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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 seven closest read across substances, toxicity on daphnia magna was predicted for 2-[(E)-2-(4-chloro-2-nitrophenyl)diazen-1-yl]-N-(4-ethoxyphenyl)-3-oxobutanamide (52320-66-8). Based on the immobility of test organism the EC50 value was estimated to be 0.133 mg/l when 2-[(E)-2-(4-chloro-2-nitrophenyl)diazen-1 -yl]-N-(4-ethoxyphenyl)-3-oxobutanamide exposed to daphnia magna for 48 hrs. Based on this value it can be concluded that the substance 2-[(E)-2-(4-chloro-2-nitrophenyl)diazen-1-yl]-N-(4-ethoxyphenyl)-3-oxobutanamideis considered to be toxic to aquatic environment and can classified as aquatic acute 1 as well as chronic 1 category as per the criteria mentioned in CLP regulation.      

Toxicity to aquatic algae and cyanobacteria:

Based on the prediction done using the OECD QSAR toolbox version 3.4 with log kow as the primary descriptor and considering the six closest read across substances, toxicity on Pseudokirchneriella subcapitata (previous names: Raphidocelis subcapitata, Selenastrum capricornutum) was predicted for 2-[(E)-2-(4-chloro-2-nitrophenyl) diazen-1-yl]-N- (4-ethoxyphenyl)-3-oxobutanamide (52320-66-8). Based on the growth rate inhibition, the EC50 value was estimated to be 0.28 mg/l when 2-[(E)-2-(4-chloro-2-nitrophenyl)diazen-1-yl]-N- (4-ethoxyphenyl)-3-oxobutanamide exposed to Pseudokirchneriella subcapitata for 72 hrs. Based on this value it can be concluded that the substance 2 -[(E)-2-(4-chloro-2-nitrophenyl) diazen-1-yl]-N-(4-ethoxyphenyl)-3-oxobutanamide (52320-66-8) is considered to be toxic to aquatic environment and classified as aquatic acute 1 as well as chronic 1 category as per the criteria mentioned in CLP regulation.  

 

Additional information

Summarized result of toxicity of 2-[(E)-2-(4-chloro-2-nitrophenyl)diazen-1-yl]-N-(4-ethoxyphenyl)-3-oxobutanamide (52320-66-8) on the growth and other activity of aquatic invertebrates, algae and cyanobacteria by considering the data for target as well as RA chemical which was selected on the basis of structural similarity and log Kow as the primary descriptor are as follows:   

Short term toxicity to aquatic invertebrates:

Various predicted data for the target compound 2-[(E)-2-(4-chloro-2-nitrophenyl)diazen-1-yl]-N-(4-ethoxyphenyl)-3-oxobutanamide (52320-66-8) and experimental studies for supporting weight of evidence studies for its closest read across substance with log Kow as the primary descriptor and on the basis of structural and functional similarity were reviewed for the toxicity on the invertebrates end point which are summarized as below: 

In a prediction done by SSS (2017), Based on the prediction done using the OECD QSAR toolbox version 3.3 with log kow as the primary descriptor and considering the seven closest read across substances, toxicity on daphnia magna was predicted for 2-[(E)-2-(4-chloro-2-nitrophenyl)diazen-1-yl]-N-(4-ethoxyphenyl)-3-oxobutanamide (52320-66-8). Based on the immobility of test organism the EC50 value was estimated to be 0.133 mg/l when 2-[(E)-2-(4-chloro-2-nitrophenyl)diazen-1 -yl]-N-(4-ethoxyphenyl)-3-oxobutanamide exposed to daphnia magna for 48 hrs. Based on this value it can be concluded that the substance 2-[(E)-2-(4-chloro-2-nitrophenyl)diazen-1-yl]-N-(4-ethoxyphenyl)-3-oxobutanamideis considered to be toxic to aquatic environment and can classified as aquatic acute 1 as well as chronic 1 category as per the criteria mentioned in CLP regulation.      

 

First predicted study was supported by the structurally and functionally similar read across chemical (103-90-2) from Environmental Toxicology and Chemistry 2006. Aim of the study was to assess the effect of chemical 4' Hydroxyacetanilidon (Acetaminophen) the growth of freshwater daphnia magna for the exposure period of 48 hrs. Testing was conducted according to the published Environment Canada biological test method. Test was conducted at 32, 10, 3.2, 1.0, and 0.1 ug/L, as well as a clean-water control. Chemical was analytically monitoring by HPLC and separation done by reverse-phase column using binary gradient elution at a constant temperature of 25°C. The neutral drugs were analyzed individually by full-scan MS in positive-ion mode, and quantitative analyses were performed using selective-ion monitoring mode. Dilutions of the stock sample solution were prepared in culture/dilution water and allowed to equilibrate. Portions of each concentration were then transferred to two glass beakers, one for testing and one for water-quality measurements. D. magna neonates younger than 24 hrs of age was used as a test organism. 10 daphnia magna were used in each test vessel. Water-quality measurements of each test vessel, including temperature, pH, and dissolved oxygen was measured after 48 hrs. Based on the immobility of daphnia magna due to the direct contact with the chemical 4' Hydroxyacetanilidon (Acetaminophen), the lethal concentration was > 0.032 mg/l. Thus based on the LC50, it can be concluded that the chemical was toxic and can be consider to be classified as aquatic acute 1 as well as chronic 1 category as per the CLP classification criteria.

 

 

Similarly in a supporting weight of evidence study for read across chemical (50-65-7) from ECOTOX database 2018 study was conducted. Study was conducted to determine the short term toxicity of 5-Chloro-N-(2-chloro-4-nitrophenyl)-2-hydroxybenzamide (Niclosamide) to water flea daphnia magna. Test was conducted under the static system for the exposure period of 24 hrs. EC50 was measured on the basis of 50 % immobility of daphnia magna. Based on the immobility of freshwater water flea daphnia magna due to chemical 5-Chloro-N-(2-chloro-4-nitrophenyl)-2-hydroxybenzamide (Niclosamide) for the total exposure period of 24 hrs, the EC50 was 0.16 mg/l. Thus based on the EC50 chemical was consider as toxic and can be consider to be classified as aquatic acute1/chronic 1 category as per the CLP classification criteria.

 

On the basis of above results for target chemical 2-[(E)-2-(4-chloro-2-nitrophenyl)diazen-1-yl]-N-(4-ethoxyphenyl)-3-oxobutanamide (52320-66-8) (from OECD QSAR toolbox version 3.4) and for its read across substance from Environmental Toxicology and Chemistry 2006 and ECOTOX database it can be concluded that the test substance 2-[(E)-2-(4-chloro-2-nitrophenyl)diazen-1-yl]-N-(4-ethoxyphenyl)-3-oxobutanamide (52320-66-8) is toxic and can be consider to be classified as aquatic acute1/chronic 1 category as per the CLP classification criteria.

 

 

Toxicity to aquatic algae and cyanobacteria:

 

Various predicted data for the target compound 2-[(E)-2-(4-chloro-2-nitrophenyl) diazen-1-yl]-N-(4-ethoxyphenyl)-3-oxobutanamide (52320-66-8) and experimental studies for supporting weight of evidence studies for its closest read across substance with log Kow as the primary descriptor and on the basis of structural and functional similarity were reviewed for the toxicity on the algal end point which are summarized as below: 

In a prediction done by SSS (2017), based on the prediction done using the OECD QSAR toolbox version 3.4 with log kow as the primary descriptor and considering the six closest read across substances, toxicity on Pseudokirchneriella subcapitata (previous names: Raphidocelis subcapitata, Selenastrum capricornutum) was predicted for 2-[(E)-2-(4-chloro-2-nitrophenyl) diazen-1-yl]-N- (4-ethoxyphenyl)-3-oxobutanamide (52320-66-8). Based on the growth rate inhibition, the EC50 value was estimated to be 0.28 mg/l when 2-[(E)-2-(4-chloro-2-nitrophenyl)diazen-1-yl]-N- (4-ethoxyphenyl)-3-oxobutanamide exposed to Pseudokirchneriella subcapitata for 72 hrs. Based on this value it can be concluded that the substance 2 -[(E)-2-(4-chloro-2-nitrophenyl) diazen-1-yl]-N-(4-ethoxyphenyl)-3-oxobutanamide (52320-66-8) is considered to be toxic to aquatic environment and classified as aquatic acute 1 as well as chronic 1 category as per the criteria mentioned in CLP regulation.  

 

First predicted study was supported by the structurally and functionally similar read across chemical (103-90-2) from Environmental Toxicology and Chemistry 2006. Aim of the study was to assess the effect of chemical 4' Hydroxyacetanilidon (Acetaminophen) on the growth of freshwater alga Selenastrum capricornutum for the exposure period of 72 hrs. Testing was conducted according to the published Environment Canada biological test method. Test chemical was analytically monitored by HPLC method and also separation done by reverse-phase column using binary gradient elution at a constant temperature of 25°C. The neutral drugs were analyzed individually by full-scan MS in positive-ion mode, and quantitative analyses were performed using selective-ion monitoring mode. Algae exposed for chemical for 72 hrs and effect was observed based on the inhibition of algal cell inhibition. Based on the inhibition of the number of living algal cells and biomass of Pseudokirchneriella subcapitala (S. capricornutum) the IC25 was >0.032 mg/l. Thus based on the IC25, it can be concluded that the chemical was toxic and can be consider to be classified as aquatic acute 1 as well as chronic 1 category as per the CLP classification criteria.

 

Similarly in a supporting weight of evidence study for read across chemical (50-65-7) from ECOTOX database 2018 study was conducted. Study was conducted to determine the short term toxicity of 5-Chloro-N-(2-chloro-4-nitrophenyl)-2-hydroxybenzamide to algae Scenedesmus subspicatus (Green Algae). Test was conducted under the static system for the total exposure period of 48 hrs. Based on the biomass inhibition of green algae (Scenedesmus subspicatus) due to the chemical 5-Chloro-N-(2-chloro-4-nitrophenyl)-2- hydroxybenzamide exposure for 48 hrs, the EC50 was 0.96 mg/l. Thus based on the EC50 chemical was consider as toxic and can be consider to be classified as aquatic acute1/chronic 1 category as per the CLP classification criteria.

 

On the basis of above results for target chemical 2-[(E)-2-(4-chloro-2-nitrophenyl)diazen-1-yl]-N-(4-ethoxyphenyl)-3-oxobutanamide (52320-66-8) (from OECD QSAR toolbox version 3.4) and for its read across substance from Environmental Toxicology and Chemistry 2006 and ECOTOX database it can be concluded that the test substance 2-[(E)-2-(4-chloro-2- nitrophenyl)diazen-1-yl]-N-(4-ethoxyphenyl)-3-oxobutanamide (52320-66-8) is toxic and can be consider to be classified as aquatic acute1/chronic 1 category as per the CLP classification criteria.