Propanoic acid, 2-hydroxy-, (1R,2S,5R)-5-methyl-2-(1-methylethyl)cyclohexyl ester, (2S)-

Endpoint summary

Description of key information

The substance was not acutely toxic via the oral or dermal route of exposure.

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:

1984-02-10 to 1984-03-13

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Study performed under GLP conditions and similar to OECD guideline 401;

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

GLP compliance:

yes

Test type:

standard acute method

Limit test:

no

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Breeding Laboratories Inc., Wilmington, USA
- Age at study initiation: young adults animals
- Weight at study initiation: males: 227.6 to 265.6 g; females: 192.8 to 210.2 g (values given as averages for different dose groups on day 1 of the experiment)
- Fasting period before study: overnight fasting
- Housing: individually in wire mesh bottom cages
- Diet (e.g. ad libitum): NIH open formula 07, Zeigler Brothers, Gardners, USA ad libitum
- Water (e.g. ad libitum): fresh tap water ad libitum
- Acclimation period: at least five days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): not reported
- Humidity (%): not reported
- Air changes (per hr): not reported
- Photoperiod (hrs dark / hrs light): not reported

Route of administration:

oral: gavage

Vehicle:

corn oil

Details on oral exposure:

VEHICLE
- Concentration in vehicle: not given
- Amount of vehicle (if gavage): substance was adiministered in 10 mL of corn oil
- Justification for choice of vehicle: use of vehicle not justified
- Lot/batch no. (if required): not given
- Purity: not given

Doses:

Limit test: 5000 mg/kg
Main test: 2000 mg/kg; 2828 mg/kg; 4000 mg/kg; 5657 mg/kg; 8000 mg/kg; 9514 mg/kg

No. of animals per sex per dose:

Each dose was administered to 5 male and 5 females.

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations: twice daily
- Frequency of weighing: on day 1, 8 and 14
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight

Statistics:

LD50 values were calculated according to Finney DJ (1971), Statistical methods in biological assays, second edition, London: Griffin Press.

Sex:

male

Dose descriptor:

LD50

Effect level:

7 871 mg/kg bw

Based on:

test mat.

95% CL:

5 972 - 13 025

Sex:

female

Dose descriptor:

LD50

Effect level:

6 571 mg/kg bw

Based on:

test mat.

95% CL:

4 807 - 11 212

Sex:

male/female

Dose descriptor:

LD50

Effect level:

7 257 mg/kg bw

Based on:

test mat.

95% CL:

5 971 - 9 675

Mortality:

No mortality of male rats occurred at doses up to 4000 mg/kg, one animal died at 5657 mg/kg, two animals died at 8000 mg/kg and 4 animals died at 9514 mg/kg. No mortality of female rats occurred at 2000 and 4000 mg/kg, one animal died at 2828 mg/kg, two animals died at 5657 and 8000 mg/kg each and all five animals died at 9514 mg/kg.

Clinical signs:

other: Observed clinical signs included decreased activity, ataxia, diarrhoea, lacrimation, wet abdomen and salivation.

Gross pathology:

Few observations were made during gross pathology including red spots of 1mm diameter on the cortical surface of kidneys (except at 5657 and 9514 mg/kg) and intestines of dark red colour containing blood-like viscous liquid (at 8000 mg/kg).

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

L-Menthyl-Lactate is not acutely toxic via the oral route with a LD50 of 7257 mg/kg body weight. The substance is not classified according to CLP.

Executive summary:

Frescolat/L-Menthyl Lactate 620105 was evaluated for acute oral toxicity (LD50) in male and female Sprague-Dawley rats. A limit test at 5000 mg/kg bw and a regular test with five dose levels ranging from 2000 to 9514 mg/kg bodyweight were performed. In the latter, five separate solutions of the sample corresponding to five doses were prepared in corn oil immediately prior to administration. All solutions were administered to overnight fasted animals at a volume of 10 mL/kg bodyweight. All animals were observed for mortality and toxic signs at least twice daily, for 14 days. Necropsy was performed with all animals. The calculated acute oral LD50 of the test article in male rats was found to be 7871 mg/kg body weight with a 95% confidence interval of 5972 to 13025 mg/kg. The calculated LD50 for females was found to be 6571 mg/kg body weight with a 95% confidence interval of 4807 to 11212 mg/kg body weight and the combined LD50 was calculated to be 7257 mg/kg body weight with a 95% confidence interval of 5971 to 9675 mg/kg.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

7 257 mg/kg bw

Quality of whole database:

The information is considered as reliable with few restrictions.

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

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Study was performed under GLP conditions according to OECD and EU guidelines

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.3 (Acute Toxicity (Dermal))

Deviations:

no

GLP compliance:

yes

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 ANIMALS
- Source: Bantin & Klingman Ltd.
- Age at study initiation: 8 - 12 weeks
- Weight at study initiation: male: 201-230g, female 200 - 227g
- Fasting period before study: not reported
- Housing: solid-floor polypropylene cages with sawdust bedding
- Diet (e.g. ad libitum):ad libitum
- Water (e.g. ad libitum):ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21 - 24°C
- Humidity (%): 40 - 56%
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12h dark / 12 h light

Type of coverage:

semiocclusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure: skin of the back and flanks, totalling about 10% of the total body surface area
- % coverage: semi-occlusive, not specified
- Type of wrap if used: self-adhesive bandage (HYPERTIE)

REMOVAL OF TEST SUBSTANCE
- Washing (if done): treated skin and surrounding hair was wiped with cotton wool moistened with distilled water
- Time after start of exposure: 24 hours after application following removal of cover

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): not reported
- Concentration (if solution): not applicable

VEHICLE
- no vehicle used

Duration of exposure:

24 hours of semi-occlusive skin contact

Doses:

10 g/kg bw of undiluted Menthyl lactate was applied onto skin area of about 4 x 5 cm

No. of animals per sex per dose:

5 male and 5 female rats

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations for overt signs of toxicity and death: 1 and 4 hours after dosing, at least once daily for 14 days
- Body weight: individual body weights were recorded on the day of treatment and on days seven and fourteen
- Necropsy of survivors performed: all animals were subjected to a gross necropsy examination for any macroscopic abnormalities
- Other examinations performed: clinical signs

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 10 000 mg/kg bw

Based on:

test mat.

Mortality:

No animal died during the study period.

Clinical signs:

other: No evidence of systemic toxicity or skin irritation was noted during the observation period of 14 days.

Gross pathology:

No abnormalities were noted at necropsy of animals killed at the end of the study.

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The acute dermal median lethal dose (LD50) of the test material, Menthyl lactate, to Sprague-Dawley rats was found to be greater than 10 g/kg bodyweight. The substance is not classified according to CLP.

Executive summary:

The acute dermal toxicity of the test material in the Sprague-Dawley rat was determined according to the OECD Guideline for Testing of Chemicals (1981) No. 402 "Acute Dermal Toxicity" with a group of ten animals (five males and five females).

A single, 24-hour, semi-occluded dermal application of the test material to intact skin, at a dose level of 10 g/kg bodyweight was given. Animals were observed for a period of 14 days after application. There were no deaths, no evidence of systemic toxicity or skin irritation and no toxicologically significant effects on bodyweight noted during the study period. Also no abnormalities were noted at necropsy of animals killed at the end of the study.

The acute dermal median lethal dose (LD50) of the test material in the Sprague-Dawley rat was found to be greater than 10 g/kg bodyweight.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Quality of whole database:

The information is considered as reliable without restrictions.

Additional information

Acute toxicity studies with rats are available for the oral and dermal routes of exposure representing also the likely routes of human exposure to menthyl lactate. The substance did not exhibit adverse effects in these two acute toxicity studies. Accordingly, the substance does not exhibit acute oral or dermal toxicity.

Justification for selection of acute toxicity – oral endpoint
This is a valid study on the acute oral toxicity of the substance similar to OECD TG 401 study. The study was performed under GLP.

Justification for selection of acute toxicity – dermal endpoint
This is a valid study on the acute dermal toxicity of the substance according to OECD TG 402. The study was performed under GLP.

Justification for classification or non-classification

- oral toxicity:

Based on the above stated assessment of the acute oral toxicity of menthyl lactate, the results from reliable with restrictions study are above the threshold value given in the CLP Regulation. Therefore menthyl lactate does not need to be classified according to Council Directive 2001/59/EC (28th ATP of Directive 67/548/EEC) and according to CLP (Regulation (EC) No 1272/2008 of the European Parliament and of the Council) as implementation of UN-GHS in the EU.

- dermal toxicity:

Based on the above stated assessment of the acute dermal toxicity, menthyl lactate does not need to be classified according to Council Directive 2001/59/EC (28th ATP of Directive 67/548/EEC) and according to CLP (Regulation (EC) No 1272/2008 of the European Parliament and of the Council) as implementation of UN-GHS in the EU.

- inhalation toxicity:

No inhalation studies are available and due to exposure considerations the conduct of studies and the classification and labelling for this endpoint is deemed not to be necessary.