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

Endpoint summary

Description of key information

Skin Irritation:

The dermal irritation potential of 1-[4-chloro-1-(4-fluorophenyl)butyl]-4-fluorobenzene was estimated using OECD QSAR toolbox v3.3 with logPow as the primary descriptor.

1-[4-chloro-1-(4-fluorophenyl)butyl]-4-fluorobenzene was estimated to be not irritating to the skin of New Zealand White rabbits.

Based on the estimated results, 1-[4-chloro-1-(4-fluorophenyl)butyl]-4-fluorobenzene can be considered to be not irritating to skin and can be classified under the category “Not Classified” as per CLP regulation.

Eye Irritation:

The ocular irritation potential of 1-[4-chloro-1-(4-fluorophenyl)butyl]-4-fluorobenzene was estimated using OECD QSAR toolbox v3.3 with logPow as the primary descriptor.

1-[4-chloro-1-(4-fluorophenyl)butyl]-4-fluorobenzene was estimated to be not irritating to the eyes of New Zealand White rabbits.

Based on the estimated results, 1-[4-chloro-1-(4-fluorophenyl)butyl]-4-fluorobenzene can be considered to be not irritating to eyes and can be classified under the category “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 v3.3 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

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:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

no data available

Type of coverage:

semiocclusive

Preparation of test site:

shaved

Vehicle:

unchanged (no vehicle)

Controls:

not specified

Amount / concentration applied:

0.5 g

Duration of treatment / exposure:

4 hours

Observation period:

72 hours

Number of animals:

3

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 irritation observed

Estimation method: Takes mode value from the 5 nearest neighbours
Domain  logical expression:Result: In Domain

(((((((("a" and ("b" and ( not "c") )  )  and ("d" and ( not "e") )  )  and "f" )  and ("g" and ( not "h") )  )  and "i" )  and ("j" and ( not "k") )  )  and ("l" and ( not "m") )  )  and ("n" and "o" )  )

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 >> Haloalkenes with Electron-Withdrawing Groups 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 cyclization OR SN2 >> Alkylation, direct acting epoxides and related after cyclization >> Nitrogen Mustards 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 >> Haloalkenes with Electron-Withdrawing Groups 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 Not possible to classify according to these rules by DPRA Cysteine peptide depletion

Domain logical expression index: "e"

Referential boundary: The target chemical should be classified as High reactive OR High reactive >> Activated haloarenes OR High reactive >> alpha,beta-carbonyl compounds with polarized multiple bonds OR High reactive >> Vinyl pyridines OR Low reactive OR Low reactive >> Primary haloalkanes OR Moderate reactive OR Moderate reactive >> Activated 1,3,5-triazine derivatives by DPRA Cysteine peptide depletion

Domain logical expression index: "f"

Referential boundary: The target chemical should be classified as High (Class III) by Toxic hazard classification by Cramer (with extensions) ONLY

Domain logical expression index: "g"

Referential boundary: The target chemical should be classified as No alert found by Protein binding alerts for Chromosomal aberration by OASIS v1.1

Domain logical expression index: "h"

Referential boundary: The target chemical should be classified as AN2 OR AN2 >> Nucleophilic addition to pyridonimine tautomer of aminopyridoindoles or aminopyridoimidazoles OR AN2 >> Nucleophilic addition to pyridonimine tautomer of aminopyridoindoles or aminopyridoimidazoles >> Heterocyclic Aromatic Amines OR Radical mechanism OR Radical mechanism >> ROS generation and direct attack of hydroxyl radical to the C8 position of nucleoside base OR Radical mechanism >> ROS generation and direct attack of hydroxyl radical to the C8 position of nucleoside base >> Heterocyclic Aromatic Amines OR SE reaction (CYP450-activated heterocyclic amines) OR SE reaction (CYP450-activated heterocyclic amines) >> Direct attack of arylnitrenium cation to the C8 position of nucleoside base OR SE reaction (CYP450-activated heterocyclic amines) >> Direct attack of arylnitrenium cation to the C8 position of nucleoside base >> Heterocyclic Aromatic Amines OR SR reaction (peroxidase-activated heterocyclic amines) OR SR reaction (peroxidase-activated heterocyclic amines) >> Direct attack of arylnitrenium radical to the C8 position of nucleoside base OR SR reaction (peroxidase-activated heterocyclic amines) >> Direct attack of arylnitrenium radical to the C8 position of nucleoside base >> Heterocyclic Aromatic Amines by Protein binding alerts for Chromosomal aberration by OASIS v1.1

Domain logical expression index: "i"

Referential boundary: The target chemical should be classified as Not bioavailable by Lipinski Rule Oasis ONLY

Domain logical expression index: "j"

Referential boundary: The target chemical should be classified as Halogens AND Non-Metals by Groups of elements

Domain logical expression index: "k"

Referential boundary: The target chemical should be classified as Metalloids by Groups of elements

Domain logical expression index: "l"

Referential boundary: The target chemical should be classified as Not known precedent reproductive and developmental toxic potential by DART scheme v.1.0

Domain logical expression index: "m"

Referential boundary: The target chemical should be classified as Known precedent reproductive and developmental toxic potential OR Toluene and small alkyl toluene derivatives (8a) by DART scheme v.1.0

Domain logical expression index: "n"

Parametric boundary:The target chemical should have a value of log Kow which is >= 5.21

Domain logical expression index: "o"

Parametric boundary:The target chemical should have a value of log Kow which is <= 6.48

Interpretation of results:

other: not irritating

Conclusions:

1-[4-chloro-1-(4-fluorophenyl)butyl]-4-fluorobenzene was estimated to be not irritating to the skin of New Zealand White rabbits.

Executive summary:

The dermal irritation potential of 1-[4-chloro-1-(4-fluorophenyl)butyl]-4-fluorobenzene was estimated using OECD QSAR toolbox v3.3 with logPow as the primary descriptor.

1-[4-chloro-1-(4-fluorophenyl)butyl]-4-fluorobenzene was estimated to be not irritating to the skin of New Zealand White rabbits.

Based on the estimated results, 1-[4-chloro-1-(4-fluorophenyl)butyl]-4-fluorobenzene can be considered to be not irritating to skin and can be classified under the category “Not Classified” as per CLP regulation.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

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:

Prediction was done using OECD QSAR toolbox v3.3

GLP compliance:

not specified

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:

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:

0.1ml

Duration of treatment / exposure:

24 hours

Observation period (in vivo):

24,48 and 72 hours

Duration of post- treatment incubation (in vitro):

no data available

Number of animals or in vitro replicates:

3

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 irritation observed

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

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

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 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 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 cyclization OR SN2 >> Alkylation, direct acting epoxides and related after cyclization >> Nitrogen Mustards 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 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"

Referential boundary: The target chemical should be classified as Halogens AND Non-Metals by Groups of elements

Domain logical expression index: "f"

Referential boundary: The target chemical should be classified as Metalloids by Groups of elements

Domain logical expression index: "g"

Parametric boundary:The target chemical should have a value of log Kow which is >= 3.53

Domain logical expression index: "h"

Parametric boundary:The target chemical should have a value of log Kow which is <= 9.45

Interpretation of results:

other: not irritating

Conclusions:

1-[4-chloro-1-(4-fluorophenyl)butyl]-4-fluorobenzene was estimated to be not irritating to the eyes of New Zealand White rabbits.

Executive summary:

The ocular irritation potential of 1-[4-chloro-1-(4-fluorophenyl)butyl]-4-fluorobenzene was estimated using OECD QSAR toolbox v3.3 with logPow as the primary descriptor.

1-[4-chloro-1-(4-fluorophenyl)butyl]-4-fluorobenzene was estimated to be not irritating to the eyes of New Zealand White rabbits.

Based on the estimated results, 1-[4-chloro-1-(4-fluorophenyl)butyl]-4-fluorobenzene 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:

In different studies, 1-[4-chloro-1-(4-fluorophenyl)butyl]-4-fluorobenzene has been investigated for potential for dermal irritation to a greater or lesser extent. The studies are based on in vivo and in vitro experiments along with predicted data for target chemical and its functionally similar read across substances, 3,3'-(1,4-Phenylene)bis(5,6-diphenyl-1,2,4-triazine) [CAS: 55514-22-2] and Terphenyl [CAS: 26140-60-3]. The predicted data using the OECD QSAR toolbox has also been compared with the experimental data.

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 for1-[4-chloro-1-(4-fluorophenyl)butyl]-4-fluorobenzene. It was estimated that 1-[4-chloro-1-(4-fluorophenyl)butyl]-4-fluorobenzene was not irritating to skin of New Zealand White rabbits.

This result is supported by the experimental study summarized in Scientific Committee on Consumer Safety - SCCS, OPINION ON UV filter S86 - Phenylene bis-diphenyltriazine ; 2015, for thefunctionally similar read across substance, 3,3'-(1,4-Phenylene)bis(5,6-diphenyl-1,2,4-triazine) [CAS: 55514-22-2]. The test was performed according to the Guidelines mentioned inAnnex IB.40, Directive 2000/33/CE from the Commission, April 25th 2000. 3 repeated applications of10% test chemical in paraffin was done to the0.5 cm2 Reconstituted Human Epidermis (RHE) made from Human Normal Keratinocytes (SkinethicTM). Abdominal skin from a 48-year-old woman was used. The treatment was continued for 20 hours.5% SDS in water and Crème reparatrice cicalfate, Avéne Laboratory, batch F2268, pure were used as positive and negative controls respectively. The MTT method was used for in vitro cytotoxicity testing. An MTT direct-interaction test was made before the main test on reconstructed epidermis.

The test chemical did not interact with MTT. 3,3'-(1,4-Phenylene)bis(5,6-diphenyl-1,2,4-triazine) does not reduce MTT in a specific way. At the concentration of 10%, the cell viability was 100%. Hence,3,3'-(1,4 -Phenylene)bis(5,6-diphenyl-1,2,4-triazine) was considered not a skin irritant.

These results are also supported by the experimental study summarized in IUCLID Dataset, EUROPEAN COMMISSION – European Chemicals Bureau, last updated 2000;for thefunctionally similar read across substance, Terphenyl [CAS: 26140-60-3]. The study was performed according to Younger Laboratory Method. Terphenyl was applied to rabbit skin and observed for signs of irritation (dose, duration and number of animals not specified).Terphenyl did not cause any irritation to rabbit skin.

Hence, terphenyl can be considered not irritating to rabbit skin.

Based on the available data for the target as well as it read across substances;and applying the weight of evidence approach, it can be concluded that1-[4-chloro-1-(4-fluorophenyl)butyl]-4-fluorobenzene was not irritating to skin.Comparing the above annotations with the criteria of CLP regulation,1-[4-chloro-1-(4-fluorophenyl)butyl]-4-fluorobenzene can be classified under the category “Not Classified”.

Eye Irritation:

In different studies, 1-[4-chloro-1-(4-fluorophenyl)butyl]-4-fluorobenzene has been investigated for potential for ocular irritation to a greater or lesser extent. The studies are based on in vivo and in vitro experiments along with predicted data for the functionally similar read across substances, Isopropyl biphenyl [CAS: 25640-78-2] and Alkanes C14-17, chloro [CAS: 85535 -85-9]. The predicted data using the OECD QSAR toolbox has also been compared with the experimental data.

In a prediction done by SSS (2017) using the OECD QSAR toolbox with log kow as the primary descriptor, the ocular irritation potential was estimated for1-[4-chloro-1-(4-fluorophenyl)butyl]-4-fluorobenzene. It was estimated that1-[4-chloro-1-(4-fluorophenyl)butyl]-4-fluorobenzene was not irritating to eyes of New Zealand White rabbits.

This result is supported by the experimental study summarized in OTS0206598, NTRL report, Last updated 1984, forthe functionally similar read across substance, Isopropyl biphenyl [CAS: 25640-78-2]. Undiluted isopropyl biphenyl was instilled into the eyes of rabbits. Some eyes were washed and some remained unwashed throughout the study (number of animals and duration not mentioned). The treated eyes were observed for signs of irritation.

Undiluted isopropyl biphenyl was essentially not irritating to unwashed and washed eyes of rabbits.

Hence, isopropyl biphenyl can be considered not irritating to eyes.

These results are also supported by the experimental study summarized in IUCLID dataset, EUROPEAN COMMISSION – European Chemicals Bureau, last updated 2000;forthe functionally similar read across substance, Alkanes C14-17, chloro [CAS: 85535-85-9]. Alkanes C14-17, chloro was instilled in to rabbit eyes and observed for signs of irritation (dose, duration and number of animals not specified).Alkanes C14-17, chloro did not cause any irritation to rabbit eyes.

Hence, Alkanes C14-17, chloro can be considered not irritating to rabbit eyes.

Based on the available data for the target as well as it read across substances;and applying the weight of evidence approach, it can be concluded that1-[4-chloro-1-(4-fluorophenyl)butyl]-4-fluorobenzene was not irritating to eyes.Comparing the above annotations with the criteria of CLP regulation,1-[4-chloro-1-(4-fluorophenyl)butyl]-4-fluorobenzene can be classified under the category “Not Classified”.

Justification for classification or non-classification

Based on the available information, 1-[4-chloro-1-(4-fluorophenyl)butyl]-4-fluorobenzene is not likely to cause any irritation to eyes and skin.

Hence,1-[4-chloro-1-(4-fluorophenyl)butyl]-4-fluorobenzene can be classified under the category “Not Classified” as per CLP regulation.