3-bromoquinoline

Endpoint summary

Description of key information

The skin sensitization potential of 3-bromoquinoline (CAS No: 5332-24-1) was estimated using OECD QSAR toolbox version 3.3 with log Pow as the primary descriptor. The chemical 3-bromoquinoline (CAS No: 5332-24-1) was estimated to be not sensitizing to the skin of Dunkin-Hartley guinea pigs. Based on the estimated result 3-bromoquinoline (CAS No: 5332-24-1) failed to induce skin sanitization effects and hence is considered to be not sensitizing to Dunkin-Hartley guinea pigs and can be classified under the category   “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 version 3.3 and QMRF report has been attached

Qualifier:

according to guideline

Guideline:

other: estimated data

Principles of method if other than guideline:

Prediction is done using QSAR Toolbox version 3.3

GLP compliance:

not specified

Type of study:

guinea pig maximisation test

Justification for non-LLNA method:

not specified

Specific details on test material used for the study:

- Name of test material : 3-Bromoquinoline
- Molecular formula : C9H6BrN
- Molecular weight : 208.057 g/mol
- Smiles notation : c12c(ncc(c1)Br)cccc2
- InChl : 1S/C9H6BrN/c10-8-5-7-3-1-2-4-9(7)11-6-8/h1-6H
- Substance type: Organic
- Physical state: Liquid

Species:

guinea pig

Strain:

Dunkin-Hartley

Sex:

male/female

Details on test animals and environmental conditions:

No data available

Route:

intradermal and epicutaneous

Vehicle:

not specified

Concentration / amount:

No data available

Day(s)/duration:

No data available

Adequacy of induction:

not specified

No.:

#1

Route:

epicutaneous, occlusive

Vehicle:

not specified

Concentration / amount:

No data available

Day(s)/duration:

No data available

Adequacy of challenge:

not specified

No. of animals per dose:

20

Details on study design:

No data available

Challenge controls:

No data available

Reading:

1st reading

Hours after challenge:

72

Group:

test chemical

Dose level:

No data available

No. with + reactions:

0

Total no. in group:

20

Clinical observations:

No skin sensitization was observed.

Remarks on result:

no indication of skin sensitisation

Cellular proliferation data / Observations:

No skin sensitization was observed.

The prediction was based on dataset comprised from the following descriptors: "Skin Sensitisation"
Estimation method: Takes mode value from the 10 nearest neighbours
Domain  logical expression:Result: In Domain

((((((((((((((("a" or "b" or "c" )  and "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 ( 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 "ad" )  )

Domain logical expression index: "a"

Referential boundary: The target chemical should be classified as SN2 AND SN2 >> Direct acting epoxides formed after metabolic activation AND SN2 >> Direct acting epoxides formed after metabolic activation >> Quinoline Derivatives AND SN2 >> SN2 at an activated carbon atom AND SN2 >> SN2 at an activated carbon atom >> Quinoline Derivatives by DNA binding by OASIS v.1.3

Domain logical expression index: "b"

Referential boundary: The target chemical should be classified as Class 2 (less inert compounds) by Acute aquatic toxicity classification by Verhaar (Modified)

Domain logical expression index: "c"

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

Domain logical expression index: "d"

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

Domain logical expression index: "e"

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: "f"

Referential boundary: The target chemical should be classified as Activated N-heterocycles OR Aldehydes by Skin irritation/corrosion Inclusion rules by BfR

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 Aromatic amines by Skin irritation/corrosion Inclusion rules by BfR

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 Ketones 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"

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 Group C Melting Point > 55 C by Skin irritation/corrosion Exclusion rules by BfR

Domain logical expression index: "o"

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: "p"

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: "q"

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: "r"

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

Domain logical expression index: "s"

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: "t"

Referential boundary: The target chemical should be classified as Group All Melting Point > 200 C by Skin irritation/corrosion Exclusion rules by BfR

Domain logical expression index: "u"

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: "v"

Referential boundary: The target chemical should be classified as Group CHal Melting Point > 65 C OR Group CHal Molecular Weight > 280 g/mol by Skin irritation/corrosion Exclusion rules by BfR

Domain logical expression index: "w"

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: "x"

Referential boundary: The target chemical should be classified as Group CNHal Aqueous Solubility < 0.001 g/L by Skin irritation/corrosion Exclusion rules by BfR

Domain logical expression index: "y"

Referential boundary: The target chemical should be classified as Aromatic heterocyclic halide AND Aryl AND Aryl halide AND Fused carbocyclic aromatic AND Fused heterocyclic aromatic AND Pyridine AND Quinoline/ Isoquinoline by Organic Functional groups

Domain logical expression index: "z"

Referential boundary: The target chemical should be classified as Alkyl halide by Organic Functional groups

Domain logical expression index: "aa"

Referential boundary: The target chemical should be classified as Aromatic heterocyclic halide AND Aryl AND Aryl halide AND Fused carbocyclic aromatic AND Fused heterocyclic aromatic AND Pyridine AND Quinoline/ Isoquinoline by Organic Functional groups

Domain logical expression index: "ab"

Referential boundary: The target chemical should be classified as Heterocyclic Phenol by Organic Functional groups

Domain logical expression index: "ac"

Parametric boundary:The target chemical should have a value of log Kow which is >= 1.45

Domain logical expression index: "ad"

Parametric boundary:The target chemical should have a value of log Kow which is <= 4.09

Interpretation of results:

other: not sensitising

Conclusions:

The chemical 3-bromoquinoline (CAS No: 5332-24-1) was estimated to be not sensitizing to the skin of Dunkin-Hartley guinea pigs. Based on the estimated result 3-bromoquinoline (CAS No: 5332-24-1) failed to induce skin sanitization effects and hence is considered to be not sensitizing to Dunkin-Hartley guinea pigs.

Executive summary:

The skin sensitization potential of 3-bromoquinoline (CAS No: 5332-24-1) was estimated using OECD QSAR toolbox version 3.3 with log Pow as the primary descriptor. The chemical 3-bromoquinoline (CAS No: 5332-24-1) was estimated to be not sensitizing to the skin of Dunkin-Hartley guinea pigs. Based on the estimated result 3-bromoquinoline (CAS No: 5332-24-1) failed to induce skin sanitization effects and hence is considered to be not sensitizing to Dunkin-Hartley guinea pigs and can be classified under the category   “Not Classified”as per CLP regulation.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not sensitising)

Additional information:

Skin sensitization:

Various studieshas been investigated for the test chemical3-bromoquinoline (CAS No: 5332-24-1)to observe the potential for skin sensitization to a greater or lesser extent. The studies are based on in vivo experiments in guinea pigs for target chemical3-bromoquinoline (CAS No: 5332-24-1) and its structurally similar read across substances1-Chloro-4-nitrobenzene (CAS no: 100-00-5) and 1,3-dichloro-5-nitrobenzene (CAS no: 618–62–2).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 3-bromoquinoline (CAS No: 5332-24-1) was estimated using OECD QSAR toolbox version 3.3 with log Pow as the primary descriptor. The chemical 3-bromoquinoline (CAS No: 5332-24-1) was estimated to be not sensitizing to the skin of Dunkin-Hartley guinea pigs. Based on the estimated result 3-bromoquinoline (CAS No: 5332-24-1) failed to induce skin sanitization effects and hence is considered to be not sensitizing to Dunkin-Hartley guinea pigs.

 

The HSDB {U.S. National Library of Medicine National Institutes of Health, Health & Human Services; 2017} conducted the Mouse ear swelling test was performed on five mice of read across chemical 1-Chloro-4-nitrobenzene (CAS no: 100-00-5) that supports the above mentioned result. During the test, the backs of 5 mice were shaved with electric clippers before induction was performed by applying 0.2 mL of a 0.05 M solution of the compound in acetone on day 1. Challenge application was performed with 20 uL of non-irritant 0.016 M solution to the surface of one ear of each mouse on day 5. Reactions were read after a further 24, 48 and 72 hours by comparison of the thickness of the ears between test mice and controls.Since no known effects were observed, the chemical1-Chloro-4-nitrobenzene (CAS no: 100-00-5) was considered to be not sensitizing to the skin of mice.

 

The above results were further supported by the Guinea pig maximisation test of read across chemical 1,3-dichloro-5-nitrobenzene (CAS no: 618–62–2) reported by EUROPEAN COMMISSION – European Chemicals Bureau {IUCLID Dataset ; EUROPEAN COMMISSION – European Chemicals Bureau; 18–FEB–2000} in albino Dunkin–Hartley Guinea pig according to the method of Magnusson and Kligman published by the EEC Annexes V and VI of the Directive 84/449 and the OECD Guideline n° 406 for the control of chemicals. During induction, the rabbits were treated with two intradermal injections of the test substance in a 5 % (W/W) solution in sterile Codex liquid paraffin, the 50/50 (V/V) mixture : test compound in a 10 % (W/W) solution in sterile Codex liquid parrafin + 50 % (V/V) solution of Freund’s complete adjuvant in isotonic injectable solution, i.e. a final 5 % concentration of the test substance. The injection of the test substance in a 5 % solution provoked a weak to moderate irritation. This was followed by topical application in which the test animals were treated with the chemical in a 5 % (W/W) dilution with sterile Codex liquid parrafin and at the dose of 0.50 ml per animal for 48 hours under occlusive condition. For the challenge exposure, the occlusive topical application for 24 hours was carried out with the test substance in a 1 % (W/W) solution with sterile Codex liquid parrafin at the dose of 0.50 ml per guinea–pig (Non–Irritant Maximum Concentration : N.I.M.C.). The test substance did not cause any reaction of cutaneous sensitization in the 19 treated guinea–pigs, no typical cutaneous abnormality, and different from the preliminary study, was noted in the 10 control guinea–pigs. Therefore the chemical 1,3-dichloro-5-nitrobenzene (CAS no: 618–62–2) was considered to be not sensitizing to the guinea pigs’ skin.

 

Thus on the basis of available data for thetarget chemical3-bromoquinoline (CAS No: 5332-24-1) and its structurally similar read across substances1-Chloro-4-nitrobenzene (CAS no: 100-00-5) and 1,3-dichloro-5-nitrobenzene (CAS no: 618–62–2),it can be concluded thatchemical 3-bromoquinoline (CAS No: 5332-24-1) 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

Justification for classification or non-classification

The skin sensitization potential of test substance 3-bromoquinoline (CAS No: 5332-24-1) and its structurally similar read across substances1-Chloro-4-nitrobenzene (CAS no: 100-00-5) and 1,3-dichloro-5-nitrobenzene (CAS no: 618–62–2) were observed in various studies. From the results obtained from these studies it is concluded that the chemical 3-bromoquinoline (CAS No: 5332-24-1) is not likely to cause skin sensitization and hence can be classified as non -skin sensitizer.