Ammonium 7-(2,6-dimethyl-8-(2,2-dimethylbutyryloxy)-1,2,6,7,8,8a-hexahydro-1-naphthyl)-3,5-dihydroxyheptanoate

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

22nd November 1988 to 25th November 1988

Reliability:

1 (reliable without restriction)

Justification for type of information:

The testing using the guinea pig maximisation test protocol was completed on 25 November 1988. The LLNA 429 was not formally adopted by the OECD until 22 July 2010.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1988

Report date:

1989

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Ammonium 7-(2,6-dimethyl-8-(2,2-dimethylbutyryloxy)-1,2,6,7,8,8a-hexahydro-1-naphthyl)-3,5-dihydroxyheptanoate

EC Number:

404-520-2

EC Name:

Ammonium 7-(2,6-dimethyl-8-(2,2-dimethylbutyryloxy)-1,2,6,7,8,8a-hexahydro-1-naphthyl)-3,5-dihydroxyheptanoate

Cas Number:

139893-43-9

Molecular formula:

C25 H43 O6 N

IUPAC Name:

ammonium 7-{8-[(2,2-dimethylbutanoyl)oxy]-2,6-dimethyl-1,2,6,7,8,8a-hexahydronaphthalen-1-yl}-3,5-dihydroxyheptanoate

Test material form:

solid: particulate/powder

Specific details on test material used for the study:

Composition:
99.2% L-654,969, 0.2% lovastatin ammonium salt, 0.2% triol

Test animals

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

Source: A. Smith, Warlingham, Surrey, England
Animals were acclimatised to laboratory conditions. The rabbits were housed in metal cages with perforated floors. Each animal was identified by a numbered aluminium tag placed through the edge of one ear.
Temperature: 19oC
Humidity: 30-70%
Light sequence: 12 hour light / 12 hour dark
Food: SDS Standard Rabbit Diet
Water: ad libitum

Test system

Type of coverage:

semiocclusive

Preparation of test site:

clipped

Vehicle:

other: Test substance was applied under a gauze pad moistened with 0.5ml distilled water

Controls:

no

Amount / concentration applied:

0.5g moistened with 0.5ml water

Duration of treatment / exposure:

4 hours

Observation period:

4 days

Number of animals:

3

Details on study design:

0.5g of the test item moistened with 0.5ml water was applied to a gauze patch (2.5cm). The treated patch was occluded with elastic adhesive dressing. Patches were removed after 4 hours. The residual test item was gently wiped off with water.
The skin sites were examined 1, 2, 3 and 4 days after removal of patches for signs of skin reaction and symptoms. Dermal reactions for erythema /eschar or oedema of test sites of each animal were scored and recorded.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Results 2

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Results 3

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

0

Remarks on result:

other: Max. duration: d; Max. value at end of observation period: 0 (related to all animals)

Results 4

Irritation parameter:

edema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Results 5

Irritation parameter:

edema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Results 6

Irritation parameter:

edema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

0

Remarks on result:

other: other: Max. duration: d; Max. value at end of observation period: 0 (related to all animals)

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

A single, semi-occlusive application of L-654,969 to intact rabbit skin for four hours elicited no dermal irritation.
The test substance does not require labelling with risk phrase R38 "Irritating to skin".

Executive summary:

The study was performed to assess the acute dermal irritation/corrosion of L-654 969 in New Zealand rabbits. The method was designed to be in accordance with OECD Guidelines 'Acute Dermal Irritation/Corrosion' (404). 

Three male rabbits were used for the study. A quantity of 0.5g of the test item was applied to the skin of each animal for an exposure period of 4 hours.  Dermal reactions (erythema/eschar and oedema) of test sites were scored at approximately 1, 2, 3 and 4 days after patch removal. 

No abnormal signs or symptoms were observed in any animal throuhout the course of the test. The scores of erythema/eschar and oedema for all animals at 1, 2, 3 and 4 days were all 0 after patch removal.  

A single, semi-occlusive application of L-654,969 to intact rabbit skin for four hours elicited no dermal irritation. The test substance does not require labelling with risk phrase R38 "Irritating to skin".