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

Endpoint summary

Description of key information

Skin irritation:

The dermal irritation potential of 5-methyl-3-phenylisoxazole-4-carbonyl chloride (CAS No: 16883-16-2) was estimated using OECD QSAR toolbox version 3.3 with logPow as the primary descriptor. The chemical 5-methyl-3-phenylisoxazole-4-carbonyl chloride (CAS No: 16883-16-2) was estimated to be irritating to the skin of New Zealand White rabbits. Based on the estimated result 5-methyl-3-phenylisoxazole-4-carbonyl chloride (CAS No: 16883-16-2) can be considered to be irritating to skin and can be classified under the category “Category 1”as per CLP regulation.

 

Eye irritation:

The ocular irritation potential of 5-methyl-3-phenylisoxazole-4-carbonyl chloride (CAS No: 16883-16-2) was estimated using OECD QSAR toolbox version 3.3 with logPow as the primary descriptor. The chemical 5-methyl-3-phenylisoxazole-4-carbonyl chloride (CAS No: 16883-16-2) was estimated to be not irritating into the eyes of New Zealand White rabbits. Based on the estimated result 5-methyl-3-phenylisoxazole-4-carbonyl chloride (CAS No: 16883-16-2) can be considered to be not irritating to eye and can be classified under the category ˋ Not Classified’ as per CLP regulation.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Endpoint:

skin irritation: in vivo

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 v3.4 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 OECD QSAR toolbox v3.4

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/mol
- 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

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

no data available

Type of coverage:

occlusive

Preparation of test site:

shaved

Vehicle:

unchanged (no vehicle)

Controls:

not specified

Amount / concentration applied:

0.5ml

Duration of treatment / exposure:

4 hours

Number of animals:

6

Details on study design:

no data available

Irritation parameter:

overall irritation score

Basis:

mean

Time point:

72 h

Reversibility:

not specified

Remarks on result:

positive indication of irritation

Irritant / corrosive response data:

Signs of irritation observed

Estimation method: Takes mode value from the 7 nearest neighbours
Domain  logical expression:Result: In Domain

((((((((((((((("a" or "b" or "c" or "d" )  and ("e" and ( not "f") )  )  and ("g" and ( not "h") )  )  and ("i" and ( not "j") )  )  and ("k" and ( not "l") )  )  and ("m" and ( not "n") )  )  and ("o" and ( not "p") )  )  and "q" )  and "r" )  and "s" )  and "t" )  and "u" )  and "v" )  and "w" )  and ("x" and "y" )  )

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 OR Unsaturated heterocyclic fragment 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 OR Unsaturated heterocyclic fragment 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 Non binder, without OH or NH2 group by Estrogen Receptor Binding

Domain logical expression index: "f"

Referential boundary: The target chemical should be classified as Non binder, impaired OH or NH2 group OR Non binder, MW>500 OR Non binder, non cyclic structure by Estrogen Receptor Binding

Domain logical expression index: "g"

Referential boundary: The target chemical should be classified as Inclusion rules not met by Skin irritation/corrosion Inclusion rules by BfR

Domain logical expression index: "h"

Referential boundary: The target chemical should be classified as Activated N-heterocycles OR Aldehydes OR Epoxides(=oxiranes) OR Esters including acrylic and methacrylic esters OR Ketones by Skin irritation/corrosion Inclusion rules by BfR

Domain logical expression index: "i"

Referential boundary: The target chemical should be classified as (!Undefined)Group All Lipid Solubility < 0.01 g/kg AND (!Undefined)Group CNHal Lipid Solubility < 4 g/kg AND (!Undefined)Group CNHal Lipid Solubility < 400 g/kg by Skin irritation/corrosion Exclusion rules by BfR

Domain logical expression index: "j"

Referential boundary: The target chemical should be classified as (!Undefined)Group CNS Surface Tension > 62 mN/m OR (N/A) OR Group All log Kow > 9 OR Group C Aqueous Solubility < 0.0001 g/L OR Group C Melting Point > 55 C by Skin irritation/corrosion Exclusion rules by BfR

Domain logical expression index: "k"

Referential boundary: The target chemical should be classified as (!Undefined)Group All Lipid Solubility < 0.01 g/kg AND (!Undefined)Group CNHal Lipid Solubility < 4 g/kg AND (!Undefined)Group CNHal Lipid Solubility < 400 g/kg by Skin irritation/corrosion Exclusion rules by BfR

Domain logical expression index: "l"

Referential boundary: The target chemical should be classified as Group CN Aqueous Solubility < 0.0001 g/L OR Group CN Aqueous Solubility < 0.1 g/L OR Group CN log Kow > 4.5 OR Group CN log Kow > 5.5 by Skin irritation/corrosion Exclusion rules by BfR

Domain logical expression index: "m"

Referential boundary: The target chemical should be classified as (!Undefined)Group All Lipid Solubility < 0.01 g/kg AND (!Undefined)Group CNHal Lipid Solubility < 4 g/kg AND (!Undefined)Group CNHal Lipid Solubility < 400 g/kg by Skin irritation/corrosion Exclusion rules by BfR

Domain logical expression index: "n"

Referential boundary: The target chemical should be classified as (!Undefined)Group C Surface Tension > 62 mN/m by Skin irritation/corrosion Exclusion rules by BfR

Domain logical expression index: "o"

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: "p"

Referential boundary: The target chemical should be classified as Group 14 - Metalloids Si,Ge by Chemical elements

Domain logical expression index: "q"

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

Domain logical expression index: "r"

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

Domain logical expression index: "s"

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

Domain logical expression index: "t"

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

Domain logical expression index: "u"

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

Domain logical expression index: "v"

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

Domain logical expression index: "w"

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

Domain logical expression index: "x"

Parametric boundary:The target chemical should have a value of log Kow which is >= 1.35

Domain logical expression index: "y"

Parametric boundary:The target chemical should have a value of log Kow which is <= 2.17

Interpretation of results:

Category 1 (corrosive) based on GHS criteria

Conclusions:

5-methyl-3-phenylisoxazole-4-carbonyl chloride was estimated to be corrosive to the skin of New Zealand White rabbits.

Executive summary:

The dermal irritation potential of 5-methyl-3-phenylisoxazole-4-carbonyl chloride was estimated using OECD QSAR toolbox v3.4 with logPow as the primary descriptor.

5-methyl-3-phenylisoxazole-4-carbonyl chloride was estimated to be corrosive to the skin of New Zealand White rabbits.

Based on the estimated results, 5-methyl-3-phenylisoxazole-4-carbonyl chloride can be considered to be corrosive to skin and can be classified under the category “Category 1” as per CLP regulation.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (corrosive)

Eye irritation

Link to relevant study records

Reference

Endpoint:

eye irritation: in vivo

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 v3.3 and the QMRF report has been attached

Qualifier:

according to guideline

Guideline:

other: Estimated data

Principles of method if other than guideline:

The study was conducted following a protocol based on BASF-internal standards.

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/mol
- 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

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

no data available

Vehicle:

unchanged (no vehicle)

Controls:

not specified

Amount / concentration applied:

0.1 mL

Duration of treatment / exposure:

24 hours

Observation period (in vivo):

upto 72 hours

Duration of post- treatment incubation (in vitro):

no data available

Number of animals or in vitro replicates:

4

Details on study design:

no data available

Other effects / acceptance of results:

no data available

Irritation parameter:

overall irritation score

Basis:

mean

Time point:

72 h

Reversibility:

not specified

Remarks on result:

no indication of irritation

Irritant / corrosive response data:

No signs of irritation observed

Estimation method: Takes mode value from the 6 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 ( not "j") )  )  and ("k" and ( not "l") )  )  and ("m" and "n" )  )

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 Non binder, without OH or NH2 group by Estrogen Receptor Binding

Domain logical expression index: "f"

Referential boundary: The target chemical should be classified as Non binder, impaired OH or NH2 group OR Non binder, MW>500 OR Non binder, non cyclic structure by Estrogen Receptor Binding

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 Inclusion rules not met by Skin irritation/corrosion Inclusion rules by BfR

Domain logical expression index: "j"

Referential boundary: The target chemical should be classified as Epoxides(=oxiranes) by Skin irritation/corrosion Inclusion rules by BfR

Domain logical expression index: "k"

Referential boundary: The target chemical should be classified as (!Undefined)Group All Lipid Solubility < 0.01 g/kg AND (!Undefined)Group CNHal Lipid Solubility < 4 g/kg AND (!Undefined)Group CNHal Lipid Solubility < 400 g/kg by Skin irritation/corrosion Exclusion rules by BfR

Domain logical expression index: "l"

Referential boundary: The target chemical should be classified as (!Undefined)Group CN Lipid Solubility < 0.4 g/kg by Skin irritation/corrosion Exclusion rules by BfR

Domain logical expression index: "m"

Parametric boundary:The target chemical should have a value of log Kow which is >= 1.35

Domain logical expression index: "n"

Parametric boundary:The target chemical should have a value of log Kow which is <= 4.21

Interpretation of results:

other: not irritating

Conclusions:

5-methyl-3-phenylisoxazole-4-carbonyl chloride was estimated to be not irritating to the eyes of New Zealand White rabbits.

Executive summary:

The ocular irritation potential of 5-methyl-3-phenylisoxazole-4-carbonyl chloride was estimated using OECD QSAR toolbox v3.3 with logPow as the primary descriptor.

5-methyl-3-phenylisoxazole-4-carbonyl chloride was estimated to be not irritating to the eyes of New Zealand White rabbits.

Based on the estimated results, 5-methyl-3-phenylisoxazole-4-carbonyl chloride can be considered to be not irritating to eyes and can be classified under the category “Not Classified” as per CLP regulation.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Skin irritation:

Various studieshas been investigated for the test chemical5-methyl-3-phenylisoxazole-4-carbonyl chloride (CAS No: 16883-16-2)to observe the potential for dermal irritation to a greater or lesser extent. The studies are based on in vivo experiments in rabbits for target chemical5-methyl-3-phenylisoxazole-4-carbonyl chloride (CAS No: 16883-16-2) and its structurally similar read across substances2-Phenylpropene (CAS No: 98-83-9)andBenzoyl chloride (CAS No: 98-88-4).The predicted data using the OECD QSAR toolbox has also been compared with the experimental data which are summarized as below;

 

In a prediction done by SSS (2017) using the OECD QSAR toolbox with log kow as the primary descriptor, the skin irritation potential was estimated for test chemical5-methyl-3-phenylisoxazole-4-carbonyl chloride (CAS No: 16883-16-2). The test substance 5-methyl-3-phenylisoxazole-4-carbonyl chloride (CAS No: 16883-16-2) is estimated to be irritating to skin of New Zealand White Rabbits.

 

The MAK Collection for Occupational Health and Safety {The MAK Collection for Occupational Health and Safety, 138–140, 2012} conducted a skin irritation study of read across substance 2-Phenylpropene(CAS No:- 98-83-9) in rabbits. In this test, undiluted test chemical was applied to the shaved skin of rabbits under a bandage for 2 to 4 weeks (10 to 20 applications). The rabbits showed moderate to severe irritation and slight necrosis was also observed. Hence, the test chemical 2-Phenylpropene (CAS No: 98-83-9) was considered to be irritating to the shaved skin of rabbits.

 

The above results were further supported by the dermal irritation study reported by the American Chemistry Council Benzoates Panel {Robust summary and test plans: benzoyl chloride; The American Chemistry Council Benzoates Panel; 2003} for read across substance Benzoyl chloride (CAS No: 98-88-4). The test was performed according to Draize method. The hair was clipped from the backs of 3 male and 3 female New Zealand White rabbits; the skin of 3 animals was abraded.0.5 ml of Benzoyl chloride was applied to clipped back skin and the wrapped with a gauze bandage. Four hours later the bandage was removed and the area washed with tepid water. The test sites were observed and scored immediately after patch removal and at 24, 72 hours. The Primary Irritation Index of benzoyl chloride after 24 and 72 hours was 3.8 Based on the scores, Benzoyl chloride can be considered to be irritating to rabbit skin.

 

 

Thus based on the available data for the target substance 5-methyl-3-phenylisoxazole-4-carbonyl chloride (CAS No: 16883-16-2) and its structurally similar read across substances2-Phenylpropene (CAS No: 98-83-9)andBenzoyl chloride (CAS No: 98-88-4),it can be concluded thatchemical 5-methyl-3-phenylisoxazole-4-carbonyl chloride (CAS No: 16883-16-2) is able to cause severe skin irritation and considered as irritating. Comparing the above annotations with the criteria of CLP regulation, it can be classified under the category “Category 1”.

 

Eye irritation:

In different studies,test chemical5-methyl-3-phenylisoxazole-4-carbonyl chloride (CAS No: 16883-16-2)has been investigated for potential for ocular irritation to a greater or lesser extentThe studies are based on in vivo experiments in rabbits for target chemical5-methyl-3-phenylisoxazole-4-carbonyl chloride (CAS No: 16883-16-2)and its structurally similar read across substancesSodium benzoate (CAS No: 532-32-1) and Methyl benzoylformate (CAS No: 15206-55-0).The predicted data using the OECD QSAR toolbox has also been compared with the experimental data which are summarized as below;

 

In a prediction done by SSS (2017) using the OECD QSAR toolbox with log kow as the primary descriptor, the eye irritation potential was estimated for test chemical5-methyl-3-phenylisoxazole-4-carbonyl chloride (CAS No: 16883-16-2).The chemical 5-methyl-3-phenylisoxazole-4-carbonyl chloride (CAS No: 16883-16-2) is estimated to be not irritating to eye of New Zealand White rabbits.

 

The IFA (GESTIS) {GESTIS - Substance Database (Information system on hazardous substances of the Berufsgenossenschaften), 2017} carried out an ocular irritation study of read across substance Sodium benzoate (CAS No: 532-32-1) in humans. The chemical Sodium benzoate was instilled into human eyes and effects were observed (dose and duration not specified). Under the conditions of the study, sodium benzoate was not irritating to human eyes.

 

Another eye irritation study of same read across substance Sodium benzoate (CAS No: 532-32-1) was conducted in rabbits according to Directive 84/449/EEC by OECD SIDS {SIDS Initial Assessment Report for 13th SIAM - Benzoates, 2001}. No known effects were observed when the chemical was applied into the eye of rabbits. Hence the chemical Sodium benzoate (CAS No: 532-32-1) was considered to be not irritating to rabbit eyes.

 

The above results were further supported by the experimental study reported by EUROPEAN COMMISSION – European Chemicals Bureau        (IUCLID DATASET for 15206-55-0; EUROPEAN COMMISSION – European Chemicals Bureau, 2000) for read across substance Methyl benzoylformate (CAS No: 15206-55-0). The study was performed according to OECD 405. Rabbits were instilled Methyl benzoylformate in to the eyes and observed for signs of irritation (dose and duration not mentioned). No signs of irritation were observed after instillation of Methyl benzoylformate. Hence, Methyl benzoylformate can be considered to be not irritating to rabbit eyes.

 

Thus on the basis of available data for thetarget chemical5-methyl-3-phenylisoxazole-4-carbonyl chloride (CAS No: 16883-16-2) and its structurally similar read across substancesSodium benzoate (CAS No: 532-32-1) and Methyl benzoylformate (CAS No: 15206-55-0),it can be concluded thatchemical 5-methyl-3-phenylisoxazole-4-carbonyl chloride (CAS No: 16883-16-2) is unable to cause eye irritation and considered as not irritating. Comparing the above annotations with the criteria of CLP regulation, it can be classified under the category “Not Classified”.

Justification for classification or non-classification

The skin and eye irritation potential of test chemical 5-methyl-3-phenylisoxazole-4-carbonyl chloride (CAS No: 16883-16-2) and its structurally similar read across substanceswere observed in various studies. The results obtained from these studies indicate that the chemical 5-methyl-3-phenylisoxazole-4-carbonyl chloride is likely to cause severe skin irritation but not able cause ocular damage. Hence 5-methyl-3-phenylisoxazole-4-carbonyl chloride (CAS No: 16883-16-2) can be classified under the category “Category 1” for skin and “Not Classified” for eye as per CLP.