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Short-term toxicity to fish

Using the EPI Suite ECOSAR version 1.10, the short term toxicity on fish was predicted for test substance 4 -nitrobenzene-1,3 -diamine (CAS: 5131 -58 -8). On the basis of effects observed in a static freshwater system, the lethal concentration LC50 value for the substance is estimated to be 2515.31 mg/l for fish for 96 hr duration. Based on this value, it can be concluded that the test chemical 4 -nitrobenzene-1,3 -diamine can be considered as non-toxic to fish at environmentally relevant concentrations and can be considered to be not-classified as per the CLP classification criteria.

Short term toxicity on aquatic invertebrates

Using the OECD QSAR toolbox version 3.4 with log kow as the primary descriptor and considering the five closest read across substances, the short term toxicity on aquatic invertebrates was predicted for 4-nitrobenzene-1,3-diamine (5131-58-8). EC50 value was estimated to be 167.65 mg/l for Daphnia magna for 48 hrs duration. Based on the value, the 4-nitrobenzene-1,3-diamine (5131-58-8) was considered to not toxic to aquatic invertebrates and can be considered to be not classified as per the CLP regulations.

Toxicity to aquatic algae and cyanobacteria

Using the OECD QSAR toolbox version 3.4 with log kow as the primary descriptor and considering the five closest read across substances, the short term toxicity on aquatic algae and cyanobacteria was predicted for target substance 4-nitrobenzene-1,3-diamine (CAS no. 5131 -58 -8) (2017). EC50 value was estimated to be 154.21 mg/l for Desmodesmus subspicatus for 72 h duration. Based on this value it can be concluded that the substance 4 -nitrobenzene-1,3 -diamine is considered to be non-toxic to aquatic environment and can be considered to be not classified as per the CLP classification criteria.

Additional information

Short-term toxicity to fish

Three studies including predicted data from validated model and experimental studies from authorative database for short term fish toxicity endpoint of target chemical 4-nitrobenzene-1, 3-diamine (Cas no. 5131-58-8) with relevant read across chemical which is structurally similar to target were summarized as follows:

First prediction using ECOSAR v.1.11 model which indicate the short term toxicity on fish for test substance 4 -nitrobenzene-1,3 -diamine (CAS: 5131 -58 -8). On the basis of effects observed in a static freshwater system, the lethal concentration LC50 value for the substance is estimated to be 2515.31 mg/l for fish for 96 hr duration. Based on this value, it can be concluded that the test chemical 4 -nitrobenzene-1,3 -diamine can be considered as non-toxic to fish at environmentally relevant concentrations and can be considered to be not-classified as per the CLP classification criteria.

Above aquatic classification supported by experiment data of read across chemical 4-nitroaniline (Cas no. 100-01-6) suggest in Acute fish toxicity data the lethal concentration (LC50) determine of test substance 4-nitroaniline for exposure period of 96 hrs. on the basis of mortality effects. Test organism was used asPimephales promelas (Fathead Minnow)in static freshwater with test temp.22 deg.C and dissolved oxygen > 40 %,pH 7.2 to 7.6,Hardness 40 to 48 mg/L CaCO3 and ALKALINITY:30 to 35 mg/L CaCO3 with conductivity 120-160 UMHOS/CM.The Lethal concentration to 50% of test organisms(LC50) on the basis of mortality effect was observed to be 101.8 mg/l for exposure period of 96 hrs.(Ecotox database by US EPA)

 Last study from same data source i.e Ecotox database for same read across chemical 4-nitroaniline (Cas no. 100-01-6) suggest the lethal concentration (LC50) determine of test substance 4-nitroaniline for exposure period of 96 hrs. on the basis of mortality effects. Test organism was used as Pimephales promelas (Fathead Minnow) of 32 days age with 20.3 MM length and 0.107 G weight in static freshwater with test temp.24.9deg.C and dissolved oxygen6.3 mg/l,pH7.5,Hardness48.3mg/L CaCO3 and ALKALINITY: 43.5mg/L CaCO3.The Lethal concentration to 50% of test organisms (LC50) on the basis of mortality effect was observed to be 125 mg/l for exposure period of 96 hrs with 95% confidence limit 110-142.

Thus all above available studies for short term fish toxicity give common conclusion as test chemical 4-nitrobenzene-1, 3-diamine (Cas no. 5131-58-8) was non hazardous to fish as per the CLP regulation since the lethal concentration (LC50) is in the range 101.8 -2515.31 mg/l.

Short term toxicity to aquatic invertebrates

Short term toxicity to aquatic invertebrates was summaries with two prediction study for 4-nitrobenzene-1,3-diamine (5131-58-8) and two experimental studies with functionally related read across are as follows.

Using the OECD QSAR toolbox version 3.4 with log kow as the primary descriptor and considering the five closest read across substances, the short term toxicity on aquatic invertebrates was predicted for4-nitrobenzene-1,3-diamine (5131-58-8). EC50 value was estimated to be 167.65 mg/l for Daphnia magna for 48 hrs duration.

Based on the prediction done by EPI suite, ECOSAR version 1.1, on the basis of similarity of structure to chemicals for which the aquatic toxicity has been previously measured by structure-activity relationships (SARs) program, the LC 50 value for short term toxicity to aquatic invertebrates was predicted. On the basis of this program, the LC 50 value for short term toxicity to aquatic invertebrates was predicted to be 1249.41 mg/l for 4-nitrobenzene-1,3-diamine in 48 hrs.

Study on read across was performed in 4-amino-N-pyrimidin-2-ylbenzenesulfonamide (68-35-9) from Chemosphere 40 (2000) 723-730 for Daphnia magna for 48 hrs according to the ISO (1989) and OECD (1996) standard procedures. The daphnia magna was culture in beaker with 20 neonates and maintained in specific test conditions. D. magna was cultured in a fully defined medium M7. Stock solutions were prepared by dissolving the appropriate amount of chemical in M7 medium. The pH of the stock solutions was adjusted to 7.5. The test was performed in static condition with 20 neonates less than 24 hrs. The test containers used were 100-ml glass beakers filled with 25 ml of test solution. The test was performed at 21±0.5°C underdark. The mobility of daphnia was observed at 24 and 48 hrs. After the experiment, the EC 50 value for 4-amino-N-pyrimidin-2-ylbenzenesulfonamide (68-35-9) for short term toxicity to aquatic invertebrates was determined to be 221 mg/l.

Study on another read across for Sulfadimethoxine (122-11-2) from Environment International 33 (2007) 370–375 was performed in Daphnia magna for 48 hrs at 199.2–296.8 mg/l concentration range. The test was performed in 6 liter of glass jar and stock solutions were prepared with dimethyl sulfoxide, from which test solutions were prepared with appropriate dilution medium for each test species. After the 48 hrs, the EC 50 value for Sulfadimethoxine (122-11-2) for short term toxicity to aquatic invertebrates was determined to be 248.0 mg/l for 48 hrs. Based on the value, the Sulfadimethoxine(122-11-2) was considered to not toxic to aquatic invertebrates and can be considered to be not classified as per the CLP regulations.

Based on the above predicted data for target and studies of functionally related read across chemicals it can be considered that all the weight of evidence studies supported the classifications and on the basis of that4-nitrobenzene-1,3-diamine (5131-58-8)was considered to be non-toxic to aquatic invertebrates and can be considered to be notclassified as per the CLP regulation.

Toxicity to aquatic algae and cyanobacteria

Various predicted data for the target chemical 4-nitrobenzene-1,3-diamine (CAS No. 5131 -58 -8) and weight of evidence study for its read across substance were reviewed to summarize the following information:

 

Short term toxicity on aquatic algae and cyanobacteria of target chemical4-nitrobenzene-1,3-diamine(CAS No. 5131-58-8) is predicted using the OECD QSAR toolbox version 3.4 with log kow as the primary descriptor and considering the five closest read across substances (2017). EC50 value was estimated to be 154.21 mg/l for Desmodesmus subspicatus for 72 h duration. Based on this value it can be concluded that the substance 4 -nitrobenzene-1,3 -diamine is considered to be non-toxic to aquatic environment and can be considered to be not classified as per the CLP classification criteria.

 

In another prediction done using the EPI Suite ECOSAR version 1.10 (EPI Suite, 2017), the short term toxicity on green algae was predicted for test substance 4-nitrobenzene-1,3-diamine(CAS No. 5131-58-8). On the basis of effects observed in a static freshwater system, the effect concentration EC50 value for the substance is estimated to be 535.358 mg/l for green algae for 96 hr duration. Based on this value, it can be concluded that the test chemical 4 -nitrobenzene-1,3 -diamine can be considered as non-toxic to green algae at environmentally relevant concentrations and can be considered to be not-classified as per the CLP classification criteria.

 

In a weight of evidencestudy from authoritative database (J-CHECK, 2016) of the read across chemical 3 -aminophenol (CAS no. 591 -27 -5),short term toxicity to green algae study was carried out for 72 hrs. The study was based on the effects of the read across compound 3 -aminophenol on green algae in a static fresh water system. Based on effect on growth rate of the test organism green algae, the 72 hr EC50 and NOEC value was determined to be 160 and 25 mg/l, and on the basis of biomass and area under the growth curve, the 72 hr EC50 and NOEC value was determined to be 62 and 25 mg/l, respectively. Thus, based on the EC50 value (160 mg/l), it can be concluded that the substance 3 -aminophenol can be considered as non-toxic to aquatic organisms and thus can be considered to be not classified as per the CLP classification criteria.

 

For the same read across chemical3 -aminophenol (CAS no. 591 -27 -5),short term toxicity to Chlorella pyrenoidosa (green algae) study was carried out for 96 hrs. The study was based on the effects of the read across compound 3 -aminophenol (CAS no. 591 -27 -5) on green algae in a static fresh water system at a temperature of 21°C along with a continuous light intensity of Philips TL 40W fluorescent white, 6400 lux, respectively. Test chemical conc. used for the study was 0.011 mg/l (10 × 10 -7M) (nominal concentrations). Chlorella pyrenoidosa was used as a test organism. Cells in log phase growth were used for all the experiments.Chlorella pyrenoidosa Chick was maintained in MBL medium at normal and 1/100 the normal Fe (i.e 6.5µg/Fe) and trace metal concentrations. Chlorella pyrenoidosa assay used 50 ml standard softwater (NaHCO3, 48 mg/l; CaSO4.2H2O, 30 mg/l; MgSO4, 30 mg/l; KCl, 2mg/l) with the addition of 1 ml of 0.5 M Herpes buffer (pH 7.0), 0.5 ml NaNO3 (2.1 g/l), and 0.5 ml of K2HPO4 (0.22 g/l), respectively. Cell density was measured initially and on three subsequent days by counting in a haemocytometer. A regression line was fitted to a plot of log (cell density/initial cell density) vs time, and cell division rate (µ) was determined from the slope or expressed as cell division/day (3.32µ). Based on effect on cell density of the test organism Chlorella pyrenoidosa, the 96 hr EC0 value was determined to be 0.011 mg/l, respectively. Thus, based on the EC50 value, it can be concluded that the substance 3 -aminophenol can be considered as toxic to aquatic organisms. Since the chemical is readily biodegradable in nature, chemical can be considered as non-toxic to aquatic organisms and thus can be considered to be not classified as per the CLP classification criteria.

 

In an another weight of evidence study for read across chemical 1,3 -diaminobenzene (CAS no. 108 -45 -2) (J-CHECK, 2017),short term toxicity to green algae study was carried out for 72 hrs. The study was based on the effects of the read across compound 1,3 -diaminobenzene on green algae in a static fresh water system. Based on effect on growth rate of the test organism green algae, the 72 hr EC50 and NOEC value was determined to be 30 and 10 mg/l, and on the AUG, the 72 hr EC50 and NOEC value was determined to be 18 and 5.6 mg/l, respectively. Thus, based on the EC50 value, it can be concluded that the substance 1,3 -diaminobenzene can be considered as toxic to aquatic organisms. Since the chemical is readily biodegradable in nature, chemical 1,3 -diaminobenzene can be considered as non-toxic to aquatic organisms and thus can be considered to be not classified as per the CLP classification criteria.

 

Thus, based on the overall reported results for target chemical4-nitrobenzene-1,3-diamine(OECD QSAR toolbox version 3.4 and EPI suite, 2017) and for its read across substance (from authoritative database J-CHECK and peer reviewed journal), it can be concluded that the test substance 4 -nitrobenzene-1,3 -diamine can be considered as non-toxic to aquatic environment and can be considered to be not classified as per the CLP classification criteria.