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

Acute Toxicity: oral

Administrative data

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

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2018

Report date:

2018

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

dated 17 December, 2001

Deviations:

no

Test guideline 2

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

Test material

Test material information

Constituent 1

Reference substance name:

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

EC Number:

949-745-1

Molecular formula:

not applicable UVCB

IUPAC Name:

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

Test material form:

liquid

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

Test animals

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

Administration / exposure

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

Results and discussion

Effect levels

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).

Applicant's summary and conclusion

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.