2-(3,5-dimethylhex-3-en-2-yloxy)-2-methylpropyl cyclopropanecarboxylate

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

From 22 May To 11 August, 2008.

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Remarks:

According to the OECD Guideline No. 402 and in compliance with GLP practices.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2008

Report date:

2008

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1200 (Acute Dermal Toxicity)

Version / remarks:

August 1998

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Version / remarks:

Adopted 24 February 1987

Deviations:

no

Test guideline 3

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

July 31, 1992

Deviations:

no

Principles of method if other than guideline:

Not applicable.

GLP compliance:

yes

Remarks:

Swiss legislation on Good Laboratory Practice (signed in September 04, 2008)

Test type:

fixed dose procedure

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

2-{[(2R)-3,5-dimethylhex-3-en-2-yl]oxy}-2-methylpropyl cyclopropanecarboxylate; 2-{[(2S)-3,5-dimethylhex-3-en-2-yl]oxy}-2-methylpropyl cyclopropanecarboxylate

EC Number:

700-118-9

Cas Number:

676532-44-8

Molecular formula:

C16H28O3

IUPAC Name:

2-{[(2R)-3,5-dimethylhex-3-en-2-yl]oxy}-2-methylpropyl cyclopropanecarboxylate; 2-{[(2S)-3,5-dimethylhex-3-en-2-yl]oxy}-2-methylpropyl cyclopropanecarboxylate

Test material form:

liquid

Details on test material:

- Description: Colourless liquid
- Formula: C16H28O3
- Molecular weight: 268,4 g/mol

Specific details on test material used for the study:

- Storage conditions: In the refrigerator at +2 to +8°C, protected from light

Test animals

Species:

rat

Strain:

other: HanRcc: WIST (SPF)

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: RCC Ltd, Laboratory Animal Services, CH-4414 Füllinsdorf/Switzerland
- Age at study initiation: male: 9 weeks; female: 11 weeks
- Diet (e.g. ad libitum): Pelleted standard Provimi Kliba 3433 rat/mouse maintenance diet (batch 21/08), ad libitum
- Water (e.g. ad libitum): Community tap water from Füllinsdorf, ad libitum
- Housing: groups of five per sex in Makrolon type-4 cages with standard sotwood bedding during acclimatisation ; then individually in Makrolon type-3 cages with standard softwood bedding during treatment and observation period.
- Acclimation period: not reported

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22±3
- Humidity (%): 30-70
- Air changes (per hr): 10-15
- Photoperiod (hrs dark / hrs light): 12/12
- Music during the daytime light period.

IN-LIFE DATES: From 27 May To 17 June, 2008

Administration / exposure

Type of coverage:

semiocclusive

Vehicle:

polyethylene glycol

Remarks:

PEG 300

Details on dermal exposure:

TEST SITE
- % coverage: 10
On day 1, the test item was applied at a dose of 2000 mg/kg bw evenly on the intact skin with a syringe and covered with a semi-occlusive dressing. the dressing was wrapped around the abdomen and fixed with an elastic adhesive bandage.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): yes. Twenty-four hours after the application dressing was removed and the skin was flushed with lukewarm tap water and dried with disposable paper towels.
- Time after start of exposure: 24 hours

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 4 mL/Kg

VEHICLE
- Lot/batch no. (if required): 1310049 (FLUKA Chemie GmbH, CH-9471 Buchs)
- Purity: no data

Duration of exposure:

The application period was 24 hours.

Doses:

2000 mg/kg

No. of animals per sex per dose:

5 males
5 females

Control animals:

not required

Details on study design:

- Duration of observation period following administration: 14 days
- Mortality/viability: daily during the acclimatization period, during the first 30 minutes and at approximately 1, 2, 3 and 5 hours after administration on test day 1, and twice daily during days 2-15.
- Body weights: On test days 1 (prior to administration), 8 and 15.
- Frequency of observations included local signs : daily during the acclimatization period, during the first 30 minutes and at approximately 1, 2, 3 and 5 hours after administration on test day 1. Once daily during days 2-15. All abnormalities were recorded.
- Necropsy of survivors performed: yes; All animals were killed at the end of the observation period by Carbon dioxide asphyxiation and discarded after macroscopic examinations were performed. No organs or tissues were retained.

Statistics:

No statistical analysis was used.

Results and discussion

Effect levels

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: No deaths occured during the study

Mortality:

No deaths ocurred during the study

Clinical signs:

other: No clinical signs were observed during the course of the study.

Gross pathology:

No macroscopic finding were observed at necropsy

Other findings:

Local signs: at removal of the application patch, no local signs were visible in all males and females. However, on test day 3, a very slight erythema was observed in all females and persisted up to test day 5. On test day 7, slight focal scabs were visible in all males and four females which persisted up to test days 10 or 11 and in one female up to test day 9. Additionally, in this female the slight focal scabs were present again on test day 11. On test day 12, slight scabs were noted in all males and two females which persisted up to test day 13 in one female and two males. Additionally, one female showed slight scabs on test days 10, 12 and 13. Slight scaling was recorded in one male 7 to 11 days after test item exposure.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

Under the test conditions, the dermal LD50 for the registered substance is higher than 2000 mg/kg bw in rats therefore it is not classified according to the Annex I of the Regulation EC No. 1272/2008 (CLP) and to the GHS.

Executive summary:

In an acute dermal toxicity study (limit test) performed according to the OECD test guideline No. 402 and in compliance with GLP, five male and five female rats were treated with the substance at 2000 mg/kg by dermal application. The test item was applied diluted in vehicle (PEG 300) at a concentration of 0.5 g/mL and administered at a volume dosage of 4 mL/kg. The test site was covered with a semi-occlusive dressing for 24 hours. Animals were observed for mortality, clinical signs, local signs and body weights for 14 days and at the end of the study the surviving animals were sacrificed for macroscopic examination.

No deaths occurred during the study. No clinical signs were observed during the course of the study.

At removal of the application patch, no local signs were visible in all males and females. However, on test day 3, a very slight erythema was observed in all females and persisted up to test day 5. On test day 7, slight focal scabs were visible in all males and four females which persisted up to test days 10 or 11 and in one female up to test day 9. Additionally, in this female the slight focal scabs were present again on test day 11. On test day 12, slight scabs were noted in all males and two females which persisted up to test day 13 in one female and two males. Additionally, one female showed slight scabs on test days 10, 12 and 13. Slight scaling was recorded in one male 7 to 11 days after test item exposure.

One female did not gain weight at the end of the study. Otherwise, the body weight of the animals was within the range commonly recorded for this strain and age. No macroscopic findings were observed at necropsy.

Dermal LD50 Combined > 2000 mg / kg bw

Under the test conditions, the dermal LD50 for the registered substance is higher than 2000 mg/kg bw in rats therefore it is not classified according to the Annex I of the Regulation EC No. 1272/2008 (CLP) and to the GHS.

This study is considered as acceptable and satisfies the requirement for acute dermal toxicity endpoint.