Ethyl trans-2,2,6-trimethylcyclohexanecarboxylate

Endpoint summary

Description of key information

A study was performed to assess the acute oral toxicity of the test material in the Sprague-Dawley strain rat. The method used followed that described in the OECD Guidelines for Testing of Chemicals (1987) No. 401 "Acute Oral Toxicity ". There were no deaths. Common signs of systemic toxicity noted were ataxia, hunched posture and lethargy with additional signs of decreased respiratory rate. Animals recovered one day after dosing. All animals showed expected gain in bodyweight during the study. No abnormalities were noted at necropsy. The acute oral median lethal dose (LD50) of the test material in the Sprague-Dawley strain rat was found to be greater than 2000 mg/ kg bodyweight.

A study was performed to assess the acute dermal toxicity of the test material in the Sprague-Dawley strain rat. The method used followed that described in the OECD Guidelines for Testing of Chemicals (1981) No. 402 "Acute Dermal Toxicity". There were no deaths. No signs of systemic toxicity or skin irritation were noted during the study. All animals showed expected gain in bodyweight during the study. No abnormalities were noted at necropsy. The acute dermal median lethal dose (LD50) of the test material in the Sprague-Dawley strain rat was found to be greater than 2000 mg/ kg bodyweight.

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:

17 November 1992 to 30 December 1992

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

yes

Remarks:

Room temperature and humidity

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 SYSTEM
Specification
Male and female Sprague-Dawley strain rats were supplied by Charles River (UK) Ltd., Manston, Kent, U.K. At the start of the main study the males weighed 148 - 174g, and the females 133 - 153g, and were approximately five to eight weeks old . After a minimum acclimatisation period of at least five days the animals were selected at random and given a unique number within the study by indelible ink marking on the tail and a number written on a cage card.

Husbandry
The animals were housed in groups of five by sex in solid - floor polypropylene cages with sawdust bedding. With the exception of an overnight fast immediately before dosing and for approximately two hours after dosing, free access to mains drinking water and food (Rat and Mouse Expanded Diet No. 1, Special Diet Services Limited, Witham, Essex, U.K.) was allowed throughout the study.The animal room was maintained at a temperature of 18 - 22°C and relative humidity of 50 - 73%. On one occasion the temperature and humidity were outside the limits specified in the protocol (19°C and 70%). These deviations were considered not to have affected the purpose or integrity of the study. The rate of air exchange was approximately 15 changes per hour and the lighting was controlled by a time switch to give 12 hours continuous light and 12 hours darkness.

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

For the purpose of the study the test material was used as supplied. The specific gravity was determined by Safepharm Laboratories Limited and used to calculate the appropriate dose volume for the required dose level.
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 its fasted bodyweight at the time of dosing.

Doses:

2000mg/ kg bodyweight

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

The animals were observed for deaths or overt signs of toxicity 1, 2 and 4 hours after dosing and subsequently once daily for 14 days.
Individual bodyweights were recorded prior to dosing on Day 0 and on Days 7 and 14.
At the end of the study the animals were killed by cervical dislocation and subjected to gross pathological examination. 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.

Statistics:

no

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

There were no deaths.

Clinical signs:

Common signs of systemic toxicity noted were ataxia, hunched posture and lethargy with additional signs of decreased respiratory rate.
All animals recovered one day after dosing.

Body weight:

All animals showed expected gain in bodyweight during the study.

Gross pathology:

No abnormalities were noted at necropsy.

Interpretation of results:

other:

Remarks:

Not classified in accordance with the CLP Regulation

Conclusions:

The acute oral median lethal dose (LD50) of the test material in the Sprague-Dawley strain rat was found to be greater than 2000 mg/ kg bodyweight.

Executive summary:

A study was performed to assess the acute oral toxicity of the test material in the Sprague-Dawley strain rat. The method used followed that described in the OECD Guidelines for Testing of Chemicals (1987) No. 401 "Acute Oral Toxicity " referenced as Method B1 in Commission Directive 84/449/EEC (which constitutes Annex V of Council Directive 67/548/EEC).

Following a range-finding study, a group of ten fasted animals (five males and five females) was given a single oral dose of undiluted test material at a dose level of 2000 mg/ kg bodyweight. The animals were observed for fourteen days after the day o f dosing and were then killed for gross pathological examination.

There were no deaths. Common signs of systemic toxicity noted were ataxia, hunched posture and lethargy with additional signs of decreased respiratory rate. Animals recovered one day after dosing.

All animals showed expected gain in bodyweight during the study.

No abnormalities were noted at necropsy.

The acute oral median lethal dose (LD50) of the test material in the Sprague-Dawley strain rat was found to be greater than 2000 mg/ kg bodyweight. No symbol and risk phrase are required according to EEC labelling regulations.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Quality of whole database:

Klimisch 1 study

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:

key study

Study period:

12 January 1993 to 26 January 1993

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 SYSTEM
Specification
Five male and five female Sprague-Dawley strain rats were supplied by Charles River (UK) Ltd., Manston, Kent, U.K. At the start of the study the males weighed 226 - 247g, and the females 205 - 232g, and were approximately ten to fourteen weeks old . After a minimum acclimatisation period of at least five days the animals were selected at random and given a unique number within the study by indelible ink marking on the tail and a number written on a cage card.
Husbandry
The animals were housed in suspended polypropylene cages furnished with softwood sawdust. The animals were housed individually during the 24-hour exposure period and in groups of five, by sex, for the remainder of the study. Free access to mains drinking water and food (Rat and Mouse Expanded Diet No. 1, Special Diet Services Limited, Witham, Essex, U.K.) was allowed throughout the study.The animal room was maintained at a temperature of 20 - 21°C and relative humidity of 52 - 67%. The rate of air exchange was approximately 15 changes per hour and the lighting was controlled by a time switch to give 12 hours continuous light and 12 hours darkness.

Type of coverage:

semiocclusive

Vehicle:

unchanged (no vehicle)

Remarks:

Aucun

Details on dermal exposure:

The calculated volume of the undiluted test material , as received, was applied uniform;y to an area of shorn skin (approximating to 10% of the total body surface area) using a graduated syringe. A piece of surgical gauze measuring 7 cm x 4 cm was placed over the treatment area and semioccluded with a piece of self-adhesive bandage (HYPERTIE). The bandage was further secured with a piece of BLENDERM wrapped around each end. The animals were caged individually for the 24-hour exposure period.

Shortly after dosing the dressings were examined to ensure that they were securely in place. After the 24-hour contact period the bandage was carefully removed and the treated skin and surrounding hair wiped with cotton wool moistened with distilled water to remove any residual test material . The animals were returned to group housing for the rest of the study.

Duration of exposure:

24 h

Doses:

2000 mg/ kg bw

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

The animals were observed for deaths or overt signs of toxicity 1/2, 1, 2 and 4 hours after dosing and subsequently once daily for 14 days.Any adverse dermal reactions, if present, were also recorded.Individual bodyweights were recorded prior to application of the test material on Day 0 and on Days 7 and 14.At the end of the study the animals were killed by cervical dislocation and subjected to gross pathological examination. 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.

Statistics:

no

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

There were no deaths.

Clinical signs:

No signs of systemic toxicity were noted during the study.

Body weight:

All animals showed expected gain in .bodyweight during the study.

Gross pathology:

No abnormalities were noted at necropsy.

Interpretation of results:

other:

Remarks:

No classification required in accordance with the CLP Regulation

Conclusions:

The acute dermal median lethal dose (LD50) of the test material , ET-344 SP, in the Sprague-Dawley strain rat was found to be greater than 2000 mg/kg bodyweight.

Executive summary:

A study was performed to assess the acute dermal toxicity of the test material in the Sprague-Dawley strain rat. The method used followed that described in the OECD Guidelines for Testing of Chemicals (1981) No. 402 "Acute Dermal Toxicity " referenced as Method B3 in Commission Directive 84/449/EEC (which constitutes Annex V of Council Directive 67/548/EEC).

A group of ten animals (five males and five females) was given a single 24-hour, semi-occluded dermal application to intact skin at a dose level of 2000 mg/ kg bodyweight. The animals were observed for fourteen days after the day of treatment and were then killed for gross pathological examination.

There were no deaths. No signs of systemic toxicity or skin irritation were noted during the study.

All animals showed expected gain in bodyweight during the study.

No abnormalities were noted at necropsy.

The acute dermal median lethal dose (LD50) of the test material in the Sprague-Dawley strain rat was found to be greater than 2000 mg/ kg bodyweight.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Quality of whole database:

Klimisch 1 study

Justification for classification or non-classification

Based on the results of the acute oral toxicity study and the acute dermal toxicity study, no classification for acute toxicity is required in accordance with the CLP Regulation.

Based on the vapour pressure on the substance (29.85 +/- 1.4 Pa according to EU method A.4), inhalation is not a likely route of exposure for this substance therefore an acute inhalation study has not been conducted with the substance.