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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:
June 1981
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Remarks:
Study may be used for classification purposes although there are deviations in its study protocol from the OECD TG 404. They do not include a 48-hour observation time and involve a 24-hour test material exposure followed by observations at 24 hour and 72 hours. Moreover, the test material is patched both on abraded and on intact skin of six rabbits per condition. The study is terminated after 72 hours.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1981
Report date:
1981

Materials and methods

Test guideline
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Version / remarks:
Study may be used for classification purposes although there are deviations in its study protocol from the OECD TG 404. They do not include a 48-hour observation time and involve a 24-hour test material exposure followed by observations at 24 hour and 72 hours. Moreover, the test material is patched both on abraded and on intact skin of six rabbits per condition. The study is terminated after 72 hours.
Principles of method if other than guideline:
Study may be used for classification purposes although there are deviations in its study protocol from the OECD TG 404. They do not include a 48-hour observation time and involve a 24-hour test material exposure followed by observations at 24 hour and 72 hours. Moreover, the test material is patched both on abraded and on intact skin of six rabbits per condition. The study is terminated after 72 hours.
GLP compliance:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
rel-(2R,4R)-2,4-dimethyl-4-phenyltetrahydrofuran
Cas Number:
99343-90-5
Molecular formula:
C12H16O
IUPAC Name:
rel-(2R,4R)-2,4-dimethyl-4-phenyltetrahydrofuran
Constituent 2
Chemical structure
Reference substance name:
rel-(2S,4R)-2,4-dimethyl-4-phenyltetrahydrofuran
Cas Number:
99343-91-6
Molecular formula:
C12H16O
IUPAC Name:
rel-(2S,4R)-2,4-dimethyl-4-phenyltetrahydrofuran
Test material form:
liquid

Test animals

Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
Not reported

Test system

Type of coverage:
occlusive
Preparation of test site:
other: Abraded or clipped
Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
0.5 ml
Duration of treatment / exposure:
24 hours
Observation period:
24 and 72 hours
Number of animals:
Twelve animals (6 per condition)
Details on study design:
Primary irritation to the skin is measured by a patch-test technique on the abraded and intact skin of albino rabbits.
Twelve healthy adult New Zealand White albino rabbits are used for 1-4 test substances. Twenty four hours prior to applying the materials, the hair is removed from the backs of the animals with an electric clipper in such a way as to avoid abrasions.
An mount of 0.5 mL of the test substance is brought on the intact or abraded skin under a surgical patch measuring 1 inch x 1 inch. The patches are fixed to the application site by means of adhesive tape and the entire trunk of the rabbits is wrapped with an impervious material to maintain the test patches in position and to retard evaporation of volatiles substances.
Six rabbits are treated on the intact skin , the other six on the abraded skin. The abrasions are minor incisions through the stratum corneum, but not sufficiently deep to disturb the derma or to produce bleeding.
After an exposure period of 24 hours the patches and the material applied are removed and the resulting skin reactions are evaluated by the method of Draize. A second reading is made 48 hours later (72 hours after application).

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
edema score
Remarks:
Mean 24 and 72 hours
Basis:
animal #1
Time point:
24/48/72 h
Score:
1.5
Max. score:
4
Reversibility:
not specified
Remarks on result:
probability of weak irritation
Irritation parameter:
edema score
Remarks:
Mean 24 and 72 hours
Basis:
animal #2
Time point:
24/48/72 h
Score:
0.5
Max. score:
4
Reversibility:
not specified
Remarks on result:
probability of weak irritation
Irritation parameter:
edema score
Remarks:
Mean 24 and 72 hours
Basis:
animal #3
Time point:
24/48/72 h
Score:
1
Max. score:
4
Reversibility:
not specified
Remarks on result:
probability of weak irritation
Irritation parameter:
edema score
Remarks:
Mean 24 and 72 hours
Basis:
animal #4
Time point:
24/48/72 h
Score:
0.5
Max. score:
4
Reversibility:
not specified
Remarks on result:
probability of weak irritation
Irritation parameter:
edema score
Remarks:
Mean 24 and 72 hours
Basis:
animal #5
Time point:
24/48/72 h
Score:
0.5
Max. score:
4
Reversibility:
not specified
Remarks on result:
probability of weak irritation
Irritation parameter:
edema score
Remarks:
Mean 24 and 72 hours
Basis:
animal #6
Time point:
24/48/72 h
Score:
0.5
Max. score:
4
Reversibility:
not specified
Remarks on result:
probability of weak irritation
Irritation parameter:
erythema score
Remarks:
Mean 24 and 72 hours
Basis:
animal #1
Time point:
24/48/72 h
Score:
3.5
Max. score:
4
Reversibility:
not specified
Remarks on result:
positive indication of irritation
Irritation parameter:
erythema score
Remarks:
Mean 24 and 72 hours
Basis:
animal #2
Time point:
24/48/72 h
Score:
1
Max. score:
4
Reversibility:
not specified
Remarks on result:
probability of weak irritation
Irritation parameter:
erythema score
Remarks:
Mean 24 and 72 hours
Basis:
animal #3
Time point:
24/48/72 h
Score:
1.5
Max. score:
4
Reversibility:
not specified
Remarks on result:
probability of mild irritation
Irritation parameter:
erythema score
Remarks:
Mean 24 and 72 hours
Basis:
animal #4
Time point:
24/48/72 h
Score:
1.5
Max. score:
4
Reversibility:
not specified
Remarks on result:
probability of mild irritation
Irritation parameter:
erythema score
Remarks:
Mean 24 and 72 hours
Basis:
animal #5
Time point:
24/48/72 h
Score:
1
Max. score:
4
Reversibility:
not specified
Remarks on result:
probability of weak irritation
Irritation parameter:
erythema score
Remarks:
Mean 24 and 72 hours
Basis:
animal #6
Time point:
24/48/72 h
Score:
1
Max. score:
4
Reversibility:
not specified
Remarks on result:
probability of weak irritation
Irritant / corrosive response data:
Rhubafurane caused moderate skin irritation. The dermal effects observed after 24 hours generally consisted of slight or well-defined erythema and/or very slight edema. Very slight ischemia, focal haemorrhages and slight edema were noted at one intact and one abraded site.
After 72 hours slight to distinct scaliness was observed at five intact and three abraded sites while two abraded sites by then showed slight incrustation.

Any other information on results incl. tables

Table 1: Individual and Average Skin Irritation Scores of Pure and Undiluted Rhubafurane

Rabbit No.

Intact skin

Rabbit No.

Abraded skin

24 hours

72 hours

24 hours

72 hours

A

B

A

B

A

B

A

B

1

4

2

3

1

7

4

2

4

2

2

1

0

1

1

8

1

0

2

1

3

2

1

1

1

9

0

0

0

0

4

1

0

2

1

10

1

1

4

1

5

1

1

1

0

11

1

1

1

0

6

0

0

2

1

12

0

0

1

1

A = Erythema

B = Edema

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
Under the test conditions, the test material is not classified as irritant to the skin according to the Annex VI of the Regulation (EC) No. 1272/2008 (CLP) and the GHS.
Executive summary:

In a dermal irritation study comparable to the OECD guideline 404, the primary irritation to the skin is measured by a patch-test technique on the abraded and intact skin of albino rabbits.


An amount of 0.5 mL of the test substance is brought on the intact or abraded skin of six healthy adult New Zealand White albino rabbits under a surgical patch fixed to the application site by means of adhesive tape.
After an exposure period of 24 hours the patches and the material applied are removed and the resulting skin reactions are evaluated by the method of Draize. A second reading is made 48 hours later (72 hours after application).

 

Rhubafurane caused moderate skin irritation. The dermal effects observed after 24 hours generally consisted of slight or well-defined erythema and/or very slight edema. Very slight ischemia, focal haemorrhages and slight edema were noted at one intact and one abraded site. After 72 hours slight to distinct scaliness was observed at five intact and three abraded sites while two abraded sites by then showed slight incrustation.

However, to use this study for classification purposes although deviations in its study protocol from the OECDTG 404 were observed, it is feasible to use such data for classification by calculating the mean values for erythema and oedema on the basis of only the 24 and 72 hours time points. Calculation of mean scores are restricted to the results obtained from intact skin. 

The mean scores calculated for each animal tested within 2 scoring times (24 and 72 h) were 3.5/1/1.5/1.5/1/1 for erythema and 1.5/0.5/1/0.5/0.5/0.5 for oedema.

 

Under the test conditions, the test material is not classified as irritant to the skin according to the Annex VI of the Regulation (EC) No. 1272/2008 (CLP) and the GHS. This study is considered as acceptable and satisfies the requirement for skin irritation endpoint.