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:
The study was conducted between 14 April 2016 and 21 April 2016
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2016
Report date:
2016

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Version / remarks:
adopted 28 July 2015
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes (incl. QA statement)

Test material

Constituent 1
Test material form:
solid: particulate/powder

Test animals

Species:
rabbit
Strain:
New Zealand White
Remarks:
Two male rabbits
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Envigo RMS (UK) Limited, Leicestershire, UK.
- Age at study initiation: 12 to 20 weeks old
- Weight at study initiation: 2.53 or 2.73 kg
- Housing :individually housed in suspended cages
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period:at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17 to 23 °C
- Humidity (%): 30 to 70%
- Air changes (per hr): at least fifteen changes per hour
- Photoperiod (hrs dark / hrs light): 12 hrs/12 hrs

IN-LIFE DATES: From: 14 April 2016 To: 21 April 2016

Test system

Type of coverage:
semiocclusive
Preparation of test site:
clipped
Vehicle:
water
Controls:
not required
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 g

VEHICLE
- Amount(s) applied (volume or weight with unit): 0.5 mL
Duration of treatment / exposure:
4 hours
Observation period:
72 hours
Number of animals:
2
Details on study design:
TEST SITE
- Area of exposure: 2.5 cm x 2.5 cm
- Type of wrap if used: To prevent the animals interfering with the patches, the trunk of each rabbit was wrapped in an elasticated corset and the animals were returned to their cages for the duration of the exposure period.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): gentle swabbing with cotton wool soaked in 74% industrial methylated spirits
- Time after start of exposure: 4 hours

OBSERVATION TIME POINTS
1, 24, 48 and 72 hours

SCORING SYSTEM:

EVALUATION OF SKIN REACTIONS
Erythema and Eschar Formation
- No erythema : 0
- Very slight erythema (barely perceptible): 1
- Well-defined erythema: 2
- Moderate to severe erythema: 3
- Severe erythema (beef redness) to eschar formation preventing grading of erythema: 4

Edema Formation
- No edema: 0
- Very slight edema (barely perceptible): 1
- Slight edema (edges of area well-defined by definite raising): 2
- Moderate edema (raised approximately 1 millimeter): 3
- Severe edema (raised more than 1 millimeter and extending beyond the area of exposure): 4

Any other skin reactions and clinical signs of toxicity, if present, were also recorded.
An additional observation was made on Day 7 to assess the reversibility of skin reactions.
Individual body weights were recorded on Day 0 (the day of dosing) and at the end of the observation period.

DATA EVALUATION
The scores for erythema and edema at the 24 and 72 Hour readings were totaled for the two test rabbits (8 values) and this total was divided by 4 to give the primary irritation index of the test item. The test item was classified according to the following scheme devised by Draize, J.H. (1959):

- Method of calculation: Draize, J.H. (1959)
Primary Irritation Index Classification of Irritancy
0 Non-irritant
> 0 to 2 Mild irritant
> 2 to 5 Moderate irritant
> 5 to 8 Severe irritant

If irreversible alteration of the dermal tissue is noted in any rabbit, as judged by the Study Director, which include ulceration and clear necrosis or signs of scar tissue, the test item is classified as corrosive to rabbit skin. Classification according to Draize may, therefore, not be applicable.
The results were also interpreted according to the Globally Harmonized System of Classification and Labelling of Chemicals.

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
other: Immediately
Score:
0
Remarks on result:
other: Orange colored staining of the test site
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
other: 1 hour
Score:
0
Remarks on result:
other: Orange colored staining of the test site
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
24 h
Score:
2
Max. score:
2
Reversibility:
fully reversible within: 7 days
Remarks on result:
other: Orange colored staining of the test site
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
48 h
Score:
2
Reversibility:
fully reversible within: 7 days
Remarks on result:
other: Orange colored staining of the test site, Loss of skin elasticity
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
72 h
Score:
2
Reversibility:
fully reversible within: 7 days
Remarks on result:
other: Orange colored staining of the test site, Loss of skin elasticity, Loss of skin flexibility
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
7 d
Score:
0
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
other: Immediately
Score:
0
Remarks on result:
other: Orange colored staining of the test site
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
other: 1 hour
Score:
0
Remarks on result:
other: Orange colored staining of the test site
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
24 h
Score:
2
Reversibility:
fully reversible within: 7 days
Remarks on result:
other: Orange colored staining of the test site
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
48 h
Score:
2
Reversibility:
fully reversible within: 7 days
Remarks on result:
other: Orange colored staining of the test site, Loss of skin elasticity
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
72 h
Score:
2
Reversibility:
fully reversible within: 7 days
Remarks on result:
other: Orange colored staining of the test site, Loss of skin elasticity, Loss of skin flexibility
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
7 d
Score:
0
Irritation parameter:
edema score
Basis:
animal #1
Time point:
other: Immediately
Score:
0
Irritation parameter:
edema score
Basis:
animal #1
Time point:
other: 1 hour
Score:
0
Irritation parameter:
edema score
Basis:
animal #1
Time point:
24 h
Score:
2
Reversibility:
fully reversible within: 7 days
Irritation parameter:
edema score
Basis:
animal #1
Time point:
48 h
Score:
2
Reversibility:
fully reversible within: 7 days
Irritation parameter:
edema score
Basis:
animal #1
Time point:
72 h
Score:
2
Reversibility:
fully reversible within: 7 days
Irritation parameter:
edema score
Basis:
animal #1
Time point:
7 d
Score:
0
Irritation parameter:
edema score
Basis:
animal #2
Time point:
other: Immediately
Score:
0
Irritation parameter:
edema score
Basis:
animal #2
Time point:
other: 1 hour
Score:
0
Irritation parameter:
edema score
Basis:
animal #2
Time point:
24 h
Score:
2
Reversibility:
fully reversible within: 7 days
Irritation parameter:
edema score
Basis:
animal #2
Time point:
48 h
Score:
2
Reversibility:
fully reversible within: 7 days
Irritation parameter:
edema score
Basis:
animal #2
Time point:
72 h
Score:
1
Reversibility:
fully reversible within: 7 days
Irritation parameter:
edema score
Basis:
animal #2
Time point:
7 d
Score:
0
Irritation parameter:
overall irritation score
Basis:
animal: 1 and 2
Time point:
other: 24 and 72 Hours
Score:
15
Reversibility:
fully reversible within: 7 days
Irritation parameter:
primary dermal irritation index (PDII)
Basis:
mean
Time point:
other: 24 and 72 hours
Score:
3.8
Reversibility:
fully reversible within: 7 days
Remarks on result:
positive indication of irritation
Irritant / corrosive response data:
The test item produced a primary irritation index of 3.8 and was classified as a moderate irritant to rabbit skin according to the Draize classification scheme. No corrosive effects were noted.
Well-defined erythema and slight edema were noted at both treated skin sites at the 24 and 48 Hour observations with well-defined erythema and very slight to slight edema noted at the 72 Hour observation.
Both treated skin sites appeared normal at the 7-Day observation.
Other effects:
- Other adverse local effects: Loss of skin flexibility and/or elasticity was noted at both treated skin sites at the 48 and 72 Hour observations. Both treated skin sites appeared normal at the 7-Day observation.
- Other adverse systemic effects: One animal showed body weight loss and the other animal showed expected gain in body weight during the study.

Any other information on results incl. tables

Orange colored staining of the test site, not preventing evaluation of skin responses, was noted at both treated skin sites during the study. The test substance is a dark orange powder.

Individual Skin Reactions

Skin Reaction

Observation Time
(following patch removal)

Individual Scores

Total

Rabbit Number and Sex

75409Male

75412Male

Erythema/Eschar Formation

Immediately

0STA

0STA

(0 )

1 Hour

0STA

0STA

( 0 )

24 Hours

2STA

2STA

4

48 Hours

2STALe

2STALe

( 4 )

72 Hours

2STALeLf

2STALeLf

4

7 Days

0

0

( 0 )

Edema Formation

Immediately

0

0

( 0 )

1 Hour

0

0

( 0 )

24 Hours

2

2

4

48 Hours

2

2

( 4 )

72 Hours

2

1

3

7 Days

0

0

( 0 )

Sum of 24 and 72‑Hour Readings (S)            :              15

Primary Irritation Index (S/4)                          :              15/4 = 3.8

Classification                                                      :              MODERATEIRRITANT


(   ) =    Total values not used for calculation of primary irritation index

STA =   Orange colored staining of the test site

Le =      Loss of skin of elasticity

Lf =       Loss of skin flexibility

Individual Body Weights and Body Weight Change

Rabbit Number
and Sex

Individual Body Weight (kg)

Body Weight Change (kg)

Day 0

Day 7

75409Male

2.73

2.84

0.11

75412Male

2.53

2.50

-0.03

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
The test item produced a primary irritation index of 3.8 and was classified as a moderate irritant to rabbit skin according to the Draize classification scheme. No corrosive effects were noted. however, the test item was classified as non irritant according to the Globally Harmonized System of Classification and Labelling of Chemicals, since the effects found were fully reversible by the end of 7 days and mean scores for erythema and edema were <2.3.

Executive summary:

Introduction

The study was performed to assess the irritancy potential of the test item to the skin of the New Zealand White rabbit.

Results

A single 4‑Hour, semi‑occluded application of the test item to the intact skin of two rabbits produced well-defined erythema, slight edema and loss of skin elasticity and flexibility. Both treated skin sites appeared normal at the 7‑Day observation.

Conclusion

The test item produced a primary irritation index of¨3.8 and was classified as amoderateirritant to rabbit skin according to the Draize classification scheme. No corrosive effects were noted. However, the test item was classified as non irritant according to the Globally Harmonized System of Classification and Labelling of Chemicals, since the effects found were fully reversible by the end of 7 days and mean scores for erythema and edema were <2.3.