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Description of key information

The acute oral median lethal dose (LD50) of the test substance in rats (2 male and 2 female) was greater than 10 ml/kg bw (> 9590 mg/kg bw).
Under the conditions of the test, the read-across substance, tris(2-ethylhexyl) benzene-1,2,4-tricarboxylate, has an acute dermal LD50 in rabbits of > 2000 mg/kg bw).

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records
Reference
Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
24 August 1983 to 7 September 1983
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Study conducted to acceptable standards.
Qualifier:
no guideline followed
Principles of method if other than guideline:
The compound as supplied was administered as a single dose by gavage to 4 rats which had been fasted for 18 hours, at a rate of 10 ml/kg.
GLP compliance:
not specified
Test type:
other: Not specified
Limit test:
yes
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
Healthy Sprague Dawley RAI f (SPFTif) derived rats, bred on the premises, or imported from CIBA-GEIGY Limited, Basle, Switzerland,. aged 5-6 weeks, having an average body weight of 180 g (2 males) and 145 g (2 females).

Husbandry
Rats were caged singly and kept in a room maintained at a temperature of 21°C. (± 2°C). Animals were subjected to 12 hours artificial light and 12 hours darkness in each 24 hour period. A commercial autoclavable pelleted diet (Labsure CRM rat and mouse) was fed ad lib. Filtered water was available at all times.
Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
The compound as supplied was administered as a single dose by gavage to rats which had been fasted for 18 hours, at a rate of 10 ml/kg.
Doses:
10 ml/kg
No. of animals per sex per dose:
2 per sex per dose
Control animals:
no
Details on study design:
Observations
After administration of the compound, the animals were observed for 14 days. Deaths and clinical symptoms were recorded. At the end of the observation period, surviving animals were killed by exsanguination under ether anaesthesia and an autopsy performed.
Statistics:
None
Preliminary study:
Not applicable
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 9 590 mg/kg bw
Based on:
test mat.
Mortality:
None
Clinical signs:
None
Body weight:
No data
Gross pathology:
No abnormalities were seen throughout the 14 day observation period nor at terminal autopsy.
Other findings:
None
Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The acute oral median lethal dose (LD50) of the substance in rats was greater than 10 ml/kg bw (> 9590 mg/kg bw).
Executive summary:

The acute oral median lethal dose (LD50) of the substance in rats (2 male and 2 female) was greater than 10 ml/kg bw (> 9590 mg/kg bw).

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
9 590 mg/kg bw
Quality of whole database:
Study not conducted to GLP. Considered to be a Klimisch 2.

Acute toxicity: via inhalation route

Link to relevant study records
Reference
Endpoint:
acute toxicity: inhalation
Data waiving:
exposure considerations
Justification for data waiving:
other:
Endpoint conclusion
Endpoint conclusion:
no study available

Acute toxicity: via dermal route

Link to relevant study records
Reference
Endpoint:
acute toxicity: dermal
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Study period:
October 23 - November 04 1981
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP compliant study conducted according to recognised test methods
Qualifier:
according to
Guideline:
other: Federal Insecticide, fungicide & rodenticide Act part 163, Title 40; Code of the federal Regulations 40 CRF 163.81 & Principles & procedures for evaluating the toxicity of household substances Publication 1138, National Academy of Sciences-National Resear
GLP compliance:
yes
Test type:
other: Limit Test
Limit test:
yes
Species:
rabbit
Strain:
New Zealand White
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Becker Centalia Kansas USA
- Weight at study initiation: 2.3-3.2 Kg
IN-LIFE DATES: From: October 22 To: November 04
Type of coverage:
semiocclusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: back with longitudinal abrasions over the exposure area. Abrasions penetrated the stratum corneum but not deeply enough to cause bleeding
- % coverage: 10
- Type of wrap if used: gauze covered by rubber dam

REMOVAL OF TEST SUBSTANCE
- Washing (if done): yes area wiped
- Time after start of exposure: 24h

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2.0 ml/kg
- Concentration (if solution): 100% (as supplied)
- Constant volume or concentration used: yes/no constant concentration
- For solids, paste formed: yes/no: N/A

VEHICLE: N/A
- Amount(s) applied (volume or weight with unit):
- Concentration (if solution):
- Lot/batch no. (if required):
- Purity:
Duration of exposure:
24h
Doses:
2.0 ml/kg
No. of animals per sex per dose:
3 male & 3 females in TOTM group
2 males & 2 females in control group
Control animals:
yes, concurrent no treatment
Details on study design:
- Duration of observation period following administration: 14 days (or other?): 14d
- Frequency of observations and weighing: weighing on d 1, 7, 14
- Necropsy of survivors performed: yes/no: yes d15
- Other examinations performed: clinical signs, body weight, organ weights, histopathology, other:
Statistics:
No. N/A single dosage used.
Preliminary study:
No data
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 mL/kg bw
Based on:
test mat.
Remarks on result:
other: No confidence limits calculable as no mortality
Mortality:
None
Clinical signs:
No signs of toxicity seen during exposure & subsequent observation periods
Body weight:
No effects of exposure on body weight. All animals gained weight on days 7 & 14.
Gross pathology:
No observed abnormalities at necropsy.

Mean (±SD) Body weights (g) of 3 male & 3 female rabbits exposed to 2.0 ml/kg TOTM and 2 male & 2 female control rabbits

Intervals

Males

Females

 

Control1

TOTM 2.0 ml/kg

Control1

TOTM 2.0 ml/kg

 

 

 

 

 

Pre-exposure

3.2

2.33 ± 0.06

2.8 ± 0.14

2.37 ± 0.06

Day 7

3.4

2. 30 ± 0.10

3.1± 0.07

2.53 ± 0.06

Day 14

3.6

2.46 ± 0.06

3.2 ± 0.14

2.67 ± 0.06

 

 

 

 

 

1Controls were untreated

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Under the conditions of this test, the read-across substance, tris(2-ethylhexyl) benzene-1,2,4-tricarboxylate, has an acute dermal LD50 in rabbits of >2.0 ml/kg.
Executive summary:

Under the conditions of this test, the read-across substance, tris(2-ethylhexyl) benzene-1,2,4-tricarboxylate, has an acute dermal LD50 in rabbits of >2.0 ml/kg bw

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
2 000 mg/kg bw
Quality of whole database:
GLP compliant study conducted according to recognised test methods therefore categorised as Klimisch 1.

Additional information

The acute oral median lethal dose (LD50) of the test substance in rats (2 male and 2 female) was greater than 10 ml/kg bw (> 9590 mg/kg bw).

In an in vivo acute dermal toxicity study, the read-across substance, tris(2-ethylhexyl) benzene-1,2,4-tricarboxylate, has an acute dermal LD50 in rabbits of > 2000 mg/kg bw.


Justification for selection of acute toxicity – oral endpoint
Only 1 study is available.

Justification for selection of acute toxicity – inhalation endpoint
The test substance has a very low vapour pressure hence the potential for the generation of inhalable forms is low. Dermal exposure is considered to be the appropriate route of exposure and has been assessed accordingly. No acute inhalation test was performed.

Justification for selection of acute toxicity – dermal endpoint
Klmisch 1 study

Justification for classification or non-classification

The above studies have all been ranked reliability 1 or 2 according to the Klimisch et al system. This ranking was deemed appropriate because the studies were conducted according to recognised test methods. Sufficient dose ranges and numbers are detailed; hence it is appropriate for use based on reliability and animal welfare grounds.

The above results triggered no classification under the Dangerous Substance Directive (67/548/EEC) and the CLP Regulation (EC No 1272/2008). No classification for acute effects is therefore required.