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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

Constituent 1
Chemical structure
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.