2-hydroxy-p-toluic acid

Endpoint summary

Description of key information

Short term toxicity to fish:

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 onDanio rerio (previous name: Brachydanio rerio)was predicted for 2-hydroxy-p-toluic acid (m cresotic acid) (50-85-1).The LC50 value was estimated to be 377.3 mg/l when 2-hydroxy-p-toluic acid (m cresotic acid)exposed toDanio rerio (previous name: Brachydanio rerio)for 96hrs.

Based on the LC50 it was concluded that the m-cresotic acid was not toxic and can be consider as not classified as per the CLP classification criteria.

Short-term toxicity to aquatic invertebrates :

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 Daphnia magna was predicted for 2-hydroxy-p-toluic acid (m cresotic acid) (50-85-1).The EC50 value was estimated to be 164.708 mg/l when 2-hydroxy-p-toluic acid (m cresotic acid)exposed to Daphnia magna for 48hrs.

Based on the EC50 it was concluded that the m-cresotic acid was not toxic and can be consider as not classified as per the CLP classification criteria.

Toxicity to aquatic algae and cynobacteria:

Based on the prediction done using the OECD QSAR toolbox version 3.4 with log kow as the primary descriptor and considering the five closest read across substances, toxicity on Desmodesmus subspicatus (previous name: Scenedesmus subspicatus)was predicted for2-hydroxy-p-toluic acid (m cresotic acid) (50-85-1).The EC50 value was estimated to be 112.814 mg/l when 2-hydroxy-p-toluic acid (m cresotic acid)exposed toDesmodesmus subspicatus for 72 hrs.

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.

Additional information

Short term toxicity to fish:

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 onDanio rerio (previous name: Brachydanio rerio)was predicted for 2-hydroxy-p-toluic acid (m cresotic acid) (50-85-1).The LC50 value was estimated to be 377.3 mg/l when 2-hydroxy-p-toluic acid (m cresotic acid)exposed toDanio rerio (previous name: Brachydanio rerio)for 96hrs.

Based on the LC50 it was concluded that the m-cresotic acid was not toxic and can be consider as not classified as per the CLP classification criteria.

The above prediction for the target was was supported by experimental study conducted by Sustainability Support Services (Europe) AB for the structurally similar read across substancesodium salicylate (CAS:54 -21 -7).

This study was designed to assess the effect of Sodium salicylate (CAS No.54-21-7) on the mortality of Danio rerio. The study was conducted in accordance with OECD Guideline 203 (Fish, Acute Toxicity Test) in a static sysytem.

Preparation of the test solutions/dispersions :The test solution was prepared by dissolving 1 g of the test substance in 10 liters deionized water with continuous stirring.

Observations (mortality, visible symptoms, pH, Temperature, dissolved oxygen content) were recorded after 24 hours, 48 hours, 72 hours and 96 hours of the start of the experiment.

Based on nominal concentration, the median lethal concentration LC-50 (96 h) for Sodium salicylate on Danio rerio was found to be >100 mg/L according to probit analysis. The fishes were found to be freely swimming in the bowl aquaria without showing any abnormal symptoms. No mortalities were observed at the test concentration of 100 mg/l.

The above experimental data was supported by another structurally similar read across substance Benzoic acid (CAS:65 -85 -0) summarized in Sewage Ind. Wastes29(6): 695-711.

Acute fish toxicity study was conducted on Gambusia affinis (Western Mosquitofish) for exposure period of 96 hrs. with test temperature 19 to 21 deg.C and Ph 3.8 to 7.0, Alkalinity:100 ppm MO in static freshwater condition.

Concentrations used as 10,18,32,56 and 100 mg/l if death not observed then same series was used between 100 and 1000 mg/l again if no death observed continue with 1000 and 10000mg/l.

During experiment the lethal concentration (LC50) was observed to be 180 mg/l on the basis of mortality effect. Thus based on the experimental result it is concluded that the test chemical Benzoic acid was non hazardous to fish.

The above experimental data was further supported by experimental study summarized in Water Quality Criteria Data Book - Vol. 3 1971

for structurally similar read across substance 4-Hydroxybenzoic acid ( CAS: 99 -96 -7).

In acute fish toxicity study on species Carassius auratus (Goldfish) time to 50% mortality of organisms (LC50) of test substance 4-Hydroxybenzoic acid was reported to be 480 mg/l on the basis of mortality effect with exposure period 3.02 hrs.Mentioned concentration indicate that the test substance 4-Hydroxybenzoic acid was non toxic to fish.

Further more, another study for toxicity to fish was summarized in Jpn. J. Toxicol. Environ. Health32(1): 46-53 for structurally similar read across substance 1,2-Benzenedicarboxylic acid (CAS: 88 -99 -3).

In short term fish toxicity of test chemical Phthalic acid on test species Oryzias latipes (Japanese Medaka) the lethal concentration (LC50) for exposure period of 48 hrs. in static freshwater system and test temperature 30 deg.C was observed to be 1000 mg/l.

Thus based on the lethal concentration it is concluded that the test substance Phthalic acid was non hazardous to aquatic environment.

It can be concluded from the value that the2-hydroxy-p-toluic acid (m cresotic acid) (50-85-1 )is no toxic to the aquatic environment can be considered to be “not classified” as per the CLP classification criteria.

Short-term toxicity to aquatic invertebrates :

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 Daphnia magna was predicted for 2-hydroxy-p-toluic acid (m cresotic acid) (50-85-1).The EC50 value was estimated to be 164.708 mg/l when 2-hydroxy-p-toluic acid (m cresotic acid)exposed to Daphnia magna for 48hrs.

Based on the EC50 it was concluded that the m-cresotic acid was not toxic and can be consider as not classified as per the CLP classification criteria.

The above prediction was suppported by another prediction for the target . Based on the average value of both models ( Leadscope Enterprise model and SciMatics SciQSAR model), the result were predicted in Battery model. Based on the Danish (Q)SAR Database, the 48 hours EC50 was estimated to be 216.1135 mg/l on Daphnia Magna for substance m-cresotic acid with immobilization effects. Thus based on this value it can be concluded that the substance can not be classified as per the criteria of CLP regulation.

The above predictions were supported by experimental study conducted byWang, W.H., and J.P. Lay summarized in Ecotoxicology and Environmental Safety  Volume 17, Issue 3, June 1989, Pages 308–316 for structurally similar read across substance Sodium salicylate (CAS:54 -21 -7).

Short term toxicity of sodium salicylate on the growth of daphnia magna was carried out for 24hrs. The effective concentration EC0and EC10 value of sodium salicylate in Daphnia magna in a 24 hr study on mortality effect was 80mg/l and 304 mg/L.Thus based on the immolization by consedring EC value for aquatic classification of the substance , it is concluded that sodium salicylate does not exhibit short term toxicity to aquatic invertebrate (Daphnia magna).

Another experimental data summarized in Sewage Works Journal Vol. 18, No. 1 (Jan., 1946), pp. 82-87 for structurally similar read across substance Sodium salicylate (CAS:54 -21 -7) .

Lethal Threshold Concentration value of Sodium salicylate in Daphnia magna in a 48 hr study on intoxication effect was found to be 1450 mg/L.Thus,considering the CLP Criteria for aquatic classification of the substance , it is concluded that Sodium salicylate does not exhibit short term toxicity to aquatic invertebrate (Daphnia magna) .

The above experimental data was further supported by experimental data summarized in Chemosphere 59 (2005) 255–261 for structurally similar read substance Benzoic acid (CAS: 65 -85 -0).

Short term toxicity to aquatic invertebrates was performed in Daphnia magna for 48 hrs. The young daphnids were obtained from continuous cultures in 1 liter glass beakers at 21 ± 0.3 degree C, in dechlorinated and conditioned tap water, the medium was renewed in three weeks and daphnids were fed daily with the green alga Selenastrum capricornutum. The pH of test solution was adjusted to 7.45 ± 0.05 with HCL and NaOH. The concentrations of the resultant solutions were checked before and after (48 h) exposure using a UV–visible spectrophotometer.

As the experiment starts neonate were placed in 50 ml of beaker with 40 ml of test solution. All experiment was made in four replicates and performed at 21 ± 0.3 degree C under 16 h light: 8 h dark photoperiod. Immobility was observed after 24 and 48 hrs and EC 50 value was calculated.

After the experiment the EC 50 value of Benzoic acid (65-85-0) for Daphnia magna was determined to be 860 mg/l in 48 hrs.

Another structurally similar read across substance Salicylic acid (CAS: 69 -72 -7) was used to support the above experimental data .

Short term toxicity study to Daphnia magnaby using chemicalsalicylic acid was carried out for 48hrs. Static method was used and the age of daphnia magna was <24hrs. Based on the immobility of daphnia magna by using chemical salicylic acid, the EC50 value was 1147.57mg/l.

Based on the CLP regulation the 2-hydroxy-p-toluic acid (m cresotic acid) (50-85 -1) is considered to be not toxic to aquatic invertebrates and can be concluded to be not classified.

Toxicity to aquatic algae and cynobacteria:

Based on the prediction done using the OECD QSAR toolbox version 3.4 with log kow as the primary descriptor and considering the five closest read across substances, toxicity on Desmodesmus subspicatus (previous name: Scenedesmus subspicatus)was predicted for2-hydroxy-p-toluic acid (m cresotic acid) (50-85-1).The EC50 value was estimated to be 112.814 mg/l when 2-hydroxy-p-toluic acid (m cresotic acid)exposed toDesmodesmus subspicatus for 72 hrs.

The above prediction was supported another prediction for the target .Based on the prediction done using thethree different models i.e, Battery, Leadscope and SciQSAR used within Danish QSAR database, the short term toxicity on green algae was predicted for test substance m cresotic acid (2 -hydroxy-p-toluic acid) for cas 50 -85 -1. The average EC50 value was given by the third model i.e, Battery model. On the basis of effects observed in a static freshwater system, the effect concentration EC50 value for the substance m cresotic acid is estimated to be 159.23 mg/l for Pseudokirchneriella subcapitata during 72 hr exposure duration. Thus, on the basis of EC50 value,it can be concluded that the test chemical m cresotic acid can be considered as non toxic to green algae at environmentally relevant concentrations and can be considered not classified as per the CLP classification criteria.

The above predictions were further supported by summarized inJapan chemicals collaborative knowledge database (J-check), 2016 for structurally similar read across substance 4-Hydroxybenzoic acid (CAS: 99 -96 -7).

Short term toxicity toalgaestudy was carried out for 72 hrs. The study was performed according toOECD guideline 201 (Algal, Growth Inhibition Test).The study was based on the effects of the test compound onalgaein a static fresh water system.Based on effect on growth rate ofalgae,the 72 hr EC50 and NOEC value was determined to be 110 and 51 mg/l, respectively, and on the basis of AUG, the 72 hr EC50 and NOEC value was determined to be 69 and 32 mg/l, respectively.Thus, based onEC50value (110 mg/l), it can be concluded that the substance4-Hydroxybenzoic acidcan be considered as non-toxic to aquatic organisms and thus cannot be classifiedas hazardous, as per the CLP criteria.

The above experimental data was further supported byEcotox database, U.S Environmental Protection Agency,2017 for structurally similar read across substance Salicylic acid (CAS: 69 -72 -7).

Short term toxicity study to Haematococcus pluvialis by using chemical salicylic acid was carried out, by using static method. Based on the growth inhibition of population of Haematococcus pluvialis, EC10 was 165 mg/l.Hence chemical salicylic acid was consider non toxic and can be concluded as not classified as per the CLP classification criteria.

Another experimental study for the structurally similar read across substance Benzoic acid (CAS: 65 -85 -0) was sumarized inECOTOX database, U. S. Environmental Protection Agency, 2016

Short term toxicity toPseudokirchneriella subcapitata(green algae) study was carried out for 48 hrs.The study was based on the effects of the test compound Benzoic acid (CAS: 65 -85 -0) onPseudokirchneriella subcapitatain a static fresh water system. On the basis of population of the test organismPseudokirchneriella subcapitata(green algae), the 48 hr EC50 value was determined to be 207.5 mg/l.

Thus, based on this values of target as well as structurally similar read across substance , it can be concluded that the substance2-hydroxy-p-toluic acid (m cresotic acid) (50-85 -1)can be considered as non-toxic to aquatic organisms and thus cannot be classified as hazardous as per the CLP criteria.

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 substance1,2-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.