5-methyl-3-phenylisoxazole-4-carbonyl chloride

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 valid (Q)SAR model and falling into its applicability domain, with limited documentation / justification

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:

- Name of test material : 5-methyl-3-phenylisoxazole-4-carbonyl chloride
- Molecular formula : C11H8ClNO2
- Molecular weight : 221.642 g/mole
- Smiles notation : c1(ccccc1)c1c(C(=O)Cl)c(on1)C
- InChl : 1S/C11H8ClNO2/c1-7-9(11(12)14)10(13-15-7)8-5-3-2-4-6-8/h2-6H,1H3
- 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

Hardness:

154.5 mg/L CaCO3

Test temperature:

22 degree C

pH:

7.7

Nominal and measured concentrations:

Estimated data

Reference substance (positive control):

not specified

Key result

Duration:

48 h

Dose descriptor:

EC50

Effect conc.:

168.204 mg/L

Nominal / measured:

estimated

Conc. based on:

test mat.

Basis for effect:

other: Intoxication

Remarks on result:

other: Nontoxic

Details on results:

No data available

Results with reference substance (positive control):

No data available

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" )  and ("e" and ( not "f") )  )  and "g" )  and "h" )  and "i" )  and ("j" and "k" )  )

Domain logical expression index: "a"

Referential boundary: The target chemical should be classified as Acyl halide OR Allyl OR Aryl OR Ketoxime derivatives OR Oxazole/ Izoxazole by Organic Functional groups ONLY

Domain logical expression index: "b"

Referential boundary: The target chemical should be classified as Acyl halide OR Allyl OR Aryl OR Ketoxime derivatives OR Overlapping groups OR Oxazole/ Izoxazole by Organic Functional groups (nested) ONLY

Domain logical expression index: "c"

Referential boundary: The target chemical should be classified as Aliphatic Carbon [CH] OR Aliphatic Carbon [-CH2-] OR Aliphatic Carbon [-CH3] OR Aromatic Carbon [C] OR Aromatic Nitrogen, five-member ring OR Aromatic Oxygen OR Carbonyl, olefinic attach [-C(=O)-] OR Chlorine, olefinic attach [-Cl] OR Miscellaneous sulfide (=S) or oxide (=O) OR Olefinic carbon [=CH- or =C<] OR Oxygen, nitrogen attach [-O-] by Organic functional groups (US EPA) ONLY

Domain logical expression index: "d"

Referential boundary: The target chemical should be classified as Aromatic compound OR Carbonic acid derivative OR Halogen derivative by Organic functional groups, Norbert Haider (checkmol) ONLY

Domain logical expression index: "e"

Referential boundary: The target chemical should be classified as Not possible to classify according to these rules by DPRA Cysteine peptide depletion

Domain logical expression index: "f"

Referential boundary: The target chemical should be classified as High reactive OR High reactive >> alpha,beta-carbonyl compounds with polarized multiple bonds OR High reactive >> Isothiazolinone derivatives OR Moderate reactive OR Moderate reactive >> Activated 1,3,5-triazine derivatives OR Moderate reactive >> Phenyl substituted cinnamaldehydes by DPRA Cysteine peptide depletion

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 Reactive unspecified by Acute aquatic toxicity MOA by OASIS ONLY

Domain logical expression index: "i"

Referential boundary: The target chemical should be classified as Bioavailable by Lipinski Rule Oasis ONLY

Domain logical expression index: "j"

Parametric boundary:The target chemical should have a value of log Kow which is >= 0.0468

Domain logical expression index: "k"

Parametric boundary:The target chemical should have a value of log Kow which is <= 3.27

Validity criteria fulfilled:

not specified

Conclusions:

Based on the intoxication of daphnia magna due to the exposure of 5-methyl-3-phenylisoxazole-4-carbonyl chloride, the EC50 was 168.204 mg/l.

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 seven closest read across substances, toxicity on Daphnia magna was predicted for 5-methyl-3-phenylisoxazole-4-carbonyl chloride (16883-16-2). The EC50 value was estimated to be 168.204mg/l when 5-methyl-3-phenylisoxazole-4-carbonyl chloride 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 seven closest read across substances, toxicity on Daphnia magna was predicted for 5-methyl-3-phenylisoxazole-4-carbonyl chloride (16883-16-2). The EC50 value was estimated to be 168.204 mg/l when 5-methyl-3 -phenylisoxazole-4-carbonyl chloride exposed to Daphnia magna for 48hrs.

Key value for chemical safety assessment

Fresh water invertebrates

Fresh water invertebrates

Effect concentration:

168.204 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 5-methyl-3-phenyl-1,2-oxazole-4-carbonyl chloride (16883-16-2) on the mobility of daphnia magna. The studies are as mentioned below:

In the first predicted weight of evidence report for the 5-methyl-3-phenyl-1,2-oxazole-4-carbonyl chloride (16883-16-2) 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 seven closest read across substances, toxicity on Daphnia magna was predicted for 5-methyl-3-phenylisoxazole-4-carbonyl chloride (16883-16-2). The EC50 value was estimated to be 168.204mg/l when 5-methyl-3-phenylisoxazole-4-carbonyl chloride exposed to Daphnia magna for 48hrs.

 

Similarly in the second predicted weight of evidence study 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 109.828 mg/l for 5-methyl-3- phenylisoxazole -4-carbonyl chloride in 48 hrs. (16883 -16 -2) . Based on this value it can be concluded that the substance 5-methyl-3-phenylisoxazole-4-carbonyl chloride is considered to be not toxic to aquatic environment and cannot be classified as toxic as per the criteria mentioned in CLP regulation.

 

Similarly in the third weight of evidence study for the read across chemical (98-85-1) (from ABITEC lab, 2016), Determination of the inhibition of the mobility of daphnids was carried out with the substance 1-phenylethanol according to OECD Guideline 202. The test substance was tested at the limit concentration 100 mg/L. After the exposure of 48hrs to daphnia magna only 4% Daphnia were immobilised at the end of the test. Based on the mortality of daphnia magna due to the exposure of chemical 1-phenylethanol, the inhibitory concentration was 100 mg/l at which only 4% inhibition was observed. Thus median effective concentration (EC50) for the test substance, 1-phenylethanol, in Daphnia magna was determined to be > 100 mg/L for 50% immobilisation effects. This value indicates that the substance is not likely to be hazardous to aquatic invertebrates as per the CLP criteria.

 

Fourth study conducted for the read across chemical (2E)-but-2-enedioic acid (110-17-8) (J. Water Pollut. Control Fed.52 (8), 1980). Short term toxicity was performed in aquatic invertebrates to determine the ability of wet oxidation to achieve maximum destruction of the material. The acute static toxicity test was performed in Daphnia magna for 48 hrs according to the “Methods for Acute Toxicity Tests with Fish, macro invertebrates and Amphibians.” The test was performed in 154.5 mg/l CaCO3hardness condition in 7.7 pH and at 22 degree C temperature. After the exposure, the EC 50 value in 48 hrs for aquatic invertebrates for (2E)-but-2-enedioic acid (110-17-8) was determined to be 212 mg/l. Based on the value, the (2E)-but-2-enedioic acid (110-17-8) was considered to be non-toxic to aquatic invertebrates and can be considered to be not classified as per the CLP regulations.

 

 

In the fifth weight of evidence study for the read across chemical (110-16-7) J. Water Pollut. Control Fed 1980. Short term toxicity was performed in aquatic invertebrates to determine the ability of wet oxidation to achieve maximum destruction of the material. The acute static toxicity test was performed in Daphnia magna for 48 hrs according to the “Methods for Acute Toxicity Tests with Fish, macro invertebrates and Amphibians.” The test was performed in 154.5 mg/l CaCO3hardness condition in 7.7 pH and at 22 degree C temperature. After the experiment, the EC 50 value in 48 hrs for aquatic invertebrates for (2Z)-but-2-enedioic acid (110-16-7) was determined to be 316.2 mg/l. Based on the value, the (2Z)-but-2-enedioic acid (110-16-7) was considered to be non-toxic to aquatic invertebrates and can be considered to be not classified as per the CLP regulations.

 

Thus based on the above data sources for target chemical 5-methyl-3-phenyl-1,2-oxazole-4-carbonyl chloride (16883-16-2) from various experimental studies and predicted studies from QSAR, ABITEC report, journal of Water Research, 1980, it was summarized that the chemical was nontoxic and can be consider to be not classified as toxic as per the CLP classification criteria.