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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:
1991
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Guideline study (GLP) with only minor deficiencies

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1991
Report Date:
1991

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
yes
Remarks:
first reading 30 min after patch removal instead of 60 min, no body weight determination at test conclusion
GLP compliance:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
Methacrolein, CAS 78-85-3
Purity: 97.02%
water: 2.7%
Aldrich Catalogue No. 13303-5
Lot No. 02505PX

Test animals

Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Froxfield Farms (U.K.) Ltd., Petersfield, Hampshire, England
- Age at study initiation: 12-13 weeks
- Weight at study initiation: 2.7-3.2 kg
- Housing: individually in metal cages, perforated floors
- Diet (e.g. ad libitum): SDS Stanrab (P) Rabbit Diet, ad libitum
- Water (e.g. ad libitum): drinking water, ad libitum
- Acclimation period: not stated


ENVIRONMENTAL CONDITIONS
- Temperature (°C): approximately 19 °C
- Humidity (%): 30-70 %
- Air changes (per hr): 19
- Photoperiod (hrs dark / hrs light): 12 hrs dark/12 hrs light

Test system

Type of coverage:
semiocclusive
Preparation of test site:
other: clipped with electric clippers
Vehicle:
unchanged (no vehicle)
Controls:
other: untreated skin of same animal
Amount / concentration applied:
TEST MATERIAL
- Amount(s) of test substance applied (volume or weight with unit): 0.5 mL, undiluted.
Duration of treatment / exposure:
4 hour(s)
Observation period:
14 days
Number of animals:
3
Details on study design:
TEST SITE
- Area of exposure: dorso-lumbar region
- % coverage: 10 cm square
- Type of wrap if used: "Elastoplast" elastic adhesive dressing


REMOVAL OF TEST SUBSTANCE
- Washing (if done): with water
- Time after start of exposure: 4 hrs


SCORING SYSTEM: According to the guideline

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
edema score
Basis:
animal: 1-3
Time point:
other: 24 h - 72 h
Score:
2.1
Max. score:
3
Reversibility:
not fully reversible within: 14 days
Irritation parameter:
erythema score
Basis:
animal: 1-3
Time point:
other: 24 h - 72 h
Score:
2
Max. score:
4
Reversibility:
not fully reversible within: 14 days
Irritant / corrosive response data:
The numerical scores awarded to the dermal reactions elicited by Methacrolein are given in Table 1.
Immediately following application of the test substance all three animals displayed signs of distress which consisted of vocalisation and rapid movement around their cages. This lasted for approximately five minutes.
Well-defined erythema with very slight to moderate oedema were evident at all three treatment sites during die first 8/9 days of the study. These responses were accompanied at all sites from either Day 3 or 4 by a whitening of the epidermis (blanching), still present at two sites on Day 14 but resolved at one site by Day 9.
By Days 9 or 10 severe reactions consisting of necrosis with very slight or slight oedema had developed at all sites. This response was still present at all sites on Day 14.

Any other information on results incl. tables

Table 1: Results

Reading (day)
 animal
 erythema
 oedema
 1*         
   1   
   2    
   2
            
   2   
   2    
   2
            
   3   
   2    
   2
 2          
   1   
   2    
   2
            
   2   
   2    
   3
            
   3   
   2    
   2
 3          
   1   
   2A   
   2
            
   2   
   2    
   3
            
   3   
   2    
   2
 4          
   1   
   2A   
   2
            
   2   
   2A   
   1
            
   3   
   2A   
   2
 5          
   1   
   2A   
   3
            
   2   
   2A   
   2
            
   3   
   2A   
   2
 6          
   1   
   2A   
   2
            
   2   
   2A   
   1
            
   3   
   2A   
   1
 7          
   1   
   2A   
   2
            
   2   
   2A   
   1
            
   3   
   2A   
   1
 8          
   1   
   2A   
   2
            
   2   
   2A   
   1
            
   3   
   2A   
   2
 9          
   1   
   4B   
   2
            
   2   
   2A   
   1
            
   3   
   2A   
   2
10          
   1   
   4B   
   2
            
   2   
   4A   
   1B
            
   3   
   4A   
   2B
11          
   1   
   4B   
   2
            
   2   
   4A   
   1B
            
   3   
   4A   
   2B
12          
   1   
   4B   
   2
            
   2   
   4B   
   1B
            
   3   
   4A   
   2B
13          
   1   
   4B   
   2
            
   2   
   4A   
   1B
            
   3   
   4A   
   2B
14          
   1   
   4B   
   2
            
   2   
   4A   
   1B
            
   3   
   4A   
   2B
mean 2      
        
   2.0  
   2.3
mean 3      
        
   2.0  
   2.3
mean 4      
        
   2.0  
   1.7
mean 2-4    
        
   2.0  
   2.1

* = approx. 30 min after removal of the dressing
A =Blanching; B =Necrosis

Applicant's summary and conclusion

Executive summary:

A single semi-occlusive application of the test substance to the intact skins of 3 rabbits for four hours elicited moderate to severe dermal reactions which were not reversible within 14 days p.a.