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Administrative data

Description of key information

The experimental results for the read across chemicals lend ample support to the results obtained from the estimation for the target chemical, affirming that 2,3-bis[(4-methylbenzoyl)oxy]succinic acid  can indeed be sensitizing to skin. Hence, by applying the weight of evidence approach, 2,3-bis[(4-methylbenzoyl)oxy]succinic acid  can be considered to be sensitizing to skin.   

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records
Reference
Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Weight of evidence based on structurally similar chemicals
Justification for type of information:
Weight of evidence based on structurally similar chemicals
Reason / purpose:
read-across: supporting information
Reason / purpose:
read-across: supporting information
Reason / purpose:
read-across: supporting information
Qualifier:
according to
Guideline:
other: Weight of evidence approach based on structurally similar chemicals
Principles of method if other than guideline:
The weight of evidence report has been prepared based on the read across substances identified based on structural and functional similarity to assess the dermal sensitization potential of 2,3-bis[(4-methylbenzoyl)oxy]succinic
GLP compliance:
not specified
Type of study:
other: Weight of evidence approach based on structurally similar chemicals
Specific details on test material used for the study:
- Name of test material: 2,3-bis[(4-methylbenzoyl)oxy]succinic acid
- IUPAC name: (+)-Di-p-toluoyl-D-tartaric Acid
- Molecular formula: C20H18O8
- Molecular weight: 386.3542 g/mole
- Smiles : Cc1ccc(cc1)C(=O)O[C@@H]([C@H](OC(=O)c2ccc(C)cc2)C(=O)O)C(=O)O
- Inchl: 1S/C20H18O8/c1-11-3-7-13(8-4-11)19(25)27-15(17(21)22)16(18(23)24)28-20(26)14-9-5-12(2)6-10-14/h3-10,15-16H,1-2H3,(H,21,22) (H,23,24)/t15-,16-/m0/s1
- Substance type: Organic
- Physical state: Solid powder (white)
Species:
other: guinea pigs and humans
Strain:
not specified
Sex:
male/female
Route:
epicutaneous, occlusive
Vehicle:
not specified
Adequacy of induction:
not specified
No.:
#1
Route:
epicutaneous, occlusive
Vehicle:
not specified
Adequacy of challenge:
not specified
No. of animals per dose:
The study is based on weight of evidence approach from the read across values
Details on study design:
The study is based on weight of evidence approach from the read across values
Challenge controls:
The study is based on weight of evidence approach from the read across values
Reading:
1st reading
Group:
test group
Clinical observations:
signs of dermal sensitization observed
Remarks on result:
positive indication of skin sensitisation
Interpretation of results:
other: sensitizer
Conclusions:
The experimental results for the read across chemicals lend ample support to the results obtained from the estimation for the target chemical, affirming that 2,3-bis[(4-methylbenzoyl)oxy]succinic acid  can indeed be sensitizing to skin. Hence, by applying the weight of evidence approach, 2,3-bis[(4-methylbenzoyl)oxy]succinic acid  can be considered to be sensitizing to skin.    
Executive summary:

Based on the available studies for the structurally similar read across substances, the weight of evidence approach was applied to assess the skin sensitization potential of 2,3-bis[(4-methylbenzoyl)oxy]succinic acid.

Skin sensitization effects were estimated by four different models i.e, Battery, Leadscope, SciQSAR and CASE Ultra used within Danish QSAR database for 2,3-bis[(4-methylbenzoyl)oxy]succinic acid. Based on estimation, skin sensitization reactions were observed in guinea pigs and humans. Therefore, 2,3-bis[(4-methylbenzoyl)oxy]succinic acid was considered to be sensitizing.

The estimated result is supported by experimental study performed on humans according to the slight modifications in the method proposed by Draize to determine the allergic potential of the structurally similar chemical. 25 healthy human volunteers, 14 males, 11 females (23 Caucasians and 2 Negroes), aged 19-49 were used in the study. None of the subjects gave positive past history of atopy or contact sensitivity. A single 48 hour application of the test chemical in 50% polystyrene was made to the backs of atleast 10 normal subjects to ensure that concentrations used were non-irritating. In the induction exposure, a small quantity of test material 50% in polystyrene was placed on the wetted central gauze portion of 1.5 inch square J&J BANDAID before application to a non hairy region of the upper back. Dermicel hypoallergic tape was used to occlude, cover and secure the patches. Patches were applied to the same sites on alternate days for 3 weeks, a total of 9 applications. They were left in place for 24 hours and then removed. The subjects were told not to expose their backs to sunlight. Residual powder was gently removed from skin using soft pads wetted with water or 70% alcohol. Challenge exposure was performed on Monday of the 6thweek following a rest period of 14 days. Patches were applied to the untreated sites of the skin of back and were left in situ for 48 hours. Reactions were graded after removal of patches and again at 96 and 144 hours. Also these 10 subjects were challenged with non irritating concentrations of undiluted polystyrene. No significant reactions were observed to the vehicle. Sensitization reactions were observed in 5 of the 10 patients. In some subjects, the challenge reactions were so reactive to necessitate removal of patches before the completion of 48 hour period. Hence, the test chemical was considered to have potential to cause dermal sensitization.

The above results are also supported by another study conducted to determine the allergenic potential of other structurally similar chemical in guinea pigs. The test chemical was applied to the skin of 5 guinea pigs and observed for signs of dermal irritation and sensitization (dose, duration, observation period).The compound was a skin sensitizer in guinea pigs producing a weak response in two animals and a moderate response in two animals. One animal showed no response. Hence, the test chemical was considered to have potential to cause dermal sensitization.

The experimental results for the read across chemicals lend ample support to the results obtained from the estimation for the target chemical, affirming that 2,3-bis[(4-methylbenzoyl)oxy]succinic acid  can indeed be sensitizing to skin. Hence, by applying the weight of evidence approach, 2,3-bis[(4-methylbenzoyl)oxy]succinic acid  can be considered to be sensitizing to skin.    

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not sensitising)
Additional information:

Based on the available studies for the structurally similar read across substances, the weight of evidence approach was applied to assess the skin sensitization potential of2,3-bis[(4-methylbenzoyl)oxy]succinic acid.

Skin sensitization effects were estimated by four different models i.e, Battery, Leadscope, SciQSAR and CASE Ultra used within Danish QSAR database for 2,3-bis[(4-methylbenzoyl)oxy]succinic acid. Based on estimation, skin sensitization reactions were observed in guinea pigs and humans. Therefore, 2,3-bis[(4-methylbenzoyl)oxy]succinic acid was considered to be sensitizing.

The estimated result is supported by experimental study performed on humans according to the slight modifications in the method proposed by Draize to determine the allergic potential of the structurally similar chemical. 25 healthy human volunteers, 14 males, 11 females (23 Caucasians and 2 Negroes), aged 19-49 were used in the study. None of the subjects gave positive past history of atopy or contact sensitivity. A single 48 hour application of the test chemical in 50% polystyrene was made to the backs of atleast 10 normal subjects to ensure that concentrations used were non-irritating. In the induction exposure, a small quantity of test material 50% in polystyrene was placed on the wetted central gauze portion of 1.5 inch square J&J BANDAID before application to a non hairy region of the upper back. Dermicel hypoallergic tape was used to occlude, cover and secure the patches. Patches were applied to the same sites on alternate days for 3 weeks, a total of 9 applications. They were left in place for 24 hours and then removed. The subjects were told not to expose their backs to sunlight. Residual powder was gently removed from skin using soft pads wetted with water or 70% alcohol. Challenge exposure was performed on Monday of the 6thweek following a rest period of 14 days. Patches were applied to the untreated sites of the skin of back and were left in situ for 48 hours. Reactions were graded after removal of patches and again at 96 and 144 hours. Also these 10 subjects were challenged with non irritating concentrations of undiluted polystyrene. No significant reactions were observed to the vehicle. Sensitization reactions were observed in 5 of the 10 patients. In some subjects, the challenge reactions were so reactive to necessitate removal of patches before the completion of 48 hour period. Hence, the test chemical was considered to have potential to cause dermal sensitization.

The above results are also supported by another study conducted to determine the allergenic potential of other structurally similar chemical in guinea pigs. The test chemical was applied to the skin of 5 guinea pigs and observed for signs of dermal irritation and sensitization (dose, duration, observation period).The compound was a skin sensitizer in guinea pigs producing a weak response in two animals and a moderate response in two animals. One animal showed no response. Hence, the test chemical was considered to have potential to cause dermal sensitization.

The experimental results for the read across chemicals lend ample support to the results obtained from the estimation for the target chemical, affirming that 2,3-bis[(4-methylbenzoyl)oxy]succinic acid  can indeed be sensitizing to skin. Hence, by applying the weight of evidence approach, 2,3-bis[(4-methylbenzoyl)oxy]succinic acid  can be considered to be sensitizing to skin.   

Justification for classification or non-classification

The results of the experimental studies from the structurally similar read across substances indicate a possibility that 2,3-bis[(4-methylbenzoyl)oxy]succinic acid can be sensitizing to skin.

Hence by applying the weight of evidence approach, 2,3-bis[(4-methylbenzoyl)oxy]succinic acid can be considered to be sensitizing to skin.