, 5 days per week, for up to 2 years, weekends and holidays excluded. Slight decreases in mean body weight gain (6-15%) were noted among rats of the 25 and 250 ppm groups, but not the 2500 ppm group, when evaluated through final sacrifice. There were no unique or unusual incidences of clinical signs that were associated with substance toxicity. Survival was decreased in male rats of the 250 and 2500 ppm groups and female rats of all 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. Urinary fluoride excretion was concentration- and time-dependent. At necropsy, the following main gross observations were made in rats that were related to 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 substance exposure. The spectrum of substance-induced tumours is similar to that induced by other similar substances, such as vinyl chloride, in rats. Under the conditions of this study, the substance was carcinogenic in male and female rats at concentrations greater than or equal to 25 ppm. A no-observable adverse effect level was not determined. Based on this information,the LOAEL for carcinogenicity was determined to be 25 ppm (47 mg/m³).

 

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 tumours in male and female animals at concentrations greater than or equal to 25 ppm, the lowest concentration tested. Pulmonary adenoma appeared to be the most sensitive indicator of test substance-induced tumourigenesis in mice based upon time-to-tumour and tumour incidence.