Dimethyl isophthalate

Carcinogenicity

Description of key information

A structural analogue of dimethyl isophthalate, dimethyl terephthalate (DMTP) was tested In chronic lifetime dietary exposure studies in rats and mice.  No adverse effects were observed. 

Key value for chemical safety assessment

Carcinogenicity: via oral route

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEL

200 mg/kg bw/day

Study duration:

chronic

Species:

rat

Quality of whole database:

adequate. There is a large amount of toxicity data available for the structural analogue, dimethyl terephthalate (DMTP). Read-across from DMTP to dimethyl isophthalate is valid as assessed in the analogue approach report format attached to this IUCLID file.

Carcinogenicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Carcinogenicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

A read-across approach from DMTP to DMIP has been proposed based on common functional groups, and substantiated by common behaviours in physico-chemical and toxicity testing. In chronic lifetime dietary exposure studies of DMTP in rats and mice, no adverse effects were observed. There is no basis for classification for repeated dose or carcinogenicity classification for DMIP.

Additional information

There is a large amount of toxicity data available for the structural analogue, dimethyl terephthalate (DMTP). Read-across from DMTP to dimethyl isophthalate is valid as assessed in the analogue approach report format attached to this IUCLID file. In the chronic (2-year feeding study of doses up to 5000 ppm (equivalent to approximately 200 mg/kg bw/d) in rats and mice, there were no adverse effects observed (on food consumption, weight gain, clinical signs, gross pathology or histopathology). The NOAEL for DMTP is > 200 mg/kg bw/day.

Data can be read-across to DMIP from DMTP, based on common functional groups. The substances are isomers. The analogue nature of these two compounds has been accepted by the U.S. Environmental Protection Agency (EPA) in its High Production Volume (HPV) Challenge Program. Support for this category approach is substantiated by the consistency of data.   The two substances have similar physico-chemical properties, low acute mammalian toxicity, and similar genotoxicity profiles.  Both are biodegradable in the environment, and have comparable acute aquatic toxicity values. The similarities in structure are likely to apply to metabolites as well, with DMIP breaking down to isophthalic acid, just as DMTP is known to break down to terephthalic acid; these are isomers. 

Thus, the result of the carcinogenicity study on DMTP is likely to be similar to that for dimethyl isophthalate (DMIP). 

Justification for selection of carcinogenicity via oral route endpoint:
chronic lifetime study in rats conducted by a reputable government agency