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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:
From January 06, 2009 to January 20, 2009
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2010
Report Date:
2010

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)
Deviations:
no
Qualifier:
according to
Guideline:
EPA OPPTS 870.2500 (Acute Dermal Irritation)
Deviations:
no
GLP compliance:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
liquid

Test animals

Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
Number of Animals: 3
Sex: Female, nulliparous and non-pregnant
Species/Strain: Rabbit/New Zealand albino
Age: Young adult
Source: Received from Robinson Services Inc., Clemmons, NC on December 31, 2008
Housing: The animals were singly housed in suspended stainless steel caging with mesh floors, which conform to the size recommendations in the most recent Guide for the Care and Use of Laboratory Animals DHEW (NIH).
Litter paper was placed beneath the cage and was changed at least three times per week.
Animal Room Temperature and Relative Humidity Ranges: 19-20ºC and 24-51%, respectively. The low humidity occurred during the study due to a temporary malfunction of the environmental control system.
Photoperiod: 12-hour light/dark cycle
Acclimation Period: 6 days
Food: Pelleted Purina Rabbit Chow #5326
Water: Filtered tap water was supplied ad-libitum by an automatic water dispensing system.
Contaminants: There were no known contaminants reasonably expected to be found in the food or water at levels, which would have interfered with the results of this study. Analyses of the food and water are conducted regularly and the records are kept in the test fecility.
Cage: Each cage was identified with a cage card indicating at least the study number and identification and sex of the animal.
Animal: A number was allocated to each rabbit on receipt and a stainless steel ear tag bearing this number was attached to the animal. This number, together with a sequential animal number assigned to study 26614, constituted unique identification.

Test system

Type of coverage:
semiocclusive
Preparation of test site:
clipped
Vehicle:
unchanged (no vehicle)
Controls:
yes, concurrent no treatment
Amount / concentration applied:
0.5 mL
Duration of treatment / exposure:
4 hours
Observation period:
14 days
Number of animals:
3
Details on study design:
Preparation and Selection of Animals
On the day before application, a group of animals was prepared by clipping the dorsal area and the trunk. On the day of dosing, but prior to application, the animals were examined for health and the skin checked for any abnormalities. Three healthy, naive animals (not previously tested) without pre-existing skin irritation were selected for test.

Application of Test Substance
Five-tenths of a milliliter of the test substance was applied to one 6-cm2 intact dose site on each animal and covered with a 1-inch x-1 inch, 4-ply gauze pad. The pad and entire trunk of each animal were then wrapped with semi-occlusive 3-inch Micropore tape to avoid dislocation of the pad. Elizabethan collars were placed on each rabbit and they were returned to their designated cages.
After 4 hours of exposure to the test substance, the pads and the collars were removed, and the test sites were gently cleansed of any residual test substance.

Evaluation of Test Sites
Individual dose sites were scored according to the Draize scoring system at approximately 30-60 minutes, 24, 48, and 72 hours and at 7, 10 and 14 days after patch removal. Additionally, the average erythema and edema scores across 24, 48 and 72 hours for each animal were calculated for EEC2 classification. The classification of irritancy was obtained by adding the average erythema and edema scores for the 30-60 minute, 24, 48, and 72-hour scoring intervals and dividing by the number of evaluation intervals.

Cage-Side Observations
The animals were observed for signs of gross toxicity and behavioral changes at least once daily during the test period. Observations included gross evaluation of skin and fur, eyes and mucous membranes, respiratory, circulatory, autonomic and central nervous systems, somatomotor activity and behavior pattern. Particular attention was directed to observation of tremors, convulsions, salivation, diarrhea, and coma.

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
1.3
Max. score:
4
Reversibility:
not reversible
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
1.3
Max. score:
4
Reversibility:
not reversible
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
2
Max. score:
4
Reversibility:
not reversible
Irritation parameter:
edema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0.3
Max. score:
4
Reversibility:
not reversible
Irritation parameter:
edema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0.3
Max. score:
4
Reversibility:
not reversible
Irritation parameter:
edema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
1
Max. score:
4
Reversibility:
not reversible
Irritant / corrosive response data:
All animals appeared active and healthy during the study. Apart from the dermal irritation noted below, there were no other signs of gross toxicity, adverse pharmacologic effects, or abnormal behavior.
One hour after patch removal, all three treated sites exhibited very slight to well-defined erythema and very slight edema. Desquamation was noted at two or three dose sites between 72 hours and Day 14. Although the overall incidence and severity of irritation decreased gradually with time, dermal irritation (erythema and/or desquamation) persisted for two animals through Day 14 (study termination).
The Primary Dermal Irritation Index for the test substance is 2.3.

Applicant's summary and conclusion

Interpretation of results:
Category 3 (mild irritant) based on GHS criteria
Conclusions:
Under the study conditions, the test substance was moderately irritating to the skin.
Executive summary:

A study was conducted to determine the skin irritation potential of the test substance in male Himalayan rabbits according to OECD Guideline 404 and EU Method B.4, in compliance with GLP. Five-tenths of a milliliter of the test substance was applied to the skin of three healthy rabbits for 4 h. Following exposure, dermal irritation was evaluated by the method of Draize et al. One hour after patch removal, all three treated sites exhibited very slight to well-defined erythema and very slight edema. Desquamation was noted at two or three dose sites between 72 h and Day 14. Although the overall incidence and severity of irritation decreased gradually with time, dermal irritation (erythema and/or desquamation) persisted for 2 animals through Day 14 (study termination). Under the study conditions, the test substance was moderately irritating to skin (Oley, 2009).