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

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

28th November 1988 to 12th December 1988

Reliability:

1 (reliable without restriction)

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 402 (Acute Dermal Toxicity)

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

GLP compliance:

yes

Test type:

standard acute method

Limit test:

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:

rat

Strain:

Crj: CD(SD)

Sex:

male/female

Details on test animals or test system and environmental conditions:

Rats were sourced from Charles River France, weight range 220 - 250g and 7 - 10 weeks old. The animals were acclimatised to the laboratory conditions for 11 days prior to the test. The rats were allocated to cages within the treatment groups in Building R14 Room 6. They were housed individually in metal cages. Each animal was identified by cage number and ear punching.
Temperature: 20-22oC
Humidity: 66%
Light sequence: 12 hour light / 12 hour dark
Food: Standard Rodent diet (Labsure LAD 1)
Water: ad libitum

Administration / exposure

Type of coverage:

occlusive

Vehicle:

water

Duration of exposure:

24 hours

Doses:

Test substance prepared at a concentration of 50%w/v in distilled water and administered at a vol of 4.0 ml/kg.
One dose

No. of animals per sex per dose:

5 x male, 5 x female

Details on study design:

One day prior to treatment, hair was removed from the dorso-lumbar region with clippers, Th test substance was applied by spreading it evenly over the prepared skin. The treated area was covered by gauze, held in place with an impermeable dressing encircled firmly around the trunk.
At the end of the 24 hour exposure period, the dressings were carefully removed and the treated skin decontaminated by washing with warm water and blotted dry with absorbent paper.
Animals were observed soon after dosing and at frequent intervals for the remainder of Day 1 (6 hours), On subsequent days the animals were observed once in the morning and once at the end of the experimental day. Clinical signs were recorded at each observation.
The treated areas of skin examined daily for signs of dermal irritation for 4 days after dosing. Body weights were recorded. All animals were subject to gross necroscopy.

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

Male: 2000 mg/kg bw; Number of animals: 5; Number of deaths: 0
Female: 2000 mg/kg bw; Number of animals: 5; Number of deaths: 0

Clinical signs:

other: Signs of toxicity related to dose levels: There were no deaths or signs of systemic reaction to treatment.

Gross pathology:

Effects on organs:
Terminal autopsy findings were normal.

Other findings:

Signs of toxicity (local):
Sites of application showed no irritation reactions or other dermal changes.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

As the LD50 was greater than 2000mg/kg bodyweight, the test substance does not require labelling with Risk Phrase R21 "Harmful in contact with skin".

Executive summary:

Objective
The study was performed to assess the acute dermal toxicity of the test substance following a single dose.  The method met OECD Guidelines for the Testing of Chemicals - Acute Dermal Toxicity (402). 

Method
A groups of 10 rats (five male and five female) were dosed at 2000 mg/kg.  Clinical observations and body weights were monitored during the study. All animals were subject to gross necroscopy.

There were no deaths amongst male or female rats dosed at 2000 mg /kg. 

Conclusions: Since the LD50 is greater than 2000mg/kg bw, the substance does not require labelling with risk phrase R21 "Harmful in contact with skin".