Registration Dossier

Toxicological information

Specific investigations: other studies

Currently viewing:

Administrative data

Link to relevant study record(s)

Description of key information

Additional information

Statistical analysis of rodent gene expression changes were conducted as part of the comprehensive toxicological assessment of HFO-1234ze. This was not a guideline study, was not GLP compliant, and is not accepted as a validated method by the regulatory authorities; however, it was conducted to provide additional information. Potential gene expression changes in liver and lung tissue were assessed following exposure of female B6C3F1 mice and changes in kidney assessed following exposure of male F344 rats to levels of 2,000 and 10,000 ppm HFO-1234ze 6 hrs/day, 5 days/wk for 13 weeks. The assessment was based on the results from a comparison of the responses seen with HFO-1234ze to both positive (tetrafluoroethylene, 1-amino-2,4-dibromoanthraquinone, and Tris(2,3-dibromopropyl)phosphate) and negative (trichlorofluoromethane, iodoform, tetrafluoroethane and N-(1-naphthyl)ethylenediamine dihydrochloride) controls. Vehicle controls were also included. In addition histopathological examination of selected tissues was conducted. 

 

Statistical classification analysis predicted HFO-1234ze (1,3,3,3-tetrafluoropropene) to be noncarcinogenic in both female mouse liver and male rat kidney, and carcinogenic in the female mouse lung. These findings had a statistical probability of selecting true negatives of 100% for kidney, 99.2% for liver and 83% for lung. The probability for a true positive being identified was 90% for the kidney, 97.2% for the liver and only 71.3% for the lung. There was no dose response relationship with respect to changes in gene expression. Furthermore, as only a limited number of genes were altered, it was concluded that for the female mouse lung, the number of genes altered was too small to perform a meaningful gene ontology enrichment analysis. No treatment related histopathological lesions were observed in the liver or kidney and mild irritation of the lung was only observed in one mouse in the low exposure group and not observed in the high exposure group. The weight of evidence suggests that HFC-1234ze is not likely to be carcinogenic. This conclusion is supported by the lack of mutagenic activity in all mammalian cell studies, the lack of significant metabolic activity, the lack of systemic toxicity and the lack of significant lesions in the livers, kidneys and lungs in any of the studies.