3-phenylpropionyl chloride

Endpoint summary

Description of key information

Acute oral toxicity:

LD50 was considered to be 2168mg/kg whenrats were treated with 3 phenylpropionyl chloride(645-45-4),orally.   

 

Acute inhalation toxicity:

LC50 was considered to be 2750 mg/m³/hwhen rats were treated with3 phenylpropionyl chloride(645-45-4), by inhalation for 4 hours.

 

Acute dermal toxicity:

 LD50 was considered to be 2278mg/kg bw when rats were treated with 3 phenylpropionyl chloride(645-45-4), on dermal application.  

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Endpoint:

acute toxicity: oral

Type of information:

(Q)SAR

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

results derived from a valid (Q)SAR model and falling into its applicability domain, with limited documentation / justification

Justification for type of information:

Data is from OECD QSAR toolbox v3.3 and the QMRF report has been attached.

Qualifier:

equivalent or similar to guideline

Guideline:

other: As mention below

Principles of method if other than guideline:

Prediction was done using OECD QSAR toolbox v3.3

GLP compliance:

not specified

Test type:

other: not specified

Limit test:

no

Specific details on test material used for the study:

- Name of test material (as cited in study report): 3-phenylpropanoyl chloride- Molecular formula: C9H9ClO- Molecular weight: 168.622 g/mol- Substance type: organic - Physical state: Liquid- Smiles notation: c1cc(CCC(Cl)=O)ccc1- InChl: 1S/C9H9ClO/c10-9(11)7-6-8-4-2-1-3-5-8/h1-5H,6-7H2

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

No data available

Route of administration:

oral: gavage

Vehicle:

not specified

Details on oral exposure:

No data available

Doses:

2168.00 mg/kg bw

No. of animals per sex per dose:

No data available

Control animals:

not specified

Details on study design:

No data available

Statistics:

No data available

Preliminary study:

No data available

Sex:

male/female

Dose descriptor:

LD50

Effect level:

2 168 mg/kg bw

Based on:

test mat.

Remarks on result:

other:

Remarks:

50% mortality was observed

Mortality:

50% mortality was observed

Clinical signs:

other: No data available

Gross pathology:

No data available

Other findings:

No data available

The prediction was based on dataset comprised from the following descriptors: LD50
Estimation method: Takes average value from the 6 nearest neighbours
Domain  logical expression:Result: In Domain

((((((("a" or "b" or "c" or "d" )  and "e" )  and "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 Acylation OR Acylation >> Direct Addition of an Acyl Halide OR Acylation >> Direct Addition of an Acyl Halide >> Acyl halide OR 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 ONLY

Domain logical expression index: "b"

Referential boundary: The target chemical should be classified as Acylation AND Acylation >> Direct acylation involving a leaving group AND Acylation >> Direct acylation involving a leaving group >> (Thio)Acyl and (thio)carbamoyl halides and cyanides  by Protein binding by OASIS v1.3

Domain logical expression index: "c"

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  by Protein binding by OASIS v1.3 ONLY

Domain logical expression index: "d"

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 >> Acyl halides (including benzyl and carbamoyl deriv.) by Protein binding by OECD

Domain logical expression index: "e"

Referential boundary: The target chemical should be classified as Acylation AND Acylation >> Direct Addition of an Acyl Halide AND Acylation >> Direct Addition of an Acyl Halide >> Acyl halide AND Michael addition AND Michael addition >> P450 Mediated Activation to Quinones and Quinone-type Chemicals AND Michael addition >> P450 Mediated Activation to Quinones and Quinone-type Chemicals >> Arenes by DNA binding by OECD ONLY

Domain logical expression index: "f"

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 ONLY

Domain logical expression index: "g"

Referential boundary: The target chemical should be classified as Not possible to classify according to these rules by DPRA Cysteine peptide depletion

Domain logical expression index: "h"

Referential boundary: The target chemical should be classified as Low reactive OR Low reactive >> Acyl halides by DPRA Cysteine peptide depletion

Domain logical expression index: "i"

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

Domain logical expression index: "j"

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

Domain logical expression index: "k"

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

Domain logical expression index: "l"

Referential boundary: The target chemical should be classified as Chlorphentermine (Hepatotoxicity) Alert by Repeated dose (HESS)

Domain logical expression index: "m"

Parametric boundary:The target chemical should have a value of log Kow which is >= 1.42

Domain logical expression index: "n"

Parametric boundary:The target chemical should have a value of log Kow which is <= 3.08

Interpretation of results:

Category 5 based on GHS criteria

Conclusions:

LD50 was estimated to be 2168 mg/kg bw when rats were orally exposed with 3-phenylpropanoyl chloride.

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 3-phenylpropanoyl chloride(645-45-4).The LD50 was estimated to be 2168mg/kg bw when rats were orally exposed with 3-phenylpropanoyl chloride(645-45-4).

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 168 mg/kg bw

Quality of whole database:

Data is Klimisch 2 and from OECD QSAR toolbox

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

4 (not assignable)

Rationale for reliability incl. deficiencies:

secondary literature

Justification for type of information:

Data from secondary source

Qualifier:

equivalent or similar to guideline

Guideline:

other: As mentioned below

Principles of method if other than guideline:

The inhalation toxicity of Hydrocinnaomyl chloride was performed in rats

GLP compliance:

not specified

Test type:

other:

Limit test:

no

Specific details on test material used for the study:

- Name of test material (as cited in study report): hydrocinnamoyl chloride- Molecular formula: C9H9ClO- Molecular weight: 168.622 g/mol- Substance type: organic - Physical state: Liquid- Smiles notation: c1cc(CCC(Cl)=O)ccc1- InChl: 1S/C9H9ClO/c10-9(11)7-6-8-4-2-1-3-5-8/h1-5H,6-7H2

Species:

rat

Strain:

not specified

Sex:

not specified

Details on test animals or test system and environmental conditions:

No data available

Route of administration:

inhalation

Type of inhalation exposure:

not specified

Vehicle:

air

Details on inhalation exposure:

No data available

Analytical verification of test atmosphere concentrations:

not specified

Duration of exposure:

4 h

Remarks on duration:

No data available

Concentrations:

2750 mg/m3/h

No. of animals per sex per dose:

No data available

Control animals:

not specified

Details on study design:

No data available

Statistics:

No data available

Preliminary study:

No data available

Sex:

male

Dose descriptor:

LC50

Effect level:

2 750 mg/m³ air (nominal)

Based on:

test mat.

Exp. duration:

4 h

Remarks on result:

other: 50% mortality was observed

Mortality:

50% mortality was observed

Clinical signs:

other: No data available

Body weight:

No data available

Gross pathology:

No data available

Other findings:

Sense Organs and Special Senses (Eye) - effect, not otherwise specified Lungs, Thorax, or Respiration - other changes Skin and Appendages was observed

Interpretation of results:

Category 5 based on GHS criteria

Conclusions:

The lethal concentration causing 50% mortality (LC50) in rats after 4 h exposure to hydrocinnamoyl chloride was considered to be 2750 mg/m3/h

Executive summary:

In the inhalation toxicity of Hydrocinnaomyl chloride was performed in rats.

The lethal concentration causing 50% mortality (LC50) in rats after 4 h exposure to hydrocinnamoyl chloride was considered to be 2750 mg/m³/h

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LC50

Value:

2 750 mg/m³ air

Quality of whole database:

Data is Klimisch 4 and from secondary source

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 from OECD QSAR toolbox v3.3 ,(2017)

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Principles of method if other than guideline:

Prediction was done using OECD QSAR toolbox v3.3

GLP compliance:

not specified

Test type:

other: not specified

Limit test:

no

Specific details on test material used for the study:

- Name of test material (as cited in study report): 3-phenylpropanoyl chloride- Molecular formula: C9H9ClO- Molecular weight: 168.622 g/mol- Substance type: organic - Physical state: Liquid- Smiles notation: c1cc(CCC(Cl)=O)ccc1- InChl: 1S/C9H9ClO/c10-9(11)7-6-8-4-2-1-3-5-8/h1-5H,6-7H2

Species:

rabbit

Strain:

New Zealand White

Sex:

male

Details on test animals or test system and environmental conditions:

No data available

Type of coverage:

not specified

Vehicle:

not specified

Details on dermal exposure:

No data available

Duration of exposure:

No data available

Doses:

2278 mg/kg

No. of animals per sex per dose:

No data available

Control animals:

not specified

Details on study design:

No data available

Statistics:

No data available

Preliminary study:

No data available

Sex:

male

Dose descriptor:

LD50

Effect level:

2 278 mg/kg bw

Based on:

test mat.

Remarks on result:

other: 50% mortality was observed

Mortality:

50% mortality was observed

Clinical signs:

other: No data available

Gross pathology:

No data available

Other findings:

No data available

The prediction was based on dataset comprised from the following descriptors: LD50
Estimation method: Takes average value from the 5 nearest neighbours
Domain  logical expression:Result: In Domain

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

Domain logical expression index: "a"

Referential boundary: The target chemical should be classified as Acylation OR Acylation >> Direct Addition of an Acyl Halide OR Acylation >> Direct Addition of an Acyl Halide >> Acyl halide OR 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 ONLY

Domain logical expression index: "b"

Referential boundary: The target chemical should be classified as Acylation AND Acylation >> Direct acylation involving a leaving group AND Acylation >> Direct acylation involving a leaving group >> (Thio)Acyl and (thio)carbamoyl halides and cyanides  by Protein binding by OASIS v1.3

Domain logical expression index: "c"

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  by Protein binding by OASIS v1.3 ONLY

Domain logical expression index: "d"

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 >> Acyl halides (including benzyl and carbamoyl deriv.) by Protein binding by OECD

Domain logical expression index: "e"

Referential boundary: The target chemical should be classified as Acylation AND Acylation >> Direct Addition of an Acyl Halide AND Acylation >> Direct Addition of an Acyl Halide >> Acyl halide AND Michael addition AND Michael addition >> P450 Mediated Activation to Quinones and Quinone-type Chemicals AND Michael addition >> P450 Mediated Activation to Quinones and Quinone-type Chemicals >> Arenes by DNA binding by OECD ONLY

Domain logical expression index: "f"

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

Domain logical expression index: "g"

Referential boundary: The target chemical should be classified as Non binder, non cyclic structure OR Strong binder, OH group by Estrogen Receptor Binding

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 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: "j"

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

Domain logical expression index: "k"

Referential boundary: The target chemical should be classified as Acyl chloride AND Acyl halide AND Aromatic compound AND Carbonic acid derivative AND Carboxylic acid derivative AND Halogen derivative by Organic functional groups, Norbert Haider (checkmol)

Domain logical expression index: "l"

Referential boundary: The target chemical should be classified as Alcohol OR Alkyl chloride OR Alkyl halide OR Carbonyl compound OR Carboxylic acid OR Carboxylic acid ester OR Dialkylether OR Ether OR Hydroxy compound OR Ketone OR Primary alcohol OR Secondary alcohol by Organic functional groups, Norbert Haider (checkmol)

Domain logical expression index: "m"

Similarity boundary:Target: O=C(Cl)CCc1ccccc1
Threshold=10%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization

Domain logical expression index: "n"

Parametric boundary:The target chemical should have a value of log Kow which is >= 0.876

Domain logical expression index: "o"

Parametric boundary:The target chemical should have a value of log Kow which is <= 4.74

Interpretation of results:

Category 5 based on GHS criteria

Conclusions:

LD50 was estimated to be 2278 mg/kg bw when rabbits were dermally exposed with 3-phenylpropanoyl chloride.

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 3-phenylpropanoyl chloride(645-45-4).The LD50 was estimated to be 2278mg/kg bw when rabbits were exposed with 3-phenylpropanoyl chloride(645-45-4) by dermal application.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 278 mg/kg bw

Quality of whole database:

Data is Klimisch 2 and from OECD QSAR toolbox

Additional information

Acute oral toxicity

In different studies, 3 phenylpropionyl chloride has been investigated for acute oral toxicity to a greater or lesser extent. Often are the studies based on in vivo experiments and estimated data in rodents, i.e. most commonly in rats for 3 phenylpropionyl chloride. The predicted data using the OECD QSAR toolbox has also been compared with the experimental studies.

In a prediction done by SSS (2017) using the OECD QSAR toolbox with log kow as the primary descriptor, the acute oral toxicity was estimated for 3 phenylpropionyl chloride. The LD50 was estimated to be 2168mg/kg bw when Sprague-Dawley male and female rats were orally exposed with 3 phenylpropionyl chloride(645-45-4).

In another prediction done by SSS (2017) using the Danish QSAR with log kow as the primary descriptor, the acute oral toxicity was estimated for 3 phenylpropionyl chloride. The LD50 was estimated to be 3200 mg/kg bw in rats (Reliability index: 0.76) exposed with 3 phenylpropionyl chloride

Also it is further supported by experimental study given by Henry F. Smyth Jr. et.al(Food and Chemical Toxicology, Volume 21, Issue 5, October 1983, Pages 647-649 ) on structurally similar read across substance Benzyl acetone(2550-26-7 )rats were treated with Benzyl acetone orally. 50% mortality was observed in treated rats at 3200 mg/kg bw. Therefore, LD50 was considered to be 3200 mg/kg bw when rats were treated with Benzyl acetone(2550-26-7)orally.   

 

Also it is further supported by experimental study given byD.L.J. Opdyke(Food and Chemical Toxicology, Volume 12, Pages 537-649, 974) on structurally similar read across substance2-Methy-4-phenyl-2-butanol(103-05-9),rats were treated with2-Methy-4-phenyl-2-butanolorally. 50% mortality was observed in treated rats at 2200mg/kg bw. Therefore, LD50 was considered to be 2200 mg/kg bw when rats were treated with2-Methy-4-phenyl-2-butanol(103-05-9)orally.   

 

Thus, based on the above studies and predictions on 3 phenylpropionyl chloride(645-45-4) and its read across substances, it can be concluded that LD50 value is above 2168mg/kg bw. Thus comparing this value with the criteria of CLP regulation 3 phenylpropionyl chloride(645-45-4) can be “Not classified” for acute oral toxicity.

Acute dermal toxicity

In different studies3 phenylpropionyl chloride(645-45-4)has been investigated for acute dermal toxicity to a greater or lesser extent. Often are the studies based on in vivo experiments and estimated data in rodents, i.e. most commonly in rabbits for3 phenylpropionyl chloride(645-45-4)

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 3 phenylpropionyl chloride. The LD50 was estimated to be 2278 mg/kg bw when New Zealand White rabbits were exposed with 3 phenylpropionyl chloride(645-45-4) by dermal application.

 

Also it is further supported by experimental study given by Henry F. Smyth Jr. et.al(Food and Chemical Toxicology, Volume 21, Issue 5, October 1983, Pages 647-649 ) on structurally similar read across substance Benzyl acetone(2550-26-7 )rats were treated with Benzyl acetone dermal application . No mortality was observed in treated rats at 5000mg/kg bw. Therefore, LD50 was considered to be >5000 mg/kg bw when rats were treated with Benzyl acetone(2550-26-7)dermal application.   

 

Also it is further supported by experimental study given by D.L.J. Opdyke(Food and Chemical Toxicology, Volume 12, Pages 537-649, 974) on structurally similar read across substance2-Methy-4-phenyl-2-butanol(103-05-9),rats were treated with2-Methy-4-phenyl-2-butanoldermal application 50%mortality was observed in treated rats at 3500mg/kg bw. Therefore, LD50 was considered to be 3500mg/kg bw when rats were treated with2-Methy-4-phenyl-2-butanol(103-05-9)by dermal application. 

 

Thus, based on the above studies on3 phenylpropionyl chloride(645-45-4)and its read across substances,it can be concluded that LD50 value is in dose range 1510-15000mg/kg bw by dermal route. Thus, comparing this value with the criteria of CLP3 phenylpropionyl chloride(645-45-4)“Not classified” for acute toxicity.

 

 

 Acute inhalation toxicity

In a study,3 phenylpropionyl chloride(645-45-4)has been investigated for acute inhalation toxicity to a greater or lesser extent. Study based on in vivo experiments in rodents, i.e. most commonly in rats for3 phenylpropionyl chloride(645-45-4)

In experimental study given by RTECS – Registry of Toxic Effects of Chemical Substances(RTECS , Canadian Center for Occupational Health and Safety (CCOHS),2017),The inhalation toxicity of3 phenylpropionyl chloridewas performed in rats.The lethal concentration causing 50% mortality (LC50) in rats after 4 h exposure to hydrocinnamoyl chloride at given dose2750 mg/m³/h. ThereforeLC50 in rats after 4 h exposure to hydrocinnamoyl chloride was considered to be2750 mg/m³/h by inhalation route.

Thus based on the above study on3 phenylpropionyl chloride(645-45-4), it can be concluded that LC50 value is 2750mg/m³/h. Thus, comparing this value with the criteria of CLP regulation3 phenylpropionyl chloride(645-45-4)“Not classified” for acute inhalation toxicity.

 

Justification for classification or non-classification

Thus, based on the above studies and predictions on 3 phenylpropionyl chloride (645-45-4) and its read across substances, it can be concluded that LD50 value 2168mg/kg bw by oral toxicity and 2278 mg/kg bw for dermal toxicity .LC 50 value 2750

mg/m³/h.by inhalation route. Thus comparing this value with the criteria of CLP regulation 3 phenylpropionyl chloride(645-45-4) can be “Not classified” for acute toxicity.