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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.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

Diss Factsheets

Administrative data

Description of key information

A series of oral sub-acute (21-day/rat-NOAEL 280 mg/kg/day; 28-day/rat-NOAEL 57 mg/kg/day) and sub-chronic repeated dose toxicity tests (90-day/Dog- NOAEL 75 mg/kg/day; 90-day/rat- 150 mg/kg/day) were conducted on DIDP. The target organ for oral sub-acute and sub-chronic DIDP toxicity in animals (rodent and dog) is the liver (increased liver weights and significant changes in liver peroxisomal enzyme activities in rodents). These effects were obtained in rat studies are related to peroxisome proliferation-mediated liver effects, which are considered to be species specific. Humans are less sensitive than rats. In a repeated dose toxicity study of limited reliability in dogs, which is considered a more relevant species to humans with respect to peroxisome proliferation, a LOAEL of 500 mg/kg bw/d was reported for increased liver weights and histological changes. The NOAEL was 75 mg/kg bw d. Current literature indicates that rodents compared to humans are particularly susceptible to peroxisome proliferative effects. In the light of peroxisome proliferative effects observed for DIDP, liver effects from DIDP exposure may not be relevant for humans.


Therefore, the overall NOAEL for systemic effects following oral exposure in rats was 150 mg/kg bw/d. Liver enlargement was due to hepatocyte hypertrophy.  The major biochemical alterations consisted of induction of both peroxisomal (increased acyl-CoA oxidase) and microsomal (lauric acid 11- and 12-hydroxylases) fatty-acid-oxidizing activities. The former is considered to be a specific marker of peroxisome proliferation.  A sub-chronic (2-week, rat inhalation study set the NOAEC of 500 mg/m3), produced local irritation but no systemic toxicity in rats at the concentrations tested.

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Endpoint conclusion
Dose descriptor:
NOAEL
150 mg/kg bw/day

Repeated dose toxicity: inhalation - systemic effects

Endpoint conclusion
Dose descriptor:
NOAEC
500 mg/m³

Additional information

Oral: The target organ for oral sub-acute and sub-chronic DIDP toxicity in animals (rodent and dog) appears to be the liver (increased liver weights and significant changes in liver peroxisomal enzyme activities in rodents). It is clear that NOAELs derived from rat studies are related to peroxisome proliferation-mediated liver effects, which are considered to be species specific. Humans are less sensitive than rats.  The overall NOAEL for systemic effects following oral exposure in rats was 150 mg/kg/d.

Inhalation: Repeated (two weeks) exposure to DIDP aerosol at concentrations approximating 500 mg/m3 produced local irritation but no systemic toxicity in rats.  Accordingly the systemic no effect level exceeded 0.5 mg/l.

In a 2-week study (General Motors Research Laboratories, 1981) designed to evaluate the fate of DIDP (see Section 5.1), toxicity was assessed. DIDP was administered to 8 male rats (6 for control) by inhalation (aerosol) at analytical concentration of 505±7 mg/m3(MMAD: 0.98 μm) 6 hours a day, 5 times per week. Rats were observed daily for body weight gain, appearance and gross behavior. Animals were sacrificed at the end of the observation period (3 weeks) and tissue samples taken for histopathology. There were no marked outward signs of toxicity during exposure. The rate of body weight gain was not different between control and exposed animals. Effects in the lungs were: moderate increase in the width of alveolar septa with slight interstitial mixed inflammatory reactions, alveolar macrophages and type II pneumocytes were increased in number, peribronchial lymphoid tissue appeared slightly more prominent. In liver, spleen and kidneys, no obvious histologic alterations were noted except for a slight hepatic fatty metamorphosis. No systemic toxicity, but local irritant effects were observed at the concentration tested, thus a NOAEL of 0.5 mg/l (500 mg/m3) can be assumed.


Repeated dose toxicity: via oral route - systemic effects (target organ) digestive: liver

Justification for classification or non-classification