Registration Dossier

Administrative data

Description of key information

There is no evidence of carcinogenicity of ethylene following evaluation in a 2 year rat study.

Key value for chemical safety assessment

Justification for classification or non-classification

There is no evidence that ethylene is carcinogenic. Ethylene does not warrant classification for carcinogenicity under Dir 67/548/EEC or GHS/CLP.

Additional information

Human information

There is no information indicating any carcinogenic effects of ethylene. 

 

Non Human information

Carcinogenicity data

The toxicity and oncogenicity of inhaled ethylene was determined in Fischer-344 rats. Groups of 120 of each sex were exposed 6 hr/day, 5 days/week, for up to 24 months to concentrations of 0, 300, 1000 or 3000 ppm ethylene. The calculated time-weighted average concentrations for the 24 months of exposure were 0, 301, 1003, and 3003 ppm, respectively. Animals were investigated for ophthalmological or haematological effects and for clinical chemistry effects on blood and urine. After 6, 12, and 18 months, groups of animals were necropsied and examined. A complete selection of tissues and organs from all animals in the control and 3000 ppm groups were examined for microscopic lesions.

There were 151 unscheduled deaths (15.7% of 960 animals). There was no difference in mortality across groups during the 2-year study. Gross examination of rats dying during the study and those killed as scheduled, did not reveal any lesions attributable to ethylene exposure. Histopathologically, whilst a variety of lesions were observed in both the control and 3000-ppm groups, they were considered typical of those seen in this strain of animal and not related to ethylene exposure.

Overall there was no evidence that repeated exposure to ethylene at concentrations up to 3000 ppm caused chronic toxicity or was carcinogenic in Fischer-344 rats. The NOAEC is 3000 ppm (equivalent to 3445 mg/m3).

Additional supporting recent data for low potential for carcinogenicity

Ethylene has been examined for mutagenicity both in vitro and in vivo in a range of recognised core assay types. It has shown negative results for mutagenicity both in vitro and in vivo. It is concluded that the available data indicate that ethylene has no significant genotoxicity. In a 4-week inhalation study in rats and mice with evaluation of Hprt mutations and micronucleus formation there were no elevations in either Hprt mutations or micronucleus in either species up to 3000 ppm ethylene (Vergnes et al 1994; Walker et al 2000). Other micronucleus studies conducted in rats at 300, 1000, 3000 and 10,000 ppm after 5 days and 90 days of exposure, evaluating both bone marrow and peripheral blood, and using the sensitive flow cytometry technique showed no elevation in micronucleus formation (Dow, 2010).

In the two-year carcinogenicity study, there was no treatment-related increase in the incidence of tumours of rats exposed up to 3,000 ppm ethylene (Hamm et al., 1984). The lack of micronucleus formation in rats exposed to up to 10,000 ppm for 90 days supports the conclusion from the two-year study that ethylene is not carcinogenic to rats.