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Toxicological information

Acute Toxicity: oral

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Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study with acceptable restrictions

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1996

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): 1,2,4 Tris benzenetricarboxylic acid (2-ethylhexyl) ester
- Molecular weight (if other than submission substance): 546.87
- Physical state: liquid
- Analytical purity: 99.0%
- Lot/batch No.: 60601
- Stability under test conditions: room temperature
- Storage condition of test material: kept in the dark at room temperature until use
- Other: stored in fridge for 7 days

Test animals

Species:
rat
Strain:
other: Crj:CD (SD)
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Japan
- Age at study initiation: 5 w
- Weight at study initiation: during treatment; males: 149-163 g; females: 126-140 g
- Fasting period before study:
- Housing: 5 same sex in stainless steel breeding cages
- Diet (e.g. ad libitum): yes, Oriental Yeast Co. Ltd, pelleted diet
- Water (e.g. ad libitum): yes drinking water
- Acclimation period: 7 d

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 23+/- 2 degrees C
- Humidity (%): 55+/- 10
- Air changes (per hr): 20
- Photoperiod (hrs dark / hrs light): 12: 12

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
corn oil
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 40% w/v
- Amount of vehicle (if gavage): 5 ml/kg
- Justification for choice of vehicle: TOTM is soluble in oil
- Lot/batch no. (if required): No batch no. but supplied by Nakaraitesuku
- Purity: No data

MAXIMUM DOSE VOLUME APPLIED: 5.0 ml/kg

DOSAGE PREPARATION (if unusual): liquid mixed with oil

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: 3 preliminary studies performed previously
Doses:
2000 mg/kg; in preliminary study 200 and 2000 mg/kg did not cause mortality.
No. of animals per sex per dose:
5 males & 5 females
Control animals:
yes
Details on study design:
- Duration of observation period following administration: 14 days (or other?) 14d
- Frequency of observations and weighing: frequently for 6h on day of dosing then twice daily
- Necropsy of survivors performed: yes/no: yes
- Other examinations performed: clinical signs, body weight, organ weights, histopathology, other: clinical signs, body weight, macroscopic pathology
Statistics:
Not required as a limit test

Results and discussion

Preliminary study:
In preliminary study 200 and 2000 mg/kg did not cause mortality.
Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: No deaths occurred
Mortality:
None in controls or TOTM group
Clinical signs:
Loose stools were seen in both control and TOTM groups from 1-4h after dosing. The incidence was similar in both groups
Body weight:
based on the weights recorded on d 0, 7 & 14 there were no changes attributed to treatment with TOTM.
Gross pathology:
There were no differences between the incidence of findings in the control & TOTM groups.
Other findings:
No data

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
LD50 was established at > 2,000 mg/kg for both sexes.
Executive summary:

Acute oral toxicity (LD50) in the rat is in excess of 2000 mg/kg