Registration Dossier

Administrative data

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Dermal irritation was evaluated in a acute dermal study (24 hours treatment, occlusive coverage of test sites)
Cross-reference
Reason / purpose:
reference to same study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1998
Report Date:
1998

Materials and methods

Principles of method if other than guideline:
Dermal irritation was evaluated in an acute dermal toxicity study performed according to EPA OPPTS 870.1200 (Acute Dermal Toxicity)
GLP compliance:
yes
Remarks:
United States Environmental Protection Agency TSCA: Good Laboratory Practice Standards, 40 CFR 792

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): s-MOIPA
- Physical state: clear, light-yellow liquid
- Purity test date: 94.1 - 95.3%
- Lot/batch No.: 7/11/97
- Storage condition of test material: the test material was stored at room temperature.

Test animals

Species:
rabbit
Strain:
other: Hra:(NZW)SPF

Test system

Type of coverage:
occlusive
Preparation of test site:
shaved
Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): the amount of test material applied to the test site in a thin and uniform layer was approximately 0.006 g/cm2 (500 mg/kg dose level) to 0.04 g/cm2 (3000 mg/kg dose level).
Duration of treatment / exposure:
24 hours
Observation period:
14 days
Number of animals:
5 males and 5 females (except the 3000 mg/kg dose group, where the treatment was interrupted for humane reasons, after 3 males were treated)
Details on study design:
TEST SITE
- Area of exposure: 180 cm2
- % coverage: occlusive
- Type of wrap if used: the area of application was covered with a zl-ply 9.5-cm x 19-cm gauze pateh secured with paper tape and overwrapped with Saran Wrap<0 and Elastoplast® tape

REMOVAL OF TEST SUBSTANCE
- Washing (if done): yes
- Time after start of exposure: after the 24-hour exposure period

SCORING SYSTEM: similar to the OECD scoring system (at least for erythema and edema; see below)
- Erythema: 0, No erythema; 1, Very slight erythema (barely perceptible); 2, Well-defined erythema; 3, Moderate to severe erythema; 4, Severe erythema (beet redness) to slight eschar formation (injuries in depth).
- Edema: 0, No edema; 1, Very slight edema (barely perceptible); 2, Slight edema (edges are well defined by definite raising); 3, Moderate edema (raised approximately 1 mm); 4, Severe edema (raised approximately 1 mm and extending beyond area of exposure).
- Atonia: 0, None; 1, Slight (slight impairment of elasticity); 2, Moderate (slow return to normal); 3, Marked (no elasticity);
- Desquamation: 0, None; 1, Slight; 2, Moderate (scales and flakes); 3, Marked (pronounced flaking with denuded areas).
- Coriaceousness: 0, None; 1, Slight (decrease in pliability); 2, Moderate (leathery texture); 3, Marked (tough and brittle).
- Fissuring: 0, None; 1, Slight (definite cracks in epidermis); 2, Moderate (cracks in dermis); 3, Marked (cracks with bleeding)

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 24-72- hour
Score:
4
Max. score:
4
Reversibility:
not fully reversible within: 14 days
Remarks on result:
other: Erythema scores in the 500 and 1000 mg/kg bw dose levels remain at 4 at the end of the observation period with echar formation and possible necrotic areas
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 1-14 days
Max. score:
4
Remarks on result:
other: see table 1
Irritant / corrosive response data:
Based to the gravity of the erythema scores, as well as crusted areas, eschar, discoloration of the underlying muscle and necrosis, and although the treatment period was 24 hours instead of 4 hours and the coverage of test sites occlusive instead of semi-occlusive, the test substance should be considered corrosive to the rabbit skin (worst case consideration giving the 24 hours treatment and the occlusive coverage of test sites; R34 according to the EU and Category 1C according to GHS).
Other effects:
All animals showed eschar formation (generally from day 3 to the end) or possible necrotic areas (generally at day 1). At necropsy, the treated skin of each animal was observed to be variable dark-brown or red, with or without crusted areas. The treated skin was also thickened in some animals. The underlying muscle in some animals was also dark-brown or tan. These findings are attributed to the irritation/injury caused by the test material.

Any other information on results incl. tables

Table 1: Individual dermal irritation observation

 

Test group

Sex

Observation

Scores

Mean 1-3 days

Day 14

 

 

 

 

 

 

 

 

 

500 mg/kg bw

First male

Erythema

4

4

Edema

2

1

Second male

Erythema

4

4

Edema

1.5

1

Third male

Erythema

4

4

Edema

1.5

1

Fourth male

Erythema

4

4

Edema

1.5

1

Fifth male

Erythema

4

1.5

Edema

1.5

1

First female

Erythema

4

4

Edema

3

1

Second female

Erythema

4

4

Edema

1.5

1

Third female

Erythema

4

4

Edema

1.5

1

Fourth female

Erythema

4

4

Edema

2

1

Fifth female

Erythema

4

1.5

Edema

2.5

1

 

 

 

 

 

 

 

 

 

1000 mg/kg bw

First male

Erythema

4

4

Edema

1.5

1

Second male

Erythema

4

4

Edema

2

1

Third male

Erythema

4

4

Edema

1.5

1

Fourth male

Erythema

4

4

Edema

1.5

1

Fifth male

Erythema

-

-

Edema

-

-

First female

Erythema

4

4

Edema

1.5

1

Second female

Erythema

4

4

Edema

1.5

1

Third female

Erythema

4

4

Edema

1.5

1

Fourth female

Erythema

4

4

Edema

1.5

1

Fifth female

Erythema

4

1.5

Edema

2

1

 

Applicant's summary and conclusion