Registration Dossier

Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2000-05-09 - 2000-06-19
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Well documented GLP study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2000
Report Date:
2000

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
Deviations:
no
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
no
Qualifier:
according to
Guideline:
EPA OPPTS 870.1200 (Acute Dermal Toxicity)
Deviations:
no
Qualifier:
according to
Guideline:
other: EEC Directive (67/548/EEC), 7th Amended Directive (92/32/EEC) & EEC Directive 93/21/EEC
Deviations:
not specified
Qualifier:
according to
Guideline:
other: GefahrstoffVerordnung (GefStofiV) of 29 September 1994 (BGB1.1, p. 2557)
Deviations:
not specified
Principles of method if other than guideline:
None
GLP compliance:
yes (incl. certificate)
Test type:
fixed dose procedure
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
other: liquid
Details on test material:
- Name of test material (as cited in study report): ATEHC, CAS-No.: 144-15-0
- Physical state: clear, colourless liquid
- Expiration date of the lot/batch: 1 November 2000 (as specified by the Sponsor)
- Storage condition of test material: at room temperature
- Other: Chemical name (as specified by the Sponsor): acetyl-tri-(2-ethylhexyl)-citrate
- Other: The test sample was labelled with project no., name of test article and batch number, name of Sponsor, date of receipt, expiry date.

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Weight at study initiation: male: 225 - 246 g; female: 168 - 182 g
- Housing: Before the animals arrived, the study room and cages were cleaned and disinfected. During the study, the room and cages were cleaned at regular intervals. The rats were housed individually in cages.
- Diet (e.g. ad libitum): Pelleted diet, offered ad libitum
- Water (e.g. ad libitum): Tap water as for human consumption was continuously available ad libitum via drinking bottles.
- Acclimation period: 6 days (range finding); 8 days (main test)
- Other: Identification with coloured markings; cage labelled with sex, study no., date of study initiation

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3° C (monitored twice daily)
- Humidity (%): between 30 and 70 % (monitored twice daily)
- Air changes (per hr): Air was changed about 16 times per hour and filtered adequately.
- Photoperiod (hrs dark / hrs light): Artificial light was set to give a cycle of 12 hours light and 12 hours dark with light on at 7.00 a.m.

Administration / exposure

Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Duration of exposure:
24 h
Doses:
2000 mg/kg
No. of animals per sex per dose:
5 male and 5 female animals
Control animals:
not required
Details on study design:
A single dermal administration of the undiluted test article was performed. Since the density of the liquid test article was 0.97 g/mL, the animals were administered a volume of 2.06 mL/kg body weight which corresponded to the dose of 2000 mg/kg. The test article was held in contact with the skin by an occlusive dressing using a 4 x 5 cm patch (filter paper). The exposure period was 24 h. All animals were weighed before dosing and the individual doses expressed as mL/kg were adjusted according to the body weight.

Results and discussion

Preliminary study:
There were no deaths in the preliminary study.
Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: after 24h and 14 d
Mortality:
No animal died during the course of the main test after the single dermal administration of 2000 mg/kg.
Clinical signs:
No abnormal clinical signs were observed.
Body weight:
There was no influence of the treatment on the body weight development in the male animals during the 14-day observation period.
In the female animals, a reduced body weight or a very slight weight gain was observed after the first week of treatment followed by a slight weight gain after the second week of treatment.
Gross pathology:
Gross pathological examinations at day 14 p.a. (terminal necropsy) revealed no test article-related findings. In one female animal, red discolouration of the thymus was observed.
Other findings:
Skin Reactions: Neither erythema nor oedema or other skin reactions were observed.

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: other: EU-GHS
Conclusions:
LD50 (rat, after 24 h and 14 d) >2000 mg/kg
Executive summary:

The acute dermal toxicity of tris(2-ethylhexyl) 2-(acetyloxy)propane-1,2,3-tricarboxylate (ATEHC) was assessed in a fixed dose procedure in one group of rats comprising 5 males and 5 females according to OECD 402 and EU method B.3 and in compliance with GLP (2000). On the basis of the range finding test, the animals were given a single dermal administration of the test substance at the dose of 2000 mg/kg. The skin was exposed to the test article for 24 h. Clinical observations were carried out at regular intervals during the 14-day observation period. Signs of erythema and oedema were evaluated once daily for 14 days. Body weights were determined immediately before treatment and on days 7 and 14 p.a. Gross pathological examinations were carried out at study termination on all animals and the following results were obtained: No animal died during the 14-day observation period, no abnormal clinical signs, neither signs of erythema nor oedema were observed. There was no influence of the treatment on the body weight development in the male animals during the 14-day observation period. In the female animals, reduced body weight and very slight to slight weight gain were recorded during the 14-day observation period. Gross pathological examinations on day 14 p.a. did not reveal test article-related findings in the rats. Since no deaths were caused in Wistar rats after the dermal treatment with the test substance at a dose of 2000 mg/kg, the LD50 values after 24 h and 14 days were as follows: Male and female > 2000 mg/kg.