Registration Dossier

Administrative data

Description of key information

Skin Irritation:

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 not irritating to skin. Hence, by applying the weight of evidence approach, 2,3-bis[(4-methylbenzoyl)oxy]succinic acid  can be considered to be not irritating to skin.

Eye Irritation:

Based on the available data for the structurally similar read across chemicals and applying the weight of

evidence approach, it can be concluded that 2,3-bis[(4-methylbenzoyl)oxy]succinic acid will tend to behave in the same manner as that of the read across chemicals. Hence, 2,3-bis[(4-methylbenzoyl)oxy]succinic acid was estimated to be irritating to eyes andit can be further classified under the category “Category 2” as per CLP regulation.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records
Reference
Endpoint:
skin irritation: in vivo
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: Weigh of evidence approach based on structurally similar chemicals
Justification for type of information:
Weigh of evidence approach 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 irritation potential of 2,3-bis[(4-methylbenzoyl)oxy]succinic acid
GLP compliance:
not specified
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:
rabbit
Strain:
not specified
Type of coverage:
occlusive
Preparation of test site:
clipped
Vehicle:
not specified
Controls:
not specified
Amount / concentration applied:
undiluted
Duration of treatment / exposure:
24 hours
Observation period:
48 hours
Number of animals:
3
Details on study design:
The study is based on weight of evidence approach from the read across values
Irritation parameter:
overall irritation score
Basis:
mean
Reversibility:
not specified
Remarks on result:
no indication of irritation
Irritant / corrosive response data:
no signs of irritation observed
Interpretation of results:
other: not irritating
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 not irritating to skin. Hence, by applying the weight of evidence approach, 2,3-bis[(4-methylbenzoyl)oxy]succinic acid  can be considered to be not irritating 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 irritation potential of 2,3-bis[(4-methylbenzoyl)oxy]succinic acid.

Skin irritation effects were estimated by four different models i.e, Battery, Leadscope, SciQSAR and CASE Ultra used within Danish QSAR database for2,3-bis[(4-methylbenzoyl)oxy]succinic acid. Based on estimation, no severe skin irritation effects were known when2,3-bis[(4-methylbenzoyl)oxy]succinic acid was exposed to rabbit skin.Hence,2,3-bis[(4-methylbenzoyl)oxy]succinic acid can be considered not irritating to skin.

This estimated result is supported by an experimental study performed to assess the dermal irritation potential of the structurally similar chemical. 0.5 ml of 1.8% aqueous solution was applied under occlusion to the clipped skin of 3 Japanese White rabbits for 24 hours. The treated skin was observed at 1, 24 and 48 hours. No signs of irritation were observed. The Draize score was 0.

Hence, the test chemical was considered to be not irritating to skin.

These results are further supported by the experimental study performed for another structurally similar chemical. 6 Japanese White rabbits were used for the study.

Erythema was observed at two animals out of six. At one animal, it was observed on the intact skin and the abraded skin. At the other animal, it was done on the only abraded skin. The erythema on the intact skin observed at 24 hrs got disappeared at 48 hrs. No more abnormality was observed during 7 days observation. The PDII was calculated to be 0.1.

The substance was considered to be not irritating to skin.

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 not irritating to skin. Hence, by applying the weight of evidence approach, 2,3-bis[(4-methylbenzoyl)oxy]succinic acid  can be considered to be not irritating to skin.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records
Reference
Endpoint:
eye irritation: in vivo
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 structrurally similar read across chemicals
Justification for type of information:
Weight of evidence based on structrurally similar read across 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 based on structrurally similar read across 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 ocular irritation potential of 2,3-bis[(4-methylbenzoyl)oxy]succinic acid
GLP compliance:
not specified
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:
rabbit
Strain:
not specified
Vehicle:
unchanged (no vehicle)
Controls:
not specified
Amount / concentration applied:
0.1 ml
Duration of treatment / exposure:
single exposure
Observation period (in vivo):
48 and 72 hours
Duration of post- treatment incubation (in vitro):
no data available
Number of animals or in vitro replicates:
3
Details on study design:
The study is based on weight of evidence approach from the read across values
Irritation parameter:
overall irritation score
Basis:
mean
Reversibility:
not specified
Remarks on result:
positive indication of irritation
Irritant / corrosive response data:
Signs of irritation observed
Interpretation of results:
Category 2 (irritating to eyes) based on GHS criteria
Conclusions:
Based on the available data for the structurally similar read across chemicals and applying the weight of
evidence approach, it can be concluded that2,3-bis[(4-methylbenzoyl)oxy]succinic acid will tend to behave in the same manner as that of the read across chemicals. Hence, 2,3-bis[(4-methylbenzoyl)oxy]succinic acid was estimated to be irritating to eyes andit can be further classified under the category “Category 2” as per CLP regulation.
Executive summary:

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

The primary eye irritation potential of the structurally similar chemical was evaluated according to Draize method. 3 female Japanese White rabbits (2.0-2.2 kg) were used for the study. The chemical (if solid= 100 mg, if liquid = 0.1ml) was instilled into the conjunctival sac of the left eye. Right eye (untreated eye) served as blank control. The eyes were examined and the grade of ocular lesions was recorded at 1, 24, 48, 72, 96 hours and 7, 14, 21 days after administration of test chemical. Corneal opacity, erythema, chemosis, secreta and iritis were recorded and classified under Draize method (Draize et.al, 1944)

The sum of values, recorded for cornea, conjunctiva and iris was divided by the number of observation times and the average scores (Draize scores) were used as grades of ocular irritation potential of the chemical. The maximum value of Draize score are as follows: Cornea =80, Conjunctiva = 20 and Iris = 5

The average Draize scores after 21 days were as follows: CORNEA = 33.9/80, iris = 0.6, conjunctiva = 5.1.

The test chemical caused moderate eye irritation recovering within 21 days of treatment.

Hence, the test chemical can be considered irritating to eyes.

This is supported by the results of other ocular irritation study performed on rabbits to determine the degree of irritation caused by the other structurally similar read across chemical. 0.1 ml of 1.8% aqueous solution was administered into one eye of 3 Japanese White rabbits. The eyes were observed at1, 24 and 48 hours. Signs of irritation were observed. The maximum total score was 2. Hence, the test chemical was considered to be irritating to eyes.

The above studies are further supported by the results of another ocular irritation study performed on rabbits to determine the degree of irritation caused by the another structurally similar read across chemical. Undiluted test chemical was instilled into the eyes of 3 rabbits and observed for effects. The treated eyes remained unwashed and Fluorescein staining was done to observe the extent of corneal damage, adnexal staining in the treated unwashed eyes.

Iritis and corneal staining were observed in one of three rabbits while adnexal staining was observed in the other two. Slight to moderate irritation was observed in the rabbit eyes when the treated eyes remained unwashed. Prompt irrigation of three additional eyes had a palliative effect.

Overall, the test chemical was considered to be a moderate eye irritant when tested in 3 unwashed eyes.

Based on the available data for the structurally similar read across chemicals and applying the weight of

evidence approach, it can be concluded that2,3-bis[(4-methylbenzoyl)oxy]succinic acid will tend to behave in the same manner as that of the read across chemicals. Hence, 2,3-bis[(4-methylbenzoyl)oxy]succinic acid was estimated to be irritating to eyes andit can be further classified under the category “Category 2” as per CLP regulation.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Skin Irritation:

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

Skin irritation effects were estimated by four different models i.e, Battery, Leadscope, SciQSAR and CASE Ultra used within Danish QSAR database for2,3-bis[(4-methylbenzoyl)oxy]succinic acid. Based on estimation, no severe skin irritation effects were known when2,3-bis[(4-methylbenzoyl)oxy]succinic acid was exposed to rabbit skin.Hence,2,3-bis[(4-methylbenzoyl)oxy]succinic acid can be considered not irritating to skin.

This estimated result is supported by an experimental study performed to assess the dermal irritation potential of the structurally similar chemical. 0.5 ml of 1.8% aqueous solution was applied under occlusion to the clipped skin of 3 Japanese White rabbits for 24 hours. The treated skin was observed at 1, 24 and 48 hours. No signs of irritation were observed. The Draize score was 0.

Hence, the test chemical was considered to be not irritating to skin.

These results are further supported by the experimental study performed for another structurally similar chemical. 6 Japanese White rabbits were used for the study.

Erythema was observed at two animals out of six. At one animal, it was observed on the intact skin and the abraded skin. At the other animal, it was done on the only abraded skin. The erythema on the intact skin observed at 24 hrs got disappeared at 48 hrs. No more abnormality was observed during 7 days observation. The PDII was calculated to be 0.1.

The substance was considered to be not irritating to skin.

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 not irritating to skin. Hence, by applying the weight of evidence approach, 2,3-bis[(4-methylbenzoyl)oxy]succinic acid  can be considered to be not irritating to skin.

 

 Eye Irritation:

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

The primary eye irritation potential of the structurally similar chemical was evaluated according to Draize method. 3 female Japanese White rabbits (2.0-2.2 kg) were used for the study. The chemical (if solid= 100 mg, if liquid = 0.1ml) was instilled into the conjunctival sac of the left eye. Right eye (untreated eye) served as blank control. The eyes were examined and the grade of ocular lesions was recorded at 1, 24, 48, 72, 96 hours and 7, 14, 21 days after administration of test chemical. Corneal opacity, erythema, chemosis, secreta and iritis were recorded and classified under Draize method (Draize et.al, 1944)

The sum of values, recorded for cornea, conjunctiva and iris was divided by the number of observation times and the average scores (Draize scores) were used as grades of ocular irritation potential of the chemical. The maximum value of Draize score are as follows: Cornea =80, Conjunctiva = 20 and Iris = 5

The average Draize scores after 21 days were as follows: CORNEA = 33.9/80, iris = 0.6, conjunctiva = 5.1.

The test chemical caused moderate eye irritation recovering within 21 days of treatment.

Hence, the test chemical can be considered irritating to eyes.

This is supported by the results of other ocular irritation study performed on rabbits to determine the degree of irritation caused by the other structurally similar read across chemical. 0.1 ml of 1.8% aqueous solution was administered into one eye of 3 Japanese White rabbits. The eyes were observed at1, 24 and 48 hours. Signs of irritation were observed. The maximum total score was 2. Hence, the test chemical was considered to be irritating to eyes.

The above studies are further supported by the results of another ocular irritation study performed on rabbits to determine the degree of irritation caused by the another structurally similar read across chemical. Undiluted test chemical was instilled into the eyes of 3 rabbits and observed for effects. The treated eyes remained unwashed and Fluorescein staining was done to observe the extent of corneal damage, adnexal staining in the treated unwashed eyes.

Iritis and corneal staining were observed in one of three rabbits while adnexal staining was observed in the other two. Slight to moderate irritation was observed in the rabbit eyes when the treated eyes remained unwashed. Prompt irrigation of three additional eyes had a palliative effect.

Overall, the test chemical was considered to be a moderate eye irritant when tested in 3 unwashed eyes.

Based on the available data for the structurally similar read across chemicals and applying the weight of

evidence approach, it can be concluded that 2,3-bis[(4-methylbenzoyl)oxy]succinic acid will tend to behave in the same manner as that of the read across chemicals. Hence, 2,3-bis[(4-methylbenzoyl)oxy]succinic acid was estimated to be irritating to eyes andit can be further classified under the category “Category 2” as per CLP regulation.

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 not irritating to skin and but causes irritation to eyes.

Hence by applying the weight of evidence approach, 2,3-bis[(4-methylbenzoyl)oxy]succinic acid can be considered to be not irritating to skin and irritating to eyes. It can be classified under the category “Not Classified” for skin irritation and “Category 2” for eye irritation as per CLP regulation.