Reaction mass of 3a,4,5,6,7,7a-hexahydro-4,7-methano-1H-inden-5-yl pivalate and 3a,4,5,6,7,7a-hexahydro-4,7-methano-1H-inden-6-yl pivalate

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1979-05-21 to 1979-06-06

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Remarks:

Non-GLP study conducted similarly to OECD Guideline 404 with deviations: no data about purity and no certificate of analysis of the test substance; no details on housing conditions of animals; observations not followed until the reversibility of the effects; different scoring system was followed in the study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1979

Report date:

1979

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

yes

Remarks:

non-GLP study; no data about purity and no certificate of analysis of the test substance; no details on housing conditions of animals; observations not followed until the reversibility of the effects; different scoring system was followed in the study

Principles of method if other than guideline:

Not applicable

GLP compliance:

no

Remarks:

pre-GLP

Test material

Test material information

Constituent 1

Reference substance name:

3a,4,5,6,7,7a-hexahydro-4,7-methano-1H-inden-6-yl pivalate

EC Number:

268-259-4

EC Name:

3a,4,5,6,7,7a-hexahydro-4,7-methano-1H-inden-6-yl pivalate

Cas Number:

68039-44-1

Molecular formula:

C15H22O2

IUPAC Name:

3a,4,5,6,7,7a-hexahydro-1H-4,7-methanoinden-6-yl pivalate

Constituent 2

Reference substance name:

3a,4,5,6,7,7a-hexahydro-4,7-methano-1H-inden-5-yl pivalate

EC Number:

268-261-5

EC Name:

3a,4,5,6,7,7a-hexahydro-4,7-methano-1H-inden-5-yl pivalate

Cas Number:

68039-45-2

Molecular formula:

C15H22O2

IUPAC Name:

3a,4,5,6,7,7a-hexahydro-1H-4,7-methanoinden-5-yl pivalate

impurity 1

Reference substance name:

rel-(1R,2S,3aR,4S,5R,6aS,7R)-octahydro-1,5:2,4-dimethanopentalen-7-yl pivalate

Molecular formula:

C15H22)2

IUPAC Name:

rel-(1R,2S,3aR,4S,5R,6aS,7R)-octahydro-1,5:2,4-dimethanopentalen-7-yl pivalate

Test material form:

other: liquid, may crystalize to white solid

Specific details on test material used for the study:

- Name of test material (as cited in study report): PM 343
- Source: PPL, UK
- Physical state: Clear liquid
- Date received: 29 March 1979

Test animals

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

- Age at study initiation: 9-12 weeks

Test system

Type of coverage:

semiocclusive

Preparation of test site:

clipped

Vehicle:

unchanged (no vehicle)

Controls:

not required

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 mL
- Concentration (if solution): 100 %

Duration of treatment / exposure:

4 h

Observation period:

72 h

Number of animals:

Eight

Details on study design:

- Area of exposure: Dorsum
- % coverage: Test substance (0.5 mL) was applied under a semi-occlusive patch to the clipped skin and the patches were held in place with an adhesive tape.
- Type of wrap used: Animals were immobilised in a canvas body sleeve for 4 h after application of the patch.

REMOVAL OF TEST SUBSTANCE
- After the removal of the patches, the application site was wiped clean of excess material.

SCORING SYSTEM: Skin reactions were observed immediately after removal of the patch and after 24, 48 and 72 h and graded according to the following 8-point anchored ordinate scale:
1 = marginal / very slight
2 = slight
3 = fairly distinct
4 = quite distinct
6 = becoming well developed
8 = well developed
10 = becoming severe
12 = severe

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

erythema score

Basis:

mean

Remarks:

of 8 animals

Time point:

other: average of 24, 48 and 72 h

Score:

3.4

Max. score:

12

Reversibility:

no data

Results 2

Irritation parameter:

edema score

Basis:

mean

Remarks:

of 8 animals

Time point:

other: average of 24, 48 and 72 h

Score:

2.8

Max. score:

12

Reversibility:

no data

Results 3

Irritation parameter:

overall irritation score

Basis:

other: sum of scores observed in 8 animals

Time point:

other: 24, 48 and 72 h

Score:

225

Max. score:

1 152

Reversibility:

no data

Irritant / corrosive response data:

- At 24 h, generally fairly distinct to distinct erythema and oedema were noted in test animals.
- By 48 and 72 h, fairly distinct to distinct erythema and slight to fairly distinct oedema with marginal to slight cracking were noted in most animals.
- The response produced by PM 343 was greater than that produced by Diethyl Phthalate which produced a generally marginal to slight response in some animals, although one animal had distinct erythema and oedema at 24 h.
- The response produced by PM 343 was slightly less than that produced by the controls, Cyclamen Aldehyde and Geraniol, which produced similar responses showing fairly distinct to fairly well developed erythema and oedema at 24 h and fairly distinct to well-developed erythema and oedema with slight cracking in some animals by 48 and 72 h.

Other effects:

None

Any other information on results incl. tables

Table 7.3.1/1: Skin irritation data for individual rabbits

Rabbit number	Irritation scores*
	24 h		48 h		72 h		Mean (24, 48 and 72 h)
	Erythema	Oedema	Erythema	Oedema	Erythema	Oedema	Erythema	Oedema
1	3^#	3	3^#	2	3^# α	2	3.0	2.3
2	4	3	4^#	3	3^#	2	3.7	2.7
3	4	3	3^#	3	3^#	2	3.3	2.7
4	2	2	3^#	2	2^#	1	2.3	1.7
5	4	3	4	4	4^# α	4	4.0	3.7
6	4	4	4	3	3^#	3	3.7	3.3
7	4^# α	4	4^# α	2	3^# α	2	3.7	2.7
8	4	3	4	3	3^#	3	3.7	3.0
Mean (all 8 animals)							3.4	2.8

*Reaction grades and scores:

1 = marginal / very slight

2 = slight

3 = fairly distinct

4 = quite distinct

6 = becoming well developed

8 = well developed

10 = becoming severe

12 = severe

^#Very slight to fairly distinct cracking

^αVery slight scaling

Applicant's summary and conclusion

Interpretation of results:

Category 2 (irritant)

Conclusions:

Under the test conditions, PM 343 is classified as ‘Category 2: Irritant’ according to the CLP Regulation and as ‘R38 Irritating to skin’ according to the Directive 67/548/EEC.

Executive summary:

In a primary dermal irritation study performed similarly to OECD Guideline 404, 0.5 mL of the test item, PM 343, was applied under a semi-occlusive patch to clipped dorsum of eight New Zealand White rabbits. After an exposure period of 4 h, the patches and the applied material were removed and skin reactions were scored immediately after removal of the patch and after 24, 48 and 72 h, according to the 8-point anchored ordinate scale ranging from very slight (score = 1) to severe reactions (score = 12).

At 24 h, generally fairly distinct to distinct erythema and oedema were noted in test animals. By 48 and 72 h, fairly distinct to distinct erythema and slight to fairly distinct oedema with marginal to slight cracking were noted in most animals. Very slight scaling was noted in 3/8 animals at 72 h. The calculated mean scores for each individual lesion for all animals within three scoring times (24, 48 and 72 h) on the 8-point anchored ordinate scale were 3.4 for erythema score and 2.8 for oedema score.

After comparing the scores with the scale in OECD Guideline, the calculated mean scores for all animals within three scoring times (24, 48 and 72 h) were as follows: 2 for erythema score and 2 for oedema score.

Under the test conditions, PM 343 is classified as ‘Category 2: Irritant’ according to the CLP Regulation and as ‘R38 Irritating to skin’ according to the Directive 67/548/EEC.