4'-cyanoacetophenone

Endpoint summary

Description of key information

Acute oral toxicity: 

Acute oral toxicity dose (LD50) of 4'-Cyanoacetophenone (1443-80-7) was predicted based on OECD QSAR toolbox 1550 mg/kg bw and different studies available on structurally similar read across substances 4'-Methylacetophenone (122-00-9) 1400 mg/kg bw and Benzonitrile (100-47-0) 800 mg/kg bw. All these studies concluded that the LD50 value is between 300-2000 mg/kg bw. Thus, comparing this value with the criteria of CLP regulation, 4'-Cyanoacetophenone can be classified as category IV of acute oral toxicity.

Acute Inhalation toxicity: 

Acute Inhalation toxicity dose (LC50) of 4'-Cyanoacetophenone (1443-80-7) was predicted based on OECD QSAR toolbox 512 mg/L air, and different studies available for the structurally similar read across substance Benzonitrile (100-47-0) 38600 mg/m3 and closely related read across substance Acetone (67-64-1) 50100 mg/m3. All these studies concluded that the LC50 value is greater than 5 mg/L air. Thus, comparing this value with the criteria of CLP regulation, 4'-Cyanoacetophenone can be classified as category V of acute inhalation toxicity.

Acute Dermal toxicity: 

Acute Dermal toxicity dose (LD50) for 4'-Cyanoacetophenone (1443-80-7) was predicted based on OECD QSAR toolbox 3174 mg/kg bwand differentstudies available on structurally similar read across substances 4'-Methylacetophenone (122-00-9) >2000 mg/kg bw and Acetophenone (98-86-2) 16400 mg/kg bw. All these studies concluded that the LD50 value is>2000 mg/kg bw. Thus, comparing this value with the criteria of CLP regulation, 4'-Cyanoacetophenone can be classified as category V of acute dermal toxicity.

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 predicted using OECD QSAR toolbox version 3.3 and the supporting QMRF report has been attached

Qualifier:

according to guideline

Guideline:

other: estimated

Principles of method if other than guideline:

Prediction is done using QSAR Toolbox version 3.3

GLP compliance:

not specified

Test type:

other: not specified

Limit test:

no

Specific details on test material used for the study:

Name: 4-Acetylbenzonitrile
InChI:1S/C9H7NO/c1-7(11)9-4-2-8(6-10)3-5-9/h2-5H,1H3
SMILES:CC(=O)c1ccc(C#N)cc1
Molecular Formula: C9H7NO
Molecular Weight: 145.16 g/mole

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

not specified

Route of administration:

oral: gavage

Vehicle:

not specified

Details on oral exposure:

not specified

Doses:

1550 mg/kg

No. of animals per sex per dose:

not specified

Control animals:

not specified

Details on study design:

not specified

Statistics:

not specified

Preliminary study:

not specified

Sex:

female

Dose descriptor:

LD50

Effect level:

1 550 mg/kg bw

Based on:

test mat.

Remarks on result:

other: 50% mortality observed.

Mortality:

not specified

Clinical signs:

other: not specified

Gross pathology:

not specified

Other findings:

not specified

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

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 Non binder, without OH or NH2 group by Estrogen Receptor Binding

Domain logical expression index: "f"

Referential boundary: The target chemical should be classified as Non binder, MW>500 OR Non binder, non cyclic structure by Estrogen Receptor Binding

Domain logical expression index: "g"

Referential boundary: The target chemical should be classified as No superfragment by Superfragments ONLY

Domain logical expression index: "h"

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

Domain logical expression index: "i"

Referential boundary: The target chemical should be classified as Ketones by Skin irritation/corrosion Inclusion rules by BfR

Domain logical expression index: "j"

Referential boundary: The target chemical should be classified as Epoxides(=oxiranes) by Skin irritation/corrosion Inclusion rules by BfR

Domain logical expression index: "k"

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

Domain logical expression index: "l"

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

Domain logical expression index: "m"

Parametric boundary:The target chemical should have a value of log Kow which is >= -4.77

Domain logical expression index: "n"

Parametric boundary:The target chemical should have a value of log Kow which is <= 1.36

Interpretation of results:

Category 4 based on GHS criteria

Conclusions:

LD50 was estimated to be 1550 mg/kg bw, when Wistar female rats were treated with 4-Acetylbenzonitrile (1443-80-7) via oral gavage route.

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 for 4-Acetylbenzonitrile (1443-80-7). The LD50 was estimated to be 1550 mg/kg bw, when Wistar female rats were treated with 4-Acetylbenzonitrile (1443-80-7) via oral gavage route.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

1 550 mg/kg bw

Quality of whole database:

Data is Klimisch 2 and from QSAR toolbox 3.3

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Endpoint:

acute toxicity: inhalation

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 predicted using OECD QSAR toolbox version 3.3 and the supporting QMRF report has been attached

Qualifier:

according to guideline

Guideline:

other: estimated

Principles of method if other than guideline:

Prediction is done using QSAR Toolbox version 3.3

GLP compliance:

not specified

Test type:

other: not specified

Limit test:

no

Specific details on test material used for the study:

Name: 4'-Cyanoacetophenone
InChI:1S/C9H7NO/c1-7(11)9-4-2-8(6-10)3-5-9/h2-5H,1H3
SMILES:CC(=O)c1ccc(C#N)cc1
Molecular Formula: C9H7NO
Molecular Weight: 145.16 g/mole

Species:

rat

Strain:

Sprague-Dawley

Sex:

male

Details on test animals or test system and environmental conditions:

not specified

Route of administration:

inhalation

Type of inhalation exposure:

whole body

Vehicle:

not specified

Remark on MMAD/GSD:

not specified

Details on inhalation exposure:

not specified

Analytical verification of test atmosphere concentrations:

not specified

Duration of exposure:

4 h

Remarks on duration:

not specified

Concentrations:

512 mg/L air

No. of animals per sex per dose:

not specified

Control animals:

not specified

Details on study design:

not specified

Statistics:

not specified

Preliminary study:

not specified

Sex:

male

Dose descriptor:

LC50

Effect level:

512 mg/L air

Based on:

test mat.

Remarks on result:

other: 50% mortality observed

Mortality:

not specified

Clinical signs:

other: not specified

Body weight:

not specified

Gross pathology:

not specified

Other findings:

not specified

The prediction was based on dataset comprised from the following descriptors: LC50
Estimation method: Takes average value from the 8 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 ( not "n") )  )  and ("o" and ( not "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 OASIS v.1.3

Domain logical expression index: "f"

Referential boundary: The target chemical should be classified as AN2 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 SN2 OR SN2 >> Alkylation, direct acting epoxides and related OR SN2 >> Alkylation, direct acting epoxides and related >> Epoxides and Aziridines 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 by DNA binding by OECD

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 >> Cyanoalkenes 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 No alert found by Protein binding by OECD

Domain logical expression index: "l"

Referential boundary: The target chemical should be classified as SN2 OR SN2 >> SN2 reaction at sp3 carbon atom OR SN2 >> SN2 reaction at sp3 carbon atom >> alpha-Haloalkenes (and related cyano, sulfate and sulfonate subs. chem.) by Protein binding by OECD

Domain logical expression index: "m"

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: "n"

Referential boundary: The target chemical should be classified as Alkyl and vinyl nitriles< C6 atoms- sub category 25 (c, d) OR Known precedent reproductive and developmental toxic potential OR Miscellaneous non-cyclic chemicals (20) OR Multi-halogenated alkyl ethers (23b) by DART scheme v.1.0

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 CN Lipid Solubility < 0.4 g/kg by Eye irritation/corrosion Exclusion rules by BfR

Domain logical expression index: "p"

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 C Aqueous Solubility < 0.0001 g/L OR Group C Aqueous Solubility < 0.0005 g/L OR Group C Melting Point > 55 C by Eye irritation/corrosion Exclusion rules by BfR

Domain logical expression index: "q"

Referential boundary: The target chemical should be classified as No alert found by in vivo mutagenicity (Micronucleus) alerts by ISS

Domain logical expression index: "r"

Referential boundary: The target chemical should be classified as H-acceptor-path3-H-acceptor by in vivo mutagenicity (Micronucleus) alerts by ISS

Domain logical expression index: "s"

Referential boundary: The target chemical should be classified as Not classified by Oncologic Primary Classification

Domain logical expression index: "t"

Referential boundary: The target chemical should be classified as Siloxane Type Compounds by Oncologic Primary Classification

Domain logical expression index: "u"

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

Domain logical expression index: "v"

Parametric boundary:The target chemical should have a value of log Kow which is >= -0.245

Domain logical expression index: "w"

Parametric boundary:The target chemical should have a value of log Kow which is <= 4.55

Interpretation of results:

Category 5 based on GHS criteria

Conclusions:

LC50 was estimated to be 512 mg/L air, when Sprague-Dawley male rats were exposed with 4-Acetylbenzonitrile for 4 h of exposure period by inhalation to whole body.

Executive summary:

In a prediction done by SSS (2017) using the OECD QSAR toolbox with log kow as the primary descriptor, the acute inhalation toxicity was estimated for 4-Acetylbenzonitrile (1443-80-7). The LC50 was estimated to be 512 mg/L air, when Sprague-Dawley male rats were exposed with 4-Acetylbenzonitrile for 4 h of exposure period by inhalation to whole body.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LC50

Value:

512 000 mg/m³ air

Quality of whole database:

Data is Klimisch 2 and QSAR toolbox 3.3.

Acute toxicity: via dermal route

Link to relevant study records

Reference

Endpoint:

acute toxicity: dermal

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 predicted using OECD QSAR toolbox version 3.3 and the supporting QMRF report has been attached

Qualifier:

according to guideline

Guideline:

other: estimated

Principles of method if other than guideline:

Prediction is done using QSAR Toolbox version 3.3

GLP compliance:

not specified

Test type:

other: not specified

Limit test:

no

Specific details on test material used for the study:

Name: 4'-Cyanoacetophenone
InChI:1S/C9H7NO/c1-7(11)9-4-2-8(6-10)3-5-9/h2-5H,1H3
SMILES:CC(=O)c1ccc(C#N)cc1
Molecular Formula: C9H7NO
Molecular Weight: 145.16 g/mole

Species:

rabbit

Strain:

other: White Russian

Sex:

male/female

Details on test animals or test system and environmental conditions:

not specified

Type of coverage:

occlusive

Vehicle:

not specified

Details on dermal exposure:

not specified

Duration of exposure:

24 hours

Doses:

3174 mg/kg

No. of animals per sex per dose:

not specified

Control animals:

not specified

Details on study design:

not specified

Statistics:

not specified

Preliminary study:

not specified

Sex:

male/female

Dose descriptor:

LD50

Effect level:

3 174 mg/kg bw

Based on:

test mat.

Remarks on result:

other: 50% mortality observed

Mortality:

not specified

Clinical signs:

other: not specified

Gross pathology:

not specified

Other findings:

not specified

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" 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 ( not "n") )  )  and ("o" and "p" )  )

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 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 by DNA binding by OASIS v.1.3

Domain logical expression index: "g"

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

Domain logical expression index: "h"

Referential boundary: The target chemical should be classified as Non binder, MW>500 OR Non binder, non cyclic structure by Estrogen Receptor Binding

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 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  by Protein binding by OASIS v1.3

Domain logical expression index: "k"

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: "l"

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: "m"

Referential boundary: The target chemical should be classified as Ketones by Skin irritation/corrosion Inclusion rules by BfR

Domain logical expression index: "n"

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: "o"

Parametric boundary:The target chemical should have a value of log Kow which is >= 0.628

Domain logical expression index: "p"

Parametric boundary:The target chemical should have a value of log Kow which is <= 2.22

Interpretation of results:

Category 5 based on GHS criteria

Conclusions:

LD50 was estimated to be 3174 mg/kg bw, when White Russian male and female rabbit was treated with 4-Acetylbenzonitrile (1443-80-7) for 24 hours by dermal application occlusively.

Executive summary:

In a prediction done by SSS (2017) using the OECD QSAR toolbox with log kow as the primary descriptor, the acute dermal toxicity was estimated for 4-Acetylbenzonitrile (1443-80-7). The LD50 was estimated to be 3174 mg/kg bw, when White Russian male and female rabbit was treated with 4-Acetylbenzonitrile for 24 hours by dermal application occlusively.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

3 174 mg/kg bw

Quality of whole database:

Data is Klimisch 2 and from QSAR toolbox 3.3

Additional information

Acute oral toxicity:

In different studies, 4'-Cyanoacetophenone (1443-80-7) has been investigated for acute oral toxicity to a greater or lesser extent. Often are the studies based on in-vivo experiments in rodents, i.e. most commonly in rats for 4'-Cyanoacetophenone along with the study available on structurally similar read across substances 4'-Methylacetophenone (122-00-9) and Benzonitrile (100-47-0). The predicted data using the OECD QSAR toolbox has also been compared with the experimental studies. The studies are summarized as below –

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 4'-Cyanoacetophenone (1443-80-7). The LD50 was estimated to be 1550 mg/kg bw, when Wistar female rats were treated with 4'-Cyanoacetophenone (1443-80-7) via oral gavage route.

The above study supported by D. L. J. Opdyke (Food and Cosmetics Toxicology, Volume 12, Issues 7–8, December 1974, Page 933), for the structurally similar read across substance 4'-Methylacetophenone (122-00-9).Theacute oral toxicity study was conducted in rats at the concentration of 1400mg/kg bw orally. 50 % mortality was observed in treated rats at 1400 mg/kg bw. Therefore, LD50 was considered to be 1400 mg/kg bw when rats was treated with 4'-Methylacetophenone via oral route.

This study is further supported by D. L. J. Opdyke (Food and Cosmetics Toxicology, Volume 17, Supplement, December 1979, Pages 723-725), for the structurally similar read across substance Benzonitrile (100-47-0). The acute oral toxicity study was conducted in rats at the concentration of 800 mg/kg bw orally. 50 % mortality was observed in treated rats. Therefore, LD50 was considered to be 800 mg/kg bw when rats was treated with Benzonitrile orally.

Thus, based on the above studies on 4'-Cyanoacetophenone (1443-80-7) and it’s read across substances, it can be concluded that LD50 value is between 300-2000 mg/kg bw. Thus, comparing this value with the criteria of CLP regulation, 4'-Cyanoacetophenone can be classified as category IV of acute oral toxicity.

Acute Inhalation toxicity: 

In different studies, 4'-Cyanoacetophenone (1443-80-7) has been investigated for acute inhalation toxicity to a greater or lesser extent. Often are the studies based on in-vivo experiments in rodents, i.e. most commonly in rats for 4'-Cyanoacetophenone along with the study available on structurally similar read across substance Benzonitrile (100-47-0) and closely related read across substance Acetone (67-64-1). The predicted data using the OECD QSAR toolbox has also been compared with the experimental studies. The studies are summarized as below –

In a prediction done by SSS (2017) using the OECD QSAR toolbox with log kow as the primary descriptor, the acute inhalation toxicity was estimated for 4'-Cyanoacetophenone (1443-80-7). The LC50 was estimated to be 512 mg/L air, when Sprague-Dawley male rats were exposed with 4'-Cyanoacetophenone for 4 h of exposure period by inhalation to whole body.

The above study is supported by GESTIS SUBSTANCE Database (2017), for the structurally similar read across substance Benzonitrile (100-47-0). The acute inhalation toxicity study was conducted in rat at the concentration of 38600 mg/m3. 50% mortality was observed at 38600 mg/m3. Rats showed the symptoms like: difficulty in breathing, ataxia, exhaustion, sedation and narcosis. No substance-related macroscopic changes to organs were observed. Therefore, LC50 was considered to be 38600 mg/m3 when rat was treated with Benzonitrile by inhalation.

These results are further supported by U.S. National Library of Medicine (ChemIDplus, 2017), for the closely related read across substance Acetone (67-64-1). The acute inhalation toxicity study was conducted in rat at the concentration of 50100 mg/m3. 50% mortality was observed at 50100 mg/m3, when exposed for 8 hours. Therefore, LC50 was considered to be 50100 mg/m3 when rat was treated with Acetone by inhalation.

Thus, based on the above studies on 4'-Cyanoacetophenone (1443-80-7) and it’s read across substances, it can be concluded that LC50 value is greater than 5 mg/L air. Thus, comparing this value with the criteria of CLP regulation, 4'-Cyanoacetophenone can be classified as category V of acute inhalation toxicity.

Acute Dermal toxicity:

In different studies, 4'-Cyanoacetophenone (1443-80-7) has been investigated for acute dermal toxicity to a greater or lesser extent. Often are the studies based on in vivo experiments in rodents, i.e. most commonly in rabbits for 4'-Cyanoacetophenone along with the study available on structurally similar read across substances 4'-Methylacetophenone (122-00-9) and Acetophenone (98-86-2). The predicted data using the OECD QSAR toolbox has also been compared with the experimental studies. The studies are summarized as below –

In a prediction done by SSS (2017) using the OECD QSAR toolbox with log kow as the primary descriptor, the acute dermal toxicity was estimated for 4'-Cyanoacetophenone (1443-80-7). The LD50 was estimated to be 3174 mg/kg bw, when White Russian male and female rabbit was treated with 4'-Cyanoacetophenone for 24 hours by dermal application occlusively.

This study is supported by D. L. J. Opdyke (Food and Cosmetics Toxicology, Volume 12, Issues 7–8, December 1974, Page 933), for the structurally similar read across substance4'-Methylacetophenone (122-00-9).The acute dermal toxicity study was conducted in rabbits at the concentration of 2000mg/kg bw. No mortality was observed at 2000 mg/kg bw. Therefore, LD50 was considered to be >2000 mg/kg bw, when rabbits were treated with 4'-Methylacetophenone by dermal application.

The above study is further supported by GESTIS SUBSTANCE Database (2017), for the structurally similar read across substance Acetophenone (98-86-2). In an acute dermal toxicity study, rabbits were treated at the concentration of 16400 mg/kg bw. 50% mortality was observed at 16400 mg/kg bw. Therefore, LD50 was considered to be 16400 mg/kg bw, when rabbits were treated with Acetophenone by dermal application.

Thus, based on the above studies on 4'-Cyanoacetophenone (1443-80-7) and it’s read across substances, it can be concluded that LD50 value is greater than 2000 mg/kg bw. Thus, comparing this value with the criteria of CLP regulation, 4'-Cyanoacetophenone can be classified as category V of acute dermal toxicity.

Justification for classification or non-classification

Based on the above studies and prediction on 4'-Cyanoacetophenone (1443-80-7) and it’s read across substances, it can be concluded that LD50 value is between 300-2000 mg/kg bw for acute oral toxicity and greater than 2000 mg/kg bw for acute dermal toxicity. LC50 value is greater than 5 mg/L air. Thus, comparing this value with the criteria of CLP regulation, 4'-Cyanoacetophenone can be classified as category IV for acute oral, category V for acute dermal and inhalation toxicity.