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Hydrolysis

On the basis of the experimental studies of the structurally and functionally similar read across chemical and applying the weight of evidence approach, the hydrolysis half-life value of the test chemical (+)-Neomenthol can be expected to be 7.3 yrs and 270 days at pH 7 and 8, respectively with a hydrolysis rate constant of 0.03 L/mol-sec. Thus, based on this half-life value, it can be concluded that the test chemical (+)-Neomenthol is not hydrolysable.

Biodegradation in water

Estimation Programs Interface Suite (2018) was run to predict the biodegradation potential of the test compound  (+)-Neomenthol (CAS no. 2216 -52 -6) 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 chemical (+)-Neomenthol is expected to be not readily biodegradable.

Biodegradation in water and sediment

Estimation Programs Interface (2018) prediction model was run to predict the half-life in water and sediment for the test compound (+)-Neomenthol (CAS No. 2216 -52 -6). If released in to the environment, 27.8% of the chemical will partition into water according to the Mackay fugacity model level III and the half-life period of (+)-Neomenthol 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 (+)-Neomenthol 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 0.15%), indicates that (+)-Neomenthol is not persistent in sediment.

 

Biodegradation in soil

The half-life period of (+)-Neomenthol (CAS No. 2216 -52 -6) in soil was estimated using Level III Fugacity Model by EPI Suite version 4.1 estimation database (2018). If released into the environment, 70.9% of the chemical will partition into soil according to the Mackay fugacity model level III. The half-life period of (+)-Neomenthol in soil is estimated to be 30 days (720 hrs). Based on this half-life value of (+)-Neomenthol, 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: aquatic / sediment

BCFBAF model (v3.01) of Estimation Programs Interface was used to predict the bioconcentration factor (BCF) of test chemical (+)-Neomenthol (CAS No. 2216 -52 -6). The bioconcentration factor (BCF) of (+)-Neomenthol was estimated to be 59.12 L/kg whole body w.w (at 25 deg C) which does not exceed the bio concentration threshold of 2000, indicating that the chemical (+)-Neomenthol is not expected to bioaccumulate in the food chain.

Adsorption / desorption

KOCWIN model (v2.00) of Estimation Programs Interface was used to predict the soil adsorption coefficient i.e Koc value of test chemical (+)-Neomenthol (CAS No. 2216 -52 -6). The soil adsorption coefficient i.e Koc value of (+)-Neomenthol was estimated to be 88.15 L/kg (log Koc=1.9452) by means of MCI method (at 25 deg C). This Koc value indicates that the substance (+)-Neomenthol has a low sorption to soil and sediment and therefore have moderate migration potential to ground water.

Additional information

Hydrolysis

Data available for the structurally and functionally similar read across chemicals has been reviewed to determine the half-life of the test chemical (+)-Neomenthol (CAS no. 2216 -52 -6). The studies are as mentioned below:

The half-life and base catalyzed second order hydrolysis rate constant was determined using a structure estimation method of the test chemical. The second order hydrolysis rate constant was determined to be 0.03L/mol-sec with a corresponding half-lives of 7.3 yrs and 270 days at pH 7 and 8, respectively. Based on the half-life values, it is concluded that the test chemical is not hydrolysable.

In an another study, the half-life of the test chemical was determined in water. Although the half-life value of test chemical was not known, but it was noted that the test chemical does not react with water and the only functional other than carbon-carbon and carbon-hydrogen bonds is the hydroxyl group, which does not hydrolyze. Thus, based on this, test substance was reported to be hydrolytically stable and thus can be considered to be not hydrolysable.

On the basis of the experimental studies of the structurally and functionally similar read across chemical and applying the weight of evidence approach, the hydrolysis half-life value of the test chemical (+)-Neomenthol can be expected to be 7.3 yrs and 270 days at pH 7 and 8, respectively with a hydrolysis rate constant of 0.03 L/mol-sec.Thus, based on this half-life value, it can be concluded that the test chemical (+)-Neomenthol is not hydrolysable.

Biodegradation in water

Predicted data for the target compound (+)-Neomenthol (CAS No. 2216-52-6) and various supporting weight of evidence studies for its structurally and functionally similar read across substance were reviewed for the biodegradation end point which are summarized as below:

 

In a prediction using the Estimation Programs Interface Suite (2018), the biodegradation potential of the test compound (+)-Neomenthol (CAS no. 2216 -52 -6) in the presence of mixed populations of environmental microorganisms was estimated. 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 chemical (+)-Neomenthol is expected to be not readily biodegradable.

 

In a supporting weight of evidence study from peer reviewed journal (Harder et al, 1995),biodegradation experiment was conducted for 21 days for evaluating the percentage biodegradability of test substance by using Pseudomonas citronellolis DSM 50332 as an inoculum.Test inoculum Pseudomonas citronellolis DSM 50332 was obtained from the Deutsche Sammlung von Mikroorganismen, Braunschweig, Germany. Initial test substance conc. used for the study was 308.5 mg/l (2 mM). Anoxic media was used for the study. The medium contained (per liter of distilled water) 1 g of NaCl, 0.1 g of MgCl2.7H2O, 0.04 g of CaCl2, 0.5 g of KCl, 0.125 g of NH4Cl, 0.2 g of Na2SO4, 0.4 g of KH2PO4, 1.2 g of K2HPO4, and 0.85 g of NaNO3. After autoclaving, 2 ml of a non-chelated trace element mixture, 2 ml of a selenite-tungstate solution, vitamins, and 20 ml of a 1 M NaHCO3 solution were added, and the pH was adjusted to 7.0.Enrichment cultures were inoculated with activated sludge obtained from a local wastewater plant (Lintel, Osterholz-Scharmbeck, Germany). Enrichment cultures were maintained and test chemical consumption was measured in 21-ml glass tubes containing 15 ml of anoxic medium (10 mM nitrate, 0.5 ml 2,2,4,4,6,8,8-heptamethylnonane (HMN), and 2 mM test chemical). The overpressure due to gas formation was measured with a syringe, and 10 mM nitrate was added when the electron acceptor was depleted. The gas formed was analyzed by gas chromatography. Bacterial growth was observed daily and required between 3 - 22 days. Monoterpene contents were determined with a gas chromatograph equipped with flame ionization detectors and connected to a digital data-analyzing system. The amounts of monoterpene dissimilated were calculated from the differences in monoterpene contents between the pasteurized controls and the grown enrichment cultures. A model MAT ITS 40 ion trap system was used for the gas chromatography-mass spectrometry analysis. Microbial growth on test chemical was observed within 10 days to 3 weeks. The disappearance of test chemical in mud-free enrichment cultures was quantified. The percentage degradation of test substance was determined to be 1.13% degradation by Test mat. analysis parameter in 21 days. Thus, based on percentage degradation, test chemical is considered to be not readily biodegradable in nature.

 

Another biodegradation study was conducted for 28 days for evaluating the percentage biodegradability of test substance (HSDB, 2017). Activated sludge was used as a test inoculum for the study. The percentage degradation of test substance was determined to be 0% by BOD parameter in 28 days. Thus, based on percentage degradation, is considered to be not readily biodegradable in nature.

 

For the test chemical from authoritative database (J-CHECK and HSDB, 2017),biodegradation study was conducted for 28 days for evaluating the percentage biodegradability of test substance. The study was performed according to OECD Guideline 301 C (Ready Biodegradability: Modified MITI Test (I) under aerobic conditions. Activated sludge was used as a test inoculums for the study. 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 0% and 5% by BOD, TOC removal and GC parameter in 28 days. Thus, based on percentage degradation, is considered to be not readily biodegradable in nature.

 

On the basis of above results for target chemical (+)-Neomenthol (from modelling database, 2018), it can be concluded that the test substance (+)-Neomenthol can be expected to be not readily biodegradable in nature.

Biodegradation in water and sediment

Estimation Programs Interface (2018) prediction model was run to predict the half-life in water and sediment for the test compound (+)-Neomenthol (CAS No. 2216 -52 -6). If released in to the environment, 27.8% of the chemical will partition into water according to the Mackay fugacity model level III and the half-life period of (+)-Neomenthol 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 (+)-Neomenthol 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 0.15%), indicates that (+)-Neomenthol is not persistent in sediment.

 

Biodegradation in soil

The half-life period of (+)-Neomenthol (CAS No. 2216 -52 -6) in soil was estimated using Level III Fugacity Model by EPI Suite version 4.1 estimation database (2018). If released into the environment, 70.9% of the chemical will partition into soil according to the Mackay fugacity model level III. The half-life period of (+)-Neomenthol in soil is estimated to be 30 days (720 hrs). Based on this half-life value of (+)-Neomenthol, 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 (+)-Neomenthol can be considered to be not readily biodegradable in nature.

Bioaccumulation: aquatic / sediment

Various predicted data for the target compound (+)-Neomenthol (CAS No. 2216-52-6) and supporting weight of evidence studies for its structurally similar read across substance were reviewed for the bioaccumulation end point which are summarized as below:

 

In a prediction done using the BCFBAF Program of Estimation Programs Interface was used to predict the bioconcentration factor (BCF) of test chemical (+)-Neomenthol (CAS No. 2216 -52 -6). The bioconcentration factor (BCF) of (+)-Neomenthol was estimated to be 59.12 L/kg whole body w.w (at 25 deg C).

 

In an another prediction done by using Bio-concentration Factor module, Bio-concentration Factor of the test substance (+)-Neomenthol (CAS no. 2216 -52 -6) was estimated to be 160, 159 and 153 dimensionless at pH range 1-12, 13 and 14, respectively.

 

Another predicted data was estimated using SciFinder database (American Chemical Society (ACS), 2017) for predicting the bioconcentration factor (BCF) of test chemical (+)-Neomenthol (CAS No. 2216 -52 -6). The bioconcentration factor (BCF) of (+)-Neomenthol was estimated to be 164 at pH range 1-10 respectively (at 25 deg C).

 

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 (+)-Neomenthol was estimated to be 23.7 dimensionless . The predicted BCF result based on the 5 OECD principles. Thus based on the result it is concluded that the test substance (+)-Neomenthol is non-bioaccumulative in nature.

 

In a supporting weight of evidence study from authoritative databases (2018) for the test item,bioaccumulation experiment was conducted for estimating the BCF (bioaccumulation factor) value of test chemical. The bioaccumulation factor (BCF) value was calculated using a water solubility and a regression derived equation. The BCF (bioaccumulation factor) value of test chemical was estimated to be 15 dimensionless.

 

For the test chemical,bioaccumulation study was conducted on test organism Cyprinus carpio for 6 weeks for evaluating the bioconcentration factor (BCF value) of test chemical (authoritative databases, 2017). The study was performed according to other guideline "Bioaccumulation test of a chemical substance in fish or shellfish" provided in "the Notice on the Test Method Concerning New Chemical Substances", respectively. Cyprinus carpio was used as a test organism for the study. Test chemical nominal conc. used for the study were 0.2 mg/land 0.02 mg/l, respectively. Test chemical solution was prepared in HCO-40. Analytical method involve the recovery ratio: Test water : 1st concentration area : 89.4 %, 2nd concentration area : 90.0 %, Fish : 74.6 %, - Limit of detection : Test water : 1st concentration area : 7.8 ng/mL, 2nd concentration area : 0.78 ng/mL, Fish : 63 ng/g. Range finding study involve theLC50(48h) 26 mg/L on Rice fish (Oryzias latipes). Lipid content of the test organism Cyprinus carpio was determined to be 4.7%. The bioconcentration factor (BCF value) of test substance on Cyprinus carpio was determined to be 0.5-15 L/Kg at a conc. of 0.2 mg/l and 4.6-11 L/Kg at a conc. of 0.02 mg/l, respectively.

 

On the basis of above results for target chemical (+)-Neomenthol (from modelling databases,2017), it can be concluded that the BCF value of test substance (+)-Neomenthol ranges from 23.7 –164 which does not exceed the bioconcentration threshold of 2000, indicating that the chemical (+)-Neomenthol is not expected to bioaccumulate in the food chain.

Adsorption / desorption

Various predicted data for the target compound (+)-Neomenthol (CAS No. 2216-52-6) and supporting weight of evidence study for its structurally similar read across substance were reviewed for the adsorption end point which are summarized as below:

 

In aprediction done using theKOCWIN Program(v2.00) of Estimation Programs Interface was used to predict the soil adsorption coefficient i.e Koc value of test chemical (+)-Neomenthol (CAS No. 2216 -52 -6). The soil adsorption coefficient i.e Koc value of (+)-Neomenthol was estimated to be 88.15 L/kg (log Koc=1.9452) by means of MCI method (at 25 deg C). This Koc value indicates that the substance (+)-Neomenthol has a low sorption to soil and sediment and therefore have moderate migration potential to ground water.

 

The Soil Adsorption Coefficient i.e Koc value of test substance (+)-Neomenthol (CAS no. 2216 -52 -6) was estimated using Adsorption Coefficient module program as Koc 1318, 1317, 1311 and 1255  at pH range 1-11, 12, 13 and 14, respectively (logKoc = 3.1 ± 1.0) (ACD (Advanced Chemistry Development)/I-Lab predictive module, 2017)). The log Koc value indicates that the test substance (+)-Neomenthol has a moderate sorption to soil and therefore have slow migration potential to groundwater.

 

Additional soil adsorption coefficient i.e Koc value of test chemicaltest chemical (+)-Neomenthol (CAS No. 2216 -52 -6)was estimated using the SciFinder database (2017).The soil adsorption coefficient i.e Koc value of (+)-Neomenthol was estimated to be 1340 at pH range 1-10, respectively (logKoc = 3.127) (at 25 deg C). The logKoc value indicates that the substance (+)-Neomenthol has a moderate sorption to soil and sediment and therefore have slow migration potential to ground water.

 

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 substance (+)-Neomenthol was estimated to be 307 L/kg (log Koc = 2.487).The predicted KOC result based on the 5 OECD principles. This Koc value indicates that the substance (+)-Neomenthol has a moderate sorption to soil and sediment and therefore have slow migration potential to ground water.

 

In a supporting weight of evidence study from experimental study report (2018) for the test item,the adsorption coefficient Koc in soil and in sewage sludge of test chemical 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 test substance and reference substances were prepared in appropriate solvents. A test item solution was prepared by accurately pipetting 4 microliter of test item and diluted with Methanol up to 10 ml. Thus, the test solution concentration was 356 mg/l. The pH of test substance was 6.2. 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 test 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 test substance was determined from its measured capacity factor. The reference substances were chosen according to functional similarity with the test substance and calibration graph prepared. The reference substances were Benzamide, Nitrobenzene, 4- Nitrobenzamide, N,N-dimethylbenzamide, N-methylbenzamide, 2 - nitrophenol having Koc value ranging from 1.239 to 2.47. The Log Koc value of test chemical was determined to be 1.805 dimensionless at 25°C. This log Koc value indicates that the substance has a low sorption to soil and sediment and therefore has moderate migration potential to ground water.

 

For the test chemical,adsorption study was conducted for estimating the adsorption coefficient (Koc) value of test chemical (HSDB, 2017). The adsorption coefficient (Koc) value was calculated using a structure estimation method based on molecular connectivity indices. The adsorption coefficient (Koc) value of test substance was estimated to be 88 dimensionless (Log Koc = 1.944). This Koc value indicates that the substance has a low sorption to soil and sediment and therefore have moderate migration potential to ground water.

 

On the basis of above overall results for target chemical (+)-Neomenthol (from modelling databases,2017), it can be concluded that the Koc value of test substance (+)-Neomenthol was estimated to be ranges from 307 to 1340, respectively, indicating that the test chemical (+)-Neomenthol has a low to moderate sorption to soil and sediment and therefore have moderate to slow migration potential to ground water.