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

Endpoint summary

Description of key information

The skin sensitization potential of 5-methyl-3-phenylisoxazole-4-carbonyl chloride (CAS No: 16883-16-2) was estimated using OECD QSAR toolbox version 3.3 with log Pow as the primary descriptor. The substance 5-methyl-3-phenylisoxazole-4-carbonyl chloride (CAS No: 16883-16-2) was estimated to be not sensitizing to the skin of Hartley guinea pigs. Based on the estimated result 5-methyl-3-phenylisoxazole-4-carbonyl chloride (CAS No: 16883-16-2) failed to induce skin sanitization effects and hence is considered to be not sensitizing to Hartley guinea pigs and can be classified under the category ˋ Not Classified’ as per CLP regulation.

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records

Reference

Endpoint:

skin sensitisation

Remarks:

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:

Prediction was done using OECD QSAR toolbox v3.3

GLP compliance:

not specified

Type of study:

other: Estimated data

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:

guinea pig

Strain:

Hartley

Sex:

male

Details on test animals and environmental conditions:

no data available

Route:

intradermal and epicutaneous

Vehicle:

not specified

Adequacy of induction:

not specified

No.:

#1

Route:

epicutaneous, semiocclusive

Vehicle:

not specified

Adequacy of challenge:

not specified

No. of animals per dose:

4

Details on study design:

no data available

Challenge controls:

no data available

Positive control substance(s):

not specified

Positive control results:

no data available

Reading:

1st reading

Group:

test chemical

Clinical observations:

no dermal reactions observed

Remarks on result:

no indication of skin sensitisation

The prediction was based on dataset comprised from the following descriptors: "Skin Sensitisation"
Estimation method: Takes highest mode 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" and "l" )  )

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 Very fast by Bioaccumulation - metabolism half-lives ONLY

Domain logical expression index: "j"

Similarity boundary:Target: CC1=C(C(=O)Cl)C(c2ccccc2)=NO1
Threshold=20%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization

Domain logical expression index: "k"

Parametric boundary:The target chemical should have a value of log Kow which is >= 0.368

Domain logical expression index: "l"

Parametric boundary:The target chemical should have a value of log Kow which is <= 2.86

Interpretation of results:

other: Not sensitizing

Conclusions:

5-methyl-3-phenylisoxazole-4-carbonyl chloride was predicted to be non sensitizing to the skin of male Hartley guinea pigs.

Executive summary:

The skin sensitization potential of 5-methyl-3-phenylisoxazole-4-carbonyl chloride was estimated by SSS (2017) using OECD QSAR toolbox v3.3 with log kow as the primary descriptor. 5-methyl-3-phenylisoxazole-4-carbonyl chloride was predicted to be non sensitizing to the skin of male Hartley guinea pigs.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not sensitising)

Additional information:

Skin sensitization:

Various studieshas been investigated for the test chemical5-methyl-3-phenylisoxazole-4-carbonyl chloride (CAS No: 16883-16-2)to observe the potential for skin sensitization to a greater or lesser extent. The studies are based on in vivo experiments in guinea pigs and humans for target chemical5-methyl-3-phenylisoxazole-4-carbonyl chloride (CAS No: 16883-16-2) and its structurally similar read across substancesButylbenzyl phthalate (BBP) (CAS no: 85-68-7) and Ethyl benzoate (CAS No: 93-89-0).The predicted data using the OECD QSAR toolbox has also been compared with the experimental data and summarized as below;

 

The skin sensitization potential of 5-methyl-3-phenylisoxazole-4-carbonyl chloride (CAS No: 16883-16-2) was estimated using OECD QSAR toolbox version 3.3 with log Pow as the primary descriptor. The substance 5-methyl-3-phenylisoxazole-4-carbonyl chloride (CAS No: 16883-16-2) was estimated to be not sensitizing to the skin of Hartley guinea pigs. Based on the estimated result 5-methyl-3-phenylisoxazole-4-carbonyl chloride (CAS No: 16883-16-2) failed to induce skin sanitization effects and hence is considered to be not sensitizing to Hartley guinea pigs.

 

The experimental study was conducted by BRUCE G. et.,al{Toxicology Industrial Health 3(2), 79-98} for read across substance Butylbenzyl phthalate (BBP) (CAS no: 85-68-7) in 200 human volunteers for 24 hours that supports the above mentioned result. Patches containing undiluted BBP were applied to the skin of 200 human volunteers for 24 hours, 3 times a week for 5 weeks. After a 2-week rest period when no patches were applied, human test subjects were rechallenged by applying patches containing BBP for 24 hours at previously untreated sites on the skin. During the induction and challenge phases, application sites were examined for signs of sensitization. No sign of sensitization was observed in any 200 human volunteers after 15 daily applications of a subsequent challenge with BBP. Therefore BBP was not considered to be a skin sensitizer in human repeated insult patch tests.

 

The above results were further supported by an Open Epicutaneous Test (OET) conducted by G. Klecak {Curr. Probl. Derm., vo1.14, pp.152-171 (Karger, Basel 1985)} on guinea pigs of read across chemical Ethyl benzoate (CAS No: 93-89-0).During the experiment, the pretest was performed to determine the primary irritating threshold concentration of test substances at various concentrations (e.g, 100,30,10 and 3%). In this test, a single application of 0.025 ml of each test concentration was simultaneously performed on one of the areas measuring 2 cm2 of the flank skin previously clipped and marked with a circular stamp. Reactions are read 24 h after the application of the test material. On the basis of pretest, the concentration selected for sensitization test was 8 %.On day 1 during induction, 0.1 ml of the Ethyl benzoate (CAS No: 93-89-0) was applied at concentrations of 8% in vehicle to an area measuring 8 cm2 on the clipped flank skin of the guinea pigs. The applications are repeated daily for 3 weeks or done 5 times weekly during 4 weeks, usually on the same skin sites. The application sites were left uncovered and the reactions, if continuous daily applications were performed, can be read 24 h after each application, or at the end of each week.To determine whether or not contact sensitization was induced, all groups of guinea pigs previously treated for 21 days, as well as 10 untreated, or only pretreated with the vehicle, controls are tested on days 21 and 35 on the contralateral flank with the test material. This test was performed by applying with a pipette 0.025 ml of chemical to skin areas measuring 2 cm2. The reactions were read after 24,48 and/or 72h.It was observed that none of the guinea pigs induced contact sensitization at challenge concentration of 8%.Thus the chemicalEthyl benzoate (CAS No: 93-89-0) was considered to be not sensitizing on skin of guinea pigs at concentration of 8% in an Open Epicutaneous Test (OET).

 

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 substancesButylbenzyl phthalate (BBP) (CAS no: 85-68-7) and Ethyl benzoate (CAS No: 93-89-0),it can be concluded thatchemical 5-methyl-3-phenylisoxazole-4-carbonyl chloride (CAS No: 16883-16-2) is unable to cause skin sensitization and considered as non-skin sensitizer. Comparing the above annotations with the criteria of CLP regulation, it can be classified under the category “Not Classified”.

Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information:

The skin sensitization potential of test substance 5-methyl-3-phenylisoxazole-4-carbonyl chloride (CAS No: 16883-16-2) and its structurally similar read across substancesButylbenzyl phthalate (BBP) (CAS no: 85-68-7) and Ethyl benzoate (CAS No: 93-89-0) were observed in various studies. From the results obtained from these studies it is concluded that the chemical 5-methyl-3-phenylisoxazole-4-carbonyl chloride (CAS No: 16883-16-2) is not likely to cause skin sensitization and hence can be classified as non -skin sensitizer.