1,1'-(4-chlorobutylidene)bis[4-fluorobenzene]

Endpoint summary

Description of key information

The skin sensitization potential of 1-[4-chloro-1-(4-fluorophenyl)butyl]-4-fluorobenzene (3312-04-7) was estimated by SSS (2017) using OECD QSAR toolbox v3.3 with log kow as the primary descriptor and considering the six closest read across substances 1-[4-chloro-1-(4-fluorophenyl)butyl]-4-fluorobenzene (3312-04-7) was predicted to be not sensitizing to the skin female Dunkin-Hartley guinea pig.

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:

equivalent or similar to guideline

Guideline:

OECD Guideline 406 (Skin Sensitisation)

Principles of method if other than guideline:

Prediction was done using OECD QSAR toolbox v3.3, 2017

GLP compliance:

not specified

Type of study:

Buehler test

Specific details on test material used for the study:

- Name of test material :1-[4-chloro-1-(4-fluorophenyl)butyl]-4-fluorobenzene
- Molecular formula): C16H15ClF2
- Molecular weight : 280.743 g/mol
- Smiles notation : c1(C(c2ccc(cc2)F)CCCCl)ccc(cc1)F
- InChl: 1S/C16H15ClF2/c17-11-1-2-16(12-3-7-14(18)8-4-12)13-5-9-15(19)10-6-13/h3-10,16H,1-2,11H2
- Substance type: Organic
- Physical state: Liquid

Species:

guinea pig

Strain:

Dunkin-Hartley

Sex:

female

Details on test animals and environmental conditions:

No data available

No. of animals per dose:

Total:30
test group:20
Control :10

Details on study design:

No data available

Challenge controls:

No data available

Positive control substance(s):

not required

Statistics:

No data available

Positive control results:

No data available

Reading:

1st reading

Group:

test chemical

Dose level:

25%

No. with + reactions:

0

Total no. in group:

20

Clinical observations:

no skin sensitization reaction observed

Remarks on result:

other: no skin sensitization reaction observed

The prediction was based on dataset comprised from the following descriptors: "Skin Sensitisation"
Estimation method: Takes highest mode value from the 6 nearest neighbours
Domain  logical expression:Result: In Domain

((("a" and ("b" and ( not "c") )  )  and "d" )  and ("e" and "f" )  )

Domain logical expression index: "a"

Referential boundary: The target chemical should be classified as Alkyl chloride OR Alkyl halide OR Aromatic compound OR Aryl fluoride OR Aryl halide OR Halogen derivative by Organic functional groups, Norbert Haider (checkmol) ONLY

Domain logical expression index: "b"

Referential boundary: The target chemical should be classified as No alert found by DNA binding by OASIS v.1.3

Domain logical expression index: "c"

Referential boundary: The target chemical should be classified as AN2 OR AN2 >>  Michael-type addition, quinoid structures OR AN2 >>  Michael-type addition, quinoid structures >> Quinones OR AN2 >> Nucleophilic addition to alpha, beta-unsaturated carbonyl compounds OR AN2 >> Nucleophilic addition to alpha, beta-unsaturated carbonyl compounds >> alpha, beta-Unsaturated Aldehydes OR AN2 >> Schiff base formation OR AN2 >> Schiff base formation >> alpha, beta-Unsaturated Aldehydes OR AN2 >> Schiff base formation >> Polarized Haloalkene Derivatives OR AN2 >> Schiff base formation by aldehyde formed after metabolic activation OR AN2 >> Schiff base formation by aldehyde formed after metabolic activation >> Geminal Polyhaloalkane Derivatives OR AN2 >> Shiff base formation for aldehydes OR AN2 >> Shiff base formation for aldehydes >> Geminal Polyhaloalkane Derivatives OR AN2 >> Shiff base formation for aldehydes >> Haloalkane Derivatives with Labile Halogen OR AN2 >> Thioacylation via nucleophilic addition after cysteine-mediated thioketene formation OR AN2 >> Thioacylation via nucleophilic addition after cysteine-mediated thioketene formation >> Polarized Haloalkene Derivatives OR Michael addition OR Michael addition >> Quinone type compounds OR Michael addition >> Quinone type compounds >> Quinone methides OR Non-covalent interaction OR Non-covalent interaction >> DNA intercalation OR Non-covalent interaction >> DNA intercalation >> Quinones OR Radical OR Radical >> Generation of ROS by glutathione depletion (indirect) OR Radical >> Generation of ROS by glutathione depletion (indirect) >> Haloalkanes Containing Heteroatom OR Radical >> Radical mechanism via ROS formation (indirect) OR Radical >> Radical mechanism via ROS formation (indirect) >> Geminal Polyhaloalkane Derivatives OR Radical >> Radical mechanism via ROS formation (indirect) >> Quinones OR Radical >> ROS formation after GSH depletion OR Radical >> ROS formation after GSH depletion >> Quinone methides OR SN1 OR SN1 >> Alkylation after metabolically formed carbenium ion species OR SN1 >> Alkylation after metabolically formed carbenium ion species >> Polycyclic Aromatic Hydrocarbon Derivatives OR SN2 OR SN2 >> Acylation involving a leaving group  OR SN2 >> Acylation involving a leaving group  >> Geminal Polyhaloalkane Derivatives OR SN2 >> Acylation involving a leaving group  >> Haloalkane Derivatives with Labile Halogen OR SN2 >> Acylation involving a leaving group after metabolic activation OR SN2 >> Acylation involving a leaving group after metabolic activation >> Geminal Polyhaloalkane Derivatives OR SN2 >> Alkylation by epoxide metabolically formed after E2 reaction OR SN2 >> Alkylation by epoxide metabolically formed after E2 reaction >> Monohaloalkanes OR SN2 >> Alkylation, direct acting epoxides and related OR SN2 >> Alkylation, direct acting epoxides and related >> Epoxides and Aziridines OR SN2 >> Alkylation, direct acting epoxides and related after P450-mediated metabolic activation OR SN2 >> Alkylation, direct acting epoxides and related after P450-mediated metabolic activation >> Polycyclic Aromatic Hydrocarbon Derivatives OR SN2 >> Alkylation, nucleophilic substitution at sp3-carbon atom OR SN2 >> Alkylation, nucleophilic substitution at sp3-carbon atom >> Haloalkane Derivatives with Labile Halogen OR SN2 >> Alkylation, nucleophilic substitution at sp3-carbon atom >> Monohaloalkanes OR SN2 >> Direct acting epoxides formed after metabolic activation OR SN2 >> Direct acting epoxides formed after metabolic activation >> Quinoline Derivatives OR SN2 >> DNA alkylation OR SN2 >> DNA alkylation >> Vicinal Dihaloalkanes OR SN2 >> Internal SN2 reaction with aziridinium and/or cyclic sulfonium ion formation (enzymatic) OR SN2 >> Internal SN2 reaction with aziridinium and/or cyclic sulfonium ion formation (enzymatic) >> Vicinal Dihaloalkanes OR SN2 >> Nucleophilic substitution after carbenium ion formation OR SN2 >> Nucleophilic substitution after carbenium ion formation >> Monohaloalkanes OR SN2 >> Nucleophilic substitution at sp3 Carbon atom OR SN2 >> Nucleophilic substitution at sp3 Carbon atom >> Haloalkanes Containing Heteroatom OR SN2 >> Nucleophilic substitution at sp3 carbon atom after thiol (glutathione) conjugation OR SN2 >> Nucleophilic substitution at sp3 carbon atom after thiol (glutathione) conjugation >> Geminal Polyhaloalkane Derivatives OR SN2 >> SN2 at an activated carbon atom OR SN2 >> SN2 at an activated carbon atom >> Quinoline Derivatives OR SN2 >> SN2 at sp3 and activated sp2 carbon atom OR SN2 >> SN2 at sp3 and activated sp2 carbon atom >> Polarized Haloalkene Derivatives by DNA binding by OASIS v.1.3

Domain logical expression index: "d"

Referential boundary: The target chemical should be classified as SN2 AND SN2 >> SN2 at an sp3 Carbon atom AND SN2 >> SN2 at an sp3 Carbon atom >> Aliphatic halides by DNA binding by OECD ONLY

Domain logical expression index: "e"

Parametric boundary:The target chemical should have a value of log Kow which is >= 2.03

Domain logical expression index: "f"

Parametric boundary:The target chemical should have a value of log Kow which is <= 7.41

Interpretation of results:

other: Not sensitizing

Conclusions:

The skin sensitization potential of 1-[4-chloro-1-(4-fluorophenyl)butyl]-4-fluorobenzene (3312-04-7) was estimated by SSS (2017) using OECD QSAR toolbox v3.3 with log kow as the primary descriptor and considering the six closest read across substances 1-[4-chloro-1-(4-fluorophenyl)butyl]-4-fluorobenzene (3312-04-7) was predicted to be not sensitizing to the skin female Dunkin-Hartley guinea pig.

Executive summary:

The skin sensitization potential of 1-[4-chloro-1-(4-fluorophenyl)butyl]-4-fluorobenzene (3312-04-7) was estimated by SSS (2017) using OECD QSAR toolbox v3.3 with log kow as the primary descriptor and considering the six closest read across substances 1-[4-chloro-1-(4-fluorophenyl)butyl]-4-fluorobenzene (3312-04-7) was predicted to be not sensitizing to the skin female Dunkin-Hartley guinea pig.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not sensitising)

Additional information:

Skin sensitization

In different studies,1-[4-chloro-1-(4-fluorophenyl)butyl]-4-fluorobenzene(3312-04-7) has been investigated for potential of skin sensitization to a greater or lesser extent. The studies are based on in vivo experiments in guinea pig for target chemical1-[4-chloro-1-(4-fluorophenyl)butyl]-4-fluorobenzene(3312-04-7) and its structurally similar read across substances3-chloropropyl)triethoxysilane(5089-70-3) and Alkanes C14-17, chloro(85535-85-9),the predicted data using the OECD QSAR toolbox has also been compared with the experimental data of read across.

The skin sensitization potential of1-[4-chloro-1-(4-fluorophenyl)butyl]-4-fluorobenzene(3312-04-7) was estimated by SSS (2017) using OECD QSAR toolbox v3.3 with log kow as the primary descriptor and considering the five closest read across substances1-[4-chloro-1-(4-fluorophenyl)butyl]-4-fluorobenzene(3312-04-7) was predicted to be not sensitizing to the skin of female Dunkin-Hartley guinea pig.

The experimental study conducted byOECD HPV SIDS(OECD HPV Chemical Programme, SIDS Dossier approved at SIAM 30, 20-22 April 2010) to evaluate the skin sensitizing potential of read across substance3-chloropropyl)triethoxysilane(5089-70-3) in guinea pig.The skin sensitization study of3-chloropropyl)triethoxysilane (5089-70-3)was performed byGuinea pig maximisation testin 15Male albino SPF guinea pigs.. An additional 5 animals served as the negative control group; a positive control group was not included in the study.In induction phase,1^stinduction given using 5% concentration inpropylene glycol by intradermal route while in 2^ndinduction done by using 10% concentration in Vaseline by topical application.Freund's Complete Adjuvant (FCA) also used in induction phase. In challenge phase, test substance 5% concentration in Vaseline applied topically. Freund's Complete Adjuvant (FCA ) produced erythema, slight edema
while 5% test substance in propylene glycol produced erythema, slight edema and
abscesses and 5% test substance in PG + FCA: erythema and slight edema
and abscesses. In second induction the 10% test substance in Vaseline induced neither erythema nor edema in the test animals upon topical application in the induction phase of the study. No skin sensitizing reaction observed after challenge application .Hence it is considered that3-chloropropyl)triethoxysilane (5089-70-3)was not skin sensitizing in guinea pig byGuinea pig maximization test.

Also it is further supported by experimental study conducted byEuropean Chemicals Agency (ECHA)(European Union Risk Assessment Report - Alkanes, C14-17, Chloro,February 2008) to evaluate the skin sensitizing potential of read across substanceD and C Violet No. 2(81-48-1) in guinea pig.The skin sensitization study ofAlkanes C14-17, chloro(85535-85-9)was performed byGuinea pig maximisation test in 20guinea pigs.. An additional 10 animals served as the control group.In induction phase,1^stinduction given using 20% concentration inmaize oil by intradermal route while in 2^ndinduction done by using undiluted test material by topical applicationis most likely to be related to pre-treatmentFreund's Complete Adjuvant (FCA) in induction phaseproducing "intense, sometimes haemorrhagic, purulent inflammation in treated group.In challenge phase, undiluted test material was applied topically for 48hr. After 48hr 1/20 test group and 1/10 control group showsscores of 1 and 3 respectively. Then re-challengetest substance50% test material in maize oil wasapplied topically for 48 hr.No indication of skin sensitization was observed.Hence it is considered thatAlkanes C14-17, chloro(85535-85-9)was not skin sensitizing in guinea pig byGuinea pig maximisation test.

Thus based on the above predictions on1-[4-chloro-1-(4-fluorophenyl)butyl]-4-fluorobenzene(3312-04-7)as well as its read across and applying weight of evidence, it can be concluded that 1-[4-chloro-1-(4-fluorophenyl)butyl]-4-fluorobenzene(3312-04-7)is not a skin sensitizer.

Thus comparing the above annotations with the criteria of CLP regulation, 1-[4-chloro-1-(4-fluorophenyl)butyl]-4-fluorobenzene(3312-04-7) can be considered as not classified for skin sensitization

Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

Thus comparing the above annotations with the criteria of CLP regulation, 1-[4-chloro-1-(4-fluorophenyl)butyl]-4-fluorobenzene(3312-04-7) can be considered as not classified for skin sensitization.