Diphenylacetic acid

Endpoint summary

Description of key information

The skin sensitization potential of Diphenylacetic acid (117-34-0) was estimated by SSS (QSAR) using OECD QSAR toolbox v3.3 with log kow as the primary descriptor and considering the six closest read across substances. Diphenylacetic acid (117-34-0) was predicted to be non sensitizing to the skin of female guinea pig.

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records

Reference

Endpoint:

skin sensitisation

Remarks:

in vivo

Type of information:

(Q)SAR

Adequacy of study:

other information

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

results derived from a valid (Q)SAR model and falling into its applicability domain, with limited documentation / justification

Justification for type of information:

Data is predicted using OECD QSAR toolbox version 3.3 and the supporting QMRF report has been attached

Qualifier:

according to guideline

Guideline:

other: as below

Principles of method if other than guideline:

Prediction is done using QSAR Toolbox version 3.3

GLP compliance:

not specified

Type of study:

guinea pig maximisation test

Justification for non-LLNA method:

not specified

Specific details on test material used for the study:

Details on test material
- Name of test material (as cited in study report):Diphenylacetic acid
- Molecular formula (if other than submission substance): C14H12O2
- Molecular weight (if other than submission substance): 212.247 g/mol
- Substance type: Organic
- Physical state: solid
- Purity: no data
- Impurities (identity and concentrations): no data

Species:

guinea pig

Strain:

CBA

Sex:

female

Details on test animals and environmental conditions:

no data

Route:

intradermal and epicutaneous

Vehicle:

other: 1st induction (intradermal): paraffin; 2nd induction (epicutaneous): vaseline;

Concentration / amount:

1st induction (intradermal): 2 % test material in paraffin and in 50% Freund's Adjuvant,
2nd induction (epicutaneous): 0.25 % test material in vaseline

Day(s)/duration:

9 days

Adequacy of induction:

not specified

No.:

#2

Route:

epicutaneous, occlusive

Vehicle:

other: vaseline

Concentration / amount:

0.25 % test material in vaseline

Day(s)/duration:

Challenge on day 22

Adequacy of challenge:

not specified

No. of animals per dose:

dose group: 10
control group: 5

Details on study design:

No data

Challenge controls:

No data

Positive control substance(s):

not specified

Positive control results:

No data

Reading:

2nd reading

Hours after challenge:

72

Group:

test chemical

Dose level:

0.5 ml of 0.25% test material in vaseline

No. with + reactions:

0

Total no. in group:

10

Clinical observations:

No skin sensitization reaction observed.

Remarks on result:

no indication of skin sensitisation

The prediction was based on dataset comprised from the following descriptors: "Skin Sensitisation"
Estimation method: Takes mode value from the 5 nearest neighbours
Domain  logical expression:Result: In Domain

(((((((("a" or "b" or "c" or "d" )  and ("e" and ( not "f") )  )  and "g" )  and ("h" and ( not "i") )  )  and ("j" and ( not "k") )  )  and ("l" and ( not "m") )  )  and ("n" and ( not "o") )  )  and ("p" and "q" )  )

Domain logical expression index: "a"

Referential boundary: The target chemical should be classified as Aryl AND Carboxylic acid by Organic Functional groups

Domain logical expression index: "b"

Referential boundary: The target chemical should be classified as Aryl AND Carboxylic acid by Organic Functional groups (nested)

Domain logical expression index: "c"

Referential boundary: The target chemical should be classified as Acid, aliphatic attach [-COOH] AND Alcohol, olefinic attach [-OH] AND Aliphatic Carbon [CH] AND Aliphatic Carbon, two phenyl attach [-C-]  AND Aromatic Carbon [C] AND Carbonyl, aliphatic attach [-C(=O)-] AND Miscellaneous sulfide (=S) or oxide (=O) AND Olefinic carbon [=CH- or =C<] AND Tertiary Carbon by Organic functional groups (US EPA)

Domain logical expression index: "d"

Referential boundary: The target chemical should be classified as Aromatic compound AND Carbonic acid derivative AND Carboxylic acid AND Carboxylic acid derivative by Organic functional groups, Norbert Haider (checkmol)

Domain logical expression index: "e"

Referential boundary: The target chemical should be classified as No alert found by DNA binding by OASIS v.1.3

Domain logical expression index: "f"

Referential boundary: The target chemical should be classified as AN2 OR AN2 >> Shiff base formation after aldehyde release OR AN2 >> Shiff base formation after aldehyde release >> Specific Acetate Esters OR Non-covalent interaction OR Non-covalent interaction >> DNA intercalation OR Non-covalent interaction >> DNA intercalation >> DNA Intercalators with Carboxamide Side Chain OR Radical OR Radical >> Radical mechanism via ROS formation (indirect) OR Radical >> Radical mechanism via ROS formation (indirect) >> Nitroarenes with Other Active Groups OR Radical >> Radical mechanism via ROS formation (indirect) >> Nitrophenols, Nitrophenyl Ethers and Nitrobenzoic Acids OR SN1 OR SN1 >> Alkylation after metabolically formed carbenium ion species OR SN1 >> Alkylation after metabolically formed carbenium ion species >> Polycyclic Aromatic Hydrocarbon Derivatives OR SN1 >> Nucleophilic attack after carbenium ion formation OR SN1 >> Nucleophilic attack after carbenium ion formation >> Specific Acetate Esters OR SN1 >> Nucleophilic attack after diazonium or carbenium ion formation OR SN1 >> Nucleophilic attack after diazonium or carbenium ion formation >> Nitroarenes with Other Active Groups OR SN1 >> Nucleophilic attack after reduction and nitrenium ion formation OR SN1 >> Nucleophilic attack after reduction and nitrenium ion formation >> Nitroarenes with Other Active Groups OR SN1 >> Nucleophilic attack after reduction and nitrenium ion formation >> Nitrophenols, Nitrophenyl Ethers and Nitrobenzoic Acids OR SN2 OR SN2 >> Acylation OR SN2 >> Acylation >> Specific Acetate Esters OR SN2 >> Alkylation, direct acting epoxides and related after P450-mediated metabolic activation OR SN2 >> Alkylation, direct acting epoxides and related after P450-mediated metabolic activation >> Polycyclic Aromatic Hydrocarbon Derivatives OR SN2 >> Nucleophilic substitution at sp3 Carbon atom OR SN2 >> Nucleophilic substitution at sp3 Carbon atom >> Specific Acetate Esters OR SN2 >> SN2 attack on activated carbon Csp3 or Csp2 OR SN2 >> SN2 attack on activated carbon Csp3 or Csp2 >> Nitroarenes with Other Active Groups by DNA binding by OASIS v.1.3

Domain logical expression index: "g"

Referential boundary: The target chemical should be classified as Bioavailable by Lipinski Rule Oasis ONLY

Domain logical expression index: "h"

Referential boundary: The target chemical should be classified as Non-Metals by Groups of elements

Domain logical expression index: "i"

Referential boundary: The target chemical should be classified as Alkali Earth OR Halogens OR Transition Metals by Groups of elements

Domain logical expression index: "j"

Referential boundary: The target chemical should be classified as Group 14 - Carbon C AND Group 16 - Oxygen O by Chemical elements

Domain logical expression index: "k"

Referential boundary: The target chemical should be classified as Group 15 - Nitrogen N OR Group 15 - Phosphorus P OR Group 16 - Sulfur S by Chemical elements

Domain logical expression index: "l"

Referential boundary: The target chemical should be classified as Not categorized by Repeated dose (HESS)

Domain logical expression index: "m"

Referential boundary: The target chemical should be classified as 3-Methylcholantrene (Hepatotoxicity) Alert OR Methyldopa (Hepatotoxicity) Alert OR Pirprofen (Hepatotoxicity) Alert by Repeated dose (HESS)

Domain logical expression index: "n"

Referential boundary: The target chemical should be classified as No alert found by Respiratory sensitisation

Domain logical expression index: "o"

Referential boundary: The target chemical should be classified as Acylation OR Acylation >> Ring opening acylation at a carbonyl OR Acylation >> Ring opening acylation at a carbonyl >> Anhydrides by Respiratory sensitisation

Domain logical expression index: "p"

Parametric boundary:The target chemical should have a value of log Kow which is >= 2.24

Domain logical expression index: "q"

Parametric boundary:The target chemical should have a value of log Kow which is <= 3.78

Interpretation of results:

not sensitising

Conclusions:

The skin sensitization potential of Diphenylacetic acid (117-34-0) was estimated by SSS (QSAR) using OECD QSAR toolbox v3.3 with log kow as the primary descriptor and considering the six closest read across substances. Diphenylacetic acid (117-34-0) was predicted to be non sensitizing to the skin of female guinea pig.

Executive summary:

The skin sensitization potential of Diphenylacetic acid (117-34-0) was estimated by SSS (QSAR) using OECD QSAR toolbox v3.3 with log kow as the primary descriptor and considering the six closest read across substances. Diphenylacetic acid (117-34-0) was predicted to be non sensitizing to the skin of female guinea pig.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not sensitising)

Additional information:

Skin sensitization 

In different studies, Diphenylacetic acid (117-34-0) has been investigated for potential of skin sensitization to a greater or lesser extent. The studies are based on in vivo experiments in guinea pig for target chemical Diphenylacetic acid (117-34-0) and its structurally similar read across substances3-hydroxy-2-naphthoic acid(92-70-6) and 4-tert-butylbenzoic acid (98-73-7 ).The predicted data using the OECD QSAR toolbox has also been compared with the experimental data of read across.

The skin sensitization potential of Diphenylacetic acid (117-34-0) was estimated by SSS (QSAR) using OECD QSAR toolbox v3.3 with log kow as the primary descriptor and considering the six closest read across substances. Diphenylacetic acid (117-34-0) was predicted to be non sensitizing to the skin of female guinea pig.

Supported by experimental study conducted by Kgzuka Tet al.(Contact Dermatitis ,1980) to evaluate the skin sensitizing potential of read across3-hydroxy-2-naphthoic acid(92-70-6) in Human. The Patch test was performed on the back of eight human volunteers for 2 days. Readings were made according to the ICDRG classification 24 h after the patches were removed. Patch test concentration is 1 % in petrolatum. All eight showed negative reaction to 3-hydroxy-2-naphthoic acid. Twenty eight healthy female volunteers, aged 20 and 21, were also tested as controls. None gave a positive reaction. On the basis of negative reaction of skin sensitization obtained it was concluded that the test material 3-hydroxy-2-naphthoic acid is not sensitizing to human.

It is further supported by experimental study conducted by Federal Environmental Agency (SIDS Initial Assessment Report For SIAM 19, 2004) to evaluate the skin sensitizing potential of read across substance3-hydroxy-2-naphthoic acid(92-70-6) in guinea pigs.In guinea pig maximization test (OECD Guide-line 406 "Skin Sensitization) the test material 3-hydroxy-2-naphthoic acid was treated with ten female Pirbright White guinea pigs to study the skin sensitization potential.Female Pirbright White guinea pigs were 10 / group (5 in the control group) in number used for the test.In induction exposure 2 % active substance 3-hydroxy-2-naphthoic acid in paraffin was applied intracutaneously on guinea pig skin. No signs of systemic toxicity were observed during the study. There was no influence on the body weight.In challenge exposure 0.25 % active substance 3-hydroxy-2-naphthoic acid in Vaseline applied occlusive epicutaneous. At challenge, neither the animals of the test group nor the animals of the control group showed any effects.Since there was no positive reaction in both the groups test and control group, the 3-hydroxy-2-naphthoic acid is concluded to be not sensitizing.

Also supported by experimental study conducted byEuropean Chemicals Bureau (European Union "Risk Assessment Report" European Chemicals Bureau, Clariant, 2003) to evaluate the skin sensitizing potential of read across substance4-tert-butylbenzoic acid (98-73-7 )in guinea pigs.In a Maximization Test (Magnusson Kligman Test) 4-tert-butyl benzoic acid with a purity of 99.6% was tested in albino guinea pigs (Himalayan spotted). Ten test and 5 control animals were used. For intradermal injection a 25% substance concentration, for dermal induction a 50% concentration and for challenge a 25% concentration was used. The vehicle was PEG 300. Slight irritation was noted after dermal induction. None of the test and control animals showed skin reactions after the challenge treatment.It is concluded form the negative test result of skin sensitization potential of 4-tertbutylbenzoic acid. Therefore the test material 4-tertbutylbenzoic acid was considered to be not sensitizing.

Thus based on the above predictions on Diphenylacetic acid (117-34-0) as well as its read across and applying weight of evidence, it can be concluded thatDiphenylacetic acid (117-34-0) is not a skin sensitizer. Thus comparing the above annotations with the criteria of CLP regulation, Diphenylacetic acid (117-34-0) can be considered as not classified for skin sensitization.

Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

Thus comparing the above annotations with the criteria of CLP regulation, Diphenylacetic acid (117-34-0) can be considered as not classified for skin sensitization.