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Key value for chemical safety assessment

Additional information

Studies in vitro

No evidence of mutagenicity was seen in a guideline-comparable Ames test (DuPont, 1979) performed with terephthalic acid. The clastogenicity of terephthalic acid was investigated in a study using cultured peripheral human lymphocytes (Fox, 2006a). This study reports a positive result in the absence of metabolic activation; however negative results are reported in studies using sodium terephthalate (Fox, 2006b; 2007a,b), indicating that the terephthalate anion itself is not clastogenic. Findings in the study with terephthalic acid are therefore likely to be a consequence of the acidity of the test substance. The results of a mouse lymphoma assay (Riach & Willington, 1994) with the read-across substance (structural isomer) isoterephthalic acid report a weak positive response; however this was non-reproducible and was associated with marked cytotoxicity and pH changes in the culture medium. The biological significance of this effect is therefore considered to be doubtful.

Studies in vivo

No evidence of unscheduled DNA synthesis (UDS) was seen in a study in the rat liver at the limit dose of 2000 mg/kg bw (Fox, 2006c). No evidence of clastogenicity was seen in a mouse bone marrow micronucleus assay (intraperitoneal dosing) at dose levels sufficient to cause toxicity (Gudi & Krsmanovic, 2001).

Although the results of the studies in mammalian cells in vitro are not universally negative, the positive or equivocal findings seen in some assays are considered likely to be due to pH changes caused by the acidic nature of the test substance (terephthalic acid or isophthalic acid) are associated with marked toxicity. The clear negative results in the two higher tier assays in vivo demonstrate that the substance is not genotoxic.

COM opinion

The available data on the genetic toxicity of terephthalic acid has also been reviewed by the independent UK Government Committee on Mutagenicity (COM). The COM concluded, on the basis of the data available, that the two in vivo studies of genotoxicity performed with terephthalic acid were adequate and negative, and indicated that terephthalic acid is not an in vivo mutagen. The COM further concluded that the available evidence supported their previous conclusion of a non-genotoxic mechanism for the bladder tumours seen in the rat carcinogenicity study.

Justification for selection of genetic toxicity endpoint
A weight of evidence approach is taken to this endpoint; there is no single key study.

Short description of key information:
An Ames test is available for terephthalic acid. Studies of clastogenicity in mammalian cells (cultured human lymphocytes) in vitro are available for terephthalic acid and its sodium salt. A study of mammalian cell mutagenicity (mouse lymphoma assay) is available for the structural isomer isophthalic acid.

Endpoint Conclusion: No adverse effect observed (negative)

Justification for classification or non-classification

Terepthalic acid is not classified for genotoxicity under CLP, based on the negative results in studies in vivo.