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Administrative data

Description of key information

Based on experimental data from analogous substances the test item is considered non carcinogenic in vivo.

Key value for chemical safety assessment

Carcinogenicity: via oral route

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed

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

Due to the results obtained with analogous substances showing a mode of action which is clearly not relevant for humans, no classification according to EU and GHS criteria is required.

Additional information

There is no data available for DPHP, however analogous substances have been assessed in the EU risk assessment. Additionally there is a chronic feeding study available for DIDP (Cho, 2008) which has not been available by the time the EU risk assessment for DIDP was conducted.

For DINP, the risk assessment concluded that "there was a significant excess of liver neoplasia in rats and mice after chronic oral administration. This is consistent with a peroxisome proliferation mode of action for hepatic tumor induction specific in rodents. It has been established that peroxisome proliferators exhibit their pleiotropic effects to activation of PPARa (peroxisome proliferatoractivated receptor a) and that PPARa is expressed only at low level in humans, explaining the absence of significant response to the action of peroxisome proliferators. Thus, there is no concern for a potential carcinogenic effect in humans."

For mononuclear cell leukemia, a clearly increased incidence was observed in two studies of DINP conducted with Fisher rats. However, this was considered as a common neoplasm in this strain of rat with no known counterpart in humans. Kidney tumors found in the rat study were not regarded as relevant to humans as they underlie the species and sex-specific alpha 2µ globulin mechanism.


For DIDP, the EU risk assessment concluded that a "positive result in the cell transformation test conducted on this chemical was in accordance with those obtained with well-known peroxisome proliferators".

This is consistent with a two year bioassay conducted later on in which DIDP was administered in the diet at concentrations of 400, 2000, and 8000 ppm to F344 rats (Cho et al., 2008). The average daily doses of DIDP were reported to be calculated from the body weights and feed consumption data using the concentrations of DIDP in the diet. For doses of 400, 2000, and 8000 ppm, the calculated average daily doses of DIDP over 2 years for male rats reported in the paper are incorrect. Actual exposures for male rats were 21.9, 110.3 and 479.2 mg/kg-bw/day and for female rats 22.9, 128.2 and 619.6 mg/kg-bw/day. Rats of both sexes exhibited significant decreases in overall survival and body weights, and increases in the relative weights of kidneys and liver with 8000 ppm DIDP.  No treatment related neoplastic lesions were observed in the internal organs, including the liver. In addition, measurement of catalase enzyme activity, a marker for cell peroxisome proliferating activity, suggests that DIDP can induce peroxisome proliferation at an early stage (12 weeks of treatment) but fails to maintain the catalase-inducing potential by 32 weeks of treatment.  An increased incidence of mononuclear cell leukemia (MNCL) was observed in this study, but MNCL is a common neoplasm in F344 rats, and the observed increased incidence is likely to be a species-specific effect with little or no relevance to humans.  Therefore, DIDP was not considered to be carcinogenic at doses up to 8000 ppm in rats.


Furthermore, in humans, activation of peroxisome proliferator-activated receptor α(PPARα) does not lead to increased relative liver weights, oxidative enzyme induction or other responses typically associated with sustained PPARα activation observed in wild-type mice (Corton et al., 2018 Arch Toxicol. 92(1): 83–119). The weight of evidence supports the conclusion that adverse effects related to a PPARα MOA is either “not relevant” or “unlikely to be relevant” in humans (Felter et al., 2018 Regulatory Toxicology and Pharmacology 92, 1 -7).