Registration Dossier

Data platform availability banner - registered substances factsheets

Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.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

Toxicological information


Currently viewing:

Administrative data

Description of key information

rat, 103 weeks, diet: not carcinogenic (NTP 1982)
mouse, 103 weeks, diet: not carcinogenic (NTP 1982)

Key value for chemical safety assessment

Carcinogenicity: via oral route

Link to relevant study records
carcinogenicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
April 1977- May 1979
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
equivalent or similar to guideline
OECD Guideline 451 (Carcinogenicity Studies)
Urinalysis, haematological and clinical biochemistry measurements were not reported
Principles of method if other than guideline:
Study was performed to detect any carcinogenic potential of DEHA; additionally clinical signs, body weights, survival, gross pathology also detecting in detail nonneoplastic effects in the tissue, and histopathology were determined.
GLP compliance:
Fischer 344
Details on test animals or test system and environmental conditions:
- Source: NCI Frederick cancer Research Center, Maryland
- Age at study initiation: 3 weeks
- Housing: 5 per cage
- Diet :e.g. ad libitum
- Water :e.g. ad libitum
- Acclimatisation period: 2 weeks

- Temperature (°C): 18-31
- Humidity (%): 10-88
- Air changes (per hr): 10
- Photoperiod (hrs dark / hrs light): 12/12

Route of administration:
oral: feed
unchanged (no vehicle)
Details on exposure:
Dietary preparation:
Test diets were prepared by mixing the chemical with an aliquot of powdered Wayne® Lab Blox animal feed (Allied Mills, Chicago, IL), placing the mixture in a Patterson-Kelly twin-shell intensifier bar V-blender with the remainder of the feed, and mixing for 10 minutes . Test diets were sealed in labelled plastic bags and stored at 4°C for no longer than 14 days.
Analytical verification of doses or concentrations:
Details on analytical verification of doses or concentrations:
The amounts of di(2-ethylhexyl)adipate in selected batches of feed were measured by vapor-phase chromatography of 50-ml methanol extracts of 2-g samples. At each dietaryconcentration, the mean of the analytical concentration was usually within +/-10% of the theoretical.
Duration of treatment / exposure:
103 weeks
Frequency of treatment:
Diet was available ad libitum for 103 weeks
Post exposure period:
Week 104-107
Doses / Concentrations:
12000, 25000 ppm (600, 1250 mg/kg bw )
nominal in diet
No. of animals per sex per dose:
50 rats
Control animals:
yes, plain diet
Details on study design:
- Dose selection rationale: based on performed subchronic pre-study (14-week study)
Positive control:
No positive control used.
Observations and examinations performed and frequency:
Body weight: yes, recorded every 4 weeks.
Clinical observations: twice daily.
In addition, survival was recorded.
Sacrifice and pathology:
Necropsy: CO2 inhalation.


Gross and microscopic examinations were performed on major tissues, major organs, and all gross lesions from killed animals and from animals found dead. Tissues were preserved in 10% neutral buffered formalin, embedded in paraffin, sectioned, and stained with hematoxylin and eosin . The following tissues were examined microscopically : skin, lungs and bronchi, trachea , bone and bone marrow, spleen, lymph nodes, heart, salivary gland, liver, pancreas, stomach, small intestine, large intestine, kidneys, urinary bladder, pituitary, adrenal, thyroid, parathyroid, mammary gland, prostate and seminal vesicles or uterus, testis or ovary, brain, thymus, larynx, and esophagus. Necropsies were performed on all animals found dead unless precluded in whole or in part by autolysis or cannibalization . Thus, the number of animals from which particular organs or tissues were examined microscopically varies and does not necessarily represent the number of animals that were placed on study in each group.
Other examinations:
No other examinations were performed.
Probabilities of survival were estimated by the product-limit procedure of Kaplan and Meier (1958). Animals were statistically censored as of the time that they died of other than natural causes or were found to be missing ; animals dying from natural causes were not statistically censored .
Statistical analyses for a possible dose-related effect on survival used the method of Cox (1972) for testing two groups for equality and Tarone's (1975) extension of Cox's methods for testing for a dose-related trend .
One-tailed P values have been reported for all tests except the departure from linearity test, which is reported only when its two-tailed P value is less than 0.05
The incidence of neoplastic or non-neoplastic lesions has been given as the ratio of the number of animals bearing such lesions at a specific anatomic site (numerator) to the number of animals in which that site is examined (denominator).
The one-tailed Fisher exact test (Cox, 1970) was used to compare the tumor incidence of a control group with that of a group of dosed animals at each dose level.
The Cochran-Armitage test for linear trend in proportions, with continuity correction (Armitage, 1971), was also used. Life table methods were used to analyze the incidence of tumors. Curves of the proportions surviving without an observed tumor were computed as in Saffiotti et al . (1972).

Details on results:
CLINICAL SIGNS AND MORTALITY: No compound- related clinical signs were observed.

BODY WEIGHT AND WEIGHT GAIN: Mean body weights of high-dose rats of either sex were lower than those of the controls throughout the study.

FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study): no data


HAEMATOLOGY: not examined


URINALYSIS: not examined

NEUROBEHAVIOUR: not examined

ORGAN WEIGHTS: not examined

GROSS PATHOLOGY: no compound-related effects occurred.

HISTOPATHOLOGY: NON-NEOPLASTIC: No compound-related lesions were observed.

HISTOPATHOLOGY: NEOPLASTIC (if applicable): Tumors that were noted were those seen routinely in this strain of rat, and they occurred in comparable numbers in control and dosed rats. There were no compound-related effects.

HISTORICAL CONTROL DATA (if applicable): no data

Under the conditions of this bioassay, di(2-ethylhexyl)adipate was not carcinogenic for F344 rats.
Dose descriptor:
Effect level:
> 25 000 ppm (nominal)
Basis for effect level:
other: At all dose levels there was no significant increase in tumor incidence at any site (25000 ppm was considered to be equivalent to 1250 mg/kg bw.)
Remarks on result:
other: Effect type: carcinogenicity (migrated information)
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
1 250 mg/kg bw/day

Justification for classification or non-classification

Based on the available data in both mice and rats it is concluded that DEHA is not considered carcinogenic to man. According to EU Directive 67/548/EEC and EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008 classification is not warranted.

Additional information

In a 103-week carcinogenicity study, DEHA was administered to F344 rats and B6C3F1 mice in the diet at very high levels of 12000 or 25000 ppm, equivalent to a daily intake of 600 or 1250 mg/kg of body weight in rats and 1715 or 3570 mg/kg of body weight in mice (conversion based on data from the WHO report (2004)).

According to the NTP, no indication of a carcinogenic potential of the test substance was found in rats, while an increase in liver neoplasms was observed in mice (not conclusively proven in male mice according to the authors). This assessment is solely based on hepatic adenomas (males) and hepatic carcinomas (females). The number of hepatic carcinomas in treated male mice was not different from control group animals. Hepatic neoplams are very common in B6C3F1 mice. Observed incidences in male and female mice were well within NTP historical control data for this mouse strain collected from 1995 - 1999 and after 2002 (change in diet) and no dose response was observed for female mice and time of observation of tumors in dosed versus control groups was not different in males. Furthermore, there is a rodent specific peroxisome proliferation mode of action for hepatic tumor induction (IARC, 1995 Report No 24; Doull, 1999 Regulatory Toxicology and Pharmacology 29, 327-357), which explains this small increase very well. It has been established that peroxisome proliferators exhibit their pleiotropic effects to activation of PPARa (peroxisome proliferatoractivated receptor alpha) 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.