4-methoxyphenylacetic acid

Endpoint summary

Description of key information

Stability

Hydrolysis

According to Annex VIII, column 2 of the REACH regulation a study on hydrolysis as a function of pH ‘does not need to be conducted because the substance ' 4-methoxyphenylacetic acid' is readily biodegradable, therefore this study was considered for waiver.

Biodegradation

Biodegradation in water

Biodegradation study was conducted for 20 days for evaluating the percentage biodegradability of test substance 4-Methoxyphenylacetic acid (CAS no. 104-01-8) (R. V. Subba-Rao and Martin Alexander, 1977). Bacteria was used as an inoculum. Microbial inoculum was isolated from Hudson Collamer silt loam. The test was performed under aerobic conditions at a temperature of 25ᵒC, respectively. The chemicals were introduced into the BOD bottles as sole carbon sources at a concentration of 2 mg of carbon per bottle. The compounds were added in acetone solutions, and the acetone was evaporated prior to the addition of O2-saturated water. Each bottle received 5 mg of Hudson Collamer silt loam as a source of the microbial inoculum. The bottles were filled with the air-saturated salts solution and closed with glass stoppers. Bottles containing O2 saturated water inoculated with soil (as a source of microbial inoculum) but no carbon source were also included in the study to account for the O2 depletion resulting from microbial oxidation of organic matter and ammonium. Test compound was also tested in combination with glucose (both at a conc. of 2 mg of carbon per bottle) to test whether the possible lack of biodegradation was a result of toxicity of the test chemical. Dissolved O2 in the bottles was measured at regular intervals using a Yellow Spring Instrument Co. oxygen analyzer, Model 53. The instrument was calibrated with the salts solution, the O2 content of which was determined by the Alsterberg modification of the Winkler method. At regular intervals, the dissolved O2 in the samples was measured after calibrating the instrument with a BOD bottle containing inoculated 02-saturated water supplemented with 0.1% KCN. The solutions in bottles showing O2 depletion were used to obtain microorganisms capable of utilizing the substrate. Based on appreciable degradation of test chemical after only a few days, 4 -Methoxyphenylacetic acid is considered to be biodegradable in nature.

Biodegradation in water and sediment

Estimation Programs Interface (EPI) Suite (2017) prediction model was run to predict the half-life in water and sediment for the test compound 4-Methoxyphenylacetic acid (CAS No.104 -01 -8). If released in to the environment, 27.4% of the chemical will partition into water according to the Mackay fugacity model level III and the half-life period of test chemical in water is estimated to be 15 days (360 hrs). The half-life (15 days estimated by EPI suite) indicates that the chemical is not persistent in water and the exposure risk to aquatic animals is moderate to low whereas the half-life period of test chemical 4-Methoxyphenylacetic acid in sediment is estimated to be 135 days (3240 hrs). However, as the percentage release of test chemical into the sediment is less than 1% (i.e, reported as 0.0718%), indicates that 4-Methoxyphenylacetic acid is not persistent in nature.

Biodegradation in soil

The half-life period of 4-Methoxyphenylacetic acid (CAS No. 104-01-8) in soil was estimated using Level III Fugacity Model by EPI Suite version 4.1 estimation database (EPI suite, 2017). If released into the environment, 72.5% of the chemical will partition into soil according to the Mackay fugacity model level III. The half-life period of 4-Methoxyphenylacetic acid in soil is estimated to be 30 days (720 hrs). Based on this half-life value of 4-Methoxyphenylacetic acid, it is concluded that the chemical is not persistent in the soil environment and the exposure risk to soil dwelling animals is moderate to low.

Bioaccumulation

Bioaccumulation: aquatic / sediment

From predicted model BCFBAF Program (v3.00) by EPI SUITE;2017 the estimated bio concentration factor (BCF) for 4-methoxyphenylacetic acid is 3.162 L/kg wet-wt which does not exceed the bioconcentration threshold of 2000.Thus it is concluded that 4-methoxyphenylacetic acid is not expected to bio accumulate in the food chain.

Transport and distribution

Adsorption / desorption

The adsorption coefficient Koc in soil and in sewage sludge 4-methoxyphenylacetic acid(CAS No.104-01-8) was determined by the Reverse Phase High Performance Liquid Chromatographic method according to OECD Guideline No. 121 for testing of Chemicals. The reference substances were chosen according to structural similarity with the test substance and calibration graph prepared. The reference substances were xylene,ethylbenzene and toluene having Koc value ranging from 2.369 to 2.649. The Log Koc value was found to be 1.15385 ± 0.0029 at 25°C. The results indicate that the chemical 4-methoxyphenylacetic acid (CAS No. 104-01-8) is likely to show low tendency of sorption to soil and sediment and show moderate migration potential to groundwater.

Additional information

Stability

Hydrolysis

According to Annex VIII, column 2 of the REACH regulation a study on hydrolysis as a function of pH ‘does not need to be conducted because the substance ' 4-methoxyphenylacetic acid' is readily biodegradable, therefore this study was considered for waiver.

Biodegradation

Biodegradation in water

1 experimental study and predicted data for the test compound 4-Methoxyphenylacetic acid (CAS No. 104-01-8) and the 4 different studies for its closest read across substance using logkow as the primary descriptor were reviewed for the biodegradation endpoint which are summarized as below:

Study 1 - Biodegradation study was conducted for 20 days for evaluating the percentage biodegradability of test substance 4-Methoxyphenylacetic acid (CAS no. 104-01-8) (R. V. Subba-Rao and Martin Alexander, 1977). Bacteria was used as an inoculum. Microbial inoculum was isolated from Hudson Collamer silt loam. The test was performed under aerobic conditions at a temperature of 25ᵒC, respectively. The chemicals were introduced into the BOD bottles as sole carbon sources at a concentration of 2 mg of carbon per bottle. The compounds were added in acetone solutions, and the acetone was evaporated prior to the addition of O2-saturated water. Each bottle received 5 mg of Hudson Collamer silt loam as a source of the microbial inoculum. The bottles were filled with the air-saturated salts solution and closed with glass stoppers. Bottles containing O2 saturated water inoculated with soil (as a source of microbial inoculum) but no carbon source were also included in the study to account for the O2 depletion resulting from microbial oxidation of organic matter and ammonium. Test compound was also tested in combination with glucose (both at a conc. of 2 mg of carbon per bottle) to test whether the possible lack of biodegradation was a result of toxicity of the test chemical. Dissolved O2 in the bottles was measured at regular intervals using a Yellow Spring Instrument Co. oxygen analyzer, Model 53. The instrument was calibrated with the salts solution, the O2 content of which was determined by the Alsterberg modification of the Winkler method. At regular intervals, the dissolved O2 in the samples was measured after calibrating the instrument with a BOD bottle containing inoculated 02-saturated water supplemented with 0.1% KCN. The solutions in bottles showing O2 depletion were used to obtain microorganisms capable of utilizing the substrate. Based on appreciable degradation of test chemical after only a few days, 4 -Methoxyphenylacetic acid is considered to be biodegradable in nature.

 

Study 2 - Estimation Programs Interface Suite (EPI suite, 2017) was run to predict the biodegradation potential of the test compound 4-Methoxyphenylacetic acid (CAS no. 104 -01 -8) in the presence of mixed populations of environmental microorganisms. The biodegradability of the substance was calculated using seven different models such as Linear Model, Non-Linear Model, Ultimate Biodegradation Timeframe, Primary Biodegradation Timeframe, MITI Linear Model, MITI Non-Linear Model and Anaerobic Model (called as Biowin 1-7, respectively) of the BIOWIN v4.10 software. The results indicate that 4-Methoxyphenylacetic acid is expected to be readily biodegradable.

 

Study 3 - Biodegradation study was conducted for evaluating the percentage biodegradability of read across substance 4-ethoxybenzoic acid (CAS no. 619-86-3) (GSBL database, 2016). The study was performed according to OECD Guideline 302 B (Inherent biodegradability: Zahn-Wellens/EMPA Test).The read across substances were prepared from stock solutions in added to such amounts that DOC concentrations of 50 – 400 mg/l or COD concentrations of 200 - 1000 mg/l were obtained. Duration of acclimatization phase (Time from test start to observable degradation) is 3 days and duration of the logarithmic degradation phase was 6 days. Activated sludge was used as an inoculum. The inoculum was extracted from the biological purification plant of the of HÖCHST 's work and is calculated in such a way that in the test batch 1.1 ± 0.1 g/l activated sludge dry substance (BTS) were included. The percentage degradation of read across substance was determined to be100% degradation by DOC removal parameter in 9 days. Thus, based on percentage degradation, 4-ethoxybenzoic acid is considered to be readily biodegradable in nature.

 

Study 4 - For read across chemical 4 -methoxybenzoic acid (CAS no. 100 -09 -4), biodegradation study was conducted for evaluating the percentage biodegradability of read across substance 4-methoxybenzoic acid (CAS no. 100-09-4)(GSBL database, 2016). The study was performed according to OECD Guideline 302 B (Inherent biodegradability: Zahn-Wellens/EMPA Test).The test substances were prepared from stock solutions in added to such amounts that DOC concentrations of 50 – 400 mg/l or COD concentrations of 200 - 1000 mg/l were obtained. Duration of acclimatization phase (Time from test start to observable degradation) is 2 days and duration of the logarithmic degradation phase was 4 days. Activated sludge was used as an inoculum. The inoculum was extracted from the biological purification plant of the of HÖCHST’s work and is calculated in such a way that in the test batch 1.1 ± 0.1 g/l activated sludge dry substance (BTS) were included. The percentage degradation of read across substance was determined to be100% degradation by DOC removal parameter in 6 days. Thus, based on percentage degradation, 4-methoxybenzoic acid is considered to be readily biodegradable in nature.

 

Study 5 - In weight of evidence study of read across 4 -methoxybenzoic acid (CAS no. 100 -09 -4), biodegradation was conducted for 28 days for evaluating the percentage biodegradability of read across substance 4-methoxybenzoic acid (CAS no. 100-09-4) (GSBL database, 2016).  The study was performed according OECD Guideline 301 E (Ready biodegradability: Modified OECD Screening Test) under aerobic conditions. The percentage degradation of read across substance was determined to be 100% degradation by DOC removal parameter in 6 days. Thus, based on percentage degradation, 4-methoxybenzoic acid is considered to be readily biodegradable in nature.

 

Study 6 - In another weight of evidence study of read across chemical 4 -methoxybenzoic acid (CAS no. 100 -09 -4), biodegradation was conducted for 28 days for evaluating the percentage biodegradability of read across substance 4-methoxybenzoic acid (CAS no. 100-09-4) (GSBL database, 2016). The study was performed according OECD Guideline 302 B (Inherent biodegradability: Zahn-Wellens/EMPA Test).The percentage degradation of read across substance was determined to be 90% degradation by DOC removal parameter in 10 days. Thus, based on percentage degradation, 4-methoxybenzoic acid is considered to be readily biodegradable in nature.

 

On the basis of above results for target chemical (study 1 and 2) and its read across substance (study 3, 4, 5 and 6 from authoritative database), it can be concluded that the test substance 4-Methoxyphenylacetic acid can be expected to be readily biodegradable in nature.

Biodegradation in water and sediment

Estimation Programs Interface (EPI) Suite (2017) prediction model was run to predict the half-life in water and sediment for the test compound 4-Methoxyphenylacetic acid (CAS No.104 -01 -8). If released in to the environment, 27.4% of the chemical will partition into water according to the Mackay fugacity model level III and the half-life period of test chemical in water is estimated to be 15 days (360 hrs). The half-life (15 days estimated by EPI suite) indicates that the chemical is not persistent in water and the exposure risk to aquatic animals is moderate to low whereas the half-life period of test chemical 4-Methoxyphenylacetic acid in sediment is estimated to be 135 days (3240 hrs). However, as the percentage release of test chemical into the sediment is less than 1% (i.e, reported as 0.0718%), indicates that 4-Methoxyphenylacetic acid is not persistent in nature.

Biodegradation in soil

The half-life period of 4-Methoxyphenylacetic acid (CAS No. 104-01-8) in soil was estimated using Level III Fugacity Model by EPI Suite version 4.1 estimation database (EPI suite, 2017). If released into the environment, 72.5% of the chemical will partition into soil according to the Mackay fugacity model level III. The half-life period of 4-Methoxyphenylacetic acid in soil is estimated to be 30 days (720 hrs). Based on this half-life value of 4-Methoxyphenylacetic acid, it is concluded that the chemical is not persistent in the soil environment and the exposure risk to soil dwelling animals is moderate to low.

On the basis of available information, the test substance 4-Methoxyphenylacetic acid can be considered to be readilybiodegradable in nature.

Bioaccumulation

Bioaccumulation: aquatic / sediment

By applying weight of evidence approach Experimental and Predicted data of Bioaccumulation endpoint for the target chemical (4-methoxyphenyl) acetic acid (Cas no. 104-01-8) and its read across chemical were reviewed to summarize as follows:  

Study 1: 

From prediction model BCFBAF Program (v3.00) by EPI SUITE;2017 the estimated bio concentration factor (BCF) for 4-methoxyphenylacetic acid is 3.162 L/kg wet-wt at 25 deg.C for target (4-methoxyphenyl) acetic acid.

 Study 2: 

Similarly other prediction model PBT profiler; 2017 indicate that the Bioaccumulation factor (BCF) was predicted to be 3.2 L/kg wet-wt at 25 deg.C for 4-methoxyphenylacetic acid.

 Study 3: 

Another predicted database i.e Scifinder; 2017 for target substance indicated the Bioconcentration factor (BCF) for target chemical 4-methoxyphenylacetic acid was predicted to be 5.10 at pH 1,5.09 at pH 2,4.93 at pH3, 3.76 at pH 4, 1.12 at pH 5, 1.0 at pH 6-10 and temperature 25 deg.C. 

 Study 4: 

And Chemspider - ACD/PhysChem Suite predicted model the Bioconcentration factor (BCF) for target chemical 4-methoxyphenylacetic acid was predicted to be 1.00 at pH 5.5 and 7.4 at temperature 25 deg.C. 

 

All 4 studies of target chemical based predicted models it is concluded that the test chemical 4-methoxyphenylacetic acid is non bioaccumulative in nature as it does not exceed the BCF criteria of 2000.

 Study 5: 

And from HSDB database; 2017 the read across chemical 4-chlorophenoxyacetic acid (Cas no. 122-88-3) indicate an estimated BCF of 3 was calculated for 4-chlorophenoxyacetic acid, using a log Kow of 2.25 and a regression derived equation. This BCF suggests the potential for bioconcentration in aquatic organisms is low.

Study 5 also support to predicted studies for target chemical.

Thus based on the above all studies it is concluded that the test substance chemical 4-methoxyphenylacetic acid (Cas no. 104-01-8) is non Bioaccumulative in aquatic environment.

Transport and distribution

Adsorption / desorption

For adsorption in soil/sediment endpoint 5 studies for test chemical (4-methoxyphenyl) acetic acid (Cas no. 104-01-8) with read across chemical which is 60-70% structurally similar to target were summarised as follows:

Study 1:

The experiment conduct by UERL; 2017to determine Adsorption coefficient (KOC) on soil and on sewage sludge of the 4-methoxyphenylacetic acid(CAS No.104-01-8) using HPLC.

According to study the adsorption coefficient Koc in soil and in sewage sludge 4-ethoxyphenylacetic acid (CAS No.104-01-8)was determined by the Reverse Phase High Performance Liquid Chromatographic method according to OECD Guideline No. 121 for testing of Chemicals. The reference substances were chosen according to structural similarity with the test substance and calibration graph prepared. The reference substances were xylene, ethylbenzene and toluene having Koc value ranging from 2.369 to 2.649. TheLog Kocvalue was found to be1.15385 ± 0.0029 at 25°C.The results indicate that the chemical 4-methoxyphenylacetic acid (CAS No. 104-01-8) is likely to show low tendency of sorption to soil and sediment and show moderate migration potential to groundwater.

Study 2:

The Soil Adsorption Coefficient i.e Koc value of 4-methoxyphenylacetic acid was estimated using EPI suite  KOCWIN Program (v2.00) program as Koc 18.94 L/kg(log Koc=1.277)  by means of MCI method at 25 deg.C, indicating that it is has a negligible sorption to soil and sediment and therefore have rapid migration potential to groundwater.

Study 3:

SciFinder, American Chemical Society (ACS); 2017 prediction database indicated the soil adsorption coefficient i.e Koc value of target substance 4-methoxyphenyl acetic acid was estimated to be 112 L/Kg i.e Log Koc= 2.049 at pH 1, 111.0 i.e Koc=2.045 at pH 2, 108.0 i.e Log Koc=2.033 at pH 3, 82.4 i.e Log Koc=1.915 at pH 4, 32.1 i.e Log Koc=1.389 at pH 5, 3.06 i.e Log Koc=0.4857 at pH 6, 1.0 i.e Log Koc=0, at pH 6-10 and temperature 25 deg.C. This Koc value at all range of pH condition indicates that the substance 4-methoxyphenylacetic acid has a low sorption to soil and sediment and therefore have rapid migration potential to groundwater. 

Study 4:

Chemspider predicted database the soil adsorption coefficient i.e Koc value of test substance 4-methoxyphenylacetic acid was estimated to be 1 13.81 i.e Log Koc= 1.140 at pH 5.5 and 1.00 i.e Log Koc=0 at pH 7.4 at temp.25 deg.C .This Koc value indicates that the substance (4-methoxyphenyl)acetic acid has a Negligible sorption to soil and sediment and therefore have rapid migration potential to groundwater.

All studies i.e 2, 3 and 4 based on the prediction results also supports the experimental study 1.

Study 5:

In final study based on the authorative database source i.e HSDB database; 2017 for read across chemical 4-chlorophenoxy acetic acid (Cas no. 122-88-3) indicate Koc of 4-chlorophenoxyacetic acid is estimated as 18, Using a structure estimation method based on molecular connectivity indices, this estimated Koc value suggests that 4-chlorophenoxy acetic acid is expected to have very high mobility in soil.

Read across study also give assistance to experimental and predicted results of the target chemical.

Thus all above experimental and other supported reports arrive at a judgement as the test substance 4-methoxyphenylacetic acid (Cas no. 104-01-8) has high mobility in soil/sediment.