Registration Dossier

Administrative data

Description of key information

Key value for chemical safety assessment

Additional information

The potential for di (2-ethylhexyl) terephthalate to cause cancer is well understood. In a 2-year study conducted according to EPA Guideline OPPTS 870.4200, groups of male and female Fischer 344 rats were provided 1500, 6000 or 12000 ppm of di (2-ethylhexyl) terephthalate ad libitum in the diet. At the highest concentration tested, this was equivalent to 666 and 901 mg/kg bw/day in males and females, respectively. These dose levels were chosen because previous studies of ortho-phthalate ester plasticizers have reported liver tumors in Fischer rats at concentrations of 6000 and 12000 ppm in the diet. Under the conditions of this assay, there was no statistically significant increase in any tumor type in either sex. Although relative liver weights in the 12000 ppm-dose groups were higher than controls, there were no significant non-neoplastic gross or microscopic changes observed in the livers of either sex.

  

 

Justification for classification or non-classification

There was no evidence of a tumorigenic response in male and female rats following lifetime exposure to up to 12000 ppm di (2-ethylhexyl) terephthalate in the diet. In addition, results were negative for induction of genetic damage in a series of in vitro mutagenicity studies as well as an in vivo study which examined gene expression in the testes of fetal rats following in utero exposure to di (2-ethylhexyl) terephthalate. Di (2-ethylhexyl) terephthalate was not previously classified under Directive 67/548/EEC, i.e., Annex I of the Dangerous Substances Directive for carcinogenicity. Based on a weight-of-the-evidence assessment, di (2-ethylhexyl) terephthalate is unlikely to pose a significant risk for the development of any type of cancer in humans exposed to this chemical and would not be classified for “Carcinogenicity” according to the UN Globally Harmonized System of Classification and Labeling (GHS) or the EU Classification, Labeling and Packaging of Substances and Mixtures (CLP) Regulation (EC) no. 1272/2008.