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Description of key information

The skin sensitization potential of 2,3-dimethylphenol (526-75-0 ) 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. 2,3-dimethylphenol (526-75-0 ) was predicted to be non sensitizing to the skin of male 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:
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 mention below
Principles of method if other than guideline:
Prediction is done using QSAR Toolbox version 3.3.
GLP compliance:
not specified
Justification for non-LLNA method:
Not specified.
Specific details on test material used for the study:
- Name of test material (as cited in study report):2,3-Dimethylphenol
- Molecular formula (if other than submission substance):C8H10O
- Molecular weight (if other than submission substance):122.166 g/mole
- Substance type:Organic
- Physical state:Solid
Species:
guinea pig
Strain:
not specified
Sex:
male
Details on test animals and environmental conditions:
TEST ANIMALS
- Weight at study initiation: approximately 400 g
Route:
intradermal
Vehicle:
physiological saline
Concentration / amount:
0.1%
Day(s)/duration:
3weeks
Route:
intradermal
Vehicle:
physiological saline
Concentration / amount:
0.1%
Day(s)/duration:
48 hour
No. of animals per dose:
No data available.
Details on study design:
Induction:
A solution of 0.1% test substance in physiological saline was prepared using sodium hydroxide to solubilize the ester when necessary. 100 µL of this solution was injected intracutaneously into the backs and upper flanks of male guinea pigs at intervals of 3 times weekly (resulting in 10 injections).

Challenge:
2 weeks after the 10th injection a challenge injection of a freshly prepared solution of the test substance was made in the area adjacent to the site of the sensitising injection. The guinea pigs were closely observed for a reaction during the next 48 hours.
Challenge controls:
No data available.
Positive control substance(s):
not specified
Reading:
other: challenge
Hours after challenge:
48
Group:
test chemical
Dose level:
0.1%
No. with + reactions:
0
Clinical observations:
No allergic response in any case were observed.
Remarks on result:
no indication of skin sensitisation

The prediction was based on dataset comprised from the following descriptors: "S M W N"
Estimation method: Takes highest mode value from the 6 nearest neighbours
Domain  logical expression:Result: In Domain

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

Domain logical expression index: "a"

Referential boundary: The target chemical should be classified as Phenols (Acute toxicity) by US-EPA New Chemical Categories

Domain logical expression index: "b"

Referential boundary: The target chemical should be classified as Alkyl arenes AND Aryl AND Phenol by Organic Functional groups

Domain logical expression index: "c"

Referential boundary: The target chemical should be classified as Alkyl arenes AND Overlapping groups AND Phenol by Organic Functional groups (nested)

Domain logical expression index: "d"

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

Domain logical expression index: "e"

Referential boundary: The target chemical should be classified as Aromatic compound AND Hydroxy compound AND Phenol by Organic functional groups, Norbert Haider (checkmol)

Domain logical expression index: "f"

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

Domain logical expression index: "g"

Referential boundary: The target chemical should be classified as Non-covalent interaction OR Non-covalent interaction >> DNA intercalation OR Non-covalent interaction >> DNA intercalation >> Coumarins OR Non-covalent interaction >> DNA intercalation >> DNA Intercalators with Carboxamide Side Chain OR Radical OR Radical >> Radical mechanism by ROS formation (indirect) or direct radical attack on DNA OR Radical >> Radical mechanism by ROS formation (indirect) or direct radical attack on DNA >> Organic Peroxy Compounds OR Radical >> Radical mechanism via ROS formation (indirect) OR Radical >> Radical mechanism via ROS formation (indirect) >> Coumarins OR Radical >> Radical mechanism via ROS formation (indirect) >> Single-Ring Substituted Primary Aromatic Amines OR SN1 OR SN1 >> Nucleophilic attack after metabolic nitrenium ion formation OR SN1 >> Nucleophilic attack after metabolic nitrenium ion formation >> Single-Ring Substituted Primary Aromatic Amines OR SN2 OR SN2 >> Direct acting epoxides formed after metabolic activation OR SN2 >> Direct acting epoxides formed after metabolic activation >> Coumarins by DNA binding by OASIS v.1.3

Domain logical expression index: "h"

Referential boundary: The target chemical should be classified as Not possible to classify according to these rules by DPRA Cysteine peptide depletion

Domain logical expression index: "i"

Referential boundary: The target chemical should be classified as High reactive OR High reactive >> alpha,beta-carbonyl compounds with polarized multiple bonds by DPRA Cysteine peptide depletion

Domain logical expression index: "j"

Referential boundary: The target chemical should be classified as Weak binder, OH group by Estrogen Receptor Binding

Domain logical expression index: "k"

Referential boundary: The target chemical should be classified as Moderate binder, OH grooup OR Non binder, impaired OH or NH2 group OR Non binder, MW>500 OR Non binder, non cyclic structure OR Strong binder, NH2 group OR Strong binder, OH group OR Very strong binder, OH group OR Weak binder, NH2 group by Estrogen Receptor Binding

Domain logical expression index: "l"

Referential boundary: The target chemical should be classified as Low (Class I) by Toxic hazard classification by Cramer (original) ONLY

Domain logical expression index: "m"

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

Domain logical expression index: "n"

Referential boundary: The target chemical should be classified as Pro-Michael Addition OR Pro-Michael Addition >> Pro-quinone and related OR Pro-Michael Addition >> Pro-quinone and related >> Hydroquinones OR Pro-Michael Addition >> Pro-quinone-methide OR Pro-Michael Addition >> Pro-quinone-methide >> 4-Allylphenols by Respiratory sensitisation

Domain logical expression index: "o"

Referential boundary: The target chemical should be classified as (!Undefined)Group All Lipid Solubility < 0.01 g/kg AND (!Undefined)Group C Surface Tension > 62 mN/m AND Group C Melting Point > 55 C by Skin irritation/corrosion Exclusion rules by BfR

Domain logical expression index: "p"

Referential boundary: The target chemical should be classified as Group All Melting Point > 200 C OR Group C Vapour Pressure < 0.0001 Pa by Skin irritation/corrosion Exclusion rules by BfR

Domain logical expression index: "q"

Referential boundary: The target chemical should be classified as Phenols by Skin irritation/corrosion Inclusion rules by BfR

Domain logical expression index: "r"

Referential boundary: The target chemical should be classified as Aldehydes by Skin irritation/corrosion Inclusion rules by BfR

Domain logical expression index: "s"

Referential boundary: The target chemical should be classified as Not categorized by OECD HPV Chemical Categories

Domain logical expression index: "t"

Referential boundary: The target chemical should be classified as m,p - Cresols by OECD HPV Chemical Categories

Domain logical expression index: "u"

Parametric boundary:The target chemical should have a value of log Kow which is >= 2

Domain logical expression index: "v"

Parametric boundary:The target chemical should have a value of log Kow which is <= 2.87

Interpretation of results:
other: Non sensitizer
Conclusions:
The skin sensitization potential of 2,3-dimethylphenol (526-75-0 ) was estimated by using OECD QSAR toolbox v3.3 with log kow as the primary descriptor and considering the six closest read across substances. 2,3-dimethylphenol (526-75-0 ) was predicted to be non sensitizing to the skin of male guinea pig.
Executive summary:

The skin sensitization potential of 2,3-dimethylphenol (526-75-0 ) was estimated by using OECD QSAR toolbox v3.3 with log kow as the primary descriptor and considering the six closest read across substances. 2,3-dimethylphenol (526-75-0 ) was predicted to be non sensitizing to the skin of male guinea pig.

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

Skin sensitization 

In different studies, 2,3-dimethylphenol (526-75-0 )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 2,3-dimethylphenol (526-75-0 ) and its structurally similar read across substancesMethyl salicylate (119-36-8) and study based on in vivo experiments in mouse for its structurally similar read across substances2,3,5-trimethylphenol (697-82-5 ).The predicted data using the OECD QSAR toolbox has also been compared with the experimental data of read across.

The skin sensitization potential of 2,3-dimethylphenol (526-75-0 ) 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. 2,3-dimethylphenol (526-75-0 ) was predicted to be non sensitizing to the skin of male guinea pig.

Supported by experimental study conducted by A. Lapczynski et al.(Food and Chemical Toxicology ,2007) to evaluate the skin sensitizing potential of read across substance Methyl salicylate (119-36-8)in guinea pigs .Skin sensitization test for Methyl Salicylate (119-36-8) was observed in Dunkin–Hartley albino guinea pigs by Guinea pig maximisation test. Group of 10 Dunkin–Hartley albino guinea pigs were used for the test. The test animals received 6 intradermal injections of 2.5% methyl salicylate in 0.01% DOBS and Freund’s complete adjuvant in the shoulder region. Six to eight days later a 48-h occluded patch with 100% methyl Salicylate was applied to the same sites. Control animals received the vehicle alone. After Twelve to 14 days of induction, test and control animals were challenged on clipped and shaved flank with 10% methyl Salicylate in acetone/polyethylene glycol 400 (70:30) with a 24 h occluded patch. Challenge sites were read 24 h later. No skin sensitization reactions were observed. Therefore Methyl Salicylate (119-36-8) was considered to be non sensitizing to guinea pigs by Guinea pig maximisation test.

It is further supported by experimental study conducted by Tetsuo Yamano et al.(Toxicology ,2007) to evaluate the skin sensitizing potential of target substance2,3,5-trimethylphenol (697-82-5 )in mouse by LLNA mode . LLNA test was conducted on male BALB/CA mice for 2,3,5 trimethylphenols (697-82-5) . On 3 consecutive days the groups of 3 mice were exposed to at 25 µl of 1M of chemical. Acetone/ olive oil, 4:1 were used as a vehicle. Three or five days after the last application, a pair of auricular lymph nodes (LNs) from each mouse was excised for the LLNA. A stimulation index was calculated as the ratio of the BrdU amount in the lymph nodes of chemical-treated mice to that of vehicle-treated mice. Stimulation index variation was observed as 0 for the test chemical.From experiment it was concluded that the 2, 3,5Trimethylphenol (697-82-5) was considered to be non-sensitizing in mice LLNA assay.

Thus based on the above predictions on 2,3-dimethylphenol (526-75-0) as well as its read across and applying weight of evidence, it can be concluded that2,3-dimethylphenol is not a skin sensitizer. Thus comparing the above annotations with the criteria of CLP regulation, 2,3-dimethylphenol (526-75-0 ) 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, 2,3-dimethylphenol (526-75-0 ) can be considered as not classified for skin sensitization.