Dimethyl isophthalate

Endpoint summary

Description of key information

There are no significant adverse health effects noted in rats or mice chronically fed a diet of dimethyl terephthalate adequate (DMTP) a close structural analogue.  There were no increases in the occurrence of tumors.  The NOAEL for DMTP is greater than the highest dose (200 mg/kg bw/day) in this 2-year bioassay.

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

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 the registered material is valid as assessed in the analogue approach report format attached to this IUCLID file.

Repeated dose toxicity: inhalation - systemic effects

Endpoint conclusion

Endpoint conclusion:

no study available

Repeated dose toxicity: inhalation - local effects

Endpoint conclusion

Endpoint conclusion:

no study available

Repeated dose toxicity: dermal - systemic effects

Endpoint conclusion

Endpoint conclusion:

no study available

Repeated dose toxicity: dermal - local effects

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

There is a large amount of toxicity data available for the structural analogue, dimethyl terephthalate (DMTP). In the chronic 2 -year feeding study of up to 5000 ppm (approximately equivalent to 200 mg/kg bw/d) in rats (600 mg/kg bw/d in mice), there were no adverse effects observed (on food consumption, weight gain, clinical signs, gross pathology or histopathology). The NOAEL in rats for DMTP is > 200 mg/kg bw/d.

Data can be read-across to dimethyl isophthalate (DMIP, target chemical) from dimethyl terephthalate (DMTP, source chemical), 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. 

 

Based on the considerations above, the results of the repeated dose studies on DMTP are likely to be similar to that for dimethyl isophthalate (DMIP). They are adequate to fulfill the information requirements of Annex IX, to be the basis for classification and labelling decisions, and for risk assessment. The dose descriptor obtained for derivation of a DNEL is adequate, with an assessment factor applied for uncertainties associated with the read-across, as recommended by ECHA.

Justification for selection of repeated dose toxicity via oral route - systemic effects endpoint:
experimental result of chronic (lifetime) exposure to test material, performed by a reputatable government agency

Justification for classification or non-classification

Dimethyl isophthalate is structurally similar to its isomeric analogue, dimethyl terephthalate (DMTP). Read-across from DMTP to the registered material is valid as assessed in the analogue approach report format attached to this IUCLID file. 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 effects.