Bicyclo[3.1.1]hept-2-ene-2-ethanol, 6,6-dimethyl-, 2-acetate, (1R,5S)-

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

01-30 March 1977

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Remarks:

Study similar to OECD Guideline No 404 with deviations: no data about purity and no certificate of analysis of the test substance; no details on test animals and environmental conditions; animals were not observed for 14 days to study the reversibility; individual animal weights not reported; different irritation scoring system

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:

1977

Report date:

1977

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

yes

Remarks:

no data about purity and no certificate of analysis; no details on test animals and environmental conditions; reversibility of irritation and systemic effects not followed; individual animal weights not reported; different irritation scoring system

Principles of method if other than guideline:

not applicable

GLP compliance:

no

Remarks:

pre-dating GLP regulation

Test material

Test material information

Constituent 1

Reference substance name:

(1R,5S)-2-(6,6-dimethylbicyclo[3.1.1]hept-2-en-2-yl) ethyl acetate

EC Number:

800-940-9

Cas Number:

35836-72-7

Molecular formula:

C13H20O2

IUPAC Name:

(1R,5S)-2-(6,6-dimethylbicyclo[3.1.1]hept-2-en-2-yl) ethyl acetate

Test material form:

liquid

Test animals

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
Age at study initiation: 9-12 weeks

Test system

Type of coverage:

semiocclusive

Preparation of test site:

other: clipped

Vehicle:

unchanged (no vehicle)

Controls:

other: cyclamen aldehyde and diethyl phthalate were used as standards for comparison

Amount / concentration applied:

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

Duration of treatment / exposure:

4 h

Observation period:

72 h

Number of animals:

8

Details on study design:

TEST SITE
Area of exposure: dorsum of rabbits.
Type of wrap if used: occlusive patches were prepared by heat-sealing 1" x 1" 24 ply gauze pads on to 1.25" x 1.25" squares of polythene sheeting, which was then attached to 3.5" x 1" strips of adhesive tape.

REMOVAL OF TEST SUBSTANCE
After removal of the patches, the treated site was wiped to remove the residual material.

SCORING SYSTEM:
Treated sites were scored for erythema, oedema, cracking and scaling and any other feature using an 8-point anchored ordinate scale ranging from "a" (very slight) to "h" (severe). For better interpretation, an equivalence with OECD guideline 404 scoring system was made (see table 7.3.1/3).

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

erythema score

Basis:

mean

Remarks:

(8 animals)

Time point:

24/48/72 h

Score:

1.2

Max. score:

4

Reversibility:

no data

Results 2

Irritation parameter:

edema score

Basis:

mean

Remarks:

(8 animals)

Time point:

24/48/72 h

Score:

0.9

Max. score:

4

Reversibility:

no data

Irritant / corrosive response data:

Nopyl acetate produced marginal to slight oedema and erythema, and slight to fairly distinct cracking and scaling.

Overall level of irritation was less than that of the control, cyclamen aldehyde, which produced fairly distinct to fairly well-developed erythema, fairly distinct to distinct oedema and slight cracking and scaling.

Response to nopyl acetate was greater than that produced by the control, diethyl phthalate, which produced only a marginal response.

Other effects:

none

Any other information on results incl. tables

Table 7.3.1/1: equivalence in scoring systems

Study scaling	OECD 404 scaling
a: marginal/very slight b: slight	1
c: fairly distinct d: quite distinct	2
e: becoming well developed f: well developed	3
g: becoming severe h: severe	4

Table 7.3.1/2: irritation scores

Animal number	4 h		24 h		48 h		72 h
	E	O	E	O	E	O	E	O
118	a	a	a	b	b	a	a	a
138	b	a	b	a	b	b	a	a
141	a	a	a	-	a	-	a	a
140	a	a	a	a	b	b	a	b
142	a	-	a	-	b	-	b	-
143	a	a	a	a	a	a	a	a
144	a	a	c	b	c	c	b	b
132	b	b	c	c	c	b	c	b

Table 7.3.1/3: equivalence in OECD 404 scaling

Animal number	4 h		24 h		48 h		72 h		Individual means at 24-48-72 h
	E	O	E	O	E	O	E	O	E	O
118	1	1	1	1	1	1	1	1	1	1
138	1	1	1	1	1	1	1	1	1	1
141	1	1	1	0	1	0	1	1	1	0.3
140	1	1	1	1	1	1	1	1	1	1
142	1	0	1	0	1	0	1	0	1	0
143	1	1	1	1	1	1	1	1	1	1
144	1	1	2	1	2	2	1	1	1.7	1.3
132	1	1	2	2	2	1	2	1	2	1.3
					Overall mean				1.2	0.9

E: erythema

O: oedema

Applicant's summary and conclusion

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Nopyl acetate induced only slight skin irritation in rabbits. As overall mean scores for erythema and oedema were lower than 2, nopyl acetate is not classified for skin irritation/corrosion according to Directive 67/548/EEC and CLP Regulation (EC) No 1272/2008.

Executive summary:

In a primary dermal irritation study (similar to OECD Guideline No 404), eight New Zealand White rabbits were dermally exposed to 0.5 mL of nopyl acetate (100 %) under a semi-occlusive dressing for 4 h. After removal of the residual test item, treated sites were scored for erythema, oedema, cracking and scaling and any other feature using an 8-point anchored ordinate scale ranging from very slight to severe at 0, 24, 48 and 72 h after exposure. Cyclamen aldehyde and diethyl phthalate were used as standards for comparison.

 

Nopyl acetate produced marginal to slight oedema and erythema, and slight to fairly distinct cracking and scaling. Overall level of irritation was less than that of the control, cyclamen aldehyde, which produced fairly distinct to fairly well-developed erythema, fairly distinct to distinct oedema and slight cracking and scaling. Response to nopyl acetate was greater than that produced by the control, diethyl phthalate, which produced only a marginal response. When using an equivalence between this scoring scale and the OECD 404 scoring system, the overall mean scores at 24, 48 and 72 h were 1.2 and 0.9 for erythema and oedema, respectively.

 

Nopyl acetate induced only slight skin irritation in rabbits. As overall mean scores for erythema and oedema were lower than 2, nopyl acetate is not classified for skin irritation/corrosion according to Directive 67/548/EEC and CLP Regulation (EC) No 1272/2008.