Bicyclo[2.2.1]heptane, 2-ethyl-5-methoxy-

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

Between 05 April 1988 and 13 April 1988

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1988

Report date:

1988

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

-

EC Number:

403-610-9

EC Name:

-

Cas Number:

122795-41-9

IUPAC Name:

1-ethyl-3-methoxytricyclo[2.2.1.0²,⁶]heptane; 2-ethyl-5-methoxybicyclo[2.2.1]heptane; 2-ethyl-6-methoxybicyclo[2.2.1]heptane

Test material form:

liquid

Test animals

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

Three New Zealand White strain rabbits in the weight range 2.0 to 3.0 kg, prior to treatment on Day 1 and approximately 9 to 13 weeks of age were obtained a reputable supplier. For full details please full study report. The rabbits selected for the study were all acclimated to the laboratory environment.

Each animal was identified by a numbered aluminium tag placed through the edge of one ear. This number was unique within the HRC Industrial Toxicology Department throughout the duration of the study.

The rabbits were individually housed in metal cages with perforated floors in Building R14 Room 5. They had free access to tap water and SDS Standard Rabbit Diet.

Animal room temperature was maintained at approximately 19°C and relative humidity at 30-70%. Air exchange was maintained at approximately 19 air
changes per hour and lighting was controlled by means of a time switch to give 12 hours of artificial light (0700-1900 hours) in each 24 hour period.

All animals were observed daily for signs of ill health or toxic signs.

Test system

Type of coverage:

semiocclusive

Preparation of test site:

clipped

Vehicle:

unchanged (no vehicle)

Controls:

no

Amount / concentration applied:

0.5 ml

Duration of treatment / exposure:

4 hours

Observation period:

9 days

Number of animals:

3

Details on study design:

TEST SITE
- Area of exposure: Approximately 24 hours prior to application of the test substance, hair was removed with electric clippers from the dorso-lumbar region of each rabbit exposing an area of skin approximately 10 cm square. A 0.5 ml aliquot of ethyl methoxy norbornane was applied under a 2.5 cm square gauze pad to one intact skin site on each animal.
- Type of wrap if used: Each treatment site was occluded with "Elastoplast" elastic adhesive dressing for a four hour period. The animals were not restrained during the exposure period and were returned to their cages.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): At the end of the exposure period, the semi-occlusive dressing and gauze pad were removed and the treatment site was washed using water to remove any residual test substance.

EVALUATION OF SKIN REACTIONS
Examination of the treated skin was made on Day 1 (i.e. approximately 30 minutes after removal of the patches) and on Days 2, 3 and 4. Additional observations were made on Days 5 to 9.

Examination of the treated skin was made on Day 1 (i.e. approximately 30 minutes after removal of the patches) and on Days 2, 3 and 4. Additional observations were made on Days 5 to 9.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

erythema score

Basis:

animal: #27

Time point:

24/48/72 h

Score:

1.33

Reversibility:

fully reversible within: 9 d

Results 2

Irritation parameter:

erythema score

Basis:

animal: #73

Time point:

24/48/72 h

Score:

2

Reversibility:

fully reversible within: 9 d

Results 3

Irritation parameter:

erythema score

Basis:

animal: #74

Time point:

24/48/72 h

Score:

1.33

Reversibility:

fully reversible within: 9 d

Results 4

Irritation parameter:

edema score

Basis:

animal: #27

Time point:

24/48/72 h

Score:

1.67

Reversibility:

fully reversible within: 7 d

Results 5

Irritation parameter:

edema score

Basis:

animal: #73

Time point:

24/48/72 h

Score:

1.67

Reversibility:

fully reversible within: 8 d

Results 6

Irritation parameter:

edema score

Basis:

animal: #74

Time point:

24/48/72 h

Score:

1

Reversibility:

fully reversible within: 7 d

Irritant / corrosive response data:

The numerical scores awarded to the dermal reactions elicited by ethyl methoxy norbornane are given in Table 1.
Well-defined erythema accompanied by very slight to slight oedema was observed in all three animals after removal of the dressings. The reactions resolved slowly and the skins were normal by Day 9 of the Study.

Any other information on results incl. tables

Table 1

Dermal reactions elicited by ethyl methoxy norbornane

 

Rabbit Number and Sex	E = Erythema O = Oedema	Day
		1	2	3	4	5	6	7	8	9
27♀	E	2	1	2	1	1	1	1	1	0
	O	1	1	2	2	2	2	0	0	0
73♀	E	2	2	2	2	2	2	1	1	0
	O	1	1	2	2	2	2	1	0	0
74♀	E	2	2	1	1	1	1	1	1	0
	O	1	1	1	1	1	1	0	0	0

Applicant's summary and conclusion

Interpretation of results:

other: Not skin irritant in accordance with EU CLP (EC no 1272/2008 and its amendments)

Conclusions:

Neoproxen is not considered to be a skin irritant.

Executive summary:

The irritant effects of Neoproxen to rabbit skin was assessed in a GLP study according to OECD Guideline No. 404. Well-defined erythema accompanied by very slight to slight oedema was observed in all three animals after removal of the dressings. The reactions resolved slowly and the skins were normal by Day 9 of the Study.