Bis(2-ethylhexyl) adipate

Specific investigations: other studies

Administrative data

Endpoint:

endocrine system modulation

Type of information:

experimental study

Adequacy of study:

supporting study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Data source

Reference

Reference Type:

publication

Title:

Unnamed

Year:

2007

Materials and methods

Type of method:

in vivo

Endpoint addressed:

toxicity to reproduction / fertility

Test material

Test material information

Constituent 1

Reference substance name:

Bis(2-ethylhexyl) adipate

EC Number:

203-090-1

EC Name:

Bis(2-ethylhexyl) adipate

Cas Number:

103-23-1

Molecular formula:

C22H42O4

IUPAC Name:

bis(2-ethylhexyl) adipate

Details on test material:

- Name of test material (as cited in study report): Di-(2-ethylhexyl) adipate (DEHA)
- Physical state: colorless liquid
- Analytical purity: 99%

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Laboratory Animal Resources, Korea Food and Drug Administration, National Institute of Toxicological Research
- Age at study initiation: 20 days
- Weight at study initiation:
- Body weight differences was less than 5g between all rats
- Diet (e.g. ad libitum): pelletized soy-bean oil-free feed AIN-76A ad lib.
- Water (e.g. ad libitum): distilled water ad lib.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 23+/- 2°C
- Humidity (%): 55 +/- 10%
- Air changes (per hr):
- Photoperiod (hrs dark / hrs light): 12h/12h

Administration / exposure

Route of administration:

subcutaneous

Vehicle:

corn oil

Duration of treatment / exposure:

3 days (animals were killed on day 4 of the experiment)

Frequency of treatment:

daily

Doses / concentrations

Remarks:

Doses / Concentrations:
40, 200, 1000 mg/kg/day
Basis:

No. of animals per sex per dose:

6

Control animals:

yes, concurrent vehicle

Details on study design:

100mg/kg BrdU was administered 1h prior to necropsy

Examinations

Examinations:

Serum FSH and LH levels
Organ weights (Kidney, Liver, Ovary, Vagina, Uterus) + Body weight
Histopathology of all organs relating to the endocrine system (such as uterus, liver, thyroid, pituitary, adrenals)
BrDU labelling to investigate cell proliferation in the reproductive organs including liver.

Positive control:

1µg/kg/day estradiol-3-benzoate in corn oil

Results and discussion

Details on results:

DEHA did not influence the levels of serum FSH and LH, and uterine morphological changes such as luminal epithelial height, myometrial thickness and numbers of uterine gland. Histopathology revealed no differences compared to the control group. There were no hints for increased cell proliferation in the reproductive organs including liver and uterus as determined by BrdU.

Absolute organ weights were comparable to the control group. The slightly reduced body weight in the high dose group led to a slight increase in relative kidney and ovary weight.

The positive control substance estradiol-3-benzoate led to the expected increase in uterine luminal height, uterine cell proliferation and uterus weight.

Applicant's summary and conclusion

Conclusions:

In this uterotrophic assay in immature rats, there was no significant variation by DEHA treatment, suggesting that DEHA appears not to be a endocrine disrupter. There were no hints for estrogenic activity after exposure for up to a dose of 1000mg/kg for 3 days.