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Diss Factsheets

Administrative data

Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
experimental study
Adequacy of study:
other information
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Remarks:
No analytical purity reported; no positive control reported; method shortly described
Cross-reference
Reason / purpose for cross-reference:
reference to same study

Data source

Reference
Reference Type:
publication
Title:
Unnamed
Year:
1991

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Deviations:
yes
Remarks:
No analytical purity reported; no positive control reported; method shortly described.
Principles of method if other than guideline:
The sensitizing potential of maleic acid dimethylester was tested on the skin of guinea pigs according to the maximization protocol developed by Magnusson and Kligman (1969).
GLP compliance:
yes
Type of study:
guinea pig maximisation test

Test material

Constituent 1
Chemical structure
Reference substance name:
Dimethyl maleate
EC Number:
210-848-5
EC Name:
Dimethyl maleate
Cas Number:
624-48-6
Molecular formula:
C6H8O4
IUPAC Name:
dimethyl (Z)-but-2-enedioate
Details on test material:
- Name of test material (as cited in study report): maleic acid dimethylester
- Analytical purity: not reported

In vivo test system

Test animals

Species:
guinea pig
Strain:
Pirbright-Hartley
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Weight at study initiation: 276-328 g

Study design: in vivo (non-LLNA)

Inductionopen allclose all
Route:
intradermal and epicutaneous
Vehicle:
other: ethanol
Concentration / amount:
A concentration of 1% maleic acid dimethylester in physiological saline solution (NaCl 0.9%) was used for the intradermal and dermal induction as well as for the dermal challenge.
Challengeopen allclose all
Route:
other: dermal challenge
Vehicle:
other: ethanol
Concentration / amount:
A concentration of 1% maleic acid dimethylester in physiological saline solution (NaCl 0.9%) was used for the intradermal and dermal induction as well as for the dermal challenge.
No. of animals per dose:
10 treated , 5, controls.
Details on study design:
RANGE FINDING TESTS: The sensitization dose was chosen based on the results of a preliminary investigation where 100, 10 and 1% maleic acid dimethylester were tested. The applied volumes were 0.1 mL (intradermal) and 0.5 mL (dermal).

Challenge controls:
no data
Positive control substance(s):
not specified

Results and discussion

In vivo (non-LLNA)

Resultsopen allclose all
Reading:
1st reading
Hours after challenge:
48
Group:
test chemical
Dose level:
1%
No. with + reactions:
10
Total no. in group:
10
Clinical observations:
During the entire observation period after the challenge treatment, positive reaction (erythema and oedema) occurred on the skin of the 10 guinea pigs treated with 1% maleic acid dimethylester.
Remarks on result:
other: see Remark
Remarks:
Reading: 1st reading. . Hours after challenge: 48.0. Group: test group. Dose level: 1%. No with. + reactions: 10.0. Total no. in groups: 10.0. Clinical observations: During the entire observation period after the challenge treatment, positive reaction (erythema and oedema) occurred on the skin of the 10 guinea pigs treated with 1% maleic acid dimethylester..
Reading:
1st reading
Hours after challenge:
48
Group:
negative control
Dose level:
1%
No. with + reactions:
0
Total no. in group:
5
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 48.0. Group: negative control. Dose level: 1%. No with. + reactions: 0.0. Total no. in groups: 5.0.
Reading:
2nd reading
Hours after challenge:
72
Group:
test chemical
Dose level:
1%
No. with + reactions:
10
Total no. in group:
10
Clinical observations:
During the entire observation period after the challenge treatment, erythema occurred on the skin of the 10 animals and oedema occured on the skin of 8 guinea pigs treated with 1% maleic acid dimethylester.
Remarks on result:
other: see Remark
Remarks:
Reading: 2nd reading. . Hours after challenge: 72.0. Group: test group. Dose level: 1%. No with. + reactions: 10.0. Total no. in groups: 10.0. Clinical observations: During the entire observation period after the challenge treatment, erythema occurred on the skin of the 10 animals and oedema occured on the skin of 8 guinea pigs treated with 1% maleic acid dimethylester..
Reading:
2nd reading
Hours after challenge:
72
Group:
negative control
Dose level:
1%
No. with + reactions:
0
Total no. in group:
5
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 72.0. Group: negative control. Dose level: 1%. No with. + reactions: 0.0. Total no. in groups: 5.0.

Any other information on results incl. tables

Table 2. Sensitization scores of guinea pigs challenged* with 1% maleic acid dimethylester in 0.9% NaCl solution (with 1.5% ethanol).

 Evaluation time (hr)  Effect                           No. of guinea-pigs affected  
 48  Control animals  1  2  3  5            
   Erythema  0  0  0  0            
   Oedema  0  0  0  0            
   Treated animals  11  12  13  14  15  16  17  18 19   20
   Erythema  2  2  2  1  4  2  4  1  4  1
   Oedema  1  1  2  1  2  2  1  1  2  1
   Open wound                  x  
   Scab formation          x    x    x  
 72  Control animals  1  2  3  5            
   Erythema  0  0  0  0            
   Oedema  0  0  0  0            
  Treated animals 11 12  13  14  15  16  17  18  19  20
   Erythema

 1

2 

2

1 

4 

3 

4 

1 

4 

1 
   Oedema

 1

1

 2

 0

 2

2 

 1

 1

2

 0
   Open wound        

 x

      

 x

  
   Scab formation

 x

      

 x

 x

 x

  

 x

  

Applicant's summary and conclusion

Interpretation of results:
Category 1 (skin sensitising) based on GHS criteria
Remarks:
Skin Sens. 1 (CLP regulation).
Executive summary:

Heimann (1991)


 


Dimethyl maleate was investigated for sensitization potential. A sensitization test was performed according to OECD guideline 406 (No analytical purity reported; no positive control reported; method shortly described).


15 female guinea pigs were used for the main study (10 treated, 5 controls). A concentration of 1% dimethyl maleate in physiological saline solution (NaCl 0.9%) was used for intradermal and dermal induction as well as for the dermal challenge. Ethanol served as a vehicle. The sensitization dose was chosen based on the results of a preliminary investigation where 100, 10, and 1% dimethyl maleate were tested. The applied volumes were 0.1 mL (intradermal) and 0.5 mL (dermal).


During the 48 h observation period after the challenge treatment, positive reaction (erythema and oedema) occurred on the skin of the 10 guinea pigs treated with 1% dimethyl maleate. Results of the maximization test in guinea pigs indicated a clear sensitizing potential of dimethyl maleate. During the 72h observation period after the challenge treatment, erythema and oedema occurred on the skin of the 10 and 8 guinea pigs respectively treated with 1% dimethyl maleate.


Based on the study results, the dimethyl maleate is skin sensitizers according to Category 1 for skin sensitization of the CLP Regulation.