3-phenylpropionyl chloride

Endpoint summary

Description of key information

The skin sensitization potential of 3-phenylpropionyl chloride (CAS NO. 645-45-4) was estimated by SSS (QSAR) using OECD QSAR toolbox v3.3 with log kow as the primary descriptor and considering the six closest read across substances. 3-phenylpropionyl chloride (CAS NO. 645-45-4) was predicted to be non sensitizing to the skin of guinea pig.

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records

Reference

Endpoint:

skin sensitisation

Remarks:

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: Predicted data

Principles of method if other than guideline:

Data is from OECD QSAR toolbox version.3.3 and QMRF report has been attached.data submitter is owner of prediction report

GLP compliance:

no

Type of study:

other: estimated data

Justification for non-LLNA method:

not specified

Specific details on test material used for the study:

- Name of test material (as cited in study report):- Molecular formula (if other than submission substance): C9H9ClO- Molecular weight (if other than submission substance): 168.622 g/mol- Substance type: Organic- Physical state: liquid- Purity: No data available- Impurities (identity and concentrations): No data available

Species:

other: Guinea Pig and Human

Strain:

not specified

Sex:

not specified

Details on test animals and environmental conditions:

No data available

Key result

Reading:

1st reading

Group:

test chemical

Clinical observations:

no positive reaction

Remarks on result:

no indication of skin sensitisation

The prediction was based on dataset comprised from the following descriptors: "Skin Sensitisation"
Estimation method: Takes highest mode 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 ( not "i") )  )  and ("j" and ( not "k") )  )  and ("l" and ( not "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 Bioavailable by Lipinski Rule Oasis ONLY

Domain logical expression index: "f"

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

Domain logical expression index: "g"

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

Domain logical expression index: "h"

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: "i"

Referential boundary: The target chemical should be classified as Group 15 - Nitrogen N OR Group 15 - Phosphorus P OR Group 16 - Sulfur S OR Group 17 - Halogens Br OR Group 17 - Halogens F OR Group 17 - Halogens I by Chemical elements

Domain logical expression index: "j"

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

Domain logical expression index: "k"

Referential boundary: The target chemical should be classified as 3-Methylcholantrene (Hepatotoxicity) Alert OR Allyl esters (Hepatotoxicity) Rank A OR Amineptine (Hepatotoxicity) Alert OR Aromatic hydrocarbons (Liver enzyme induction) Rank C OR Chlorphentermine (Hepatotoxicity) Alert OR Oxyphenistain (Hepatotoxicity) Alert OR Pirprofen (Hepatotoxicity) Alert OR Tamoxifen (Hepatotoxicity) Alert by Repeated dose (HESS)

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 C Surface Tension > 62 mN/m OR Group All Melting Point > 200 C OR Group C Aqueous Solubility < 0.0001 g/L OR Group C Melting Point > 55 C OR Group C Molecular Weight > 350 g/mol OR Group C Vapour Pressure < 0.0001 Pa OR Group CHal Melting Point > 65 C OR Group CHal Molecular Weight > 280 g/mol OR Group CHal Molecular Weight > 370 g/mol by Skin irritation/corrosion Exclusion rules by BfR

Domain logical expression index: "n"

Parametric boundary:The target chemical should have a value of log Kow which is >= 0.858

Domain logical expression index: "o"

Parametric boundary:The target chemical should have a value of log Kow which is <= 2.97

Interpretation of results:

other: Not sensitizing

Conclusions:

3-phenylpropionyl chloride estimated to be sensitizing when applied to human and guinea pig skin.

Executive summary:

Using OECD QSAR toolbox version 3.3 with logPow as the primary descriptor 3-phenylpropionyl chloride (CAS NO. 645-45-4) was estimated to be not sensitizng to the skin of mouse.

Based on the estimated results, 3-phenylpropionyl chloride (CAS NO. 645-45-4) can be considered not

sensitizing to skin and can be classified under the category “Not Classified” as per CLP regulation.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not sensitising)

Additional information:

In different studies, 3-phenylpropionyl chloride (CAS NO. 645-45-4) has been investigated for potential of skin sensitization to a greater or lesser extent. The studies are based on in vivo experiments in guinea pig for target chemical 3-phenylpropionyl chloride (CAS NO. 645-45-4) and its structurally similar read across substancesBenzyl acetate(CAS NO.140-11-4). The predicted data using the OECD QSAR toolbox has also been compared with the experimental data of read across.   The skin sensitization potential of 3-phenylpropionyl chloride (CAS NO. 645-45-4) was estimated by SSS (QSAR) using OECD QSAR toolbox v3.3 with log kow as the primary descriptor and considering the fiveclosest read across substances. Benzyl acetate (CAS NO. 140-11-4) was predicted to be non sensitizing to the skin of female guinea pig.   Supported by another estimated study Using Battery algorithm model of Danish QSAR, 3-phenylpropionyl chlorideestimated to be not sensitizing when applied to human and guinea pig skin.   It is further supported by experimental study conducted byD. McGinty , D. Vitale, C.S. Letizia, A.M. Api(Food and Chemical Toxicology, 2012) to evaluate the skin sensitizing potential of read acrossbenzyl acetate(140-11-4) inguinea pig.A guinea pig maximization test according to the Magnusson and Kligman was conducted in 20 Hartley albino guinea pigs. In the induction phase of the study, test animals received two intradermal injections each of 0.1 mL of 50% Freund’s complete adjuvant (FCA) in distilled water; 10% benzyl acetate in saline; and 10% benzyl acetate in FCA, for a total of six injections. On day 7 or 8, 0.8 mL of 30% benzyl acetate in petrolatum was applied to the test animals for 48 h using a double Webril patch. Control animals received intradermal injections of 50% FCA in distilled water, undiluted saline or 50% saline in FCA followed by dermal application of 0.8 mL of petrolatum. On day 19 or 21, a challenge concentration of 1%, 3% or 10% of benzyl acetate in petrolatum was applied for 24 h. The control group received 10% benzyl acetate in petrolatum. The application sites were evaluated at 24 and 48 h after patch removal. There was no incidence of sensitization at any concentration of benzyl acetate. Thus on the basis of negative skin reaction it can be concluded that thebenzyl acetateis not a skin sensitizer.

Thus based on the above predictions on 3-phenylpropionyl chloride (CAS NO. 645-45-4) as well as its read across and applying weight of evidence, it can be concluded that 3-phenylpropionyl chloride (CAS NO. 645-45-4) is not a skin sensitizer. Thus comparing the above annotations with the criteria of CLP regulation, 3-phenylpropionyl chloride (CAS NO. 645-45-4) can be considered as not classified for skin sensitization.

Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

Thus comparing the above annotations with the criteria of CLP regulation, 3-phenylpropionyl chloride (CAS NO. 645-45-4) can be considered as not classified for skin sensitization.