Anisoyl chloride

Endpoint summary

Description of key information

Skin irritation

The dermal irritation potential of target chemical Anisoyl chloride (CAS No: 100-07-2) was assessedin various experimental studies which were conducted on rabbits and guinea pigs for target chemicalAnisoyl chloride (CAS No: 100-07-2) and its structurally similar read across substancesp-anisyl acetate (CAS No: 104-21-2)andAnisic alcohol (CAS No: 105-13-5). The predicted data usingQSAR toolboxhas also been compared with the experimental data.Based on the available data for the target and read across substances and applying the weight of evidence approach, it can be concluded that chemical Anisoyl chloride (CAS No: 100-07-2) is unable to cause skin irritation and thus 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

An ocular irritation potential of target chemical Anisoyl chloride (CAS No: 100-07-2) was assessedin various experimental studies which were conducted on rabbits for target chemicalAnisoyl chloride (CAS No: 100-07-2) and its structurally similar read across substancesp-anisyl acetate (CAS No: 104-21-2)andp-Methoxybenzaldehyde (CAS No: 123-11-5). The predicted data usingQSAR toolboxhas also been compared with the experimental data.Based on the available data for the target and read across substances and applying the weight of evidence approach, it can be concluded that chemical Anisoyl chloride (CAS No: 100-07-2) is unable to cause eye damage and thus can be considered as not irritating. Comparing the above annotations with the criteria of CLP regulation, it can be classified under the category “Not Classified”.

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:

- IUPAC name: Anisoyl chloride
- Common name: 4-Methoxybenzoyl Chloride
- Molecuar formula: C8H7ClO2
- Molecular weight: 170.5943 mg/l
- Smiles: c1(ccc(cc1)OC)C(=O)Cl
- Inchl: 1S/C8H7ClO2/c1-11-7-4-2-6(3-5-7)8(9)10/h2-5H,1H3
- Substance type: Organic

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:

24 hours

Observation period:

72 hours

Number of animals:

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 skin irritation was observed in treated rabbits.

Estimation method: Takes mode 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 ("j" and ( not "k") )  )  and ("l" and ( not "m") )  )  and ("n" and ( not "o") )  )  and ("p" and ( not "q") )  )  and ("r" and ( not "s") )  )  and ("t" and ( not "u") )  )  and "v" )  and ("w" and ( not "x") )  )  and ("y" and "z" )  )

Domain logical expression index: "a"

Referential boundary: The target chemical should be classified as Acyl chloride OR Acyl halide OR Alkylarylether OR Aromatic compound OR Carbonic acid derivative OR Carboxylic acid derivative OR Ether 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 Aliphatic Carbon [CH] OR Aliphatic Carbon [-CH2-] OR Aliphatic Carbon [-CH3] OR Aromatic Carbon [C] OR Carbonyl, olefinic attach [-C(=O)-] OR Carbonyl, one aromatic attach [-C(=O)-] OR Chlorine, olefinic attach [-Cl] OR Miscellaneous sulfide (=S) or oxide (=O) OR Olefinic carbon [=CH- or =C<] OR Oxygen, one aromatic attach [-O-] by Organic functional groups (US EPA) ONLY

Domain logical expression index: "c"

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

Domain logical expression index: "d"

Referential boundary: The target chemical should be classified as Acyl halide OR Aryl OR Ether 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, impaired OH or NH2 group OR 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 alert found by DNA alerts for AMES, MN and CA 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 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 acylation involving a leaving group OR SN2 >> Direct acylation involving a leaving group >> Acyl Halides by DNA alerts for AMES, MN and CA by OASIS v.1.3

Domain logical expression index: "i"

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

Domain logical expression index: "j"

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

Domain logical expression index: "k"

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: "l"

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

Domain logical expression index: "m"

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

Domain logical expression index: "o"

Referential boundary: The target chemical should be classified as (!Undefined)Group CNHal Lipid Solubility < 4 g/kg by Skin 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 by Skin irritation/corrosion Exclusion rules by BfR

Domain logical expression index: "q"

Referential boundary: The target chemical should be classified as Group All log Kow < -3.1 by Skin irritation/corrosion Exclusion rules by BfR

Domain logical expression index: "r"

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

Domain logical expression index: "s"

Referential boundary: The target chemical should be classified as Group All Melting Point > 200 C by Skin irritation/corrosion Exclusion rules by BfR

Domain logical expression index: "t"

Referential boundary: The target chemical should be classified as Substituted benzoic acid halogenides by Skin irritation/corrosion Inclusion rules by BfR

Domain logical expression index: "u"

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

Domain logical expression index: "v"

Similarity boundary:Target: COc1ccc(C(=O)Cl)cc1
Threshold=20%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization

Domain logical expression index: "w"

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

Domain logical expression index: "x"

Referential boundary: The target chemical should be classified as Tamoxifen (Hepatotoxicity) Alert OR Thiocarbamates/Sulfides (Hepatotoxicity) No rank by Repeated dose (HESS)

Domain logical expression index: "y"

Parametric boundary:The target chemical should have a value of log Kow which is >= 0.547

Domain logical expression index: "z"

Parametric boundary:The target chemical should have a value of log Kow which is <= 3.13

Interpretation of results:

other: not irritating

Conclusions:

The chemical Anisoyl chloride (CAS No: 100-07-2) was estimated to be not irritating to the skin of New Zealand White rabbits. Based on the estimated results, Anisoyl chloride (CAS No: 100-07-2) can be considered to be not irritating to skin.

Executive summary:

The dermal irritation potential of Anisoyl chloride (CAS No: 100-07-2) was estimated using OECD QSAR toolbox v3.3 with logPow as the primary descriptor. The chemical Anisoyl chloride (CAS No: 100-07-2) was estimated to be not irritating to the skin of New Zealand White rabbits. Based on the estimated results, Anisoyl chloride (CAS No: 100-07-2) 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 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:

- IUPAC name: Anisoyl chloride
- Common name: 4-Methoxybenzoyl Chloride
- Molecuar formula: C8H7ClO2
- Molecular weight: 170.5943 mg/l
- Smiles: c1(ccc(cc1)OC)C(=O)Cl
- Inchl: 1S/C8H7ClO2/c1-11-7-4-2-6(3-5-7)8(9)10/h2-5H,1H3
- Substance type: Organic

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 observed in treated rabbits.

Estimation method: Takes mode value from the 6 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" )  )

Domain logical expression index: "a"

Referential boundary: The target chemical should be classified as Acyl chloride OR Acyl halide OR Alkylarylether OR Aromatic compound OR Carbonic acid derivative OR Carboxylic acid derivative OR Ether 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 Aliphatic Carbon [CH] OR Aliphatic Carbon [-CH2-] OR Aliphatic Carbon [-CH3] OR Aromatic Carbon [C] OR Carbonyl, olefinic attach [-C(=O)-] OR Carbonyl, one aromatic attach [-C(=O)-] OR Chlorine, olefinic attach [-Cl] OR Miscellaneous sulfide (=S) or oxide (=O) OR Olefinic carbon [=CH- or =C<] OR Oxygen, one aromatic attach [-O-] by Organic functional groups (US EPA) ONLY

Domain logical expression index: "c"

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

Domain logical expression index: "d"

Referential boundary: The target chemical should be classified as Acyl halide OR Aryl OR Ether 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, impaired OH or NH2 group OR 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 (!Undefined)Group All Lipid Solubility < 0.01 g/kg by Eye irritation/corrosion Exclusion rules by BfR

Domain logical expression index: "h"

Referential boundary: The target chemical should be classified as (!Undefined)Group CN Lipid Solubility < 0.4 g/kg OR (!Undefined)Group CNHal Lipid Solubility < 400 g/kg 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 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 CHal Melting Point > 65 C 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 CNHal Aqueous Solubility < 0.1 g/L 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: "i"

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: "j"

Referential boundary: The target chemical should be classified as AN2 OR AN2 >> Michael addition to activated double bonds OR AN2 >> Michael addition to activated double bonds >> alpha, beta - Unsaturated Carbonyls and Related Compounds OR AN2 >> Michael addition to alpha, beta-unsaturated acids and esters OR AN2 >> Michael addition to alpha, beta-unsaturated acids and esters >> alpha, beta - Unsaturated Carboxylic Acids and Esters by Protein binding alerts for Chromosomal aberration by OASIS v1.1

Domain logical expression index: "k"

Referential boundary: The target chemical should be classified as Substituted benzoic acid halogenides by Skin irritation/corrosion Inclusion rules by BfR

Domain logical expression index: "l"

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: "m"

Parametric boundary:The target chemical should have a value of log Kow which is >= 0.788

Domain logical expression index: "n"

Parametric boundary:The target chemical should have a value of log Kow which is <= 2.37

Interpretation of results:

other: not irritating

Conclusions:

The chemical Anisoyl chloride (CAS No: 100-07-2)was estimated to be not irritating to the eyes of New Zealand White rabbits. Based on the estimated results, Anisoyl chloride (CAS No: 100-07-2) can be considered to be not irritating to eyes.

Executive summary:

The ocular irritation potential of Anisoyl chloride (CAS No: 100-07-2)was estimated using OECD QSAR toolbox v3.3 with logPow as the primary descriptor. The chemical Anisoyl chloride (CAS No: 100-07-2)was estimated to be not irritating to the eyes of New Zealand White rabbits. Based on the estimated results, Anisoyl chloride (CAS No: 100-07-2)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:

Various studieshas been investigated for the test chemicalAnisoyl chloride (CAS No: 100-07-2)to observe the potential for dermal irritation to a greater or lesser extent. The studies are based on in vivo experiments in rabbits and rats for target chemicalAnisoyl chloride (CAS No: 100-07-2) and its structurally similar read across substancesp-anisyl acetate (CAS No: 104-21-2)and Anisic alcohol (CAS No: 105-13-5).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 skin irritation potential was estimated for test chemicalAnisoyl chloride (CAS No: 100-07-2) .The chemical Anisoyl chloride (CAS No: 100-07-2) is estimated to be not irritating to skin of rabbits.

 

Toshio Takenaka, Eiko Hasegawa, Umeko Takenaka, Fumio Saito M. D. and Tazuko Odaka M. D. (1968) and D. McGinty, C.S. Letizia,A.M. Api (2012) reporteda patch test onstructurally similar read across substancep-anisyl acetate (CAS No: 104-21-2) on 80 patients. In this patch test, Anisyl acetate was applied as a closed patch to the back, forearm and upperarm of 80 male/female humans in Japan. The test material was applied at a concentration of 0.05-0.5%. Cream base or ethyl alcohol was used as a vehicle. The patches were applied for 24–48 h and the sites evaluated 30 min after the patches were removed. No irritation was noted in any of the human (0/80). Therefore Anisyl acetate(CAS No: 104-21-2) was considered to be non-irritant to the skin.

 

The above results were further supported by thePreliminary irritation testcarried out byD.W. SHARP {Toxicology, 9 (1978) 261-271} forread across substanceAnisic alcohol (CAS No: 105-13-5)in guinea pigs to determine the concentration suitableforthe sensitization study[injection challenge concentration (ICC) and application challenge concentration(ACC)].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 concentrations of Anisic alcohol at which no irritation was observed were 0.25% for the ICC and 10% for ACC.Since the test chemical did not induce any cutaneous effects at these concentrations, the Anisic alcohol (CAS No: 105-13-5) was considered to be not irritating to the skin of guinea pigs.

 

Based on the available data for thetarget chemicalAnisoyl chloride (CAS No: 100-07-2) and its structurally similar read across substancesp-anisyl acetate (CAS No: 104-21-2)and Anisic alcohol (CAS No: 105-13-5),it can be concluded thatchemical Anisoyl chloride (CAS No: 100-07-2) 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 chemicalAnisoyl chloride (CAS No: 100-07-2) 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 chemicalAnisoyl chloride (CAS No: 100-07-2) its structurally similar read across substancesp-anisyl acetate (CAS No: 104-21-2)andp-Methoxybenzaldehyde (CAS No: 123-11-5).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 ocular irritation potential was estimated for test chemicalAnisoyl chloride (CAS No: 100-07-2) .The chemical Anisoyl chloride (CAS No: 100-07-2) is estimated to be not irritating to eye of rabbits.

 

The D. McGinty, C.S. Letizia,A.M. Api (2012) conducted an ocular irritation study ofread across substancesp-anisyl acetate (CAS No: 104-21-2) in four female SPF albino rabbits in order to assess their eye irritation potential.In this study,0.1 ml aliquot of undiluted p-anisyl acetate was instilled into the left eye then gently closed for 1 s. The untreated right eye of each animal served as a control. Observations were made at 1, 24, 48 and 72 h. Slight to moderate conjunctive irritation (4/4) was observed 1 hour after application. All effects were reversible within 48 h. As all the observed effects were cleared, the chemical p-anisyl acetate (CAS No: 104-21-2) was considered to be non-irritant to the eyes of SPF albino rabbits.

 

The above results were further supported by the experimental studies reported by OECD SIDS for read across chemical p-Methoxybenzaldehyde (CAS No: 123-11-5) conducted on three Vienna White rabbits to determine the degree of eye irritancy.The undiluted chemical was instilled into the eye of each rabbit and eyes were not rinsed. The eyes were scored according toDraize method. Moderate discharge was observed 1 h and slight discharge was observed 24 h after application in 3/3 animals. All the observed effects were reversible within 72 hours. According to the conditions of the test, the test substance does not fullfil the criteria of 67/548/EEC and GHS UN for classification, respectively. Therefore, the chemical p-Methoxybenzaldehyde (CAS No: 123-11-5) wasconsidered to be not irritating to theeyes of Vienna White rabbits.

 

Based on the available data for thetarget chemicalAnisoyl chloride (CAS No: 100-07-2) and its structurally similar read across substancesp-anisyl acetate (CAS No: 104-21-2)andp-Methoxybenzaldehyde (CAS No: 123-11-5) 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 Anisoyl chloride (CAS No: 100-07-2) and its structurally similar read across substanceswere observed in various studies. The results obtained from these studies indicates that the chemical Anisoyl chloride (CAS No: 100-07-2) is unlikely to cause skin and eye irritation. Hence Anisoyl chloride (CAS No: 100-07-2) can be classified under the category “Not Classified” for skin and eye as per CLP.