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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.

The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.

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Ames test

 

Jones & Churchill (1991) report a negative result in an Ames test performed with Salmonella typhimurium strains TA 98, TA 100, TA 1535, TA 1537 and TA 1538 at concentrations up to 5000 µg/plate in the presence and absence of exogenous metabolic activation.

 

In contrast, however, San & Wagner (1990) report a positive result for isophthalic acid (IPA) in an Ames test using Salmonella typhimurium strains TA 98, TA 100, TA 1535, TA 1537 and TA 1538 at concentrations of 667, 1000, 3333, 6667 and 10000 µg in the presence and absence of exogenous metabolic activation with S-9 fraction. Reproducible positive responses were seen in strains TA 98 and TA 1538 in the presence of S-9 and in strain TA 1538 in the absence of S-9. Precipitaion of the test material was noted at concentrattions of 5000 µg/plate (the limit concentration) and above, which may have confounded the interpretaion of this assay.

A negative Ames test with the structural isomer terephthalic acid (TPA) is also available (DuPont, 1979).

 

Chromosome aberration

 

The potential clastogenicity of isophthalic acid was investigated in vitro in CHO cells (Putnam & Morris, 1991). Duplicate cultures were exposed to the test material (in DMSO) in the presence and absence of an exogenous metabolic activation system (Aroclor 1254 -induced male Sprague-Dawley rat liver S9 fraction) at concentrations of 625, 1250, 2500 and 5000 µg/ml. Cells were arrested in metaphase by the addition of Colcemid two hours prior to harvest. Cells were exposed for 10 hours (-S9) or 2 hours (+S9) and harvested after 12 hours (-S9) or 10 hours (+S9) and 100 cells/duplicate flask assessed for chromosomal aberrations

 

Mammalian cell mutation

 

Riach & Willington (1994) investigated the mutagenicity of isophthalic acid in a mouse lymphoma assay in the absence and presence of a rat liver preparation and the co-factors required for mixed-function oxidase activity (S9 mix). In four independent mutation assays (2 in the absence and 2 in the presence of S9 mix), results were obtained where the final concentrations of IPA in the treatment medium ranged between 150 -750 µg/ml. In both assays in the presence of S9 mix, and the first assay in the absence of S9 mix, the steepness of the toxicity curve prevented results from being obtained at critically toxic dose levels. No indication of mutagenic activity was obtained, however in any of these assays. In the second assay in the absence of S9 mix, results were obtained in the region of 10% cell survival. These results gave a marginal increase (1.85 -fold) in mutant fraction over the vehicle control values. The biological significance of such a weak effect at such high concentrations is doubtful. Positive controls demonstrated the sensitivity of the assay and the effectiveness of the S9 mix.

 

Jacobsen-Kram & Sigler (1991) investigated the mutagenic potential of isophthalic acid on its ability to induce forward mutations at the HGPRT locus of CHO cells in the presence and absence of metabolic activation with S-9 mix. When isophthalic acid was applied at dose levels of 500, 1000, 2000, 3000, 3200, 3500 and 4000 µg/mL in both the presence and absence of metabolic activation, it was concluded that isophthalic acid was negative in both the presence and absence of exogenous metabolic activation.

 

Studies in vivo

 

Read-across is proposed, based on structural similarity, to studies performed with the substance terephthalic acid (TPA).

 

No evidence of UDS was seen in a study in the rat liver at the limit dose of 2000 mg/kg bw (Fox, 2006). 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). The available data on the genetic toxicity of terephthalic acid was 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 TPA 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 with TPA in the rat carcinogenicity study.


Short description of key information:
The genotoxicity of the substance has been adequately investigated in an appropriate battery of studies in vitro and in vivo, in accordance with REACH guidance. A positive result was reported in one of two Ames tests, however negative results are reported in two studies of mammalian cell mutation and in a study of clastogenicity in vitro. Negative results in studies in vivo investigating mutational and chromosomal endpoints are available for the read-across substance terephthalic acid, leading to the conclusion that isophthalic acid is not genotoxic in vivo.

Endpoint Conclusion: No adverse effect observed (negative)

Justification for classification or non-classification

A positive result is reported for one of two Ames tests performed with isopthalic acid, however negative results are reported in two studies of mammalian cell mutation and in a study of clastogenicity in vitro. The results of rat liver UDS assay and a mouse bone marrow micronucleus assay performed in vivo with the read-across compound terephthalic acid are negative. Isophthalic acid is therefore not considered to be genotoxic in vivo and no classification for genotoxicity is proposed according to CLP.