4-methoxy-N-phenyl-o-toluidine

Endpoint summary

Description of key information

Biodegradation:

Biodegradation in water:

Biodegradability of test chemical 4-methoxy-2-methyl-N-phenylaniline (CAS no. 41317 -15 -1) was estimated by using OECD QSAR tool box v3.3 by considering eight closest read across chemicals with log Kow as primary descriptor. Percent degradability of test chemical 4-methoxy-2-methyl-N-phenylaniline was estimated to be 0.550 % by considering BOD as parameter  and microorganisms as inoculum in 28 days. On the basis of percent degradability value it is concluded that this test chemical is not readily biodegradable.

Biodegradation in water and sediments:

Estimation Programs Interface (EPI Suite, 2017) prediction model was run to predict the half-life in water and sediment for the test compound 4-methoxy-2-methyl-N-phenylaniline (CAS No. 41317 -15 -1). If released in to the environment, 35 % 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 37.5 days (900 hrs). The half-life (37.5 days estimated by EPI suite) indicates that the chemical is not persistent in water and the exposure risk to aquatic animals is low whereas the half-life period of test chemical 4-methoxy-2-methyl-N-phenylaniline in sediment is estimated to be 337.5 days (8100 hrs). However, as the percentage release of test chemical into the sediment is less than 1 % (i.e, reported as 0.0835 %), indicates that test chemical 4-methoxy-2-methyl-N-phenylaniline is not persistent in sediment.

Biodegradation in soil:

The half-life period of test chemical 4-methoxy-2-methyl-N-phenylaniline (CAS No. 41317 -15 -1) 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, 81.2 % of the chemical will partition into soil according to the Mackay fugacity model level III. The half-life period of test chemical 4-methoxy-2-methyl-N-phenylaniline in soil is estimated to be 75.0 days (1800 hrs). Based on this half-life value of test chemical 4-methoxy-2-methyl-N-phenylaniline, it is concluded that the chemical is not persistent in the soil environment and the exposure risk to soil dwelling animals is low.

Bioaccumulation:

Bioaccumulation: aquatic/sediments:

Using BCFBAF Program (v3.00) model of EPI suite (2017) the estimated bio concentration factor (BCF) for 4-methoxy-2-methyl-N-phenylaniline (CAS No. 2244-16-8) is 179.1 L/kg wet-wt at 25 deg. c which does not exceed the bioconcentration threshold of 2000. Therefore it is concluded that test chemical 4-methoxy-2-methyl-N-phenylaniline is non bioaccumulative in food chain.

Transport and distribution:

Adsorption/desorption:

The Soil Adsorption Coefficient i.e. Koc value of test chemical 4-methoxy-2-methyl-N-phenylaniline (CAS No. 41317-15-1) was estimated using EPI suite KOCWIN Program (v2.00) as 866.3 L/kg (log Koc= 2.9377) by means of MCI method at 25 deg. C.  This log Koc value indicates that test chemical 4-methoxy-2-methyl-N-phenylaniline has moderate sorption to soil and therefore test chemical has slow migration potential to ground water.

Additional information

Biodegradation:

Biodegradation in water:

Predicted data for the target compound 4-methoxy-2-methyl-N-phenylaniline (CAS no. 41317 -15 -1)and supporting weight of evidence studies for its structurally similar read across substance were reviewed for the biodegradation end point which are summarized as below:

 

In first predicted data study the biodegradability of test chemical 4-methoxy-2-methyl-N-phenylaniline (CAS no. 41317 -15 -1) was estimated by using OECD QSAR tool box v3.3 by considering eight closest read across chemicals with log Kow as primary descriptor. Percent degradability of test chemical 4-methoxy-2-methyl-N-phenylaniline was estimated to be 0.550 % by considering BOD as parameter and microorganisms as inoculum in 28 days. On the basis of percent degradability value it is concluded that this test chemical is not readily biodegradable.

 

Next predicted data study was done by using estimation Programs Interface Suite (EPI suite, 2017) to estimate the biodegradation potential of the test compound 4-methoxy-2-methyl-N-phenylaniline (CAS no. 41317 -15 -1) 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 Biowin 1-7, respectively) of the BIOWIN v4.10 software. The results indicate that chemical 4-methoxy-2-methyl-N-phenylanilineis expected to be not readily biodegradable.

 

Further to support the above studies of target chemical experimental study have been conducted for read across chemical from authoritative database J- CHECK (2017)in this study Biodegradation experiment was conducted for 28 days for evaluating the percentage biodegradability of read across substance 2-(2-Methylpropoxy) naphthalene. Concentration of inoculum i.e, sludge used was 30 mg/l and initial test substance conc. used in the study was 100 mg/l, respectively. The percentage degradation of test substance was determined to be 1 and 19% by BOD and HPLC parameters respectively in 28 days. Thus, based on percentage degradation, 2-(2-Methylpropoxy)naphthalene is considered to be not readily biodegradable in nature.

 

One more experimental study have been conducted to support predicted data of target chemical same source as mentioned above (J-CHECK, 2017) in this study read across chemical Benzenamine, N-phenyl- (CAS no.122 -39 -4) was subjected to biodegradation test by taking activated sludge as inoculums at 30 mg/L concentration. Biodegradation was analysed by using three parameter namely BOD, GC and UV Vis . The initial concentration of read across chemical was 100 mg/L. The read across chemical Benzenamine, N-phenyl- showed 0 % biodegradability by BOD parameter 6.5 % by GC parameter and 5.0 % by UV vis parameter by using activated sludge as inoculumin 14 days. On the basis of percent biodegradability it is concluded that read acros chemical Benzenamine, N-phenyl- is not readily biodegradable.

 

On the basis of results of above mentioned studies for target chemical 4-methoxy-2-methyl-N-phenylaniline (CAS no. 41317 -15 -1) (from OECD QSAR tool box v3.3 and EPI suite) and supporting weight of evidence study (from J Check, 2017). It is concluded that the test chemical 4-methoxy-2-methyl-N-phenylaniline can be expected to be not readily biodegradable.

Biodegradation in water and sediments:

Estimation Programs Interface (EPI Suite, 2017) prediction model was run to predict the half-life in water and sediment for the test compound 4-methoxy-2-methyl-N-phenylaniline (CAS No. 41317 -15 -1). If released in to the environment, 35 % 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 37.5 days (900 hrs). The half-life (37.5 days estimated by EPI suite) indicates that the chemical is not persistent in water and the exposure risk to aquatic animals is low whereas the half-life period of test chemical 4-methoxy-2-methyl-N-phenylaniline in sediment is estimated to be 337.5 days (8100 hrs). However, as the percentage release of test chemical into the sediment is less than 1 % (i.e, reported as 0.0835 %), indicates that test chemical 4-methoxy-2-methyl-N-phenylaniline is not persistent in sediment.

Biodegradation in soil:

The half-life period of test chemical 4-methoxy-2-methyl-N-phenylaniline (CAS No. 41317 -15 -1) 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, 81.2 % of the chemical will partition into soil according to the Mackay fugacity model level III. The half-life period of test chemical 4-methoxy-2-methyl-N-phenylaniline in soil is estimated to be 75.0 days (1800 hrs). Based on this half-life value of test chemical 4-methoxy-2-methyl-N-phenylaniline, it is concluded that the chemical is not persistent in the soil environment and the exposure risk to soil dwelling animals is low.

Bioaccumulation:

Bioaccumulation: aquatic/sediments:

Various predicted data for the target compound 4-methoxy-2-methyl-N-phenylaniline (CAS No. 41317-15-1)and supporting weight of evidence study for its read across chemical were reviewed for the bioaccumulation end point and their results are summarized as below:

The first predicted data study was done by using BCFBAF Program (v3.00) model of Estimation Program Interface (EPI suite,2017) in this study the estimated bio concentration factor (BCF) for 4-methoxy-2-methyl-N-phenylaniline (CAS No. 41317-15-1) is 179.1 L/kg wet-wt at 25 deg. c which does not exceed the bioconcentration threshold of 2000.

 

Next predicted data study was done by using Bio-concentration Factor (v12.1.0.50374) module of(ACD (Advanced Chemistry Development)/I-Lab predictive module, 2017) module in this study the Bio-concentration Factor at range pH 0-4  of the chemical 4-methoxy-2-methyl-N-phenylaniline estimated to be  in range 10 - 217  dimensionless and at pH range 5-14 BCF value estimated was 218 dimensionless. These values indicate that the chemical 4-methoxy-2-methyl-N-phenylanilineis non-bioaccumulative in aquatic organisms as this value does not exceed 2000 criteria.

Another prediction was done by using SciFinder database of American Chemical Society (ACS, 2017) in this study the Bioconcentration factor (BCF) of test substance 4-methoxy-2-methyl-N-phenylanilineat temperature 25 °C was estimated to be in range 131-417 dimensionless  at pH range 1-4 and at pH range 5-10 the BCF value estimated was 418 dimensionless in aquatic organism. These BCF values at pH 1-10 and temperature 25 °C suggests that the test chemical 4-methoxy-2-methyl-N-phenylaniline is non bioaccumulative in aquatic organisms.

 

Similarly another prediction was done by using Chemspider data base of Royal Society of Chemistry (RCS, 2017) in this study the Bioconcentration factor (BCF) of test substance 4-methoxy-2-methyl-N-phenylaniline at pH 5.5  was estimated to be 330.93 dimensionless and pH 7.4 was estimated to be 330.95 dimensionless. This BCF value suggests that the test chemical 4-methoxy-2-methyl-N-phenylaniline is non bioaccumulative in aquatic organisms.

 

Last predicted data study was done from CompTox Chemistry Dashboard using OPERA (OPEn (quantitative) structure-activity Relationship Application)  V1.02 model in which calculation based on PaDEL descriptors (calculate molecular descriptors and fingerprints of chemical) the bioaccumulation i.e BCF for test substance 4-methoxy-2-methyl-N-phenylaniline(CAS no.41317 -15 -1) was estimated to be 190 dimensionless . The predicted BCF result was based on the 5 OECD principles.

 

Further to support the results of predicted data of target chemical experimental studies have been conducted for structurally similar read across chemicals from authoritative database JCHECK , 2017.

 In first experimental study the Bioaccumulation experiment was conducted for 6 weeks for determination the bioconcentration factor (BCF) of read across chemical 4-(anilino)phenol (CAS no 122-37-2) on test organism Cyprinus carpio. Nominal concentrations used were 1st Concentration area: 0.1 mg/L (w/v), 2nd Concentration area: 0.01 mg/L (w/v) and Range finding study was carried out on Rice fish (Oryzias latipes) LC50 (48h) 0.714 mg/L. The vehicle used in this study was HCO-40, olive oil. The lipid content of fish at start of exposure was 4.2%.

Thus according to flow through Fish Test the BCF value for read across chemical 4-(anilino)phenol was observed to be to be in range 3.3-9.2 dimensionless at dose concentration 0.1 mg/L and 14-49 dimensionless at dose concentration 0.01 mg/L on test organism Cyprinus carpio during 6 weeks period.

These BCF values indicate that the read across substance 4-(anilino)phenol is not bioaccumulative in fish and food chain as these values are far less than 2000 criteria.

 

In another study bioaccumulation experiment was conducted for 8 weeks for determination the bioconcentration factor (BCF) of read across chemical 2-(2-methylpropoxy) naphthalene(CAS no 2173-57-1) on test organism Cyprinus carpio.

Recovery ratio : Test water : 1st concentration area : 87.3 %, 2nd concentration area : 90.0 %, Fish : 91.0 %, - Limit of detection : Test water 1st concentration area : 2.4 ng/mL, 2nd concentration area : 0.23 ng/mL, Fish : 69 ng/g. Nominal concentrations used in the study are 1st Concentration area: 50 mg/L, 2nd Concentration area: 5.0 mg/L and Range finding study was carried out on Rice fish (Oryzias latipes) LC50 (48h) 11.1 mg/L. The lipid content at start of exposure was 4.1 %. The vehicle used in this study was HCO-40 and 1 st Concentration area was 500 microg/L, 2nd Concentration area was 50 microg/L. Thus according to static Fish Test the bioconcentration factor (BCF) for read across chemical 2-(2-methylpropoxy) naphthalene was determined according static fish test. The BCF value was observed to 431-1180 L/kg at dose concentration 0.5 mg/L and 398-873 L/kg at dose concentration 0.05 mg/L on test organism Cyprinus carpio during 8 weeks period. On the basis of BCF values it is concluded that read across chemical 2-(2-methylpropoxy)naphthalene is non bioaccumulativein fish and food chain as these values are far less than 2000 criteria.

 

On the basis of above results for target chemical 4-methoxy-2-methyl-N-phenylaniline (CAS No. 41317-15-1) (from EPI suite, ACD labs, Sci Finder database, Chemspider and CompTox Chemistry Dashboard 2017) and for its read across chemicals (From J CHECK) it can be concluded that the BCF value of test substance 4-methoxy-2-methyl-N-phenylaniline (CAS No. 41317-15-1) ranges from 179.1 to 418 dimensionless which does not exceed the bioconcentration threshold of 2000, indicating that the chemical 4-methoxy-2-methyl-N-phenylaniline (CAS No. 41317-15-1)is expected to be non-bioaccumulative in the food chain.

Transport and distribution:

Adsorption/desorption:

Various predicted data for the target compound of 4-methoxy-2-methyl-N-phenylaniline (CAS No. 41317-15-1)and supporting weight of evidence study for its read across chemical were reviewed for the Adsorption end point and their results are summarized as below.

In first predicted data study the Soil Adsorption Coefficient i.e. Koc value of test chemical 4-methoxy-2-methyl-N-phenylaniline (CAS No. 41317-15-1) was estimated using Estimation Program Interface (EPI suite , 2017) KOCWIN Program (v2.00) as 866.3 L/kg (log Koc= 2.9377) by means of MCI method at 25 deg. C.  This log Koc value indicates that test chemical 4-methoxy-2-methyl-N-phenylaniline has moderate sorption to soil and therefore test chemical has slow migration potential to ground water.

 

In next predicted data study the Soil Adsorption Coefficient i.e Koc value of test substance 4-methoxy-2-methyl-N-phenylaniline (CAS no.41317 -15 -1) was estimated using Adsorption Coefficient module (v12.1.0.50374) program of (ACD (Advanced Chemistry Development)/I-Lab predictive module, 2017)as Koc 1641 dimensionless (log Koc= 3.2151) at pH range 6 -14. This log Koc value indicates that the test substance 4-methoxy-2-methyl-N-phenylanilinehas a moderate sorption to soil and therefore has slow migration potential to groundwater.

Another predicted data study was done by using Sci Finder database of American Chemical Society (ACS, 2017) in this study the soil adsorption co-efficient i.e., Koc value of test chemical 4-methoxy-2-methyl-N-phenylaniline was estimated to be 2620 dimensionless (log Koc = 3.4183) at pH range 5-10 at temperature 25 deg.c. this value suggests that this test chemical has strong sorption to soil.

 

Similarly another prediction was done by using Chemspider-ACD/Phy chem suite of Royal Society of Chemistry (RCS, 2017) in this study the soil adsorption co-efficient i.e., Koc value of test substance 4-methoxy-2-methyl-N-phenylaniline (CAS no. 41317 -15 -1) was estimated to be 2214.23 dimensionless (log Koc= 3.3452) at pH 5.5 and 2214.39 dimensionless (Log Koc= 3.3452) at pH 7.4 and temperature 25 deg.C These Koc values at different pH indicates that the chemical 4-methoxy-2-methyl-N-phenylaniline has moderate sorption to soil and sediments and therefore test chemical has slow migration potential to ground water.

 

Last predicted data study was done from CompTox Chemistry Dashboard using OPERA (OPEn (quantitative) structure-activity Relationship Application)  V1.02 model in which calculation based on PaDEL descriptors (calculate molecular descriptors and fingerprints of chemical)  the adsorption coefficient i.e KOC for test substance4-methoxy-2-methyl-N-phenylaniline(CAS no. 41317 -15 -1) was estimated to be 1510 L/kg (log Koc = 3.1789) .The predicted KOC result based on the 5 OECD principles. Thus based on the result it is concluded that the test substance4-methoxy-2-methyl-N-phenylanilinehas a moderate sorption to soil and sediment and therefore has slow migration potential to ground water.

 

Further to support the results of predicted data of target chemical experimental study have been conducted for structurally similar read across chemicals from UERL lab 2017 in this study the adsorption coefficient Koc in soil and in sewage sludge of read across chemical Ethyl 2-naphthyl ether (CAS No.93 -18 -5) was determined by the Reverse Phase High Performance Liquid Chromatographic method according to OECD Guideline No. 121 for testing of Chemicals. The solutions of the read across substance and reference substances were prepared in appropriate solvents. The read across chemical solution was prepared by accurately weighing 4 mg of test item and diluted with ACN up to10ml. Thus, the read across solution concentration was 400 mg/l. The pH of read across substance was 6.23. Each of the reference substance and test substance were analysed by HPLC at 210 nm. After equilibration of the HPLC system, Urea was injected first, the reference substances were injected in duplicate, followed by the test chemical solution in duplicate. Reference substances were injected again after read across sample, no change in retention time of reference substances was observed. Retention time tR were measured, averaged and the decimal logarithms of the capacity factors k were calculated. The graph was plotted between log Koc versus log k (Annex - 2). The linear regression parameter of the relationship log Koc vs. log k were also calculated from the data obtained with calibration samples and therewith, log Koc of the read across substance was determined from its measured capacity factor. The reference substances were chosen according to estimated Koc range of the test substance and generalized calibration graph was prepared or chosen according to functionally similarity with the read across substance and calibration graph prepared. The reference substances were Xylene, Ethylbenzene, Toluene, Naphthalene, phenanthrene having Koc value ranging from 2.369 to 4.09 The Log Koc value was determined to be 3.490 ± 0.003at 25°C. This log Koc value indicates that the substance Ethyl 2-naphthyl ether has a strong sorption to soil and sediment and therefore has negligible to slow migration potential to ground water.

 

On the basis of above results for target chemical 4-methoxy-2-methyl-N-phenylaniline (CAS No. 41317-15-1)(from EPI suite, ACD labs, Sci Finder database, Comptox chemistry dashboard and Chemspider 2017) and for its read across chemical (From UERL lab) it can be concluded that the log Koc value of test chemical 4-methoxy-2-methyl-N-phenylaniline ranges from 2.9377 to 3.4183 indicating that the chemical 4-methoxy-2-methyl-N-phenylaniline (CAS No. 41317-15-1) has moderate to strong sorption to soil and sediment and therefore it has slow migration potential to ground water.