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Toxicity to microorganisms

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Reference
Endpoint:
toxicity to microorganisms
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 QMRF report has been attached
Qualifier:
according to
Guideline:
other: as mentioned below
Principles of method if other than guideline:
Prediction was done by using OECD QSAR toolbox v3.3
GLP compliance:
not specified
Specific details on test material used for the study:
Name of test material : 2-hydroxy-p-toluic acid (m cresotic acid)
Molecular formula :C8H8O3
Molecular weight :152.148 g/mol
Smiles notation :Cc1ccc(c(c1)O)C(=O)O
InChl :1S/C8H8O3/c1-5-2-3-6(8(10)11)7(9)4-5/h2-4,9H,1H3,(H,10,11)
Substance Type: Organic
Physical State: Solid
Analytical monitoring:
not specified
Details on sampling:
No data available
Vehicle:
not specified
Details on test solutions:
No data available
Test organisms (species):
Tetrahymena pyriformis
Details on inoculum:
No data available
Test type:
static
Water media type:
freshwater
Limit test:
no
Total exposure duration:
48 h
Key result
Duration:
48 h
Dose descriptor:
other: IGC50
Effect conc.:
219.91 mg/L
Conc. based on:
test mat.
Basis for effect:
other: Growth

The prediction was based on dataset comprised from the following descriptors: IGC50
Estimation method: Takes average 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 ( not "m") )  )  and "n" )  and ("o" and ( not "p") )  )  and "q" )  and "r" )  and ("s" and ( not "t") )  )  and ("u" and ( not "v") )  )  and ("w" and ( not "x") )  )  and ("y" and ( not "z") )  )  and ("aa" and ( not "ab") )  )  and ("ac" and "ad" )  )

Domain logical expression index: "a"

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

Domain logical expression index: "b"

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

Domain logical expression index: "c"

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

Domain logical expression index: "d"

Referential boundary: The target chemical should be classified as Acid moiety AND Phenols by Aquatic toxicity classification by ECOSAR

Domain logical expression index: "e"

Referential boundary: The target chemical should be classified as Class 2 (less inert compounds) by Acute aquatic toxicity classification by Verhaar (Modified)

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 AN2 OR AN2 >> Carbamoylation after isocyanate formation OR AN2 >> Carbamoylation after isocyanate formation >> Hydroxamic Acids OR AN2 >> Carbamoylation after isocyanate formation >> N-Hydroxylamines OR AN2 >> Shiff base formation for aldehydes OR AN2 >> Shiff base formation for aldehydes >> Haloalkane Derivatives with Labile Halogen OR Non-covalent interaction OR Non-covalent interaction >> DNA intercalation OR Non-covalent interaction >> DNA intercalation >> DNA Intercalators with Carboxamide Side Chain OR Non-covalent interaction >> DNA intercalation >> Fused-Ring Nitroaromatics OR Radical OR Radical >> Radical mechanism by ROS formation OR Radical >> Radical mechanism by ROS formation >> Polynitroarenes OR Radical >> Radical mechanism via ROS formation (indirect) OR Radical >> Radical mechanism via ROS formation (indirect) >> C-Nitroso Compounds OR Radical >> Radical mechanism via ROS formation (indirect) >> Fused-Ring Nitroaromatics OR Radical >> Radical mechanism via ROS formation (indirect) >> Hydrazine Derivatives OR Radical >> Radical mechanism via ROS formation (indirect) >> N-Hydroxylamines OR Radical >> Radical mechanism via ROS formation (indirect) >> Nitroaniline Derivatives 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 Radical >> Radical mechanism via ROS formation (indirect) >> p-Substituted Mononitrobenzenes OR Radical >> Radical mechanism via ROS formation (indirect) >> Single-Ring Substituted Primary Aromatic Amines OR SN1 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 metabolic nitrenium ion formation OR SN1 >> Nucleophilic attack after metabolic nitrenium ion formation >> N-Hydroxylamines OR SN1 >> Nucleophilic attack after metabolic nitrenium ion formation >> Single-Ring Substituted Primary Aromatic Amines OR SN1 >> Nucleophilic attack after reduction and nitrenium ion formation OR SN1 >> Nucleophilic attack after reduction and nitrenium ion formation >> Fused-Ring Nitroaromatics OR SN1 >> Nucleophilic attack after reduction and nitrenium ion formation >> Nitroaniline Derivatives 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 SN1 >> Nucleophilic attack after reduction and nitrenium ion formation >> Polynitroarenes OR SN1 >> Nucleophilic attack after reduction and nitrenium ion formation >> p-Substituted Mononitrobenzenes OR SN1 >> Nucleophilic substitution after glutathione-induced nitrenium ion formation OR SN1 >> Nucleophilic substitution after glutathione-induced nitrenium ion formation >> C-Nitroso Compounds OR SN2 OR SN2 >> Acylation OR SN2 >> Acylation >> Hydroxamic Acids OR SN2 >> Acylation involving a leaving group  OR SN2 >> Acylation involving a leaving group  >> Haloalkane Derivatives with Labile Halogen OR SN2 >> Alkylation, nucleophilic substitution at sp3-carbon atom OR SN2 >> Alkylation, nucleophilic substitution at sp3-carbon atom >> Haloalkane Derivatives with Labile Halogen OR SN2 >> Direct acting epoxides formed after metabolic activation OR SN2 >> Direct acting epoxides formed after metabolic activation >> Quinoline Derivatives OR SN2 >> SN2 at an activated carbon atom OR SN2 >> SN2 at an activated carbon atom >> Quinoline Derivatives 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: "h"

Referential boundary: The target chemical should be classified as No alert found by DNA binding by OECD

Domain logical expression index: "i"

Referential boundary: The target chemical should be classified as Acylation OR Acylation >> P450 Mediated Activation to Isocyanates or Isothiocyanates OR Acylation >> P450 Mediated Activation to Isocyanates or Isothiocyanates >> Benzylamines-Acylation OR Michael addition OR Michael addition >> P450 Mediated Activation to Quinones and Quinone-type Chemicals OR Michael addition >> P450 Mediated Activation to Quinones and Quinone-type Chemicals >> Alkyl phenols OR Michael addition >> P450 Mediated Activation to Quinones and Quinone-type Chemicals >> Arenes OR Michael addition >> P450 Mediated Activation to Quinones and Quinone-type Chemicals >> Hydroquinones OR Schiff base formers OR Schiff base formers >> Chemicals Activated by P450 to Mono-aldehydes OR Schiff base formers >> Chemicals Activated by P450 to Mono-aldehydes >> Benzylamines-Schiff base OR SN1 OR SN1 >> Carbenium Ion Formation OR SN1 >> Carbenium Ion Formation >> Allyl benzenes OR SN1 >> Iminium Ion Formation OR SN1 >> Iminium Ion Formation >> Aliphatic tertiary amines OR SN1 >> Nitrenium Ion formation OR SN1 >> Nitrenium Ion formation >> Aromatic azo OR SN1 >> Nitrenium Ion formation >> Aromatic nitro OR SN1 >> Nitrenium Ion formation >> Primary aromatic amine OR SN1 >> Nitrenium Ion formation >> Secondary aromatic amine by DNA binding by OECD

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, NH2 group OR Moderate binder, OH grooup OR Non binder, impaired OH or NH2 group OR Non binder, non cyclic structure OR Non binder, without OH or NH2 group OR Strong binder, OH group OR Very strong binder, OH group by Estrogen Receptor Binding

Domain logical expression index: "l"

Referential boundary: The target chemical should be classified as No alert found by Protein binding by OASIS v1.3

Domain logical expression index: "m"

Referential boundary: The target chemical should be classified as Acylation OR Acylation >> Ester aminolysis OR Acylation >> Ester aminolysis >> Amides OR Schiff base formation OR Schiff base formation >> Schiff base formation with carbonyl compounds OR Schiff base formation >> Schiff base formation with carbonyl compounds >> Aldehydes OR SN2 OR SN2 >> Nucleophilic substitution on benzilyc carbon atom OR SN2 >> Nucleophilic substitution on benzilyc carbon atom >> alpha-Activated benzyls  by Protein binding by OASIS v1.3

Domain logical expression index: "n"

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

Domain logical expression index: "o"

Referential boundary: The target chemical should be classified as No Data by Ultimate biodeg

Domain logical expression index: "p"

Referential boundary: The target chemical should be classified as > 100 days by Ultimate biodeg

Domain logical expression index: "q"

Referential boundary: The target chemical should be classified as Reactive unspecified by Acute aquatic toxicity MOA by OASIS ONLY

Domain logical expression index: "r"

Referential boundary: The target chemical should be classified as Acid moiety AND Phenols by Aquatic toxicity classification by ECOSAR ONLY

Domain logical expression index: "s"

Referential boundary: The target chemical should be classified as Alkyl substituent on aromatic ring AND Aromatic acid   [-C(=O)-OH] AND Aromatic alcohol  [-OH] AND Aromatic-CH3 AND Aromatic-H AND Benzene by Bioaccumulation - metabolism alerts

Domain logical expression index: "t"

Referential boundary: The target chemical should be classified as Aromatic ether  [-O-aromatic carbon] by Bioaccumulation - metabolism alerts

Domain logical expression index: "u"

Referential boundary: The target chemical should be classified as Alkyl substituent on aromatic ring AND Aromatic acid   [-C(=O)-OH] AND Aromatic alcohol  [-OH] AND Aromatic-CH3 AND Aromatic-H AND Benzene by Bioaccumulation - metabolism alerts

Domain logical expression index: "v"

Referential boundary: The target chemical should be classified as Aromatic-CH2 by Bioaccumulation - metabolism alerts

Domain logical expression index: "w"

Referential boundary: The target chemical should be classified as Alkyl substituent on aromatic ring AND Aromatic acid   [-C(=O)-OH] AND Aromatic alcohol  [-OH] AND Aromatic-CH3 AND Aromatic-H AND Benzene by Bioaccumulation - metabolism alerts

Domain logical expression index: "x"

Referential boundary: The target chemical should be classified as -CH2-  [cyclic] OR -CH2-  [linear] by Bioaccumulation - metabolism alerts

Domain logical expression index: "y"

Referential boundary: The target chemical should be classified as Alkyl substituent on aromatic ring AND Aromatic acid   [-C(=O)-OH] AND Aromatic alcohol  [-OH] AND Aromatic-CH3 AND Aromatic-H AND Benzene by Bioaccumulation - metabolism alerts

Domain logical expression index: "z"

Referential boundary: The target chemical should be classified as Ketone   [-C-C(=O)-C-] by Bioaccumulation - metabolism alerts

Domain logical expression index: "aa"

Referential boundary: The target chemical should be classified as Methyldopa (Hepatotoxicity) Alert by Repeated dose (HESS)

Domain logical expression index: "ab"

Referential boundary: The target chemical should be classified as p-Alkylphenols (Hepatotoxicity) Rank A by Repeated dose (HESS)

Domain logical expression index: "ac"

Parametric boundary:The target chemical should have a value of log Kow which is >= 1.39

Domain logical expression index: "ad"

Parametric boundary:The target chemical should have a value of log Kow which is <= 2.97

Validity criteria fulfilled:
not specified
Conclusions:
The IGC50 value was estimated to be 219.9 mg/l when 2-hydroxy-p-toluic acid (m cresotic acid)exposed to Tetrahymena pyriformis for 48hrs.
Executive summary:

Based on the prediction done using the OECD QSAR toolbox version 3.3 with log kow as the primary descriptor and considering the six closest read across substances, toxicity on Tetrahymena pyriformis was predicted for2-hydroxy-p-toluic acid (m cresotic acid) (50-85-1).The IGC50 value was estimated to be 219.9 mg/l when 2-hydroxy-p-toluic acid (m cresotic acid)exposed to Tetrahymena pyriformis for 48hrs.

Description of key information

Toxicity to microorganisms:

Based on the prediction done using the OECD QSAR toolbox version 3.3 with log kow as the primary descriptor and considering the six closest read across substances, toxicity onTetrahymena pyriformiswas predicted for2-hydroxy-p-toluic acid (m cresotic acid) (50-85-1).The IGC50 value was estimated to be 219.9 mg/l when 2-hydroxy-p-toluic acid (m cresotic acid)exposed toTetrahymena pyriformisfor 48hrs.

Key value for chemical safety assessment

EC50 for microorganisms:
219.9 mg/L

Additional information

Toxicity to microorganisms:

Based on the prediction done using the OECD QSAR toolbox version 3.3 with log kow as the primary descriptor and considering the six closest read across substances, toxicity onTetrahymena pyriformiswas predicted for2-hydroxy-p-toluic acid (m cresotic acid) (50-85-1).The IGC50 value was estimated to be 219.9 mg/l when 2-hydroxy-p-toluic acid (m cresotic acid)exposed toTetrahymena pyriformisfor 48hrs.

The above prediction was further supported by experimental data summarized in Concise International Chemical Assessment Document 26 for BENZOIC ACID AND SODIUM BENZOATE World Health Organization Geneva, 2000 for structurally similar read across substane Benzoic acid (CAS:65 -85 -0).

Benzoic acid was used as a test material to evaluate toxicity to microorganisms as per OECD guideline 209.

Activated sludge was used as the test culture at pH 7.5 for 3 h The EC50 value on the basis of respiration inhibition test was observed to be >1000 mg/l.

The above experimental data was further supported by experimental result summarized by Ganiyat K. Oloyede on Arabian Journal of Chemistry Volume 9, Supplement 1, September 2016, Pages S840-S845 for structurally similar read across substance Methyl salicylate (CAS: 119 -36 -3).

An overnight culture of each organism S. aureus was prepared. The 0.1 ml oforganism was taken into 9.9 ml of sterile distilled water (SDW) to give 10 ml of 1:100 (10 ) dilution.

 The stock was maintained on nutrient agar slant and sub-cultured in nutrient broth for incubation at 37 °C prior to each antimicrobial testing.

Inoculation of the test organisms on nutrient agar-prepared plates was achieved by flaming a wire loop on a spirit lamp, cooling the wire loop (air cooling) and fetching the test organisms.

 The discs were prepared using a Grade No. 1 Whatman filter paper. One hundred discs were obtained by punching and putting in vial bottles and sterilizing in an oven at 150 °C for 15 min. Thereafter the cups (9 mm diameter) were aseptically bored into the solid nutrient agar using a sterile cork-borer.

The test solution of Methyl salicylate was introduced .

 The plates were left at room temperature for 2 h, allowed to diffuse into the medium, turned upside-down and thereafter incubated at 37 °C for 24 h in an incubator.

The minimum inhibition concentration (MIC)of Methyl salicylate on Staphylococcus aureus was observed to be 200mg/l

Another structurally similar read across substance 1,2-Benzenedicarboxylic acid, monopotassium salt (CAS: 877 -24 -7) was used to support above experimental data.

In a study of toxicity of Phthalates to the Marine Dinoflagellate Gymnodinium breve the effect of Potassium hydrogen phthalate was evaluated. The test substance was tested in a concentration of 0,1,10, 20, 50, 100, 200, 500, 1000 and 1000 ppm. The results show Median growth when concentration of test material (ppm) versus the growth rate (linear axis of graph), expressed as a percentage of the growth of a "no-add" control at 498.52 and 997 mg/l. Therefore, EC50 of Potassium hydrogen phthalate was considered to be be 498.52 and 997 mg/l when tested on Marine Dinoflagellate Gymnodinium breve for 96 hours.