Registration Dossier

Toxicological information

Skin irritation / corrosion

Currently viewing:

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:
other: see 'Remark'
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-referenceopen allclose all
Reason / purpose:
reference to same study
Reason / purpose:
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:
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

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
other: liquid
Details on test material:
Name of the test item (as cited in the study report): Nopyl Acetate
Source: Proprietary Perfumes LTD
Colour: clear

Test animals

Species:
rabbit
Strain:
New Zealand White
Details on test animals 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

Resultsopen allclose all
Irritation parameter:
erythema score
Basis:
mean
Remarks:
(8 animals)
Time point:
other: 24, 48 and 72 h
Score:
1.2
Max. score:
4
Reversibility:
no data
Irritation parameter:
edema score
Basis:
mean
Remarks:
(8 animals)
Time point:
other: 24, 48 and 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

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.