2-[2,4-bis(tert-pentyl)phenoxy]-N-(3,5-dichloro-4-ethyl-2-hydroxyphenyl)butyramide

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

August 2018

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2018

Report date:

2018

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

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

GLP compliance:

yes (incl. QA statement)

Test type:

acute toxic class method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

2-[2,4-bis(tert-pentyl)phenoxy]-N-(3,5-dichloro-4-ethyl-2-hydroxyphenyl)butyramide

EC Number:

300-634-0

EC Name:

2-[2,4-bis(tert-pentyl)phenoxy]-N-(3,5-dichloro-4-ethyl-2-hydroxyphenyl)butyramide

Cas Number:

93951-12-3

Molecular formula:

C28H39Cl2NO3

IUPAC Name:

2-[2,4-bis(tert-pentyl)phenoxy]-N-(3,5-dichloro-4-ethyl-2-hydroxyphenyl)butyramide

Test material form:

solid

Details on test material:

Batch 44029
colour : White to off-white
retest date : 01/06/2019

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

female

Details on test animals or test system and environmental conditions:

Six Sprague Dawley rats (SPF Caw) supplied by Elevage JANVIER LABS (53940 Le Genest St Isle – France), were used after an acclimatization period of at least five days. The animals were nulliparous and non-pregnant. At the beginning of the study, the animals were 8-week old. They were identified prior to inclusion in the test by means of a numbered ring on the edge of one ear.
Housing:
Healthy female rats were housed by group of three in solid-bottomed clear polycarbonate cages with a stainless steel mesh lid. Each cage contains sawdust bedding which was changed at least 2 times a
week. Each cage was installed in conventional air conditioned animal husbandry. The temperature and relative humidity during the main test were controlled to remain within target ranges of 19°C to 25°C and 30% to 70%, respectively. The rate of air exchange was at least ten changes per hour and the lighting was controlled by a time switch to give twelve hours continuous light (07.00 to 19.00) and twelve hours darkness.

Food and drink:
Drinking water (tap-water from public distribution system) and foodstuff (ENVIGO - 2016) were supplied ad libitum. Food was removed on day 1 and then redistributed 4 hours after the test item
administration. Microbiological and chemical analyses of the water were carried out once every six months by Bureau Veritas – Eurofins (FRANCE). The results of analysis were kept in the Quality Assurance department and then were retained in the Phycher archives as meta-data.

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

DMSO

Details on oral exposure:

Each preparation was administered under a volume of 10 mL/kg body weight using a suitable syringe graduated fitted with an oesophageal metal canula.

Doses:

As there are no toxicological properties by oral route of the test item, the starting dose was 2000 mg/kg.
The animals of the treated group received an effective dose of 2000 mg/kg body weight of test item 80ACQ. Dimethyl sulfoxide (DMSO) was chosen as it produced the most suitable formulation at the requested concentration.In the first and second step of the study, 2.00037 g and 2.0007 g of the test item were weighed and DMSO was added to two 10 mL volumetric flasks. Just before the administration, the preparations were stirred using a vortex during 3 minutes to obtain homogeneous colourless suspensions.

No. of animals per sex per dose:

Group treated (2000 mg/kg): 3 female rats Rf2801 to Rf2803 (Step 1) and 3 female rats Rf2809 to Rf2811 (Step 2)

Control animals:

yes

Details on study design:

Current Control Study
Introduction:
The study identified No. TAO423-2018-003 was performed to assess the comportment of the strain of rat used at this laboratory in this environment and to give additional historical data.
The method was designed to meet the requirements of the following:
OECD Guideline for the Testing of Chemicals No.423 dated December 17th, 2001
Method B1tris of Council regulation No. 440/2008
Test Item: Dimethyl sulfoxide
Study dates: 27 March 2018 to 10 April 2018
Methods:
Three animals, received the control item Dimethyl sulfoxide, administered by gavage under a volume of 10 mL/kg body weight using a suitable syringe graduated fitted with an oesophageal metal canula.
Results:
Clinical examinations: Nothing to report. Animal normal (3/3)
Bodyweight evolution: normal during the test
Necropsy: No treatment related changes were observed

Results and discussion

Effect levels

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 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. Due to a gavage injury, a decrease of spontaneous activity, an increase of salivation and dyspnea associated with noisy breathing were noted on the first day

Other findings:

The macroscopic examination of the animals at the end of the study did not reveal treatment related changes.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

In conclusion, the LD50 of the test item 80ACQ is higher than 2000 mg/kg body weight.
In accordance with the O.E.C.D. 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.
The test item 80ACQ does not have to be classified in accordance with the Regulation EC No. 1272/2008 on classification, labelling and packaging of substances and mixtures.
No signal word or hazard statement is required.

Executive summary:

The test item 80ACQ was administered to a group of 6 female Sprague Dawley rats at the dose of 2000 mg/kg body weight.

The experimental protocol was established according to the official method as defined in the O.E.C.D.

Test Guideline No. 423 dated December 17th, 2001 and the test method B.1tris of the Council regulation No. 440/2008 of 30 May 2008.

No mortality occurred during the study.

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

Due to a gavage injury, a decrease of spontaneous activity, an increase of salivation and dyspnea associated with noisy breathing were noted on the first day of the test in one animal. A decrease of body weight (-15%) was noted on Day 2 versus Day 0. The animal recovered a normal activity on day 3.

The body weight evolution of the animals remained normal during the study.

The macroscopic examination of the animals at the end of the study did not reveal treatment related changes.