o-anisic acid

Endpoint summary

Description of key information

The skin sensitization potential of 2-methoxybenzoic acid (579-75-9) was estimated by SSS (2017) using OECD QSAR toolbox v3.3 with log kow as the primary descriptor and considering the six closest read across substances. 2-methoxybenzoic acid (579-75-9) was predicted to be non sensitizing to the skin of guinea pig.

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records

Reference

Endpoint:

skin sensitisation: in vivo (non-LLNA)

Remarks:

in vivo

Type of information:

(Q)SAR

Adequacy of study:

weight of evidence

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:

Prediction is done using OECD QSAR Toolbox version 3.3 and the supporting QMRF report has been attached

Qualifier:

according to guideline

Guideline:

other: As mention below

Principles of method if other than guideline:

Prediction is done using QSAR Toolbox version 3.3 with log kow as the primary discriptors.

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:

- Name of the test material: 2-methoxybenzoic acid
- IUPAC name: 2-methoxybenzoic acid
- Molecular formula: C8H8O3
- Molecular weight: 152.1482 g/mol
- Substance type: Organic

Species:

guinea pig

Strain:

not specified

Sex:

not specified

Details on test animals and environmental conditions:

No data available.

Route:

intradermal

Vehicle:

not specified

Route:

epicutaneous, occlusive

Vehicle:

not specified

Day(s)/duration:

24 hour

No. of animals per dose:

test control -10 animals

Details on study design:

No data available.

Challenge controls:

No data available.

Positive control substance(s):

yes

Remarks:

acetylsalicylic acid anhydride (ASAN)

Statistics:

No data available.

Reading:

1st reading

Hours after challenge:

24

Group:

test chemical

No. with + reactions:

0

Total no. in group:

10

Clinical observations:

No skin sensitization effect were 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 "i" )  )

Domain logical expression index: "a"

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

Domain logical expression index: "b"

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

Domain logical expression index: "c"

Referential boundary: The target chemical should be classified as Acid, aromatic attach [-COOH] AND Alcohol, olefinic attach [-OH] AND Aliphatic Carbon [CH] AND Aliphatic Carbon [-CH2-] AND Aliphatic Carbon [-CH3] AND Aromatic Carbon [C] AND Carbonyl, olefinic attach [-C(=O)-] AND Carbonyl, one aromatic attach [-C(=O)-] AND Miscellaneous sulfide (=S) or oxide (=O) AND Olefinic carbon [=CH- or =C<] AND Oxygen, one aromatic attach [-O-] by Organic functional groups (US EPA)

Domain logical expression index: "d"

Referential boundary: The target chemical should be classified as Alkylarylether AND Aromatic compound AND Carbonic acid derivative AND Carboxylic acid AND Carboxylic acid derivative AND Ether 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 OECD

Domain logical expression index: "f"

Referential boundary: The target chemical should be classified as SN1 OR SN1 >> Nitrenium Ion formation OR SN1 >> Nitrenium Ion formation >> Aromatic azo OR SN1 >> Nitrenium Ion formation >> Aromatic nitro by DNA binding by OECD

Domain logical expression index: "g"

Referential boundary: The target chemical should be classified as No superfragment by Superfragments ONLY

Domain logical expression index: "h"

Parametric boundary:The target chemical should have a value of log Kow which is >= 1.13

Domain logical expression index: "i"

Parametric boundary:The target chemical should have a value of log Kow which is <= 5.8

Interpretation of results:

other: not sensitising

Conclusions:

The skin sensitization potential of 2-methoxybenzoic acid (579-75-9) was estimated by SSS (2017) using OECD QSAR toolbox v3.3 with log kow as the primary descriptor and considering the six closest read across substances. 2-methoxybenzoic acid (579-75-9) was predicted to be non sensitizing to the skin of guinea pig.

Executive summary:

The skin sensitization potential of 2-methoxybenzoic acid (579-75-9) was estimated by SSS (2017) using OECD QSAR toolbox v3.3 with log kow as the primary descriptor and considering the six closest read across substances. 2-methoxybenzoic acid (579-75-9) was predicted to be non sensitizing to the skin of guinea pig.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not sensitising)

Additional information:

Skin sensitization

In different studies, 2-methoxybenzoic acid (579-75-9) has been investigated for potential for dermal sensitization to a greater or lesser extent. The prediction and studies are based on in vivo experiments in guinea pig and human for target chemical 2-methoxybenzoic acid (579-75-9) and its structurally similar read across substances2-acetoxybenzoic acid (50-78-2) and Benzoic acid (65-85-0. The predicted data using the OECD QSAR toolbox has also been compared with the experimental data of read across.

The skin sensitization potential of 2-methoxybenzoic acid (579-75-9) was estimated by SSS (2017) using OECD QSAR toolbox v3.3 with log kow as the primary descriptor and considering the six closest read across substances. 2-methoxybenzoic acid (579-75-9) was predicted to be non sensitizing to the skin of guinea pig.

Supported by experimental data conducted by OECD SIDS (IUCLID dataset - European Chemicals Bureau, 2000) on structurally similar read across substance 2-acetoxybenzoic acid (50-78-2) in guinea pigs.The read across substances share high similarity in structure and log kow .Therefore, it is acceptable to derive information on skin sensitization from the analogue substance. 2-acetoxybenzoic acid (50-78-2) was assessed for its possible contact allergenic potential in guinea pig. No skin sensitization effects were observed .Therefore 2-acetoxybenzoic acid (50-78-2) was considered to be non sensitizing in guinea pig.

It is further supported byexperimental data conducted by SCCP (SCCP OPINION ON Benzoic Acid and Sodium Benzoate, 2005) on structurally similar read across substanceBenzoic acid (65-85-0)in human.The read across substances share high similarity in structure and log kow .Therefore, it is acceptable to derive information on skin sensitization from the analogue substance. A Human maximization test was observed for Benzoic acid (65 -85 -0) in 25 human volunteers. When 2% concentration of human volunteers in petrolatum was applied as patch tests for five times in 48 hour over a period of 10 days in 25 human volunteers. When challenged 10-14 d after the induction phase with a final 48 h closed patch test with 2 % benzoic acid in petrolatum. No sensitization was observed in any 25 human volunteers. Therefore Benzoic acid was considered to be non sensitizing in human and cannot be classified as skin sensitizer.

Thus based on the above predictions on 2-methoxybenzoic acid (579-75-9) as well as its read across substances and applying weight of evidence, it can be concluded that 2-methoxybenzoic acid is not a skin sensitizer. Thus comparing the above annotations with the criteria of CLP regulation, 2-methoxybenzoic acid (579-75-9) can be considered as not classified for skin sensitization effects.

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, 2-methoxybenzoic acid (579-75-9) can be considered as not classified for skin sensitization effects.