Registration Dossier

Toxicological information

Skin irritation / corrosion

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Administrative data

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
02-11-1976 - 13-12-1976
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1976
Report Date:
1976

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
yes
Remarks:
10 animals used; different scoring system; observation < 14 days (Reversibility check); positve and negative control substances used.
GLP compliance:
no

Test material

Reference
Name:
Unnamed
Test material form:
liquid

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:
not required
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 ml
- Concentration (if solution): 100%

Controls:
Positive control: Cyclamen Aldehyde
Negative control: Diethyl Phthalate
Duration of treatment / exposure:
4 hours
Observation period:
at 4, 24, 48 and 72 hours
Number of animals:
10
Details on study design:
TEST SITE
- Area of exposure: dorsal
- % coverage: no data
- Type of wrap if used: Patches are prepared by heat-sealing 1" x 1" 24 ply gauze pads on to 1 1/4" x 1 1/4" squares of polythene sheeting which is then attached to 3 1/2" x 1" strips of adhesive tape. Test solutions are applied to a dry patch. The patches are firmly attached to ensure good contact between the skin and test substance.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): wiped clean
- Time after start of exposure:4 hours

SCORING SYSTEM: The sites are 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). At the end of the test the reaction grades are converted to corresponding numerical scores which are used to calculate the total irritation score per animal, an overall score per treatment group, a mean irritation score per site, and a mean irritation score per site per day for each treatment group. A mean irritation ranking for each treatment group is also given.
Reaction Grades and Scores of erythema, oedema, cracking and scaling:
a marginal/very slight = 1
b slight = 2
c fairly distinct =3
d quite distinct = 4
e becoming well developed = 6
f well developed = 8
g becoming severe = 10
h severe = 12

STATISTICS:
The Wilcoxon Matched-Pairs Signed Ranks Test, which considers the size and direction of differences between reactions is used to test the significance of differences between pairs of treatment groups.

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
erythema score
Basis:
animal: 1, 2, 4, 5, 6, 7, 8, and 9
Time point:
24/48/72 h
Score:
1
Max. score:
4
Reversibility:
not fully reversible within: 72 hours
Remarks on result:
other: Animal 1, 2, 4, 5, 6, 7, 8, and 9
Irritation parameter:
erythema score
Basis:
animal: 3
Time point:
24/48/72 h
Score:
1.33
Max. score:
4
Reversibility:
not fully reversible within: 72 hours
Remarks on result:
other: Animal 3
Irritation parameter:
erythema score
Basis:
animal: 10
Time point:
24/48/72 h
Score:
1.67
Max. score:
4
Reversibility:
not fully reversible within: 72 hours
Remarks on result:
other: Animal 10
Irritation parameter:
edema score
Basis:
animal: 6 and 9
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
other: Animal 6 and 9
Irritation parameter:
edema score
Basis:
animal: 1 and 8
Time point:
24/48/72 h
Score:
0.33
Max. score:
4
Reversibility:
other: not fully reversible in 72 hours in 1/2 animals
Remarks on result:
other: Animal 1 and 8
Irritation parameter:
edema score
Basis:
animal: 2, 3, 4, 5, 7, and 10
Time point:
24/48/72 h
Score:
1
Max. score:
4
Reversibility:
other: not fully reversible in 72 hours in 5/6 animals
Remarks on result:
other: Animal 2, 3, 4, 5, 7, and 10
Irritant / corrosive response data:
Under the conditions of this test the test substance produced slight to moderate irritation consisting of marginal to slight erythema and oedema with variable cracking and scaling ranging from slight to distinct. The test substance was significantly more irritant than the negative control, diethyl phthalate, which produced only a marginal response. The test ingredient was significantly less irritant than the positive control, cyclamen aldehyde, which produced well-developed erythema fairly distinct cracking and slight scaling.

Any other information on results incl. tables

Table 1: Skin irritation scoring from test report

 

4 h

4 h

24 h

24 h

48 h

48 h

72 h

72 h

Animal

Er

Ed

Er

Ed

Er

Ed

Er

Ed

1

A

-

B

A

B

-

B

-

2

A

B

B

A

B

A

B

A

3

B

B

C

B

A

A

A

A

4

A

-

B

A

A

A

A

A

5

A

B

A

A

A

A

A

A

6

A

-

A

-

A

-

B

-

7

B

B

B

B

B

B

B

A

8

A

-

A

-

A

-

A

A

9

A

-

A

-

B

-

A

-

10

A

A

C

B

C

A

B

-

Er = Erythema; Ed = Edema

Table 2: Recalculated scoring system based on proposed conversion (see any other information on materials and methods).

 

4 h

4 h

24 h

24 h

48 h

48 h

72 h

72 h

Mean 24/48/72h

Mean 24/48/72h

Animal

Er

Ed

Er

Ed

Er

Ed

Er

Ed

Er

Ed

1

1

0

1

1

1

0

1

0

1

0.33

2

1

1

1

1

1

1

1

1

1

1

3

1

1

2

1

1

1

1

1

1.33

1

4

1

0

1

1

1

1

1

1

1

1

5

1

1

1

1

1

1

1

1

1

1

6

1

0

1

0

1

0

1

0

1

0

7

1

1

1

1

1

1

1

1

1

1

8

1

0

1

0

1

0

1

1

1

0.33

9

1

0

1

0

1

0

1

0

1

0

10

1

1

2

1

2

1

1

0

1.67

1

Er = Erythema; Ed = Edema 

Applicant's summary and conclusion

Interpretation of results:
other: Not a skin irritant
Remarks:
according to EU CLP (EC 1272/2008 and its amendments)
Conclusions:
In the in vivo rabbit skin irritation test according to OECD TG 404, the substance is not a skin irritant.
Executive summary:

The skin irritation/corrosion potential of Cyclacet was investigated in a study similar to OECD Test Guideline 404 (Acute Dermal Irritation / Corrosion). In this Rabbit Covered Patch Skin Irritation Test, ten New Zealand White rabbits were exposed to the test substance for 4 hours under semi-occlusive conditions and reactions were scored after removal, and after 24, 48 and 72 hours. The test substance caused slight to moderate irritation, consisting of marginal to slight erythema and oedema with variable cracking and scaling ranging from slight to distinct. The mean erythema scores over the 24, 48 and 72 hour time period, were 1 (8 animals), 1.33 (1 animal) and 1.67 (1 animal). The mean edema scores over the 24, 48 and 72 hour time period, were 0 (2 animals), 0.33 (2 animals), and 1 (6 animals). As all animals had scorings below 2.3, the test substance is not considered to be a skin irritant.