Esterification products of Guerbet alcohols, C24-26, branched and cyclic with benzene-1,2,4-tricarboxylic acid 1,2-anhydride (3:1)

Endpoint summary

Description of key information

The test item was administered to a group of 6 female Sprague Dawley rats at the dose of 2000 mg/kg body weight. The study was performed according to the official method as defined in the OECD Test Guideline No. 423 dated December 17th, 2001, and in compliance with the principles of the Good Laboratory Practice (GLP).

No mortality occurred during the study. No clinical signs related to the administration of the test item were observed during the study. The body weight evolution of the animals remained normal during the study. The macroscopic examination of the animals at the end of the study revealed a red spot on corpus in one animal (1/6).

In conclusion, the LD50 of the test item is higher than 2000 mg/kg body weight. In accordance with the OECD Test Guideline No. 423, the LD50 cut-off of the test item may be considered as 5000 mg/kg body weight by oral route 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:

25 September - 10 October 2018

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Remarks:

GLP compliant

Qualifier:

according to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

Version / remarks:

dated 17 December, 2001

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)

Version / remarks:

dated 30 May 2008

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Remarks:

Certificate of Compliance with Good Laboratory Practices according to Directives 2004/9/CE and 2004/10/CE, Groupe Interministeriel des Produits Chimiques, Republique Francaise, Certificat n°: 2017/33, dated 27 April 2017

Test type:

acute toxic class method

Limit test:

yes

Specific details on test material used for the study:

SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: received from sponsor on 04 September 2018, batch No. 05347/MA
- Expiration date of the lot/batch: June 2022

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: room temperature, darkness
- Solubility and stability of the test substance in the solvent/vehicle: test item was used as supplied

Species:

rat

Strain:

Sprague-Dawley

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Elevage JANVIER LABS (53940 Le Genest St Isle, France)
- Females (if applicable) nulliparous and non-pregnant: yes
- Age at study initiation: 8 weeks
- Weight at study initiation: 185 - 219g, mean: 201.3g ± 11.4g
- Fasting period before study: yes, food was removed the day before treatment and redistributed 4 hours after test item administration
- Housing: housed by groups of three in solid-bottomed clear polycarbonate cages with stainless steel mesh lid, each cage containing sawdust bedding wich was changed at least 2 times a week
- Diet: Teklad Global 16% Protein Rodent Diet from ENVIGO (2016) ad libitum
- Water: tap-water from public distribution system ad libitum; microbiological and chemical analyses of the water carried out once every six months by Bureau Veritas - Eurofins (France)
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 - 25
- Humidity (%): 30 - 70
- Air changes (per hr): 10
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 25 September 2018 To: 10 October 2018

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

MAXIMUM DOSE VOLUME APPLIED: 2.13 ml/kg bw (corresponding to 2 g/kg bw according to the calculated density)

CLASS METHOD
- Rationale for the selection of the starting dose: No information was available regarding a possible systemic toxicity, the first test dose was chosen to be 2000 mg/kg bw.

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

6

Control animals:

yes

Remarks:

A control study with distilled water (3 animals used), identified No. TAO423-2018-004, was performed in the laboratory to assess the comportment of the strain of rat used and to give additional historical data.

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: daily observations of behavioural or toxic effects on the major physiological functions and of mortality; weighing on Day 0 (just before administration of the test item), then on Days 2, 7 and 14.
- Necropsy of survivors performed: yes
- Other examinations performed: body weight changes were calculated

Key result

Sex:

male/female

Dose descriptor:

LD50 cut-off

Effect level:

5 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality occurred during the study.

Clinical signs:

other: No clinical signs related to the administration of the test item were observed during the study.

Gross pathology:

The macroscopic examination of the animals at the end of the study revealed a red spot on corpus in one animal (1/6).

Interpretation of results:

GHS criteria not met

Conclusions:

The LD50 of the test item is higher than 2000 mg/kg body weight. In accordance with the OECD Test Guideline No. 423, the LD50 cut-off of the test item may be considered as 5000 mg/kg body weight by oral route in the rat.

Executive summary:

The test item was administered to a group of 6 female Sprague Dawley rats at the dose of 2000 mg/kg body weight. The study was performed according to the official method as defined in the OECD Test Guideline No. 423 dated December 17th, 2001, and in compliance with the principles of the Good Laboratory Practice (GLP).

No mortality occurred during the study. No clinical signs related to the administration of the test item were observed during the study. The body weight evolution of the animals remained normal during the study. The macroscopic examination of the animals at the end of the study revealed a red spot on corpus in one animal (1/6).

In conclusion, the LD50 of the test item is higher than 2000 mg/kg body weight. In accordance with the OECD Test Guideline No. 423, the LD50 cut-off of the test item may be considered as 5000 mg/kg body weight by oral route in the rat.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

discriminating dose

Value:

5 000 mg/kg bw

Quality of whole database:

Klmisch 1

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:

experimental study

Adequacy of study:

supporting study

Study period:

from 2009-05-18 to 2009-06-18

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system 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 encyrcling the trunk of the animal with a lenght 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

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Mortality:

no mortality occurred

Clinical signs:

other: no clinical signs were observed

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 ranimnif animals.

Interpretation of results:

GHS criteria not met

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 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 o 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

Additional information

Experimental studies in rats show a very low acute oral toxicity for Esterification products of Guerbet alcohols, C24-26, branched and cyclic with benzene-1,2,4-tricarboxylic acid 1,2-anhydride (3:1). No clinical effects at doses of 2000 mg/kg.

One acute dermal toxicity study of the read-across substance 1,2,4 -Benzenetricarboxylic acid, mixed decyl and octyl triesters shows also a low dermal toxicity. No mortalities nor clinical effects were observed at the limit dose of 2000 mg/kg.

Based on the available data it can be concluded that Esterification products of Guerbet alcohols, C24-26, branched and cyclic with benzene-1,2,4-tricarboxylic acid 1,2-anhydride (3:1) is of very low acute oral and dermal toxicity.

Justification for classification or non-classification

The oral and acute LD50 -values exceed clearly the cut-off value for classification according to Regulation (EC) No 1272/2008.

Overall, the acute oral toxicity of Esterification products of Guerbet alcohols, C24-26, branched and cyclic with benzene-1,2,4-tricarboxylic acid 1,2-anhydride (3:1) (Reaction product of guerbet alcohols, C24 -26, branched and cyclic with 1,2,4-Benzenetricarboxylic acid)

and the dermal toxicity of the read-across substance 1,2,4-Benzenetricarboxylic acid, mixed decyl and octyl triesters is low and therefore the test item does not need to be classified.