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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:
23 April - 14 June 2018
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Remarks:
The study was conducted under GLP in accordance with the international guideline.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2018
Report Date:
2018

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Version / remarks:
2015
Deviations:
no
Qualifier:
according to
Guideline:
other: “Regulation on Test Methods for Chemical Substances” Notification No. 2017-4, National Institute of Environmental Research, Republic of Korea
Version / remarks:
2017
Deviations:
no
GLP compliance:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid: particulate/powder
Details on test material:
- Storage condition of test material: At room temperature

Test animals

Species:
rabbit
Strain:
New Zealand White

Test system

Type of coverage:
semiocclusive
Preparation of test site:
clipped
Controls:
other: Untreated site
Amount / concentration applied:
0.5 g
Duration of treatment / exposure:
4 hours
Observation period:
1, 24, 48 and 72 hours plus additional observation until day 4
Number of animals:
3
Details on study design:
In the initial test, two sites of one rabbit’s clipped back along the midline were selected as application sites. One site was designated as test substance site. The other site was served as control site. 0.5 g of test substance was placed on the test substance site, moistened with water for injection and held in contact with the skin by a semi-occlusive dressing for 4 hours. No severe irritant effect was observed in the initial test, thus a confirmatory test was conducted using two additional animals. The observation of application sites for skin response was conducted at 1, 24, 48 and 72 hours after patch removal and the skin response scored according to the ‘Evaluation of skin reactions (Method of Draize: 1959)1)’. The degree of skin irritation was classified according to the Draize’s method).In both the initial and confirmatory tests, skin irritation was observed at 72 hours after patch removal. Therefore, additional dermal observations were conducted until Day 4.

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
primary dermal irritation index (PDII)
Basis:
mean
Time point:
other: 24 hr and 4 days
Score:
ca. 0.8
Max. score:
4
Reversibility:
other: irritation
Remarks on result:
probability of weak irritation
Irritation parameter:
edema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
ca. 0.8
Max. score:
4
Reversibility:
other: irritant
Remarks on result:
probability of weak irritation
Irritation parameter:
edema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
ca. 0.8
Max. score:
4
Reversibility:
other: irritant
Remarks on result:
probability of weak irritation
Irritation parameter:
edema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
ca. 0.8
Max. score:
4
Reversibility:
other: irriatnt
Remarks on result:
probability of weak irritation
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
ca. 0.8
Max. score:
4
Reversibility:
other: irritant
Remarks on result:
probability of weak irritation
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
ca. 0.8
Max. score:
4
Reversibility:
other: irritant
Remarks on result:
probability of weak irritation
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
ca. 0.8
Max. score:
4
Reversibility:
other: irritant
Remarks on result:
probability of weak irritation
Irritant / corrosive response data:
The substance is not corrosive but slightly irritating

Any other information on results incl. tables

Table 3. Irritation scores

Applied area

Group

Animal ID

Score of erythema and eschar/Score of edema Intervals (hour)

Score of erythema and eschar/Score of edema Intervals

IndividualP.I.I.a)

P.I.I.b)

Classification of skin irritation

1

24

48

72

4

100% test Item

Initial

1101

0/0

1/0

1/0

1/0

0/0

0.8

0.8

Slightly irritant

Confirmatory

1102

0/0

1/0

1/0

1/0

0/0

0.8

1103

0/0

1/0

1/0

1/0

0/0

0.8

Control (only patch)

Initial

1101

0/0

0/0

0/0

0/0

0/0

0/0

0.0

Non irritant

Confirmatory

1102

0/0

0/0

0/0

0/0

0/0

0/0

1103

0/0

0/0

0/0

0/0

0/0

0/0

hour: Observation after patch removal

a: Individual P.I.I.(Primary skin irritation index) was determined by dividing the total scores of reactions for erythema and eschar/edema formation observed at 1, 24, 48 and 72 hours after patch removal by 4.

b: P.I.I. was determined by dividing the totaled individual P.I.I. by 3 animals to obtain the average

Table 4. Body weights

Applied area

Group

Animal ID

Body weight (kg/day)

Gain (kg)

1

4

 

G1

Initial

1101

2.05

2.16

0.11

Confirmatory

1102

2.06

2.18

0.12

1103

2.19

2.30

0.11

Mean

2.10

2.21

0.11

SD

0.08

0.08

0.01

N

3

3

3

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
Under the condition of the study, the primary irritation index (PII) of the test item was 0.8, following exposure to clipped rabbit skin under semi-occlusive condition. Therefore the test item does not meet the criteria for classification according to the Globally Harmonized Classification System or the criteria for classification under the Regulation (EC) No. 1272/2008, relating to the Classification, Labelling and Packaging of Substances and Mixtures.
Executive summary:

OECD 404 (2018): The irritant or corrosive effects of the test item, was assessed following application to the clipped skin of white New Zealand rabbit. 0.5 g of test item was placed on the test substance site, moistened with water for injection and held in contact with the skin by a semi-occlusive dressing for 4 hours. No severe irritant effect was observed in the initial test, thus a confirmatory test was conducted using two additional animals. The observation of application sites for skin response was conducted at 1, 24, 48 and 72 hours after patch removal and the skin response scored according to the ‘Evaluation of skin reactions (Method of Draize: 1959)’. The degree of skin irritation was classified according to the Draize’s method. In both the initial and confirmatory tests, skin irritation was observed at 72 hours after patch removal. Therefore, additional dermal observations were conducted until Day 4.

Animals were observed for mortality, toxicological and pharmacological effects at least once daily. Body weights were recorded pre-test and at termination.

No adverse signs were observed in any animal throughout the course of the study. All animals exhibited normal body weight gain. The mean body weight gain throughout the observation period was 0.11 kg. 


The test item sites did not reveal any sign of adverse skin reactions such as erythema and edema in any of three animals at one hour after patch removal. Erythema of score 1 was observed in three animals from 24 hours to 72 hours after patch. Skin reactions were not observed on Day 4.  In both the initial and confirmatory tests, the control sites did not reveal any sign of adverse skin reactions during the observation period. 


The individual primary skin irritation index (Individual P.I.I.) of the test substance was ‘0.8’ for all animals. Therefore, the P.I.I. of the test substance was ‘0.8’. The degree of irritation of the test substance was classified as ‘Slightly irritant’ according to the Draize’s method. 


However, the test item does not meet the criteria for classification under the Globally Harrmonised Classification System or the Regulation (EC) No. 1272/2008, relating to the Classification, Labelling and Packaging of Substances and Mixtures.