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:
14 June 2010 - 21 Feb 2011
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2011
Report Date:
2011

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Version / remarks:
adopted 24 April 2002)
Deviations:
not specified
Qualifier:
according to
Guideline:
EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)
Version / remarks:
No. 440/2008
Deviations:
not specified
GLP compliance:
yes (incl. certificate)

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
liquid
Details on test material:
SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: TD-9024390, received November 1, 2010
- Expiration date of the lot/batch: November 1, 2011
- Purity: 99.63%

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: room temperature in the dark

TREATMENT OF TEST MATERIAL PRIOR TO TESTING
- Treatment of test material prior to testing: the test item was used as supplied.
Specific details on test material used for the study:
SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: TD-9024390, received November 1, 2010
- Expiration date of the lot/batch: November 1, 2011
- Purity: 99.63%

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: room temperature in the dark

TREATMENT OF TEST MATERIAL PRIOR TO TESTING
- Treatment of test material prior to testing: the test item was used as supplied.

OTHER SPECIFICS:
- Appearance: pale yellow liquid
- pH measurement inmediately prior to commencement of the study: undiluted material pH 6.5, diluted (90% v/v) aquous solution pH 5.0.

Test animals

Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Harlan Laboratories U.K. Ltd., Loughborough, UK
- Age at study initiation: twelve to twenty weeks
- Weight at study initiation: 2.21 or 2.49 kg
- Housing: individually, in suspended cages
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: at least five days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17 to 23°C
- Humidity (%): 30 to 70%
- Air changes (per hr): fifteen changes per hour
- Photoperiod (hrs dark / hrs light): twelve hours continuous light (06:00 to 18:00) and twelve hours darkness

Test system

Type of coverage:
semiocclusive
Preparation of test site:
clipped
Vehicle:
unchanged (no vehicle)
Controls:
not specified
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 mL
- Concentration (if solution): Undiluted

Duration of treatment / exposure:
4 hours
Observation period:
Immediately after removal, and after 1, 24, 48 and 72 hours
Number of animals:
3
Details on study design:
TEST SITE
- Area of exposure: Back
- % coverage:2.5 cm x 2.5 cm
- Type of wrap if used: cotton gauze

REMOVAL OF TEST SUBSTANCE
- Washing (if done): residual test item was removed by gentle swabbing with cotton wool soaked in distilled water.
- Time after start of exposure: 4 hours

OBSERVATION TIME POINTS
Immediately after removal, and after 1, 24, 48 and 72 hours, Days 7 and 14

SCORING SYSTEM:
- Method of calculation: The scores for erythema and oedema at the 24 and 72-Hour readings were totalled for the three test rabbits (12 values) and this total was divided by six 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) "Dermal Toxicity" In: Appraisal of the Safety of Chemicals in Foods, Drugs and Cosmetics. Association of Food and Drug Officials of the United States, Austin, Texas, p.46-59

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

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

Any other skin reactions and clinical signs of toxicity, if present, were also recorded.
Individual bodyweights were recorded on Day 0 (the day of dosing) and at the end of the observation period.

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
erythema score
Basis:
animal: #1, 2 and 3
Time point:
24/48/72 h
Score:
2
Max. score:
4
Reversibility:
fully reversible within: 14 days
Remarks:
Slight desquamation was observed after 14 days in 1 animal
Irritation parameter:
edema score
Basis:
animal: #1, 2 and 3
Time point:
24/48/72 h
Score:
>= 1 - <= 2
Max. score:
4
Reversibility:
fully reversible within: 14 days
Remarks:
at 7 days 1 animal still showed adverse reaction which prevented the accurate evaluation of oedema
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
7 d
Max. score:
4
Reversibility:
fully reversible within: 14 days
Remarks:
Slight desquamation was observed
Remarks on result:
not determinable
Irritation parameter:
edema score
Basis:
animal #1
Time point:
7 d
Max. score:
4
Reversibility:
fully reversible within: 14 days
Remarks on result:
not determinable
Irritation parameter:
primary dermal irritation index (PDII)
Basis:
animal: #1, 2 and 3
Time point:
other: 24/72 hours
Score:
3.7
Max. score:
8
Reversibility:
fully reversible within: 14 days
Remarks:
Slight desquamation was observed after 14 days in 1 animal
Remarks on result:
probability of moderate irritation
Irritant / corrosive response data:
Well-defined erythema and slight oedema were noted at one treated skin site immediately and one hour after patch removal. Well-defined erythema and very slight or slight oedema were noted at all treated skin sites at the 24, 48 and 72-Hour observations. Light brown discolouration of the epidermis and loss of skin flexibility and/or elasticity were noted at one treated skin site at the 24, 48 and 72-Hour observations with crust formation, which prevented accurate evaluation of erythema and oedema, noted at this treated skin site at the 7-Day observation and slight desquamation at the 14-Day observation. Slight desquamation was noted at the other two treated skin sites at the 7-Day observation. the Primary Irritation Index was calculated to be 3.7.

Applicant's summary and conclusion

Interpretation of results:
other: Category 2 irritant
Remarks:
Annex I of the CLP Regulation (1272/2008/EC).
Conclusions:
Based on the results in this study the compound should be classified as a category 2 irritant in accordance with the criteria outlined in Annex I of the CLP Regulation (1272/2008/EC).
Executive summary:

The study was performed to assess the irritancy potential of methyl n-amyl ketone to the skin of the New Zealand White rabbit. The method was compliant with OECD TG 404 and EC Method 84 No. 440/2008. One of the rabbits was initially treated, to determine the effects of exposure after 3-minute and 1-hour semi-occluded applications of the test item to the intact skin. The substance produced no corrosive effects. A single 4-hour, semi-occluded application of the test item to the intact skin of three rabbits produced well-defined erythema and slight immediately and one hour after patch removal. Well-defined erythema and very slight or slight oedema were noted at all treated skin sites at the 24, 48 and 72-Hour observations. Other signs of skin irritation noted were light brown discolouration of the epidermis, loss of skin flexibility and/or elasticity, crust formation and slight desquamation. The test item produced a primary irritation index of 3.7 and was classified as a moderate irritant to rabbit skin according to the Draize classification scheme. Based on the results in this study the compound should be classified as a category 2 irritant in accordance with the criteria outlined in Annex I of the CLP Regulation (1272/2008/EC).