Methyl 2-[[3-[4-(1,1-dimethylethyl)phenyl]-2-methylpropylidene]amino]benzoate

Endpoint summary

Description of key information

Acute oral toxicity: OECD TG 420: LD50 > 2000 mg/kg bw.

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:

This study was conducted between 28 November 2016 and 28 December 2016

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Reliability 1 is assigned because the study conducted according to OECD TG 420 in compliance with GLP, without deviations that influence the quality of the results.

Qualifier:

according to guideline

Guideline:

OECD Guideline 420 (Acute Oral Toxicity - Fixed Dose Method)

Version / remarks:

2001

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.1 bis (Acute Oral Toxicity - Fixed Dose Procedure)

Version / remarks:

EC No. 440/2008

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

fixed dose procedure

Limit test:

no

Specific details on test material used for the study:

SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: Sponsor Batch No. B007723574
- Expiration date of the lot/batch: 10 May 2019
- Purity test date: 10 May 2016
- Purity: 85.6%
- Storage condition of test material: Room temperature in the dark under nitrogen

Species:

rat

Strain:

Wistar

Remarks:

RccHan™:WIST

Sex:

female

Details on test animals or test system and environmental conditions:

Dissiminated (delete when editing) Fill see puzzle pieces TEST ANIMALS
- Source: Envigo RMS (UK) Limited, Oxon, UK
- Females (if applicable) nulliparous and non-pregnant: yes
- Age at study initiation: 8 - 10 weeks
- Weight at study initiation: 1+0 - 171 g
- Fasting period before study: overnight
- Housing :in groups of up to four in suspended solid floor polypropylene cages furnished with woodflakes
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: >5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 - 25”C
- Humidity (%): 30 - 70%
- Air changes (per hr): >15
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 28 November 2016 to 28 Decemeber 2016

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

Test Item Preparation and Analysis
For the purpose of the study the test item was used as supplied. The specific gravity was determined and used to calculate the appropriate dose volume for the required dose level.

Study Design
Using available information on the toxicity of the test item, 2000 mg/kg was chosen as the starting dose.
A single animal was treated as follows:
Dose Level (mg/kg) Specific Gravity Dose Volume (mL/kg) Number of Rats
Female
2000 1.029 1.95 1

In the absence of toxicity at a dose level of 2000 mg/kg, an additional group of animals was treated as follows:
Dose Level(mg/kg) Specific Gravity Dose Volume (mL/kg) Number of Rats
Female
2000 1.02 1.95 4

A total of five animals were therefore treated at a dose level of 2000 mg/kg in the study.
All animals were dosed once only by gavage, using a metal cannula attached to a graduated syringe. The volume administered to each animal was calculated according to the fasted body weight at the time of dosing. Treatment of animals was sequential. Sufficient time was allowed between each dose group to confirm the survival of the previously dosed animals.

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

All animals were dosed once only by gavage, using a metal cannula attached to a graduated syringe. The volume administered to each animal was calculated according to the fasted body weight at the time of dosing. Treatment of animals was sequential. Sufficient time was allowed between each dose group to confirm the survival of the previously dosed animals.
Clinical observations were made 30 minutes, 1, 2, and 4 hours after dosing and then daily for 14 days. Morbidity and mortality checks were made twice daily, early and late during normal working days, and once daily at weekends and public holidays.
Individual body weights were recorded on Day 0 (the day of dosing) and on Days 7 and 14.
At the end of the observation period the animals were killed by cervical dislocation. All animals were subjected to gross necropsy. This consisted of an external examination and opening of the abdominal and thoracic cavities. The appearance of any macroscopic abnormalities was recorded. No tissues were retained.

Preliminary study:

No toxicity at a dose level of 2000 mg/kg

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: No toxicity

Mortality:

There were no deaths.

Clinical signs:

No signs of systemic toxicity were noted during the observation period.

Body weight:

All animals showed expected gains in body weight over the observation period.

Gross pathology:

No abnormalities were noted at necropsy.

Interpretation of results:

study cannot be used for classification

Conclusions:

The acute oral toxicity test showed an LD50 of xx mg/kg bw

Executive summary:

Acute oral toxicity: In this study, 5 female rats were administered the substance at dose levels of 2000 mg/kg bw. The rats showed no mortality, clinical signs, body weight, or abnormalities on necropsy.

The acute oral median lethal dose (LD50) of the test item in the female Wistar strain rat was estimated to be greater than 2000 mg/kg body weight.

The test item did not meet the criteria for classification according to Regulation (EC) No. 1272/2008 on the Classification, Labelling and Packaging of Substances and Mixtures.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Acute toxicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Additional information

Acute oral toxicity:

A study was performed to assess the acute oral toxicity of the substance, in accordance with OECD 420 (Acute Oral Toxicity -

Fixed Dose Method) and GLP principles.

In this study, 5 female rats were administered the substance at dose levels of 2000 mg/kg bw. The rats showed no mortality, clinical signs, body weight, or abnormalities on necropsy.

The acute oral median lethal dose (LD50) of the test item in the female Wistar strain rat was estimated to be greater than 2000 mg/kg body weight.

Justification for classification or non-classification

According to the criteria outlined in Annex VI of 1272/2008/EC (CLP), the substance does not have to be classified as acute toxic by the oral route.