2-chloro-4-nitrophenol

Short-term toxicity to aquatic invertebrates

Link to relevant study record(s)

Reference

Endpoint:

short-term toxicity to aquatic invertebrates

Type of information:

(Q)SAR

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

results derived from a (Q)SAR model, with limited documentation / justification, but validity of model and reliability of prediction considered adequate based on a generally acknowledged source

Justification for type of information:

Data is from OECD QSAR toolbox version 3.3 and the QMRF report has been attached.

Qualifier:

according to guideline

Guideline:

other: Estimated data

Principles of method if other than guideline:

Prediction was done using the OECD QSAR toolbox version 3.3.

GLP compliance:

not specified

Specific details on test material used for the study:

- IUPAC Name: 2-chloro-4-nitrophenol
- Common Name: Nitrofungin
- Mol. formula: C6H4ClNO3
- Molecular Weight: 173.555 g/mol
- Smiles: c1(cc(c(O)cc1)Cl)[N+](=O)[O-]
- InChI: 1S/C6H4ClNO3/c7-5-3-4(8(10)11)1-2-6(5)9/h1-3,9H
- Substance type: Organic
- Physical state: Solid

Analytical monitoring:

not specified

Vehicle:

not specified

Test organisms (species):

Daphnia magna

Details on test organisms:

- Common name: Water flea

Test type:

static

Water media type:

freshwater

Total exposure duration:

48 h

Remarks on exposure duration:

No data available

Post exposure observation period:

No data available

Reference substance (positive control):

not specified

Key result

Duration:

48 h

Dose descriptor:

EC50

Effect conc.:

144.953 mg/L

Nominal / measured:

estimated

Conc. based on:

test mat.

Basis for effect:

mobility

Remarks on result:

other: Nontoxic

Details on results:

50% Immobility was observed at the concentration of 144.9530 mg/l.

Reported statistics and error estimates:

No data available

The prediction was based on dataset comprised from the following descriptors: EC50
Estimation method: Takes average value from the 5 nearest neighbours
Domain  logical expression:Result: In Domain

(((((((((((((((((((("a" or "b" or "c" or "d" or "e" or "f" )  and "g" )  and "h" )  and ("i" and ( not "j") )  )  and ("k" and ( not "l") )  )  and ("m" and ( not "n") )  )  and ("o" and ( not "p") )  )  and ("q" and ( not "r") )  )  and ("s" and ( not "t") )  )  and ("u" and ( not "v") )  )  and ("w" and ( not "x") )  )  and ("y" and ( not "z") )  )  and ("aa" and ( not "ab") )  )  and ("ac" and ( not "ad") )  )  and ("ae" and ( not "af") )  )  and ("ag" and ( not "ah") )  )  and ("ai" and ( not "aj") )  )  and "ak" )  and ("al" and ( not "am") )  )  and ("an" and "ao" )  )

Domain logical expression index: "a"

Referential boundary: The target chemical should be classified as Phenols (Acute toxicity) by US-EPA New Chemical Categories

Domain logical expression index: "b"

Referential boundary: The target chemical should be classified as Radical AND Radical >> Radical mechanism via ROS formation (indirect) AND Radical >> Radical mechanism via ROS formation (indirect) >> Nitroarenes with Other Active Groups AND Radical >> Radical mechanism via ROS formation (indirect) >> Nitrophenols, Nitrophenyl Ethers and Nitrobenzoic Acids AND SN1 AND SN1 >> Nucleophilic attack after diazonium or carbenium ion formation AND SN1 >> Nucleophilic attack after diazonium or carbenium ion formation >> Nitroarenes with Other Active Groups AND SN1 >> Nucleophilic attack after reduction and nitrenium ion formation AND SN1 >> Nucleophilic attack after reduction and nitrenium ion formation >> Nitroarenes with Other Active Groups AND SN1 >> Nucleophilic attack after reduction and nitrenium ion formation >> Nitrophenols, Nitrophenyl Ethers and Nitrobenzoic Acids AND SN2 AND SN2 >> SN2 attack on activated carbon Csp3 or Csp2 AND SN2 >> SN2 attack on activated carbon Csp3 or Csp2 >> Nitroarenes with Other Active Groups by DNA binding by OASIS v.1.3

Domain logical expression index: "c"

Referential boundary: The target chemical should be classified as SN1 AND SN1 >> Nitrenium Ion formation AND SN1 >> Nitrenium Ion formation >> Aromatic nitro by DNA binding by OECD

Domain logical expression index: "d"

Referential boundary: The target chemical should be classified as Moderate binder, OH grooup by Estrogen Receptor Binding

Domain logical expression index: "e"

Referential boundary: The target chemical should be classified as Phenols and Anilines by Acute aquatic toxicity MOA by OASIS

Domain logical expression index: "f"

Referential boundary: The target chemical should be classified as Phenols by Aquatic toxicity classification by ECOSAR

Domain logical expression index: "g"

Referential boundary: The target chemical should be classified as Class 3 (unspecific reactivity) by Acute aquatic toxicity classification by Verhaar (Modified) ONLY

Domain logical expression index: "h"

Referential boundary: The target chemical should be classified as Phenols and Anilines by Acute aquatic toxicity MOA by OASIS ONLY

Domain logical expression index: "i"

Referential boundary: The target chemical should be classified as Phenols by Aquatic toxicity classification by ECOSAR

Domain logical expression index: "j"

Referential boundary: The target chemical should be classified as Anilines (Unhindered) by Aquatic toxicity classification by ECOSAR

Domain logical expression index: "k"

Referential boundary: The target chemical should be classified as Phenols by Aquatic toxicity classification by ECOSAR

Domain logical expression index: "l"

Referential boundary: The target chemical should be classified as Halo Epoxides OR Hydrazines by Aquatic toxicity classification by ECOSAR

Domain logical expression index: "m"

Referential boundary: The target chemical should be classified as Phenols by Aquatic toxicity classification by ECOSAR

Domain logical expression index: "n"

Referential boundary: The target chemical should be classified as Hydroquinones OR Methacrylates OR Phenol Amines by Aquatic toxicity classification by ECOSAR

Domain logical expression index: "o"

Referential boundary: The target chemical should be classified as Phenols by Aquatic toxicity classification by ECOSAR

Domain logical expression index: "p"

Referential boundary: The target chemical should be classified as Phenols, Poly OR Polynitrobenzenes OR Vinyl/Allyl Esters by Aquatic toxicity classification by ECOSAR

Domain logical expression index: "q"

Referential boundary: The target chemical should be classified as Aromatic alcohol  [-OH] AND Aromatic chloride   [-CL] AND Aromatic nitro  [-NO2] AND Aromatic-H AND Benzene by Bioaccumulation - metabolism alerts

Domain logical expression index: "r"

Referential boundary: The target chemical should be classified as Alkyl substituent on aromatic ring by Bioaccumulation - metabolism alerts

Domain logical expression index: "s"

Referential boundary: The target chemical should be classified as Aromatic alcohol  [-OH] AND Aromatic chloride   [-CL] AND Aromatic nitro  [-NO2] AND Aromatic-H AND Benzene by Bioaccumulation - metabolism alerts

Domain logical expression index: "t"

Referential boundary: The target chemical should be classified as Aldehyde   [-CHO] by Bioaccumulation - metabolism alerts

Domain logical expression index: "u"

Referential boundary: The target chemical should be classified as Aromatic alcohol  [-OH] AND Aromatic chloride   [-CL] AND Aromatic nitro  [-NO2] AND Aromatic-H AND Benzene by Bioaccumulation - metabolism alerts

Domain logical expression index: "v"

Referential boundary: The target chemical should be classified as Aliphatic ether  [C-O-C] by Bioaccumulation - metabolism alerts

Domain logical expression index: "w"

Referential boundary: The target chemical should be classified as Aromatic alcohol  [-OH] AND Aromatic chloride   [-CL] AND Aromatic nitro  [-NO2] AND Aromatic-H AND Benzene by Bioaccumulation - metabolism alerts

Domain logical expression index: "x"

Referential boundary: The target chemical should be classified as Biphenyl by Bioaccumulation - metabolism alerts

Domain logical expression index: "y"

Referential boundary: The target chemical should be classified as Aromatic alcohol  [-OH] AND Aromatic chloride   [-CL] AND Aromatic nitro  [-NO2] AND Aromatic-H AND Benzene by Bioaccumulation - metabolism alerts

Domain logical expression index: "z"

Referential boundary: The target chemical should be classified as -C=CH  [alkenyl hydrogen] OR Carbon with 4 single bonds & no hydrogens by Bioaccumulation - metabolism alerts

Domain logical expression index: "aa"

Referential boundary: The target chemical should be classified as Aromatic alcohol  [-OH] AND Aromatic chloride   [-CL] AND Aromatic nitro  [-NO2] AND Aromatic-H AND Benzene by Bioaccumulation - metabolism alerts

Domain logical expression index: "ab"

Referential boundary: The target chemical should be classified as -CH2-  [linear] by Bioaccumulation - metabolism alerts

Domain logical expression index: "ac"

Referential boundary: The target chemical should be classified as Aromatic alcohol  [-OH] AND Aromatic chloride   [-CL] AND Aromatic nitro  [-NO2] AND Aromatic-H AND Benzene by Bioaccumulation - metabolism alerts

Domain logical expression index: "ad"

Referential boundary: The target chemical should be classified as Cyanide / Nitriles   [-C#N] by Bioaccumulation - metabolism alerts

Domain logical expression index: "ae"

Referential boundary: The target chemical should be classified as Aromatic alcohol  [-OH] AND Aromatic chloride   [-CL] AND Aromatic nitro  [-NO2] AND Aromatic-H AND Benzene by Bioaccumulation - metabolism alerts

Domain logical expression index: "af"

Referential boundary: The target chemical should be classified as Unsubstituted phenyl group (C6H5-) OR Urea   [N-C(=O)-N] by Bioaccumulation - metabolism alerts

Domain logical expression index: "ag"

Referential boundary: The target chemical should be classified as Aromatic alcohol  [-OH] AND Aromatic chloride   [-CL] AND Aromatic nitro  [-NO2] AND Aromatic-H AND Benzene by Bioaccumulation - metabolism alerts

Domain logical expression index: "ah"

Referential boundary: The target chemical should be classified as Ester   [-C(=O)-O-C] by Bioaccumulation - metabolism alerts

Domain logical expression index: "ai"

Referential boundary: The target chemical should be classified as Group 14 - Carbon C AND Group 15 - Nitrogen N AND Group 16 - Oxygen O AND Group 17 - Halogens Cl AND Group 17 - Halogens F,Cl,Br,I,At by Chemical elements

Domain logical expression index: "aj"

Referential boundary: The target chemical should be classified as Group 17 - Halogens Br by Chemical elements

Domain logical expression index: "ak"

Similarity boundary:Target: Oc1ccc(N(=O)=O)cc1Cl
Threshold=30%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization

Domain logical expression index: "al"

Referential boundary: The target chemical should be classified as Aromatic compound AND Aryl chloride AND Aryl halide AND Halogen derivative AND Hydroxy compound AND Nitro compound AND Phenol by Organic functional groups, Norbert Haider (checkmol)

Domain logical expression index: "am"

Referential boundary: The target chemical should be classified as Alkylarylether by Organic functional groups, Norbert Haider (checkmol)

Domain logical expression index: "an"

Parametric boundary:The target chemical should have a value of log Kow which is >= 1.19

Domain logical expression index: "ao"

Parametric boundary:The target chemical should have a value of log Kow which is <= 4.12

Validity criteria fulfilled:

not specified

Conclusions:

The EC50 value was estimated to be 144.95 mg/l when 2-chloro-4-nitrophenol exposed to Daphnia magna for 48hrs.

Executive summary:

 Based on the prediction done using the OECD QSAR toolbox version 3.3 with log kow as the primary descriptor and considering the five closest read across substances, toxicity on Daphnia magna was predicted for 2-chloro-4-nitrophenol (619-08-9). The EC50 value was estimated to be 144.95 mg/l when 2-chloro- 4-nitrophenol exposed to Daphnia magna for 48hrs.

Description of key information

Based on the prediction done using the OECD QSAR toolbox version 3.3 with log kow as the primary descriptor and considering the five closest read across substances, toxicity on Daphnia magna was predicted for 2-chloro-4-nitrophenol (619-08-9). The EC50 value was estimated to be 144.95 mg/l when 2-chloro- 4-nitrophenol exposed to Daphnia magna for 48hrs.

Key value for chemical safety assessment

Fresh water invertebrates

Fresh water invertebrates

Effect concentration:

144.95 mg/L

Additional information

Based on the various experimental data and prediction data for the target chemical as well as RA chemical which was selected on the basis of structure similarity study have been reviewed to determine the toxic nature of 2-chloro-4-nitrophenol (619-08-9). on the mobility of daphnia magna. The studies are as mentioned below:

In the first predicted weight of evidence report for the 2-chloro-4-nitrophenol (619-08-9) from SSS (QSAR, 2017) toxicity study was carried out. Based on the prediction done using the OECD QSAR toolbox version 3.3 with log kow as the primary descriptor and considering the five closest read across substances, toxicity on Daphnia magna was predicted for 2-chloro-4-nitrophenol (619-08-9). The EC50 value was estimated to be 144.95 mg/l when 2-chloro- 4-nitrophenol exposed to Daphnia magna for 48hrs.

Similarly in the second weight of evidence study for the read across chemical 3 – Nitrobenzene sulfonic acid (127-68-4) (from ABITEC lab, 2016) Determination of the inhibition of the mobility of daphnids was carried out with the substance 3 – Nitrobenzene sulfonic acid according to OECD Guideline 202. The test substance was tested at the limit concentration 100 mg/l. Effects on immobilisation were observed for 48 hours. Based on the % inhibition of daphnia magna, due to the exposure of chemical 3 – Nitrobenzene sulfonic acid, the IC8 was 100 mg/l. This value indicates that the substance is likely to be non-hazardous to aquatic invertebrates and cannot be classified as toxic as per the CLP criteria.

 

Third study conducted for the RA chemical 4-hydroxy benzoic acid ((99-96-7) from journal of Water Research, 1989) Short term toxicity to Daphnia sp. study was carried out for 48 hrs. Acute Daphnia test was performed according to DIN 38412, Part II. The study was based on the effects of the test compound 4-hydroxy benzoic acid (CAS no. 99-96-7) on Daphnia magna in a static fresh water system at a temperature of 20°C and pH of 8.0±0.2, respectively. Test organism used for the study was 6-24 hr old and no feeding to the organism Daphnia magna was done during the test period. Exact concentration of test chemical used for the study was not known, but the concentration steps of the test solution were selected so as to give 3-4 EC values in a range between EC0 and EC100, of which at least one value was below and one above EC50.The test vessels were two 50 ml beakers and for volatile or strongly smelling substances, two 50 ml bottles with ground-glass stoppers each with 20 ml useful capacity. Two parallel preparations were made for each concentration step. Loading amounted to one test animal per 2 ml test medium as ten 6-24 h old daphnids were placed in each test and control vessel, i.e: 20 animals per concentration step. After a test period of 24 h and again after 48 h, the no. of animals in the control and test solutions that could still swim were counted. After 48 h it was also possible to measure the pH value in order to determine whether the hydrogen ion concentrations were in an acceptable range for the daphnids or whether the result had to be considered as having been influenced by a change in pH during the course of the test. Furthermore, the oxygen content was determined at the end of the test period in order to ensure that it had not fallen below a minimum oxygen concentration of 2 mg/l. The test was considered as valid when fewer than 10% of the animals in the control solutions were unable to swim, when the pH value was not below 7.0 and the O2 value was not below 4.0 m/l. Based on effect on mobility of the test organism Daphnia magna, the 24 hr EC0, EC50 and EC100 value was determined to be 181, 104 and 286 mg/l, respectively and 48 hr EC0, EC50 and EC100 value was determined to be 173, 19 and 204 mg/l, respectively. Thus, based on the 24 and 48 h EC50 value, it can be concluded that the substance 4-hydroxy benzoic acid can be considered as non-toxic to aquatic organisms and thus can be considered to be not classified as per the CLP classification criteria.

 

Similarly fourth study was conducted for the same read across chemical 4-hydroxy benzoic acid (99-96-7), j-check 2017. Determination of short term toxicity of 4-Hydroxybenzoic Acid on the mobility of daphnia magna for 48hrs. Study was performed according to the OECD Guideline 202 (Daphnia sp. Acute Immobilisation Test. Static method was used for the measurement of toxicity. After the exposure of 48hrs, 50% immobilization was observed at 140 mg/l. Based on the immobilization of daphnia magna due to the exposure of chemical 4-Hydroxybenzoic acid, the EC50 was 140 mg/l. Thus based on the EC50 value it can be concluded that the chemical was nontoxic and can be consider to be not classified as toxic as per the CLP classification criteria.

 

In the fifth weight of evidence study for the read across chemical (26787-78-0) Ecotoxicology 2008, short term toxicity study of chemical was studied. Study was conducted to determine the toxicity of chemical (2S,5R,6R)-6-[(2R)-2-amino-2-(4-hydroxyphenyl) acetamido]-3,3-dimethyl-7-oxo-4-thia-1-azabicyclo [3.2.0]heptane-2-carboxylic acid (Amoxicillin) on the mobility of daphnia magna and Moina macrocopa. Effect concentration of chemical on Freshwater daphnia and Moina was tested by static system. Different measured concentration was directly prepared in dilution water. Organisms fed daily during the test. All water parameters measured daily. Immobilization was employed as an endpoint and considered to happen if no movement was detected for 15 s after gentle shaking of the test vehicle. Immobilization measured by probit analysis. Based on the immobilization of daphnia magna and Moina macrocopa due to the exposure of chemical (2S,5R,6R)-6-[(2R)-2-amino-2-(4-hydroxyphenyl)acetamido]- 3,3-dimethyl-7-oxo-4-thia-1-azabicyclo [3.2.0]heptane-2-carboxylic acid ; (Amoxicillin) for 24 and 48hr, the EC50 was >1000 mg/l for both the organism. Thus it is concluded that the chemical was nontoxic and can be consider to be not classified as toxic to aquatic environment as per the CLP classification criteria.

 

Similarly in the sixth weight of evidence study for another read across chemical (88-89-1) ECOTOX, 2017, Determination of short term toxicity of chemical 2,4,6-trinitrophenol on the growth and mobility of aquatic invertebrate daphnia magna. 6-24hrs newborn Daphnis were used in the study. Static method was performed in which daphnia exposed for 24hrs with the chemical 2,4,6-trinitrophenol. After the exposure of chemical for 24hrs, immobilization was observed at the concentration at which 50% daphnia killed. Based on the immobilization of daphnia magna due to the exposure of chemical for 24hrs, the EC50 was 104 mg/l. Based on the EC50 value, it can be concluded that the chemical was nontoxic and can be consider to be not classified as toxic as per the CLP classification criteria.

 

Thus based on the above data sources for target chemical 2-chloro-4-nitrophenol (619-08-9) from various experimental studies and predicted studies from QSAR, ABITEC report, journal of Water Research, 1989, Ecotoxicology 2008, j-check and ECOTOX, it was summarized that the chemical was nontoxic and can be consider to be not classified as toxic as per the CLP classification criteria.