Tetrakis(2-ethylhexyl) benzene-1,2,4,5-tetracarboxylate

Acute Toxicity: oral

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:

test procedure in accordance with national standard methods with acceptable restrictions

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1996

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

no

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Tris(2-ethylhexyl) benzene-1,2,4-tricarboxylate

EC Number:

222-020-0

EC Name:

Tris(2-ethylhexyl) benzene-1,2,4-tricarboxylate

Cas Number:

3319-31-1

Molecular formula:

C33H54O6

IUPAC Name:

tris(2-ethylhexyl) benzene-1,2,4-tricarboxylate

Details on test material:

- Name of test material (as cited in study report): 1,2,4 Tris benzenetricarboxylic acid (2-ethylhexyl) ester
- Molecular weight: 547
- Physical state: liquid
- Analytical purity: 99.0%
- Lot/batch No.: 60601
- Source: Daihachi Kagaku Kogyo Co., Ltd.
- 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:

Crj: CD(SD)

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Japan
- Age at study initiation: 6 weeks old for both sexes
- Weight at study initiation: males: 149-163 g; females: 126-140 g
- Housing: 5 animals of the 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 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 23 +/- 2 °C
- Humidity (%): 55 +/- 10
- Air changes (per hr): 20
- Photoperiod (hrs dark / hrs light): 12:12
- Light intensity: 150-300 lux

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: tris(2-ethylhexyl) benzene-1,2,4-tricarboxylate is soluble in oil
- Lot/batch no. (if required): supplied by Nakaraitesuku
- Purity: Not reported

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:

0 and 2000 mg/kg; in preliminary study 200 and 2000 mg/kg did not cause mortality.

No. of animals per sex per dose:

5 animals per sex per dose

Control animals:

yes

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: each rat was weighed immediately prior to treatment, 7 and 14 days after post-treatment observation period. The rats were observed each hour to 6hr, after that, twice a day for signs of toxicity.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, organ weights, histopathology, other: clinical signs, body weight, macroscopic pathology
- Post exposure observation period: two weeks

Statistics:

Not applicable (limit test)

Results and discussion

Preliminary study:

In preliminary study 200 and 2000 mg/kg did not cause any mortality.

Effect levels

Key result

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:

No deaths occurred of either male or female animals.

Clinical signs:

other: Loosening erring of the stool attributable to the treatment with corn oil (vehicle) was observed for 3 hours from the administration for both sexes in the groups given 0 and 2,000mg/kg.

Gross pathology:

No macroscopic abnormalities that could be attributed to treatment with the test substance was seen on pathological examination.

Any other information on results incl. tables

Table 1 Mortality

Sex	Group	Dose level (mg/kg)	Number of animals	Number of deaths on the day														Mortality (%)
				1	2	3	4	5	6	7	8	9	10	11	12	13	14
Male	1	0	5	0														0
	2	2000	5	0														0
Female	3	0	5	0														0
	4	2000	5	0														0

Table 2 Clinical Signs

Sex: Female                Dose level: 0 mg/kg                              Number of animals: 5
Signs	Hours							Days
	1	2	3	4	5	6	24	2	3	4	5	6	7	8	9	10	11	12	13	14
Normal	0	0	0	5	5	5	5	5	5	5	5	5	5	5	5	5	5	5	5	5
General condition loose stool	5	5	5
Dead
Number of affected animals: 5                      Number of recovered animals: 5                  Mortality: 0/5

Sex: Female                Dose level: 2000 mg/kg                              Number of animals: 5
Signs	Hours							Days
	1	2	3	4	5	6	24	2	3	4	5	6	7	8	9	10	11	12	13	14
Normal	0	0	0	5	5	5	5	5	5	5	5	5	5	5	5	5	5	5	5	5
General condition loose stool	5	5	5
Dead
Number of affected animals: 5                      Number of recovered animals: 5                  Mortality: 0/5

Sex: Male                Dose level: 0 mg/kg                              Number of animals: 5
Signs	Hours							Days
	1	2	3	4	5	6	24	2	3	4	5	6	7	8	9	10	11	12	13	14
Normal	0	0	0	5	5	5	5	5	5	5	5	5	5	5	5	5	5	5	5	5
General condition loose stool	5	5	5
Dead
Number of affected animals: 5                      Number of recovered animals: 5                  Mortality: 0/5

Sex: Male                Dose level: 0 mg/kg                              Number of animals: 5
Signs	Hours							Days
	1	2	3	4	5	6	24	2	3	4	5	6	7	8	9	10	11	12	13	14
Normal	0	0	0	5	5	5	5	5	5	5	5	5	5	5	5	5	5	5	5	5
General condition loose stool	5	5	5
Dead
Number of affected animals: 5                      Number of recovered animals: 5                  Mortality: 0/5

Table 3 Cross Findings

Sex: Male             Dose level: 0 mg/kg
Animal ID-No.	Classification	Days after administration	Organ	Findings and comments
1001	Sacrificed	14		Normal
1002
1003
1004
1005
Sex: Male             Dose level: 2000 mg/kg
1101	Sacrificed	14		Normal
1102
1103
1104
1105
Sex: Female             Dose level: 0 mg/kg
2001	Sacrificed	14		Normal
2002
2003
2004
2005
Sex: Female             Dose level: 2000 mg/kg
2101	Sacrificed	14		Normal
2102
2103
2104
2105

Applicant's summary and conclusion

Interpretation of results:

other: EU GHS (CLP) criteria not met

Conclusions:

LD50 was established at > 2,000 mg/kg for both sexes.

Executive summary:

The acute oral toxicity of the test item has been determined according to OECD Guideline 401 and in compliance with GLP standards. Five rats per sex were orally exposed via gavage to a single dose of 0 and 2,000 mg/kg test item suspended in 40% w/v% corn oil.

Each rat was weighed immediately prior to treatment, 7 and 14 days after post-treatment observation period. The rats were observed each hour to 6 hours, after that, 2 times for one day during this time for signs of toxicity. The test substance did not cause any changes in body weight. Loosening erring of the stool attributable to the treatment with corn oil was

observed for 3 hours from the administration for both sexes in the groups given 0 and 2000 mg/kg. No deaths were recorded in treated and control group. No macroscopic abnormalities that could be attributes to treatment with the test substance were seen on pathological examination.

The LD50 for rats was determined in this limit test to be greater than 2000 mg/kg for acute oral toxicity.