Anisoyl chloride

Endpoint summary

Description of key information

Acute oral toxicity: 

Acute oral toxicity dose (LD50) of 4-Methoxybenzoyl Chloride (CAS no: 100-07-2) was predicted based on OECD QSAR toolbox 2266 mg/kg bw and different studies available for the structurally similar read across substances Methyl 2-naphthyl ether (93-04-9)>2000 mg/kg bw and 4-methoxybenzyl acetate (104-21-2)2250 mg/Kg bw. All these studies concluded that the LD50 is >2000 mg/kg bw. Thus, comparing this value with the criteria of CLP regulation, 4-Methoxybenzoyl Chloride cannot be classified for acute oral toxicity.

Acute Inhalation toxicity: 

Acute Inhalation toxicity dose (LC50) for 4-Methoxybenzoyl Chloride (CAS no: 100-07-2) was predicted based on OECD QSAR toolbox 17.6 mg/L (17600 mgm3)and different study available for the structurally similar read across substance Anisol (100-66-3)>5000 mg/ m3 (>5 mg/L). Both these studies concluded that the LC50 value is >5 mg/L air. Thus, comparing this value with the criteria of CLP regulation, 4-Methoxybenzoyl Chloride cannot be classified for acute Inhalation toxicity.

Acute Dermal toxicity: 

Acute Dermal toxicity dose (LD50) for 4-Methoxybenzoyl Chloride (CAS no: 100-07-2) was predicted based on OECD QSAR toolbox 4117 mg/kg bw and different studies available for the structurally similar read across substances Methyl 2-naphthyl ether (93-04-9) >2000 mg/kg bw, 4-methoxybenzyl acetate (104-21-2) >5000 mg/kg bw and 4-methoxybenzyl alcohol (105-13-5) 3000 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-Methoxybenzoyl Chloride cannot be classified for 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 data

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:

- IUPAC Name: 4-Methoxybenzoyl Chloride
- InChI:1S/C8H7ClO2/c1-11-7-4-2-6(3-5-7)8(9)10/h2-5H,1H3
- SMILES:COc1ccc(C(=O)Cl)cc1
- Mol. formula: C8H7ClO2
- Molecular Weight: 170.5943 g/mole

Species:

rat

Strain:

other: Spartan

Sex:

male/female

Details on test animals or test system and environmental conditions:

not specified

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

not specified

Doses:

2266 mg/kg bw

No. of animals per sex per dose:

10

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:

2 266 mg/kg bw

Based on:

test mat.

Remarks on result:

other: 50% mortality was 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 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 "j" )  and ("k" and "l" )  )

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 SN2 AND SN2 >> Direct acylation involving a leaving group AND SN2 >> Direct acylation involving a leaving group >> Acyl Halides 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 >> Polarized Haloalkene Derivatives OR AN2 >> Shiff base formation after aldehyde release OR AN2 >> Shiff base formation after aldehyde release >> Specific Acetate Esters 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 No alert found OR Non-covalent interaction OR Non-covalent interaction >> DNA intercalation OR Non-covalent interaction >> DNA intercalation >> Quinones OR Radical OR Radical >> Generation of reactive oxygen species OR Radical >> Generation of reactive oxygen species >> Thiols OR Radical >> Radical mechanism by ROS formation (indirect) or direct radical attack on DNA OR Radical >> Radical mechanism by ROS formation (indirect) or direct radical attack on DNA >> Organic Peroxy Compounds 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 SN1 >> Nucleophilic attack after carbenium ion formation OR SN1 >> Nucleophilic attack after carbenium ion formation >> Specific Acetate Esters OR SN2 >> Acylation OR SN2 >> Acylation >> Specific Acetate Esters 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 >> Haloalkenes with Electron-Withdrawing Groups OR SN2 >> Alkylation, direct acting epoxides and related after P450-mediated metabolic activation >> Polycyclic Aromatic Hydrocarbon Derivatives OR SN2 >> Nucleophilic substitution at sp3 Carbon atom OR SN2 >> Nucleophilic substitution at sp3 Carbon atom >> Specific Acetate Esters 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: "g"

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: "h"

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

Domain logical expression index: "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 Acyl halide AND Aryl AND Ether by Organic Functional groups ONLY

Domain logical expression index: "k"

Parametric boundary:The target chemical should have a value of log Kow which is >= 0.0175

Domain logical expression index: "l"

Parametric boundary:The target chemical should have a value of log Kow which is <= 2.47

Interpretation of results:

other: Not classified

Conclusions:

LD50 was estimated to be 2266 mg/kg bw, when 10 male and female Spartan rats were treated with 4-Methoxybenzoyl Chloride (CAS no: 100-07-2) via oral gavage route.

Executive summary:

In a prediction done by SSS (2018) using the OECD QSAR toolbox with log kow as the primary descriptor, the acute oral toxicity was estimated for 4-Methoxybenzoyl Chloride (CAS no: 100-07-2). The LD50 was estimated to be 2266 mg/kg bw, when 10 male and female Spartan rats were treated with 4-Methoxybenzoyl Chloride (CAS no: 100-07-2) via oral gavage route.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 266 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 data

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:

- IUPAC Name: 4-Methoxybenzoyl Chloride
- InChI:1S/C8H7ClO2/c1-11-7-4-2-6(3-5-7)8(9)10/h2-5H,1H3
- SMILES:COc1ccc(C(=O)Cl)cc1
- Mol. formula: C8H7ClO2
- Molecular Weight: 170.5943 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: vapour

Type of inhalation exposure:

nose only

Vehicle:

not specified

Remark on MMAD/GSD:

not specified

Details on inhalation exposure:

not specified

Duration of exposure:

4 h

Remarks on duration:

not specified

Concentrations:

17.6 mg/L (17600 mgm3)

No. of animals per sex per dose:

6

Control animals:

not specified

Details on study design:

not specified

Statistics:

not specified

Preliminary study:

not specified

Sex:

male

Dose descriptor:

LC50

Effect level:

17.6 mg/L air

Based on:

test mat.

Exp. duration:

4 h

Remarks on result:

other: 50% mortality was 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 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 "k" )  and "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 Not known precedent reproductive and developmental toxic potential by DART scheme v.1.0

Domain logical expression index: "h"

Referential boundary: The target chemical should be classified as AhR binders.Polycyclic aromatic hydrocarbons (PAHs) (3b-3) OR Glycidyl ether derivatives (16c) OR Known precedent reproductive and developmental toxic potential OR Toluene and small alkyl toluene derivatives (8a) by DART scheme v.1.0

Domain logical expression index: "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 Acyl chloride AND Acyl halide AND Alkylarylether AND Aromatic compound AND Carbonic acid derivative AND Carboxylic acid derivative AND Ether AND Halogen derivative by Organic functional groups, Norbert Haider (checkmol) ONLY

Domain logical expression index: "k"

Referential boundary: The target chemical should be classified as Acyl halide AND Aryl AND Ether by Organic Functional groups ONLY

Domain logical expression index: "l"

Similarity boundary:Target: COc1ccc(C(=O)Cl)cc1
Threshold=30%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization

Domain logical expression index: "m"

Parametric boundary:The target chemical should have a value of log Kow which is >= 1.35

Domain logical expression index: "n"

Parametric boundary:The target chemical should have a value of log Kow which is <= 4.07

Interpretation of results:

other: Not classified

Conclusions:

LC50 was estimated to be 17.6 mg/L (17600 mgm3), when 6 male Sprague-Dawley rats were exposed with 4-Methoxybenzoyl Chloride (CAS no: 100-07-2) via inhalation route by vapour nose only exposure for 4 h.

Executive summary:

In a prediction done by SSS (2018) using the OECD QSAR toolbox with log kow as the primary descriptor, the acute inhalation toxicity was estimated for 4-Methoxybenzoyl Chloride (CAS no: 100-07-2). The LC50 was estimated to be 17.6 mg/L (17600 mgm3), when 6 male Sprague-Dawley rats were exposed with 4-Methoxybenzoyl Chloride (CAS no: 100-07-2) via inhalation route by vapour nose only exposure for 4 h.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LC50

Value:

17 600 mg/m³ air

Quality of whole database:

Data is Klimisch 2 and from 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 data

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:

- IUPAC Name: 4-Methoxybenzoyl Chloride
- InChI:1S/C8H7ClO2/c1-11-7-4-2-6(3-5-7)8(9)10/h2-5H,1H3
- SMILES:COc1ccc(C(=O)Cl)cc1
- Mol. formula: C8H7ClO2
- Molecular Weight: 170.5943 g/mole

Species:

rabbit

Strain:

other: New Zealand giant albino

Sex:

male

Details on test animals or test system and environmental conditions:

not specified

Type of coverage:

occlusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

not specified

Duration of exposure:

24 hours

Doses:

4117 mg/kg bw

No. of animals per sex per dose:

4

Control animals:

not specified

Details on study design:

not specified

Statistics:

not specified

Preliminary study:

not specified

Sex:

male

Dose descriptor:

LD50

Effect level:

4 117 mg/kg bw

Based on:

test mat.

Remarks on result:

other: 50% mortality was 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 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 "r" )  and "s" )  and "t" )  and ("u" and "v" )  )

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, 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 Not possible to classify according to these rules (GSH) by Protein binding potency

Domain logical expression index: "h"

Referential boundary: The target chemical should be classified as Highly reactive (GSH) OR Highly reactive (GSH) >> 2-Alken-1-als (MA) OR Highly reactive (GSH) >> Acrylates (MA) OR Highly reactive (GSH) >> Cinnamaldehydes (MA) OR Moderately reactive (GSH) OR Moderately reactive (GSH) >> 2-Vinylpyridine (MA) OR Moderately reactive (GSH) >> Alkyl 2-alkenoates (MA) OR Moderately reactive (GSH) >> Substituted 1-Alken-3-ones (MA) OR Moderately reactive (GSH) >> Substituted 2-Alken-1-als (MA) OR Slightly reactive (GSH) OR Slightly reactive (GSH) >> 2-Alkenyl carbonitriles (MA) OR Slightly reactive (GSH) >> Methacrylates (MA) by Protein binding potency

Domain logical expression index: "i"

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: "j"

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 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 by Eye irritation/corrosion Exclusion rules by BfR

Domain logical expression index: "k"

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

Domain logical expression index: "l"

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

Domain logical expression index: "m"

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

Domain logical expression index: "n"

Referential boundary: The target chemical should be classified as Group 14 - Carbon C AND Group 16 - Oxygen O AND Group 17 - Halogens Cl AND Group 17 - Halogens F,Cl,Br,I,At by Chemical elements

Domain logical expression index: "o"

Referential boundary: The target chemical should be classified as Group 15 - Phosphorus P by Chemical elements

Domain logical expression index: "p"

Similarity boundary:Target: COc1ccc(C(=O)Cl)cc1
Threshold=30%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization

Domain logical expression index: "q"

Referential boundary: The target chemical should be classified as Acyl halide AND Aryl AND Ether by Organic Functional groups ONLY

Domain logical expression index: "r"

Referential boundary: The target chemical should be classified as Acyl halide AND Aryl AND Ether by Organic Functional groups ONLY

Domain logical expression index: "s"

Referential boundary: The target chemical should be classified as Acyl halide AND Aryl AND Ether by Organic Functional groups ONLY

Domain logical expression index: "t"

Referential boundary: The target chemical should be classified as Acyl halide AND Aryl AND Ether by Organic Functional groups ONLY

Domain logical expression index: "u"

Parametric boundary:The target chemical should have a value of log Kow which is >= 0.368

Domain logical expression index: "v"

Parametric boundary:The target chemical should have a value of log Kow which is <= 2.27

Interpretation of results:

other: Not classified

Conclusions:

LD50 was estimated to be 4117 mg/kg bw, when 4 male New Zealand giant albino rabbits were treated with 4-Methoxybenzoyl Chloride (CAS no: 100-07-2) for 24 hours by dermal application occlusively.

Executive summary:

In a prediction done by SSS (2018) using the OECD QSAR toolbox with log kow as the primary descriptor, the acute dermal toxicity was estimated for 4-Methoxybenzoyl Chloride (CAS no: 100-07-2). The LD50 was estimated to be 4117 mg/kg bw, when 4 male New Zealand giant albino rabbits were treated with 4-Methoxybenzoyl Chloride (CAS no: 100-07-2) for 24 hours by dermal application occlusively.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

4 117 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-Methoxybenzoyl Chloride (CAS no: 100-07-2) 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-Methoxybenzoyl Chloride along with the study available on structurally similar read across substances Methyl 2-naphthyl ether (93-04-9) and 4-methoxybenzyl acetate (104-21-2). 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 (2018) using the OECD QSAR toolbox with log kow as the primary descriptor, the acute oral toxicity was estimated for 4-Methoxybenzoyl Chloride (CAS no: 100-07-2). The LD50 was estimated to be 2266 mg/kg bw, when 10 male and female Spartan rats were treated with 4-Methoxybenzoyl Chloride (CAS no: 100-07-2) via oral gavage route.

This study is supported by Sustainability Support Services (Europe) AB, (Report No. 14_49_057, 2014) was designed for the structurally similar read across substance Methyl 2-naphthyl ether (93-04-9) in rats. Acute oral toxicity study was performed as per OECD No. 423 in 6 female Wistar rats. The test material was dissolved in corn oil and given in dose concentration 2000 mg/kg bw by oral gavage route. The animals were fasted for minimum 16-18 hours prior to dosing and for 4 hours post dosing, with food withheld but drinking water provided ad libitum. The time intervals between dosing were determined by the onset, duration and severity of toxic signs. 3 rats of group G1 were dosed with starting dose of 2000 mg/kg body weight and the animals showed no mortality post dosing, so another 3 rats of the same group were dosed with 2000 mg/kg weight and no mortality was observed. Hence, further dosing was stopped. Mean body weight of all six animals was observed with gain on day 7 and 14. Normal clinical signs were observed throughout the experimental period. No external and internal gross pathological examination was seen in all the six animals treated with 2000 mg/kg body weight during terminal sacrifice. Hence the LD50 value was considered to be >2000 mg/kg bw, when female Wistar rats were treated with Methyl 2-naphthyl ether (93-04-9) orally.

These studies are further supported by McGinty et al.(Food and Chemical Toxicology, 50, (2012), S502–S506) for the structurally similar read across substance 4-methoxybenzyl acetate (104-21-2). Acute Oral toxicity study was conducted in 5 animals per dose Sprague-Dawley rats at the concentration of 1470, 2150, 3160 and 4640 mg/kg bw. The given test chemical was dissolved as 50% in corn oil and administered via oral gavage route. The animals were observed for clinical signs and mortality for 14 days. 50% mortality was observed at 2250 mg/kg bw. Clinical signs such as, depression, hypopnea and ataxia was observed. Necropsy revealed dark red areas of the lungs of rats in all dose groups except the 2150 mg/kg group. In a preliminary study, 1/2 rats died from a gavage dose of 5000 mg/kg. Therefore, LD50 was considered to be 2250 mg/Kg, when rats were treated with 4-methoxybenzyl acetate (104-21-2) via oral gavage route.

Thus, based on the above prediction on 4-Methoxybenzoyl Chloride (CAS no: 100-07-2) and it’s read across substances, it can be concluded that LD50 value is >2000 mg/kg bw. Thus, comparing this value with the criteria of CLP regulation, 4-Methoxybenzoyl Chloride cannot be classified for acute oral toxicity.

Acute Inhalation Toxicity:

In different studies, 4-Methoxybenzoyl Chloride (CAS no: 100-07-2) 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-Methoxybenzoyl Chloride along with the study available on structurally similar read across substance Anisol (100-66-3). 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 (2018) using the OECD QSAR toolbox with log kow as the primary descriptor, the acute inhalation toxicity was estimated for 4-Methoxybenzoyl Chloride (CAS no: 100-07-2). The LC50 was estimated to be 17.6 mg/L (17600 mgm3), when 6 male Sprague-Dawley rats were exposed with 4-Methoxybenzoyl Chloride (CAS no: 100-07-2) via inhalation route by vapour nose only exposure for 4 h.

This study is supported by U.S. National Library of Medicine (Chemidplus, 2017) and Jay A. Brown (Haz-Map®: Information on Hazardous Chemicals and Occupational Diseases, U.S. National Library of Medicine, October 2017) for the structurally similar read across substanceAnisol (100-66-3). The acute inhalation toxicity study was conducted in rats at the concentration of 5000 mg/m3 inhaled as a Single dose. No mortality was observed at 5000 mg/m3. Therefore, LC50 value was considered to be >5000 mg/ m3 (>5 mg/L) when rats were exposed with Anisol (100-66-3) by inhalation route.

Thus, based on the above studies on 4-Methoxybenzoyl Chloride (CAS no: 100-07-2) and it’s read across substance, it can be concluded that LC50 value is >5 mg/L air. Thus, comparing this value with the criteria of CLP regulation, 4-Methoxybenzoyl Chloride cannot be classified for acute Inhalation toxicity.

Acute Dermal toxicity:

In different studies, 4-Methoxybenzoyl Chloride (CAS no: 100-07-2) 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 rabbit and rat for 4-Methoxybenzoyl Chloride along with the study available on the structurally similar read across substances Methyl 2-naphthyl ether (93-04-9), 4-methoxybenzyl acetate (104-21-2) and 4-methoxybenzyl alcohol (105-13-5). 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 (2018) using the OECD QSAR toolbox with log kow as the primary descriptor, the acute dermal toxicity was estimated for 4-Methoxybenzoyl Chloride (CAS no: 100-07-2). The LD50 was estimated to be 4117 mg/kg bw, when 4 male New Zealand giant albino rabbits were treated with 4-Methoxybenzoyl Chloride (CAS no: 100-07-2) for 24 hours by dermal application occlusively.

The above study is supported by Sustainability Support Services (Europe) AB, (Report No. 14_49_058, 2014) was designed for the structurally similar read across substance Methyl 2-naphthyl ether (93-04-9) in rats. Acute dermal toxicity study was performed as per OECD No. 402. 5 male and 5 female healthy young adult rats were randomly selected and used for conducting acute dermal toxicity study. Rats free from injury and irritation of skin were selected for the study. 24 hours prior to dermal application of test item, approximately 10% of body surface area of each rat was clipped. A limit dose of 2000 mg/ kg body weight of test item moistened with 0.2 ml distilled water was applied by single dermal application and observed for 14 days after treatment. On test day 0, an amount of test item moistened with 0.2 ml distilled water was applied directly on the intact skin of clipped area of rats; the porous gauze dressing was put on to the intact skin of clipped area. This porous gauze dressing was covered with a non-irritating tape. After the 24-hour application period, the dressings were removed and the skin was gently wiped with distilled water. The skin reactions were assessed. All the animals were observed for mortality, clinical signs, body weight and gross pathology. No mortality was observed in any animal, normal clinical signs were observed. Mean body weight of male and female was observed with increase on day 7 and 14, as compared to day 0. No pathological abnormality was observed. Thus the LD50 value was considered to be >2000 mg/kg bw, when male and female wistar rats were treated with Methyl 2-naphthyl ether (93-04-9) by dermal application.

This study is supported by McGinty et al.(Food and Chemical Toxicology, 50, (2012), S502–S506) for the structurally similar read across substance 4-methoxybenzyl acetate (104-21-2). The acute dermal toxicity study was conducted in 6 New Zealand albino rabbits at the concentration of 5000 mg/kg bw. The application sites of 3 of the rabbits were intact prior to application while the other 3 rabbits had slightly abraded sites. The test material was covered with a rubber sleeve and Webril padding. The animals were observed for mortality and clinical signs for 14 days. No mortality was observed at 5000 mg/kg bw. No clinical signs of toxicity were observed in any of the animals. Necropsy showed one animal with dark red specks on the lungs. Well-defined to moderate erythema was seen in all rabbits and edema ranged from slight to severe in 5 rabbits. Therefore, LD50 was considered to be >5000 mg/kg bw, when 6 New Zealand albino rabbits were treated with 4-methoxybenzyl acetate by dermal application for 24 hours.

All the above studies are further supported by D. L. J. Opdyke (Food and Cosmetics Toxicology, Volume 12, Issues 7–8, December 1974, Page 825), IFA GESTIS (GESTIS SUBSTANCE Database, 2017), Scognamiglio et al.(Food and Chemical Toxicology 50 (2012) S134–S139) and RTECS (registry of toxic effect of chemical substance data base, 2018), for the structurally similar read across substance 4-methoxybenzyl alcohol (105-13-5). Acute dermal toxicity study was conducted in rabbit at the concentration of 1250, 2500, and 5000 mg/kg bw. Animals were observed for clinical signs. Mortalities included 1 rabbit from the 2500 g/kg group on day 1, and all 4 rabbits from the 5000 mg/kg group by day 6.Clinical signs of toxicity included loss of coordination and muscle tone in 2 animals at 5000 mg/kg and 1 animal at 2500 mg/kg. Slight to moderate erythema and edema was also observed in all animals. Therefore, LD50 was considered to be 3000 mg/kg with 95% confidential limit of 1940-4060 mg/kg bw, when rabbit was treated with 4-methoxybenzyl alcohol by dermal application.

Thus, based on the above studies on 4-Methoxybenzoyl Chloride (CAS no: 100-07-2) and it’s read across substance, it can be concluded that LD50 value is >2000 mg/kg bw. Thus, comparing this value with the criteria of CLP regulation, 4-Methoxybenzoyl Chloride cannot be classified for acute dermal toxicity.

Justification for classification or non-classification

Based on the above studies and prediction on 4-Methoxybenzoyl Chloride (CAS no: 100-07-2) and it’s read across substances, it can be concluded that LD50 value is >2000 mg/kg bw for acute oral and dermal toxicity; and LC50 value is >5 mg/L air for acute inhalation toxicity. Thus, comparing these values with the criteria of CLP regulation, 4-Methoxybenzoyl Chloride cannot be classified for acute oral, dermal and inhalation toxicity.