Registration Dossier

Administrative data

Description of key information

- Acute toxicity:
Oral: LD50: >2000 mg/kg in the rat
Dermal: LD50: > 2000 mg/kg in the rat

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:
2001
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP compliant study conducted in accordance with internationally recognised test methods.
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
not specified
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes
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 weeks
- Weight at study initiation: males: 116-127 g; females: 97-108 g
- Fasting period before study: 18 hours
- Housing: 5 same sex in stainless steel breeding cages
- Diet (e.g. ad libitum): yes, except during pre-dose fasting period
- Water (e.g. ad libitum): yes
- Acclimation period: 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 23+/- 2 degrees C
- Humidity (%): 55+/- 10
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12: 12

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
- 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 (based on findings of preliminary study in which doses of 1000 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
- Frequency of observations and weighing: frequently for 6 hours on day of dosing then daily
- Necropsy of survivors performed: yes
- Other examinations performed: body weight - Days 1, 2, 4, 8, 11 and 15
Statistics:
Student t-test applied to bodyweight data control vs. test groups
Preliminary study:
In preliminary study 1000 and 2000 mg/kg did not cause mortality.
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 test group
Clinical signs:
Mucoid faeces were seen in animals from both control and test groups 1-3 hours after dosing. The incidence between groups was similar.
Body weight:
There were no changes attributed to treatment.
Gross pathology:
There were no abnormalities noted in any animal from either control or treatment group.
Other findings:
No data
Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The median lethal dose (LD50) in the rat was established at > 2,000 mg/kg for both sexes.
Executive summary:

Acute oral toxicity has been investigated in the rat using methods described in OECD TG 401. No mortality or effects of treatment occurred following administration of a single dose at a level of 2000 mg/kg body weight. The median lethal dose (LD50) in the rat is therefore in excess of 2000 mg/kg

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
discriminating dose
Value:
2 000 mg/kg bw
Quality of whole database:
No applicable

Acute toxicity: via inhalation route

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:
from 2009-05-18 to 2009-06-18
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: GLP guideline study. For read-across justification see Section 13.
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Harlan Italy S.r.l., San Pietro al Natisone (UD), Italy
- Age at study initiation: 6 to 8 weeks
- Weight at study initiation: 275.0 ± 3.7 g (mean weight males), 215.6 ± 10.9 g (mean weight females)
- Housing: Polycarbonate cages measuring 42.5x26.6x18 cam with stainless steel mesh lid and floor
- Diet (e.g. ad libitum): 4 RF 18 ad libitum, supplied by Mucedola S.r.l., Settimo Milanese (MI), Italy
- Water (e.g. ad libitum): drinking water ad libitum
- Acclimation period: at least 5 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 2
- Humidity (%): 55 ± 15
- Air changes (per hr): 15 - 25
- Photoperiod (hrs dark / hrs light): 12/12


IN-LIFE DATES: From: 2009-06-3 To: 2009-06-18
Type of coverage:
semiocclusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: dorsal surfaces of the trunk
- % coverage: 10 %
- Type of wrap if used: A patch of surgical gauze covered by a strip of synthetic film was placed over the treated site and the whole assembly held in place by encircling the trunk of the animal with a length of elastic adhesive bandage.


REMOVAL OF TEST SUBSTANCE
- Washing (if done): yes, by gentle swabbing of the skin with cotton wool soaked with lukewarm water
- Time after start of exposure: 24 hours


TEST MATERIAL
- Amount(s) applied (volume or weight with unit): Aliquots were weighed accordingly to the body weight of each animal measured prior to dosing, no further details mentioned
Duration of exposure:
24 hours
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Mortality and morbidity twice daily, clinical signs were recorded on dosing, approx. 1, 2 and 4 hours after dosing and daily thereafter, body weights were recorded on the day of allocation (day -1), days 1, 8 and 15 (day of necropsy)
- Necropsy of survivors performed: yes
- Other examinations performed: no
Statistics:
not performed
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Mortality:
no mortality occurred
Clinical signs:
no clinical signs were observed
Body weight:
changes in body weight were within the expected range
Gross pathology:
At necropsy examination performed on all animals at termination of the study red areas (multiple, pinpoint) in the right lobe of the thymus were noted in a single female animal. No abnormalities were found in the animals.
Interpretation of results:
practically nontoxic
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The acute toxicity of 1,2,4-Benzenetricarboxylic acid, mixed decyl and octyl triesters was investigated following dermal administration of a single dose to the rat at 2000 mg/kg.
No mortality occurred following dosing and no signs of toxicity were observed.
These results indicated that the test item has no toxic effect on the rat following dermal exposure over a 24 hour period at a level of 2000 mg/kg. The lack of mortality demonstrated the LD50 to be greater than 2000 mg/kg.
Executive summary:

The acute toxicity of a structural analogue of the substance (1,2,4 -Benzenetricarboxylic acid, mixed decyl and octyl triesters) was investigated following dermal administration of a single dose to the rat at 2000 mg/kg according to OECD guideline 402, adopted on 24 February 1987 and Test method B.3 "Acute Toxicity (dermal)" described in Council Regulation (EC) No. 440/2008.

A single dose of 2000 mg/kg was administered to a group of 5 male and 5 female animals for 24 hours. After 14 days all animals were killed and subjected to necropsy examination. No mortality occurred following dosing and no signs of toxicity were observed. The body weight changes observed during the study were within the expected range for this species and age of animals. No significant abnormalities were found at necropsy in the animals at termination of the study. No abnormalities were observed at the treated site.

These results indicated that the test item has no toxic effect on the rat following dermal exposure over a 24 hour period at a level of 2000 mg/kg.

The lack of mortality demonstrated the LD50 to be greater than 2000 mg/kg.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
discriminating dose
Value:
2 000 mg/kg bw
Quality of whole database:
Not applicable

Additional information

Data are available from a single study for the oral route. Information for the dermal route has been obtained by read-across from a structurally related substance, 1,2,4 -benzenetricarboxylic acid with linear C8- and C10 -alcohols, produced by esterification of trimellitic anhydride with a mixture of linear C8-C10-alcohols (40 - 60 % C8 and 40 - 60 % C10) rather than C8 alcohol alone. No data are available regarding inhalation toxicity although the predicted low vapour pressure suggest exposure to vapours is unlikely and the generation of significant aerosol concentrations of respirable size during normal use is unlikely.


Justification for selection of acute toxicity – oral endpoint
Single study available

Justification for classification or non-classification

Classification with regard to acute oral and dermal toxicity is not justified based on the observed lack of mortality at a dose level of 2000 mg/kg and taking into account the provisions laid down in Council Directive 67/548/EEC and CLP (1272/2008/EC).