Reaction mass of (+-)-(1RS,2SR,5SR,7RS,8SR)-5-METHYLTRICYCLO[6.2.1.02,7]UNDECAN-4-ONE and (+-)-(1RS,2SR,5RS,7RS,8SR)-5-METHYLTRICYCLO[6.2.1.02,7]UNDECAN-4-ONE

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

From October 16 to November 30, 1978

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

The study was performed prior to the OECD test guideline No. 402 but the protocol is similar to the TG with the following exeptions: occlusive dressing (worst-case condition) was used and only 3 animals per sex were included. However, a repeat study under standard conditions is unlikely to show worse effects, therefore this study was considered sufficiently robust to cover this endpoint.

Cross-reference

Cross-reference 1

Reason / purpose for cross-reference:

reference to same study

Cross-reference 2

Reason / purpose for cross-reference:

reference to other study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1978

Report date:

1978

Materials and methods

Test guideline

Test guideline 1

Qualifier:

no guideline followed

Test guideline 2

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

yes

Remarks:

occlusive dressing

Principles of method if other than guideline:

Study was performed according to a modification of the techniques described in Appraisal of the Safety of Chemicals in Foods, Drugs and Cosmetics, compiled by the staff of the Division of Pharmacology, Food and Drug Administration.

GLP compliance:

no

Remarks:

(pre-GLP)

Test type:

standard acute method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Reaction mass of (+-)-(1RS,2SR,5SR,7RS,8SR)-5-METHYLTRICYCLO[6.2.1.02,7]UNDECAN-4-ONE and (+-)-(1RS,2SR,5RS,7RS,8SR)-5-METHYLTRICYCLO[6.2.1.02,7]UNDECAN-4-ONE

Molecular formula:

C12H18O

IUPAC Name:

Reaction mass of (+-)-(1RS,2SR,5SR,7RS,8SR)-5-METHYLTRICYCLO[6.2.1.02,7]UNDECAN-4-ONE and (+-)-(1RS,2SR,5RS,7RS,8SR)-5-METHYLTRICYCLO[6.2.1.02,7]UNDECAN-4-ONE

Test material form:

not specified

Details on test material:

- Name of test material (as cited in study report): 0878/2
- Other: Specific gravity: 1.05

Test animals

Species:

rabbit

Strain:

not specified

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Summit View Farm, Belvidere, New Jersey, USA.
- Weight at study initiation: 1.33-2.17 kg
- Diet: Wayne animal feeds, ad libitum
- Water: Water, ad libitum
- Acclimation period: Animals were conditioned prior to use.

Administration / exposure

Type of coverage:

occlusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure: Mid-dorsal area of the trunk.
- % coverage: Approximately 10 % of the body surface
- Type of wrap if used: Test material was applied under gauze and then covered with an impermeable plastic wrapping for 24 h.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Test material was removed and skin gently cleansed with water.
- Time after start of exposure: 24 h

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2000 mg/kg bw

Duration of exposure:

24 h

Doses:

Range-finding study: 500, 1000, 3000 and 5000 mg/kg bw
Main study: 2000 mg/kg bw

No. of animals per sex per dose:

1 male/dose (range-finding study)
3/sex/dose (main study)

Control animals:

not required

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
Animals were observed for signs of pharmacologic activity and toxicity at 1, 3, 6 and 24 h after dosing and daily thereafter for 14 days.
- Necropsy of survivors performed: Yes; non-survivors and animals sacrificed at the end of the 14-day observation period were subjected to gross necropsy.

Statistics:

None

Results and discussion

Preliminary study:

Not applicable

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: 3/6 animals were died.

Mortality:

- In the range-finding study, no mortality was observed at 500, 1000 and 3000 mg/kg bw. At 5000 mg/kg bw, one male animal was died (100 % mortality) within 3 h of dosing.
- In the main study, 2 animals (1 male + 1 female) treated with 2000 mg/kg bw were died within 24 h of dosing. Another female animal was died on Day 5 of dosing. 50 % mortality (3/6 animals, all with intact skin) was observed.

Clinical signs:

other: - Range-finding study: Depression was observed in a male animal treated with 3000 mg/kg bw between 3-6 h of dosing. Skin dryness, flaking and redness was observed in male animals treated with 1000, 3000 and 5000 mg/kg bw dose, respectively. - Main study:

Gross pathology:

- Range-finding study: A male animal treated with 5000 mg/kg bw showed enlargement of right kidney at anterior end (15 cm in diameter), thickened capsule and sub capsular space was filled with grey-white pus.
- Main study: No abnormality was observed at necropsy in animals treated with 2000 mg/kg bw.

Other findings:

None

Any other information on results incl. tables

None

Applicant's summary and conclusion

Interpretation of results:

Toxicity Category IV

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Dermal LD50 Combined = 2000 mg/kg bw

Executive summary:

In an acute dermal toxicity, the intact or abraded skin of albino rabbits (3/sex) was occlusively exposed to undiluted test material at dose of 2000 mg/kg bw for 24 h. The animals were observed for mortality, clinical signs and body weight for 14 days and then necropsied for macroscopic observations. Range finding study was conducted at the dose levels of 500, 1000, 3000 and 5000 mg/kg bw (1 male/dose, intact skin) to determine the dose for main study.

In the range-finding study, 0, 0, 0 and 100 % mortality were observed at 500, 1000, 3000 and 5000 mg/kg bw, respectively. Depression was observed at 3000 mg/kg bw; skin dryness, flaking and redness was observed at 1000, 3000 and 5000 mg/kg bw dose, respectively. Gross necropsy of dead animal showed enlargement of right kidney at anterior end, thickened capsule and sub capsular space was filled with grey-white pus. 

In the main study, 3/6 animals (1 male + 2 females, all with intact skin) died (50 % mortality) at 2000 mg/kg bw. Clinical signs observed in animals were slight to severe depression and skin blanching. One female with intact skin showed sign of irritation (skin moderately reddened) and faeces loose. In animals with abraded skin, sloughing and scab formation were observed. Surviving animals (2/3) showed decreased body weight gain over the 14 day study period. No abnormality was observed at necropsy.

Dermal LD50 Combined = 2000 mg/kg bw

Under the test conditions, the test material is classified as ‘Category 4: Harmful in contact with skin’ according to the annex VI of the Regulation EC No. 1272/2008 (CLP).

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