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Acute Toxicity: oral

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Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2001
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2001
Report date:
2001

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

Constituent 1
Chemical structure
Reference substance name:
Trioctyl benzene-1,2,4-tricarboxylate
EC Number:
201-877-4
EC Name:
Trioctyl benzene-1,2,4-tricarboxylate
Cas Number:
89-04-3
Molecular formula:
C33H54O6
IUPAC Name:
trioctyl benzene-1,2,4-tricarboxylate
Details on test material:
- Name of test material (as cited in study report): 1,2,4-benzenetricarboxylic acid, trioctyl ester (BCTO)
- Molecular formula (if other than submission substance): C33-H54-O6
- Molecular weight (if other than submission substance): 546.79
- Smiles notation (if other than submission substance): CCCCCCCCOC(=O)c1ccc(c(c1)C(=O)OCCCCCCCC)C(=O)OCCCCCCCC
- InChl (if other than submission substance): 1S/C33H54O6/c1-4-7-10-13-16-19-24-37-31(34)28-22-23-29(32(35)38-25-20-17-14-11-8-5-2)30(27-28)33(36)39-26-21-18-15-12-9-6-3/h22-23,27H,4-21,24-26H2,1-3H3
- Substance type: pale yellow clear liquid
- Physical state: liquid
- Analytical purity: >= 99.0%
- Lot/batch No.: C-120
- Stability under test conditions: Stated to be stable
- Storage condition of test material: Ambient conditions

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Charles River Japan Atsugi Breeding Center
- Age at study initiation: 5 weeks
- Weight at study initiation: males: 115.8-126.8 g; females: 97-107.6 g
- Fasting period before study: 16 hours
- Housing: 5 same sex in stainless steel breeding cages
- Diet: solid food (CE-2) from Clea Japan Inc., ad libitum
- Water: tap water from the Hatano City municipal water supply, ad libitum
- Acclimation period: 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 23 -24
- Humidity (%): 47.5 -65.5
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 29 March 2000 To: 13 April 2000

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
corn oil
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 20% w/v
- Amount of vehicle (if gavage): 10 mL/kg
- Lot/batch no. (if required): V9F1299 from Nacalai Tesque Co., Ltd.
- Justification for choice of vehicle: Substance is not miscible in aqueous vehicles but is water miscible in oil

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg

DOSAGE PREPARATION (if unusual): liquid test substance mixed with vehicle
Doses:
2000 mg/kg bodyweight
No. of animals per sex per dose:
10
Control animals:
yes
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations: for 1 hour after administration, and in the following 6 hours they were checked at hourly intervals. From observation day 2 to 15, observations were carried out once per day
- Frequency of weighing: prior to administration, then on observation days 2, 4, 8, 11 and 15
- Necropsy of survivors performed: yes
Statistics:
For body weight measurements, the mean and standard deviation for each group was calculated. Next, variance between the control group and the test substance group was tested by F-test, Student’s t-test was performed for homoscedasticity and Aspin-Welch test performed for heteroscedasticity. In all tests significance level was 5%.

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: No mortality occurred
Mortality:
0/10
Clinical signs:
On observation day 1, mucous feces and perianal smudges were observed in 2-3 of both the females and males in the control group and in the treatment group, however from observation day 2 onwards no abnormalities in general condition were observed.
Body weight:
Similar body weight changes were observed in males and females in the treatment group and the control group, no significant differences were found on weighing days.
Gross pathology:
In necropsy performed on observation day 15, there were no abnormal macroscopic organ/tissue findings in any of the animals, either male or female.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
In this acute oral toxicity study performed according to OECD guideline 401 (limit test) and GLP, the (LD50) of the 1,2,4-benzenetricarboxylic acid, trioctyl ester (C8TM) was >2000 mg/kg bodyweight in male and female rats.
Executive summary:

The test material 1,2,4-benzenetricarboxylic acid, trioctyl ester was tested for acute oral toxicity (RL2, according to OECD TG 401, GLP conform study). In this limit test 5 male and 5 female Sprague-Dawley rats were exposed to the limit dose of 2000 mg/kg bodyweight. Acontrol group received only vehicle (corn oil). Animals were checked for mortality, clinical signs and body weight changes during the 14 days observation period. At the end of the study animals were sacrificed and necropsy was performed. No mortality, relevant clinical signs or differnec in between body weight development between control and treatment group were observed. Based on the results obtained, the LD50 was judged to be > 2000 mg/kg bodyweight in male/female rats.

These findings are supported by another study