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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:
2000/10/12-2000/10/18
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: According to OECD test guideline 404. GLP
Justification for type of information:
A discussion and report on the read across strategy is given as an attachment in IUCLID Section 13.
Cross-reference
Reason / purpose:
read-across: supporting information
Reference
Endpoint:
skin irritation: in vivo
Type of information:
read-across based on grouping of substances (category approach)
Adequacy of study:
key study
Study period:
2000/10/12-2000/10/18
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: According to OECD test guideline 404. GLP
Justification for type of information:
A discussion and report on the read across strategy is given as an attachment in IUCLID Section 13.
Reason / purpose:
read-across source
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
Source:Covance Research Products Inc.
Number of Animals: Three males
Age at study initiation: Approximately 13 weeks
Weight at study initiation: 2.7-3.2 kg
Housing: Individually
Diet (e.g. ad libitum): PMI Cert. Rabbit Diet; limited
Water (e.g. ad libitum): Automatic watering system, ad libitum
Acclimation period: 8d

ENVIRONMENTAL CONDITIONS
Temperature (°F): 64 to 72
Humidity (%): 30 to 70%
Photoperiod (hrs dark / hrs light): 12/12
Monitored at least once a day
Type of coverage:
semiocclusive
Preparation of test site:
shaved
Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
Amount(s) applied (volume or weight): 0.5 ml
Concentration (if solution): neat
Duration of treatment / exposure:
Test material was administered to the clipped backs as a single dose introduced under a gauze patch (secured with non-irritating tape) and held in contact with the skin by means of a semi-occlusive dressing for 4 hours. Residual test material was then removed.
Observation period:
24, 48, and 72h post application and once per day until Day 14
Number of animals:
Three males
Details on study design:
SCORING SYSTEM: Draize scale for dermal irritation
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 24 hours
Score:
ca. 2
Max. score:
2
Reversibility:
fully reversible within: 14 days
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 48 hours
Score:
ca. 2.3
Max. score:
3
Reversibility:
fully reversible within: 14 days
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 72 Hours
Score:
ca. 2.7
Max. score:
3
Reversibility:
fully reversible within: 14 days
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 24-72 hours
Score:
2.33
Max. score:
3
Reversibility:
fully reversible within: 14 days
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 24 hours
Score:
ca. 1.3
Max. score:
2
Reversibility:
fully reversible
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 48 hours
Score:
ca. 1.3
Max. score:
2
Reversibility:
fully reversible
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 72 hours
Score:
ca. 1.7
Max. score:
2
Reversibility:
fully reversible
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 24-72 hours
Score:
1.1
Max. score:
2
Reversibility:
fully reversible
Irritant / corrosive response data:
All animals survived to study termination, were free of adverse clinical signs, and displayed normal body weight patterns during the test period.

Topical application of the test substance to the skin of rabbits elicited dermal irritation in all animals during the study. Erythema and edema were observed in all animals.

Erythema started as Grade 2 erythema in all animals at the 60-minute evaluation and remained the same at the 24-hour evaluation. Erythema increased slightly at the 48- hour evaluation when two animals displayed Grade 2 erythema and one animal displayed Grade 3 erythema. Erythema reached its maximum severity at the 72- hour evaluation when one animal displayed Grade 2 erythema and two animals displayed Grade 3 erythema. Erythema subsided after the 72-hour evaluation and on Days 7 and 10 all animals displayed Grade 1 erythema. At the Day 14 evaluation one animal displayed Grade 1 erythema.

Edema was first noted and was most severe at the 60-minute evaluation. Grade 2 edema was noted for all animals at this interval. Edema decreased slightly at the 24 and 48-hour evaluations when Grade 1 edema was noted in two animals and Grade 2 edema was noted in one animal. Edema increased slightly at the 72-hour evaluation when one animal displayed Grade 1 edema and two animals displayed Grade 2 edema. At the Day 7 evaluation Grade 1 edema was displayed by two animals and Grade 3 edema was displayed for one animal. After the Day 7 evaluation edema subsided. One animal displayed Grade 2 edema at Day 10 and one animal displayed Grade 1 edema at Day 14.
Supplemental dermal observations, which included desquamation and cracking, were noted on Days 7 and 10. Desquamation was noted for all animals at both intervals and cracking was noted for one animal on Day 7.
Interpretation of results:
other: Irritating
Remarks:
R38 Criteria used for interpretation of results: EU
Conclusions:
The average erythema score (24, 48, and 72 hours) was 2.33. The average edema score (24, 48, and 72 hours) was 1.1. The test material would be classified as a Category 2 dermal irritant under the new Regulation (EC) 1272/2008 on classification, labeling and packaging of substances and mixtures (CLP). The test material would be classified as an R38 dermal irritant under Directive 67/518/EEC for dangerous substances and Directive 1999/45/EC for preparations.
Executive summary:

In this study, 3 rabbits were subjected to a 4h dermal (shaved) exposure of 0.5 ml of MRD-00-710 via a semi-occluded patch. Dermal responses were evaluated at 1, 24, 48, and 72h post-dosing and once a day for a total of 14 days according to the Draize method of scoring. Topical application of MRD-00-710 elicited dermal responses in all animals. Well defined erythema and slight odema followed exposure.  The average erythema score (24, 48, and 72 hours) was 2.33.  The average edema score (24, 48, and 72 hours) was 1.1.  The test material would be classified as a Category 2 dermal irritant under the new Regulation (EC) 1272/2008 on classification, labeling and packaging of substances and mixtures (CLP). The test material would be classified as an R38 dermal irritant under Directive 67/518/EEC for dangerous substances and Directive 1999/45/EC for preparations.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2004
Report Date:
2001

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent

Test animals

Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
Source:Covance Research Products Inc.
Number of Animals: Three males
Age at study initiation: Approximately 13 weeks
Weight at study initiation: 2.7-3.2 kg
Housing: Individually
Diet (e.g. ad libitum): PMI Cert. Rabbit Diet; limited
Water (e.g. ad libitum): Automatic watering system, ad libitum
Acclimation period: 8d

ENVIRONMENTAL CONDITIONS
Temperature (°F): 64 to 72
Humidity (%): 30 to 70%
Photoperiod (hrs dark / hrs light): 12/12
Monitored at least once a day

Test system

Type of coverage:
semiocclusive
Preparation of test site:
shaved
Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
Amount(s) applied (volume or weight): 0.5 ml
Concentration (if solution): neat
Duration of treatment / exposure:
Test material was administered to the clipped backs as a single dose introduced under a gauze patch (secured with non-irritating tape) and held in contact with the skin by means of a semi-occlusive dressing for 4 hours. Residual test material was then removed.
Observation period:
24, 48, and 72h post application and once per day until Day 14
Number of animals:
Three males
Details on study design:
SCORING SYSTEM: Draize scale for dermal irritation

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 24 hours
Score:
ca. 2
Max. score:
2
Reversibility:
fully reversible within: 14 days
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 48 hours
Score:
ca. 2.3
Max. score:
3
Reversibility:
fully reversible within: 14 days
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 72 Hours
Score:
ca. 2.7
Max. score:
3
Reversibility:
fully reversible within: 14 days
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 24-72 hours
Score:
2.33
Max. score:
3
Reversibility:
fully reversible within: 14 days
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 24 hours
Score:
ca. 1.3
Max. score:
2
Reversibility:
fully reversible
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 48 hours
Score:
ca. 1.3
Max. score:
2
Reversibility:
fully reversible
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 72 hours
Score:
ca. 1.7
Max. score:
2
Reversibility:
fully reversible
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 24-72 hours
Score:
1.1
Max. score:
2
Reversibility:
fully reversible
Irritant / corrosive response data:
All animals survived to study termination, were free of adverse clinical signs, and displayed normal body weight patterns during the test period.

Topical application of the test substance to the skin of rabbits elicited dermal irritation in all animals during the study. Erythema and edema were observed in all animals.

Erythema started as Grade 2 erythema in all animals at the 60-minute evaluation and remained the same at the 24-hour evaluation. Erythema increased slightly at the 48- hour evaluation when two animals displayed Grade 2 erythema and one animal displayed Grade 3 erythema. Erythema reached its maximum severity at the 72- hour evaluation when one animal displayed Grade 2 erythema and two animals displayed Grade 3 erythema. Erythema subsided after the 72-hour evaluation and on Days 7 and 10 all animals displayed Grade 1 erythema. At the Day 14 evaluation one animal displayed Grade 1 erythema.

Edema was first noted and was most severe at the 60-minute evaluation. Grade 2 edema was noted for all animals at this interval. Edema decreased slightly at the 24 and 48-hour evaluations when Grade 1 edema was noted in two animals and Grade 2 edema was noted in one animal. Edema increased slightly at the 72-hour evaluation when one animal displayed Grade 1 edema and two animals displayed Grade 2 edema. At the Day 7 evaluation Grade 1 edema was displayed by two animals and Grade 3 edema was displayed for one animal. After the Day 7 evaluation edema subsided. One animal displayed Grade 2 edema at Day 10 and one animal displayed Grade 1 edema at Day 14.
Supplemental dermal observations, which included desquamation and cracking, were noted on Days 7 and 10. Desquamation was noted for all animals at both intervals and cracking was noted for one animal on Day 7.

Applicant's summary and conclusion

Interpretation of results:
other: Irritating
Remarks:
R38 Criteria used for interpretation of results: EU
Conclusions:
The average erythema score (24, 48, and 72 hours) was 2.33. The average edema score (24, 48, and 72 hours) was 1.1. The test material would be classified as a Category 2 dermal irritant under the new Regulation (EC) 1272/2008 on classification, labeling and packaging of substances and mixtures (CLP). The test material would be classified as an R38 dermal irritant under Directive 67/518/EEC for dangerous substances and Directive 1999/45/EC for preparations.
Executive summary:

In this study, 3 rabbits were subjected to a 4h dermal (shaved) exposure of 0.5 ml of MRD-00-710 via a semi-occluded patch. Dermal responses were evaluated at 1, 24, 48, and 72h post-dosing and once a day for a total of 14 days according to the Draize method of scoring. Topical application of MRD-00-710 elicited dermal responses in all animals. Well defined erythema and slight odema followed exposure.  The average erythema score (24, 48, and 72 hours) was 2.33.  The average edema score (24, 48, and 72 hours) was 1.1.  The test material would be classified as a Category 2 dermal irritant under the new Regulation (EC) 1272/2008 on classification, labeling and packaging of substances and mixtures (CLP). The test material would be classified as an R38 dermal irritant under Directive 67/518/EEC for dangerous substances and Directive 1999/45/EC for preparations.