Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1999-12-08 - 2000-05-11
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: 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
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Version / remarks:
(1996-03-22)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)
Version / remarks:
(1996-09-30)
Deviations:
no
Principles of method if other than guideline:
None
GLP compliance:
yes (incl. QA statement)
Test type:
acute toxic class method
Limit test:
yes

Test material

Constituent 1
Chemical structure
Reference substance name:
Tris(2-ethylhexyl) 2-(acetyloxy)propane-1,2,3-tricarboxylate
EC Number:
205-617-0
EC Name:
Tris(2-ethylhexyl) 2-(acetyloxy)propane-1,2,3-tricarboxylate
Cas Number:
144-15-0
Molecular formula:
C32H58O8
IUPAC Name:
1,2,3-tris(2-ethylhexyl) 2-(acetyloxy)propane-1,2,3-tricarboxylate
Test material form:
other: liquid
Details on test material:
- Name of test material (as cited in study report): ATEHC
- Physical state: liquid
- Expiration date of the lot/batch: May 31, 2000
- Stability under test conditions: Stable; stability of test article dilution: 2 hours.
- Storage condition of test material: At room temperature (17-23°C) away from direct sunlight (dry).
- Other: Safety precautions - gloves, goggles and face mask were sufficient to assure personnel health and safety.

Test animals

Species:
rat
Strain:
other: HanIbm: WIST (SPF)
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Age at study initiation: Females: 10 weeks, males: 8 weeks
- Fasting period before study: approximately 16.5 to 17.5 hours, but with free access to water
- Diet (e.g. ad libitum): Pelleted standard Kliba 3433, batch no. 42/99, rat maintenance diet available ad libitum (except for the overnight fasting period prior to application).
- Water (e.g. ad libitum): Community tap water from Itingen, available ad libitum.
- Acclimation: Under laboratory conditions, after health examination. Only animals without any visible signs of illness were used for the study.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22±3°C
- Humidity (%): relative humidity 40-70% (values above 70% during cleaning process possible)
- Air changes (per hr): Air-conditioned with 10-15 air changes per hour
- Photoperiod (hrs dark / hrs light): 12 hour light/dark cycle
- Other: Recorded music was played for approximately 8 hours during the light period

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
polyethylene glycol
Remarks:
PEG 400
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 0.2 g/mL
- Amount of vehicle (if gavage): 10 mL/kg

MAXIMUM DOSE VOLUME APPLIED: 2000 mg/kg

DOSAGE PREPARATION: The test article was placed into a glass beaker on a tared Mettler balance and the vehicle (polyethylene glycol PEG 400) was added. A weight by volume dilution was prepared using a magnetic stirrer as homogenizer. Homogenicity of the test article in the vehicle was maintained during treatment. The preparation was made shortly before each dosing.
Doses:
2000 mg/kg
No. of animals per sex per dose:
3 rats per sex per dose
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Mortality / Viability - Four times during test day 1 and once daily during days 2-15; body weights - On test day 1 (pre-administration), 8 and 15; clinical signs - Each animal was examined for changes in appearance and behaviour four times during day 1, and once daily during days 2-15.
- Necropsy of survivors performed: yes
Statistics:
No statistical analysis was used as no deaths occurred.

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No death occurred during the study.
Clinical signs:
No clinical signs were noted during the observation period.
Body weight:
The body weight of the animals was within the range commonly recorded for this strain and age.
Gross pathology:
No macroscopic findings were observed at necropsy.

Any other information on results incl. tables

The median lethal dose of the substance after single oral administration to rats of both sexes, observed over a period of 14 days, could not be estimated as no death occurred.

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: other: EU-GHS
Conclusions:
The LD50 was identified to be >2000 mg/kg body weight. The test material did not induce treatment-related mortality. Further no clinical signs or macroscopic findings were observed.
Executive summary:

tris(2-ethylhexyl) 2-(acetyloxy)propane-1,2,3-tricarboxylate (ATEHC) was tested in an acute oral toxicity study according to the acute toxic class method (OECD 423 and EU method B.1 tris; 2000). Two groups, each using three female or three male HanIbm: WIST (SPF) rats, were treated with the test substance at 2000 mg/kg by oral gavage. The test article was suspended in vehicle (polyethylene glycol PEG 400) at a concentration of 0.2 g/mL and administered at a volume of 10 mL/kg. The animals were examined for clinical signs and mortality / viability. Body weights were recorded and all animals were necropsied and examined macroscopically. No death occurred during the study, also no clinical signs were noted during the observation period; the body weight of the animals was within the range commonly recorded for this strain and age and no macroscopic findings were observed at necropsy.

The median lethal dose after single oral administration to rats of both sexes, observed over a period of 14 days, could not be estimated as no death occurred. The LD50 (rat) was identified to be >2000 mg/kg body weight, therefore the test material was considered to be relatively non-toxic under the conditions of the test.