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

Endpoint summary

Description of key information

LD50 was estimated to be 10780mg/kg bw when rats were orally exposed with 1-[4-chloro-1-(4-fluorophenyl) butyl]-4-fluorobenzene.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Endpoint:

acute toxicity: oral

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:

other: As mention below

Principles of method if other than guideline:

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

GLP compliance:

not specified

Test type:

standard acute method

Limit test:

no

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:

rat

Strain:

Fischer 344

Sex:

male/female

Details on test animals or test system and environmental conditions:

No data available

Route of administration:

oral: gavage

Vehicle:

corn oil

Details on oral exposure:

No data available

Doses:

10780mg/kg bw

No. of animals per sex per dose:

Total :10
Male: 5
Female:5

Control animals:

not specified

Details on study design:

No data available

Statistics:

No data available

Preliminary study:

No data available

Sex:

male/female

Dose descriptor:

LD50

Effect level:

10 780 mg/kg bw

Based on:

test mat.

Remarks on result:

other: 50% mortality observed

Mortality:

No data available

Clinical signs:

other: No data available

Gross pathology:

No data available

Other findings:

No data available

The prediction was based on dataset comprised from the following descriptors: LD50
Estimation method: Takes average value from the 5 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" and "i" )  )

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 >> 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 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"

Referential boundary: The target chemical should be classified as SN2 AND SN2 >> Nucleophilic substitution at sp3 carbon atom AND SN2 >> Nucleophilic substitution at sp3 carbon atom >> Alkyl halides  by Protein binding alerts for skin sensitization by OASIS v1.3

Domain logical expression index: "f"

Referential boundary: The target chemical should be classified as No alert found by Protein binding alerts for skin sensitization by OASIS v1.3

Domain logical expression index: "g"

Referential boundary: The target chemical should be classified as Alkyl halide AND Aryl halide by Organic Functional groups (nested) ONLY

Domain logical expression index: "h"

Parametric boundary:The target chemical should have a value of log Kow which is >= 3.54

Domain logical expression index: "i"

Parametric boundary:The target chemical should have a value of log Kow which is <= 7.4

Interpretation of results:

other: Not clissified

Conclusions:

LD50 was estimated to be 10780mg/kg bw when rats were orally exposed with 1-[4-chloro-1-(4-fluorophenyl) butyl]-4-fluorobenzene.

Executive summary:

In a prediction done by SSS (2017) using the OECD QSAR toolbox with log kow as the primary descriptor, the acute oral toxicity was estimated for1-[4-chloro-1-(4-fluorophenyl) butyl]-4-fluorobenzene (3312-04-7).The LD50 was estimated to be 10780mg/kg bw when male and female Fischer 344 rats were exposed with1-[4-chloro-1-(4-fluorophenyl) butyl]-4-fluorobenzene (3312-04-7) by orally.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

10 780 mg/kg bw

Quality of whole database:

Data is Klimicsh 2 and from QSAR Toolbox 3.3. (2017)

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Acute oral toxicity

In different studies, 1-[4-chloro-1-(4-fluorophenyl) butyl]-4-fluorobenzene (3312-04-7) has been investigated for acute oral toxicity to a greater or lesser extent. Often are the studies based on in vivo experiments and estimated data in rodents, i.e. most commonly in rats for 1-[4-chloro-1-(4-fluorophenyl) butyl]-4-fluorobenzene (3312-04-7). The predicted data using the OECD QSAR toolbox has also been compared with the experimental studies.

In a prediction done by SSS (2017) using the OECD QSAR toolbox with log kow as the primary descriptor, the acute oral toxicity was estimated for 1-[4-chloro-1-(4-fluorophenyl) butyl]-4-fluorobenzene (3312-04-7).The LD50 was estimated to be 10780mg/kg bw when male and female Fischer 344 rats were exposed with1-[4-chloro-1-(4-fluorophenyl) butyl]-4-fluorobenzene (3312-04-7) by orally.

 In experimental study given byThe Danish Environmental Protection Agency (The Danish Environmental Protection Agency, 2013) on structurally similar read across substanceAlkanes C14-17, chloro (85535-85-9).Acute oral toxicity study was done in rat usingAlkanes C14-17, chloro .No mortality observed in treated rat at dose 15000mg/kg. Clinical signs like urinary incontinence or “oily/moist pelt around the anal-genital region”were observed in treated rats. HenceLD50 was considered to be >15000mg/kgbody weight.

 

Also it is further supported by experimental study given by Chlorinated Paraffins (EHC 181, 1996) (International Programme On Chemical Safety,Environmental Health Criteria 181,1996) on structurally similar read across substance Alkanes C10-13, chloro (85535-84-8).Acute oral toxicity study was done in rat usingAlkanes C10-13, chloro(85535-84-8).3male and 3 femaleWistar rats were used.Dose concentration 4000 -13000mg/kg bw were given by gavage route and observed for 7 days.There were no deaths except for one rat treated with 13000mg /kg body weight of C10-13;.Clinical signs of toxicity, such as piloerection, muscular incoordination and faecal and urinary incontinence, were observed in treated rats that received doses of 2000mg /kg body weight or more.On macroscopic examination revealed "minimal signs of stress" in the spleen, blotchy or pale liver with slight fatty changes and inflamed stomach.Hence LD50 was considered to be 4000-13000 mg/kg body weight. When rats were treated with Alkanes C10-13, chloro (85535-84-8) orally.

Thus, based on the above studies and predictions on 1-[4-chloro-1-(4-fluorophenyl) butyl]-4-fluorobenzene (3312-04-7) and it’s read across substances, it can be concluded that LD50 value is less than 10780 mg/kg bw. Thus, comparing this value with the criteria of CLP regulation 1-[4-chloro-1-(4-fluorophenyl) butyl]-4-fluorobenzene (3312-04-7) can be “Not classified” for acute oral toxicity.

 

Justification for classification or non-classification

Thus, comparing this value with the criteria of CLP regulation 1-[4-chloro-1-(4-fluorophenyl) butyl]-4-fluorobenzene (3312-04-7) can be “Not classified” for acute oral toxicity.