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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:
24 May 1988 to 23 March 1989
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
test procedure in accordance with generally accepted scientific standards and described in sufficient detail

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1988
Report Date:
1988

Materials and methods

Test guidelineopen allclose all
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
not specified
Qualifier:
equivalent or similar to
Guideline:
EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)
Deviations:
not specified
GLP compliance:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
liquid: viscous
Details on test material:
- Appearance: Viscous brown liquid
- Storage conditions: Ambient temperature

Test animals

Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Age at study initiation: 26-28 weeks old
- Housing: The animals were housed individually in stainless-steel support bar-bottom cages in an air-conditioned room.
- Diet: The animals were fed a daily ration of high fibre rabbit chow.
- Water: Ad libitum
- Acclimation period: There was a conditioning period of 18 weeks before dosing.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): Ranged from 20 to 22 °C
- Humidity (%): Ranged from 58 to 83 %
- Photoperiod (hrs dark / hrs light): 12-hour light/dark cycle

Test system

Type of coverage:
semiocclusive
Preparation of test site:
other: clipped and abraded
Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
The test material was applied neat.
Duration of treatment / exposure:
Four hours
Observation period:
14 days
Number of animals:
Six
Details on study design:
TEST SITE
- Area of exposure: The back of the rabbit.
The fur on the back o each rabbit was clipped the day before dosing. One half-millilitre of the test material was applied to each of two intact and two abraded sites on the back of each rabbit. Epidermal abrasions (cross-hatching) were made with a hypodermic needle penetrating the stratum corneum over areas of approximately one square inch.
- % coverage: Not specified
- Type of wrap if used: Each treated site was covered with a gauze patch secured by porous tape. The trunk of each animal was loosely wrapped in sheet of plastic film, and paper towels were wrapped around the plastic to prevent tearing. A collar was placed on each animal to protect the wrappings during the exposure period.

REMOVAL OF TEST SUBSTANCE
- Washing: The skin was wiped with gauze pads moistened with mineral oil and then with dry gauze to remove any remaining test material.
- Time after start of exposure: 4 hours

OBSERVATION TIME POINTS
Irritation was scored at 1, 24, 48 and 72 hours after removal of the test material and at 7 and 14 days.
All animals on study were observed at least once each day for behavioural or physiological abnormalities.

SCORING SYSTEM:
- Method of calculation: Modified Draize method.
Erythema and eschar formation:
0=No erythema
1=Slight erythema (barely perceptible)
2=Well-defined erythema
3=Moderate erythema
4=Severe erythema (beet redness) to slight eschar formation (injuries in depth)

Oedema formation:
0=No oedema
1=Slight oedema (barely perceptible)
2=Well-defined 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)

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
4
Max. score:
4
Reversibility:
not fully reversible within: 14 days
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
4
Max. score:
4
Reversibility:
not fully reversible within: 14 days
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
4
Max. score:
4
Reversibility:
not fully reversible within: 14 days
Irritation parameter:
erythema score
Basis:
animal #4
Time point:
24/48/72 h
Score:
4
Max. score:
4
Reversibility:
not fully reversible within: 14 days
Irritation parameter:
erythema score
Basis:
animal #5
Time point:
24/48/72 h
Score:
4
Max. score:
4
Reversibility:
not fully reversible within: 14 days
Irritation parameter:
erythema score
Basis:
animal #6
Time point:
24/48/72 h
Score:
4
Max. score:
4
Reversibility:
not fully reversible within: 14 days
Irritation parameter:
edema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
3
Max. score:
4
Reversibility:
not fully reversible within: 14 days
Irritation parameter:
edema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
3
Max. score:
4
Reversibility:
not fully reversible within: 14 days
Irritation parameter:
edema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
3
Max. score:
4
Reversibility:
not fully reversible within: 14 days
Irritation parameter:
edema score
Basis:
animal #4
Time point:
24/48/72 h
Score:
3.5
Max. score:
4
Reversibility:
not fully reversible within: 14 days
Irritation parameter:
edema score
Basis:
animal #5
Time point:
24/48/72 h
Score:
3
Max. score:
4
Reversibility:
not fully reversible within: 14 days
Irritation parameter:
edema score
Basis:
animal #6
Time point:
24/48/72 h
Score:
4
Max. score:
4
Reversibility:
not fully reversible within: 14 days
Irritant / corrosive response data:
The primary irritation score was 6.9
The test material caused well-defined to severe erythema (eschar formation) with well-defined to moderate oedema one hour after unwrapping.
Severe erythema (eschar formation, necrosis or scar tissue) was observed at 24 hours persisting through Day 7.
Well-defined to severe oedema was observed at 24 hours, increasing to moderate to severe oedema through 72 hours before decreasing to slight to well-defined oedema on Day 7. On Day 14, well-defined to severe erythema (with scar tissue) and no to well-defined edema was observed; dry and flaky skin was also noted.
Other effects:
PATHOLOGY
- Macroscopic Pathology:
The following macroscopic findings were observed in the skin of rabbits (male) of this study. (Group 1, Treated): red discoloration, swollen or dry and flaky areas, scabs, and/or the presence of scar tissue. The above findings were seen at the treated sites.
 
- Microscopic Pathology:
Several microscopic findings were observed in the treated skins examined. These included acanthosis, hyperkeratosis, sub-acute inflammation. The presence of brown pigment and fibrosis was occasionally observed in some rabbits. As with the macroscopic findings, these were seen in most rabbits at all four treated sites.
The above listed findings were considered to be related to the dermal exposure to the compound and are indications of mild dermal irritation.

The dermal findings in this study were considered to be related to the dermal exposure to the compound and are indications of mild dermal irritation.

Any other information on results incl. tables

Mean Skin Irritation Scores and Primary Score for Adult Albino Male Rabbits Treated for 4 Hours with the Test Material

Time after Treatment

Irritation

Mean Score*

Intact

Abraded

1 Hour

Erythema

3.7

3.8

Oedema

2.3

2.3

24 Hours

Erythema

4.0

4.0

 Oedema

3.2

3.2

48 Hours

Erythema

4.0

4.0

 Oedema

3.4

3.4

72 Hours

Erythema

4.0

4.0

 Oedema

3.5

3.5

7 Days

Erythema

4.0

4.0

 Oedema

1.7

1.3

14 Days

Erythema

3.2

3.3

 Oedema

1.0

0.7

Primary Irritation Score**: 6.9

* Mean of six animals.

** Sum of the combined individual scores for erythema and oedema at each site at 1, 24 and 72 hours divided by 72 observations.

Applicant's summary and conclusion

Interpretation of results:
Category 2 (irritant) based on GHS criteria
Conclusions:
The test material caused skin irritation under the conditions tested. Histopathological effects were observed at all treated sites.
Executive summary:

A study was performed to assess the irritancy potential of the test material to six male albino rabbits; Dougherty (1989). The report does not specify a guideline, however the methodology and techniques described within the report are similar to those of the standardised guidelines OECD 404 and EU Method B.4 and in compliance with GLP. The study was assigned as the key study and allocated a reliability score of 2 in line with the principles for assessing data quality as defined by Klimisch et al. (1997).

 

0.5 mL of test material was applied to two intact and two abraded areas on the back of each of six rabbits for four hours under occluded conditions after which the test area was wiped free of test material with gauze pads moistened with mineral oil.

Irritation was scored at 1, 24, 48 and 72 hours after removal of the test material and at 7 and 14 days using a modified Draize method.

The test material caused well-defined to severe erythema with well-defined to moderate oedema one hour after unwrapping.

Severe irritation continued through Day 14; dry and flaky skin was also observed on Day 14. The primary irritation score was 6.9. There were no differences between intact and abraded skin.

 

At sacrifice on Day 14, treated sites were red, swollen, dry/flaky, scabbed, and/or scarred. Compound-related acanthosis, hyperkeratosis, and subacute inflammation were observed. Brown pigment and fibrosis were occasionally observed in some rabbits.

 

Under the conditions of the study the test material caused severe skin irritation under the conditions tested. Histopathological effects were observed at all treated sites. The test material is therefore classified for skin irritation (Category 2).