Reaction Mass of (1R)-1-[(1S)-3,3-dimethylcyclohexyl]ethyl formate and (1R,2S)-2,6,6-trimethylcycloheptyl formate

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

21 Jan 1982 to 24 Feb 1982

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

comparable to guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1982

Report date:

1982

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

yes

Remarks:

Abrasion of the skin (in 1/2 of the animals)

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Reaction Mass of (1R)-1-[(1S)-3,3-dimethylcyclohexyl]ethyl formate and (1R,2S)-2,6,6-trimethylcycloheptyl formate

EC Number:

939-618-9

Cas Number:

25225-08-5

Molecular formula:

C11H20O2

IUPAC Name:

Reaction Mass of (1R)-1-[(1S)-3,3-dimethylcyclohexyl]ethyl formate and (1R,2S)-2,6,6-trimethylcycloheptyl formate

Test material form:

liquid

Test animals

Species:

rabbit

Strain:

not specified

Remarks:

albino

Sex:

not specified

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Ace Animals
- Weight at study initiation: 2.1-2.9 kg
- Fasting period before study: no
- Housing: 2/cage in suspended wire mesh cages. Bedding was placed beneath the cages.
- Diet: fresh Purina Rabbit Chow (Diet #53-21), ad libitum
- Water: ad libitum
- Acclimation period: at least one week

Administration / exposure

Type of coverage:

occlusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

- Test site: Prior to application of the test article the abdomen of each animal was clipped free of hair. The prepared site was approximately 10% of the body surface. The clipped sites in 1/2 of the animals were abraded with a bent tip needle. Six or seven abrasions about 2-3 cm apart, extending the length of the exposure site, were made. Abrasions were sufficiently deep to penetrate the stratum corneum, but not deep enough to produce bleeding.
- Test material application: The test article was applied to the prepared dermal site, one time, by a syringe type applicator. The test article was covered with a gauze patch and gentle pressure was applied to the gauze to aid the distribution of the test article over the prepared site. The torso was wrapped with plastic which was secured with tape. At 24 hours, the patches were removed and the site was wiped.

Duration of exposure:

24 hours

Doses:

5.0 g/kg bw

No. of animals per sex per dose:

5/dose without abrasion
5/dose with abrasion

Control animals:

no

Details on study design:

- Observations: Animals were observed daily for 14 days for mortality, toxicity and pharmacological effects.
- Frequency of observations and weighing: before the test and at termination in the survivors
- Necropsy of survivors performed: yes
- Other examinations performed: The test sites were scored for dermal irritation at 24 hours post-dose and on days 7 and 14 using the numerical Draize scale.

Results and discussion

Effect levels

Key result

Sex:

not specified

Dose descriptor:

LD50

Effect level:

> 5 000 mg/kg bw

Based on:

test mat.

Mortality:

One animal died on day 7, with predeath toxic signs of yellow nasal discharge, few feces, lethargy and difficulty walking due to severe dermal reactions.

Clinical signs:

other: Alopecia and diarrhea were observed in 6 animals; yellow nasal discharge was observed in 2 animals; lethargy was observed in 3 animals; ptosis and few feces were observed in one animal. Dermal responses, slight to moderate on Day 1, were slight to severe

Gross pathology:

3 out of 9 survivors were normal. The remaining animals showed signs of peritoneal cavity and intestinal abnormalities, as well as alopecia. The rabbit that died on day 7 showed lung and intestinal abnormalities (congested lungs and intestinal contents fluid; small intestine and stomach empty).

Applicant's summary and conclusion

Interpretation of results:

other: Not harmful

Remarks:

In accordance with EU CLP (EC no 1272/2008 and its amendments)

Conclusions:

In the acute dermal toxicity study in rabbits (strain and sex not specified) the LD50 was >5000 mg/kg bw in a study with a protocol similar to OECD TG 402.

Executive summary:

An acute dermal toxicity study with the substance was conducted in rabbits, according to a protocol similar to OECD TG 402 and in compliance with GLP. An amount of 5.0 g/kg bw of the substance was applied to the clipped abdomen (ca. 10% body area) of 10 animals for 24 hours under occlusive conditions. The clipped sites of 1/2 of the animals were abraded with a bent tip needle. Six or seven abrasions ca. 2 -3 cm apart, extending the length of the exposure, were made. Abrasions were sufficiently deep to penetrate the stratum corneum, but not deep enough to produce bleeding. The plastic wrapping was removed and the test substance wiped after 24 hours and the animals were observed for 14 days and necropsied. Skin reactions were assessed at 24 hours post-dose and on days 7 and 14 using the numerical Draize scale. One animal died on day 7. The autopsy showed congested lungs and intestinal abnormalities. The main clinical signs in the survivors were alopecia and diarrhea. No pathological findings were found at necropsy in 3 out of 9 survivors; remaining animals showed signs of peritoneal cavity and intestinal abnormalities. Based on the results of the study, the LD50 was > 5000 mg/kg bw.