4'-cyanoacetophenone

Endpoint summary

Description of key information

Skin irritation:

The dermal irritation potential of 4’-Cyanoacetophenone (CAS No: 1443-80-7) was estimated using OECD QSAR toolbox version 3.3 with logPow as the primary descriptor. The chemical 4’-Cyanoacetophenone (CAS No: 1443-80-7) was estimated to be not irritating to the skin of New Zealand White rabbits. Based on the estimated result 4’-Cyanoacetophenone (CAS No: 1443-80-7) can be considered to be not irritating to skin and can be classified under the category ˋ Not Classified’ as per CLP regulation.

 

Eye irritation:

The ocular irritation potential of 4’-Cyanoacetophenone (CAS No: 1443-80-7) was estimated using OECD QSAR toolbox version 3.3 with logPow as the primary descriptor. The chemical 4’-Cyanoacetophenone (CAS No: 1443-80-7) was estimated to be not irritating into the eyes of New Zealand White rabbits. Based on the estimated result 4’-Cyanoacetophenone (CAS No: 1443-80-7) can be considered to be not irritating to eye and can be classified under the category ˋ 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 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

Specific details on test material used for the study:

- Name of test material : 4'-Cyanoacetophenone
- Molecular formula : C9H7NO
- Molecular weight : 145.16 g/mol
- Smiles notation : CC(=O)c1ccc(C#N)cc1
- InChl : 1S/C9H7NO/c1-7(11)9-4-2-8(6-10)3-5-9/h2-5H,1H3
- Substance type: Organic
- Physical state: Solid

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

No data available

Type of coverage:

occlusive

Preparation of test site:

shaved

Vehicle:

not specified

Controls:

not specified

Amount / concentration applied:

No data available

Duration of treatment / exposure:

4 hours

Observation period:

24/48/72 hours

Number of animals:

3

Details on study design:

No data available

Irritation parameter:

overall irritation score

Basis:

mean

Time point:

24/48/72 h

Reversibility:

not specified

Remarks on result:

no indication of irritation

Irritant / corrosive response data:

No skin irritation was observed.

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

(((((((((((("a" or "b" or "c" or "d" )  and ("e" and ( not "f") )  )  and ("g" and ( not "h") )  )  and ("i" and ( not "j") )  )  and "k" )  and ("l" and ( not "m") )  )  and ("n" and ( not "o") )  )  and "p" )  and ("q" and ( not "r") )  )  and ("s" and ( not "t") )  )  and "u" )  and ("v" and "w" )  )

Domain logical expression index: "a"

Referential boundary: The target chemical should be classified as Aromatic compound OR Carbonyl compound OR Ketone OR Nitrile by Organic functional groups, Norbert Haider (checkmol) ONLY

Domain logical expression index: "b"

Referential boundary: The target chemical should be classified as Acetylenic Carbon [#C] OR Aliphatic Carbon [CH] OR Aliphatic Carbon [-CH2-] OR Aliphatic Carbon [-CH3] OR Aromatic Carbon [C] OR Carbonyl, aliphatic attach [-C(=O)-] OR Carbonyl, olefinic attach [-C(=O)-] OR Carbonyl, one aromatic attach [-C(=O)-] OR Cyano, aromatic attach [-C#N] OR Miscellaneous sulfide (=S) or oxide (=O) OR Olefinic carbon [=CH- or =C<] by Organic functional groups (US EPA) ONLY

Domain logical expression index: "c"

Referential boundary: The target chemical should be classified as Aryl OR Ketone OR Nitrile OR Overlapping groups by Organic Functional groups (nested) ONLY

Domain logical expression index: "d"

Referential boundary: The target chemical should be classified as Aryl OR Ketone OR Nitrile by Organic Functional groups ONLY

Domain logical expression index: "e"

Referential boundary: The target chemical should be classified as No alert found by DNA binding by OECD

Domain logical expression index: "f"

Referential boundary: The target chemical should be classified as Michael addition OR Michael addition >> P450 Mediated Activation to Quinones and Quinone-type Chemicals OR Michael addition >> P450 Mediated Activation to Quinones and Quinone-type Chemicals >> Arenes OR Michael addition >> P450 Mediated Activation to Quinones and Quinone-type Chemicals >> Polycyclic (PAHs) and heterocyclic (HACs) aromatic hydrocarbons-Michael addition OR Michael addition >> Polarised Alkenes-Michael addition OR Michael addition >> Polarised Alkenes-Michael addition >> Alpha, beta- unsaturated aldehydes OR Michael addition >> Polarised Alkenes-Michael addition >> Alpha, beta- unsaturated ketones OR Schiff base formers OR Schiff base formers >> Direct Acting Schiff Base Formers OR Schiff base formers >> Direct Acting Schiff Base Formers >> Alpha-beta-dicarbonyl OR SN1 OR SN1 >> Carbenium Ion Formation OR SN1 >> Carbenium Ion Formation >> Polycyclic (PAHs) and heterocyclic (HACs) aromatic hydrocarbons-SN1 OR SN2 OR SN2 >> Direct Acting Epoxides and related OR SN2 >> Direct Acting Epoxides and related >> Epoxides by DNA binding by OECD

Domain logical expression index: "g"

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

Domain logical expression index: "h"

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 Non-covalent interaction OR Non-covalent interaction >> DNA intercalation OR Non-covalent interaction >> DNA intercalation >> Quinones OR Radical OR Radical >> Radical mechanism via ROS formation (indirect) OR Radical >> Radical mechanism via ROS formation (indirect) >> Quinones OR SN2 OR SN2 >> Direct acting epoxides formed after metabolic activation OR SN2 >> Direct acting epoxides formed after metabolic activation >> Quinoline 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: "i"

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

Domain logical expression index: "j"

Referential boundary: The target chemical should be classified as Acylation OR Acylation >> Direct acylation involving a leaving group OR Acylation >> Direct acylation involving a leaving group >> (Thio)Acyl and (thio)carbamoyl halides and cyanides  OR Michael Addition OR Michael Addition >> Michael addition on conjugated systems with electron withdrawing group OR Michael Addition >> Michael addition on conjugated systems with electron withdrawing group >> alpha,beta-Carbonyl compounds with polarized double bonds  OR Michael Addition >> Michael addition on conjugated systems with electron withdrawing group >> Cyanoalkenes OR Michael Addition >> Polarised Alkenes OR Michael Addition >> Polarised Alkenes >> Polarised Alkene - alkenyl pyridines, pyrazines, pyrimidines or triazines  OR Nucleophilic addition OR Nucleophilic addition >> Addition to carbon-hetero double bonds OR Nucleophilic addition >> Addition to carbon-hetero double bonds >> Ketones OR Schiff base formation OR Schiff base formation >> Direct acting Schiff base formers OR Schiff base formation >> Direct acting Schiff base formers >> 1,2-Dicarbonyls and 1,3-Dicarbonyls  by Protein binding by OASIS v1.3

Domain logical expression index: "k"

Referential boundary: The target chemical should be classified as Class 5 (Not possible to classify according to these rules) by Acute aquatic toxicity classification by Verhaar (Modified) ONLY

Domain logical expression index: "l"

Referential boundary: The target chemical should be classified as (!Undefined)Group All Lipid Solubility < 0.01 g/kg AND (!Undefined)Group CN Lipid Solubility < 0.4 g/kg by Eye irritation/corrosion Exclusion rules by BfR

Domain logical expression index: "m"

Referential boundary: The target chemical should be classified as (!Undefined)Group All Aqueous Solubility < 0.000005 g/L OR (!Undefined)Group All Aqueous Solubility < 0.00002 g/L OR (!Undefined)Group All log Kow < -3.1 OR (!Undefined)Group All log Kow > 9 OR (!Undefined)Group All Melting Point > 200 C OR Exclusion rules not met OR Group All Aqueous Solubility < 0.000005 g/L OR Group All Aqueous Solubility < 0.00002 g/L OR Group All log Kow < -3.1 OR Group All log Kow > 9 OR Group All Melting Point > 200 C OR Group All Molecular Weight > 650 g/mol OR Group C Aqueous Solubility < 0.0001 g/L OR Group C Aqueous Solubility < 0.0005 g/L OR Group C Melting Point > 55 C OR Group C Molecular Weight > 380 g/mol OR Group CN Aqueous Solubility < 0.1 g/L OR Group CN log Kow > 4.5 OR Group CN Molecular Weight > 290 g/mol OR Group CNS log Kow > 1.5 OR Group CNS Melting Point > 50 C by Eye irritation/corrosion Exclusion rules by BfR

Domain logical expression index: "n"

Referential boundary: The target chemical should be classified as (!Undefined)Group All Lipid Solubility < 0.01 g/kg AND (!Undefined)Group CN Lipid Solubility < 0.4 g/kg by Skin irritation/corrosion Exclusion rules by BfR

Domain logical expression index: "o"

Referential boundary: The target chemical should be classified as (!Undefined)Group C Surface Tension > 62 mN/m OR Group CN Vapour Pressure < 0.001 Pa by Skin irritation/corrosion Exclusion rules by BfR

Domain logical expression index: "p"

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

Domain logical expression index: "q"

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

Domain logical expression index: "r"

Referential boundary: The target chemical should be classified as Alkali Earth OR Halogens by Groups of elements

Domain logical expression index: "s"

Referential boundary: The target chemical should be classified as Not categorized by Repeated dose (HESS)

Domain logical expression index: "t"

Referential boundary: The target chemical should be classified as Aliphatic nitriles (Hepatotoxicity) Rank B OR Tamoxifen (Hepatotoxicity) Alert by Repeated dose (HESS)

Domain logical expression index: "u"

Similarity boundary:Target: CC(=O)c1ccc(C#N)cc1
Threshold=20%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization

Domain logical expression index: "v"

Parametric boundary:The target chemical should have a value of log Kow which is >= -0.262

Domain logical expression index: "w"

Parametric boundary:The target chemical should have a value of log Kow which is <= 1.94

Interpretation of results:

other: not irritating

Conclusions:

The chemical 4’-Cyanoacetophenone (CAS No: 1443-80-7)was estimated to be not irritating to the skin of New Zealand White rabbits. Based on the estimated result 4’-Cyanoacetophenone (CAS No: 1443-80-7) can be considered to be not irritating to skin.

Executive summary:

The dermal irritation potential of 4’-Cyanoacetophenone (CAS No: 1443-80-7) was estimated using OECD QSAR toolbox version 3.3 with logPow as the primary descriptor. The chemical 4’-Cyanoacetophenone (CAS No: 1443-80-7)was estimated to be not irritating to the skin of New Zealand White rabbits. Based on the estimated result 4’-Cyanoacetophenone (CAS No: 1443-80-7)can be considered to be not irritating to skin and can be classified under the category ˋ 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 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

Specific details on test material used for the study:

- Name of test material : 4'-Cyanoacetophenone
- Molecular formula : C9H7NO
- Molecular weight : 145.16 g/mol
- Smiles notation : CC(=O)c1ccc(C#N)cc1
- InChl : 1S/C9H7NO/c1-7(11)9-4-2-8(6-10)3-5-9/h2-5H,1H3
- Substance type: Organic
- Physical state: Solid

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

No data available

Vehicle:

not specified

Controls:

not specified

Amount / concentration applied:

No data available

Duration of treatment / exposure:

single application

Observation period (in vivo):

72 hours

Number of animals or in vitro replicates:

3

Details on study design:

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 eye irritation was obsrved in treated rabbits.

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

((((((((((((((("a" or "b" or "c" or "d" )  and ("e" and ( not "f") )  )  and ("g" and ( not "h") )  )  and ("i" and ( not "j") )  )  and ("k" and ( not "l") )  )  and "m" )  and ("n" and ( not "o") )  )  and ("p" and ( not "q") )  )  and "r" )  and "s" )  and "t" )  and "u" )  and "v" )  and "w" )  and ("x" and "y" )  )

Domain logical expression index: "a"

Referential boundary: The target chemical should be classified as Aromatic compound OR Carbonyl compound OR Ketone OR Nitrile by Organic functional groups, Norbert Haider (checkmol) ONLY

Domain logical expression index: "b"

Referential boundary: The target chemical should be classified as Acetylenic Carbon [#C] OR Aliphatic Carbon [CH] OR Aliphatic Carbon [-CH2-] OR Aliphatic Carbon [-CH3] OR Aromatic Carbon [C] OR Carbonyl, aliphatic attach [-C(=O)-] OR Carbonyl, olefinic attach [-C(=O)-] OR Carbonyl, one aromatic attach [-C(=O)-] OR Cyano, aromatic attach [-C#N] OR Miscellaneous sulfide (=S) or oxide (=O) OR Olefinic carbon [=CH- or =C<] by Organic functional groups (US EPA) ONLY

Domain logical expression index: "c"

Referential boundary: The target chemical should be classified as Aryl OR Ketone OR Nitrile OR Overlapping groups by Organic Functional groups (nested) ONLY

Domain logical expression index: "d"

Referential boundary: The target chemical should be classified as Aryl OR Ketone OR Nitrile by Organic Functional groups ONLY

Domain logical expression index: "e"

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

Domain logical expression index: "f"

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 >> Dicarbonyl compounds 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 >> Radical mechanism via ROS formation (indirect) 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 >> 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 >> Direct acting epoxides formed after metabolic activation OR SN2 >> Direct acting epoxides formed after metabolic activation >> Quinoline 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: "g"

Referential boundary: The target chemical should be classified as No alert found by DNA binding by OECD

Domain logical expression index: "h"

Referential boundary: The target chemical should be classified as Michael addition OR Michael addition >> P450 Mediated Activation to Quinones and Quinone-type Chemicals OR Michael addition >> P450 Mediated Activation to Quinones and Quinone-type Chemicals >> Arenes OR Michael addition >> P450 Mediated Activation to Quinones and Quinone-type Chemicals >> Polycyclic (PAHs) and heterocyclic (HACs) aromatic hydrocarbons-Michael addition OR Michael addition >> Polarised Alkenes-Michael addition OR Michael addition >> Polarised Alkenes-Michael addition >> Alpha, beta- unsaturated ketones by DNA binding by OECD

Domain logical expression index: "i"

Referential boundary: The target chemical should be classified as Non binder, without OH or NH2 group by Estrogen Receptor Binding

Domain logical expression index: "j"

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: "k"

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

Domain logical expression index: "l"

Referential boundary: The target chemical should be classified as Acylation OR Acylation >> Direct acylation involving a leaving group OR Acylation >> Direct acylation involving a leaving group >> (Thio)Acyl and (thio)carbamoyl halides and cyanides  OR Michael Addition OR Michael Addition >> Michael addition on conjugated systems with electron withdrawing group OR Michael Addition >> Michael addition on conjugated systems with electron withdrawing group >> alpha,beta-Carbonyl compounds with polarized double bonds  OR Michael Addition >> Polarised Alkenes OR Michael Addition >> Polarised Alkenes >> Polarised Alkene - alkenyl pyridines, pyrazines, pyrimidines or triazines  OR Nucleophilic addition OR Nucleophilic addition >> Addition to carbon-hetero double bonds OR Nucleophilic addition >> Addition to carbon-hetero double bonds >> Ketones by Protein binding by OASIS v1.3

Domain logical expression index: "m"

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

Domain logical expression index: "n"

Referential boundary: The target chemical should be classified as (!Undefined)Group All Lipid Solubility < 0.01 g/kg AND (!Undefined)Group CN Lipid Solubility < 0.4 g/kg by Eye irritation/corrosion Exclusion rules by BfR

Domain logical expression index: "o"

Referential boundary: The target chemical should be classified as Group All Aqueous Solubility < 0.000005 g/L OR Group All Aqueous Solubility < 0.00002 g/L OR Group All log Kow < -3.1 OR Group All log Kow > 9 OR Group All Melting Point > 200 C OR Group C Aqueous Solubility < 0.0001 g/L OR Group C Aqueous Solubility < 0.0005 g/L OR Group C Melting Point > 55 C OR Group CN Aqueous Solubility < 0.1 g/L OR Group CN log Kow > 4.5 OR Group CNS log Kow > 1.5 OR Group CNS Melting Point > 50 C by Eye irritation/corrosion Exclusion rules by BfR

Domain logical expression index: "p"

Referential boundary: The target chemical should be classified as (!Undefined)Group All Lipid Solubility < 0.01 g/kg AND (!Undefined)Group CN Lipid Solubility < 0.4 g/kg by Skin irritation/corrosion Exclusion rules by BfR

Domain logical expression index: "q"

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: "r"

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

Domain logical expression index: "s"

Referential boundary: The target chemical should be classified as Aryl AND Ketone AND Nitrile by Organic Functional groups ONLY

Domain logical expression index: "t"

Referential boundary: The target chemical should be classified as Aryl AND Ketone AND Nitrile by Organic Functional groups ONLY

Domain logical expression index: "u"

Referential boundary: The target chemical should be classified as Aryl AND Ketone AND Nitrile by Organic Functional groups ONLY

Domain logical expression index: "v"

Referential boundary: The target chemical should be classified as Aryl AND Ketone AND Nitrile by Organic Functional groups ONLY

Domain logical expression index: "w"

Referential boundary: The target chemical should be classified as Aryl AND Ketone AND Nitrile by Organic Functional groups ONLY

Domain logical expression index: "x"

Parametric boundary:The target chemical should have a value of log Kow which is >= 0.548

Domain logical expression index: "y"

Parametric boundary:The target chemical should have a value of log Kow which is <= 3.02

Interpretation of results:

other: not irritating

Conclusions:

The chemical 4’-Cyanoacetophenone (CAS No: 1443-80-7) was estimated to be not irritating into the eyes of New Zealand White rabbits. Based on the estimated result 4’-Cyanoacetophenone (CAS No: 1443-80-7) can be considered to be not irritating to eye.

Executive summary:

The ocular irritation potential of 4’-Cyanoacetophenone (CAS No: 1443-80-7) was estimated using OECD QSAR toolbox version 3.3 with logPow as the primary descriptor. The chemical 4’-Cyanoacetophenone (CAS No: 1443-80-7)was estimated to be not irritating into the eyes of New Zealand White rabbits. Based on the estimated result 4’-Cyanoacetophenone (CAS No: 1443-80-7) can be considered to be not irritating to eye and can be classified under the category ˋ 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:

Various studieshas been investigated for the test chemical4’-Cyanoacetophenone (CAS No: 1443-80-7)to observe the potential for dermal irritation to a greater or lesser extent. The studies are based on in vivo experiments in rabbits, guinea pigs and humans for target chemical4’-Cyanoacetophenone (CAS No: 1443-80-7) and its structurally similar read across substancesAcetophenone (CAS No: 98-86-2)andβ-methyl naphthyl ketone (CAS no: 93-08-3).The predicted data using the OECD QSAR toolbox andDanish QSAR databasehas also been compared with the experimental data and summarized as below;

 

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 for test chemical4’-Cyanoacetophenone (CAS No: 1443-80-7) .The chemical 4’-Cyanoacetophenone (CAS No: 1443-80-7) is estimated to be not irritating to skin of New Zealand White rabbits.

 

According to Danish QSAR database , the skin irritation effects were estimated by using four different models i.e, Battery, Leadscope, SciQSAR and CASE Ultra for 4’-Cyanoacetophenone (CAS No: 1443-80-7)(CAS No: 98 -97 -5). Based on estimation, no skin irritation reactions were observed in rabbits. Therefore, 4’-Cyanoacetophenone (CAS No: 1443-80-7) was considered to be not irritating.

 

The D.W. SHARP {Toxicology, 9 (1978) 261-271} conducted preliminary irritation test for read across chemicalAcetophenone (CAS No: 98-86-2)in guinea pigs to determine the concentration suitableforthe sensitization study[injection challenge concentration (ICC) and application challenge concentration(ACCthat supports the above mentioned results.In the preliminary test, the guinea pigs were treated intradermally and dermally.4 guinea pigs were (same sex) were injected intradermally in the clipped and shaved flanks with 0.1ml aliquots of a range of concentration of test substance in physiological saline. 24 hours later, the skin was examined for erythema and edema.The concentration giving slight but perceptible irritation with no oedema was selected as the injection challenge concentration (ICC).Aliquots of 0.1ml using a range of concentration of the test substance in distilled water were applied in small circular areas to the shaved flanks of 4 previously untreated guinea pigs.24 hours later, the skin was examined for erythema and the highest concentration which caused no irritation was selected as the application challenge concentration (ACC).As a result of preliminary studies, the concentration of Acetophenone at which no irritation was observed were 5% for the ICC and 20% for ACC.Since the test chemical did not induce any cutaneous effects at these concentrations, the Acetophenone (CAS No: 98-86-2) was considered to be not irritating to the skin of guinea pigs.

 

The above results were further supported by the patch test performed by D. L. J. Opdyke {Food and Cosmetics Toxicology, Volume 13, Issue 6, Page 867, 1979}for read across chemical β-methyl naphthyl ketone (CAS no: 93-08-3) on 24 human volunteers.The undiluted chemical was applied to the skin of each subjects for 24 hours and later observed for skin reaction.Only one of the 24 volunteer showed skin irritation but no irritation was observed in other subjects. Hence,2,4-diamino-6-phenyl-1,3,5-triazine can be considered to be not irritating to rabbit eyes. Hence the chemicalβ-methyl naphthyl ketone (CAS no: 93-08-3) was considered to be not irritating to the skin of human volunteers.

 

Thus on the basis of available data for thetarget chemical4’-Cyanoacetophenone (CAS No: 1443-80-7) and its structurally similar read across substancesAcetophenone (CAS No: 98-86-2)andβ-methyl naphthyl ketone (CAS no: 93-08-3),it can be concluded thatchemical 4’-Cyanoacetophenone (CAS No: 1443-80-7) is unable to cause skin irritation and considered as not irritating. Comparing the above annotations with the criteria of CLP regulation, it can be classified under the category “Not Classified”.

 

 

Eye irritation:

In different studies,the test chemical4’-Cyanoacetophenone (CAS No: 1443-80-7) has been investigated for potential for ocular irritationto a greater or lesser extent. The studies are based on in vivo experiments in rabbits for target chemical4’-Cyanoacetophenone (CAS No: 1443-80-7) andits structurally similar read across substancesBenzophenone (CAS No: -119-61-9)andbenzonitrile (CAS No: 100-47-0).The predicted data using the OECD QSAR toolbox has also been compared with the experimental data and summarized as below;

 

In a prediction done by SSS (2017) using the OECD QSAR toolbox with log kow as the primary descriptor, the eye irritation potential was estimated for test chemical4’-Cyanoacetophenone (CAS No: 1443-80-7) .The chemical 4’-Cyanoacetophenone (CAS No: 1443-80-7) is estimated to be not irritating to eye of New Zealand White rabbits.

 

The IFA (GESTIS) {GESTIS SUBSTANCE Database (information system in hazardous substance of the Berufsgenossenscheftn), 2017} reported an eye irritation study of read across substance Benzophenone (CAS No: -119-61-9) in rabbits which supports the above mentioned result. The test substance was placed in rabbit’s eye at volume of 0.1ml and observed for any ocular changes. Since the chemical did not induce any adverse effects, Benzophenone (CAS No: -119-61-9) was considered to be not irritating to rabbits’ eye.

 

The above results were further supported by the experimental study carried out by BG Chemie {BG Chemie InfoCenter, TOXIKOLOGISCHE BEWERTUNGEN; TOXICOLOGICAL EVALUATION last updated: 06/2000 } for read across substance benzonitrile (CAS No: 100-47-0) in rabbits according to FDA method. Six New Zealand white rabbits received 0.1 ml of the test chemical instilled into the conjunctival sac. The untreated eye served as the control. The findings were assessed 24, 48 and 72 hours as well as 7 days after instillation. After 24, 48 and 72 hours, reddening of the conjunctivae was observed in 6, 4 and 4 of the 6 animals, respectively (irritation index 1 from a maximum score of 3). Chemosis occurred in 2 of the 6 animals 24 hours after instillation (irritation index 1 from a maximum score of 4). The cornea and iris were without findings. Slight Irritation was observed, which cleared completely after 7 days. Conjunctivae score – 1; chemosis score – 1; cornea score -0, iris score- 0. Based on these findings and the FDA criteria, benzonitrile was evaluated as not irritating to rabbit eyes.

 

Thus on the basis of available data for thetarget chemical4’-Cyanoacetophenone (CAS No: 1443-80-7) and its structurally similar read across substancesBenzophenone (CAS No: -119-61-9)andbenzonitrile (CAS No: 100-47-0),it can be concluded thatchemical 4’-Cyanoacetophenone (CAS No: 1443-80-7) is unable to cause eye irritation and considered as not irritating. Comparing the above annotations with the criteria of CLP regulation, it can be classified under the category “Not Classified”.

Justification for classification or non-classification

The skin and eye irritation potential of test chemical 4’-Cyanoacetophenone (CAS No: 1443-80-7) and its structurally similar read across substanceswere observed in various studies. The results obtained from these studies indicate that the chemical 4’-Cyanoacetophenone is unlikely to cause skin and eye irritation. Hence 4’-Cyanoacetophenone (CAS No: 1443-80-7) can be classified under the category “Not Classified” for skin and eye as per CLP.