3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropanecarbonyl chloride

Endpoint summary

Description of key information

The skin sensitization potential of 3-(2,2-dichloroethenyl)-2,2-dimethylcyclopropane-1-carbonyl chloride (CAS No: 52314-67-7) was estimated using OECD QSAR toolbox version 3.3 with log Pow as the primary descriptor. 3-(2,2-dichloroethenyl)-2,2-dimethylcyclopropane-1-carbonyl chloride (CAS No: 52314-67-7) was estimated to be sensitizing to the skin guinea pigs. Based on the estimated result 3-(2,2-dichloroethenyl)-2,2-dimethylcyclopropane-1-carbonyl chloride (CAS No: 52314-67-7) induced skin sanitization effects and hence is considered to sensitizing to guinea pigs.

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: estimated data

Principles of method if other than guideline:

Prediction is done using QSAR Toolbox version 3.3

GLP compliance:

not specified

Type of study:

not specified

Justification for non-LLNA method:

not specified

Specific details on test material used for the study:

- Name of test material: 3-(2,2-dichloroethenyl)-2,2-dimethylcyclopropane-1-carbonyl chloride
- Molecular formula: C8H9Cl3O
- Molecular weight: 227.517
- Smiles notation: O=C([C@@H]1C(C)(C)[C@@H]1\C=C(/Cl)Cl)Cl
- InChl: 1S/C8H9Cl3O/c1-8(2)4(3-5(9)10)6(8)7(11)12/h3-4,6H,1-2H3
- Substance type: Organic

Species:

guinea pig

Strain:

not specified

Sex:

not specified

Details on test animals and environmental conditions:

No data available

Route:

other: No data available

Route:

other: No data available

No. of animals per dose:

No data available

Details on study design:

No data available

Challenge controls:

No data available

Reading:

1st reading

Group:

test chemical

Dose level:

No data available

Clinical observations:

Skin sensitization reaction was observed.

Remarks on result:

positive indication of skin sensitisation

Cellular proliferation data / Observations:

Skin sensitization reaction was observed.

The prediction was based on dataset comprised from the following descriptors: EC3
Estimation method: Takes highest mode value from the 5 nearest neighbours
Domain  logical expression:Result: In Domain

(((("a" or "b" or "c" or "d" or "e" )  and "f" )  and "g" )  and ("h" and "i" )  )

Domain logical expression index: "a"

Referential boundary: The target chemical should be classified as Acid Chlorides by US-EPA New Chemical Categories

Domain logical expression index: "b"

Referential boundary: The target chemical should be classified as AN2 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 SN2 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 >> Direct acylation involving a leaving group OR SN2 >> Direct acylation involving a leaving group >> Acyl Halides by DNA binding by OASIS v.1.3 ONLY

Domain logical expression index: "c"

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 by DNA binding by OECD 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 >> (Thio)Acyl and (thio)carbamoyl halides and cyanides  by Protein binding by OASIS v1.3 ONLY

Domain logical expression index: "e"

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 ONLY

Domain logical expression index: "f"

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 by DNA binding by OECD ONLY

Domain logical expression index: "g"

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

Domain logical expression index: "h"

Parametric boundary:The target chemical should have a value of log Kow which is >= 0.888

Domain logical expression index: "i"

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

Interpretation of results:

other: sensitizing

Conclusions:

 The chemical 3-(2,2-dichloroethenyl)-2,2-dimethylcyclopropane-1-carbonyl chloride (CAS No: 52314-67-7) was estimated to be sensitizing to the skin guinea pigs. Based on the estimated result 3-(2,2-dichloroethenyl)-2,2-dimethylcyclopropane-1-carbonyl chloride (CAS No: 52314-67-7) induced skin sanitization effects and hence is considered to sensitizing to guinea pigs

Executive summary:

The skin sensitization potential of 3-(2,2-dichloroethenyl)-2,2-dimethylcyclopropane-1-carbonyl chloride (CAS No: 52314-67-7) was estimated using OECD QSAR toolbox version 3.3 with log Pow as the primary descriptor. 3-(2,2-dichloroethenyl)-2,2-dimethylcyclopropane-1-carbonyl chloride (CAS No: 52314-67-7) was estimated to be sensitizing to the skin guinea pigs. Based on the estimated result 3-(2,2-dichloroethenyl)-2,2-dimethylcyclopropane-1-carbonyl chloride (CAS No: 52314-67-7) induced skin sanitization effects and hence is considered to sensitizing to guinea pigs.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (sensitising)

Additional information:

Various studies has been investigated for the test chemical3-(2,2-dichloroethenyl)-2,2-dimethylcyclopropane-1-carbonyl chloride (CAS No: 52314-67-7)to observe the potential for skin sensitization to a greater or lesser extent. The studies are based on in vivo experiments in guinea pigs for target chemical3-(2,2-dichloroethenyl)-2,2-dimethylcyclopropane-1-carbonyl chloride (CAS No: 52314-67-7) and its structurally similar read across substancesNonanoyl Chloride (CAS no: 764-85-2) and Benzoyl chloride (CAS no: 98-88-4).The predicted data using the OECD QSAR toolbox has also been compared with the experimental data and summarized as below;

 

 

The skin sensitization potential of 3-(2,2-dichloroethenyl)-2,2-dimethylcyclopropane-1-carbonyl chloride (CAS No: 52314-67-7) was estimated using OECD QSAR toolbox version 3.3 with log Pow as the primary descriptor. 3-(2,2-dichloroethenyl)-2,2-dimethylcyclopropane-1-carbonyl chloride (CAS No: 52314-67-7) was estimated to be sensitizing to the skin guinea pigs. Based on the estimated result 3-(2,2-dichloroethenyl)-2,2-dimethylcyclopropane-1-carbonyl chloride (CAS No: 52314-67-7) induced skin sanitization effects and hence is considered to sensitizing to guinea pigs.

 

 

The OECD SIDS (2008) conducted Murine local lymph node assay on groups of mice at various concentrations on the dorsum of both ears for structurally similar read across substance Nonanoyl Chloride (CAS no: 764-85-2) to determine its sensitization potential in accordance with OECD 429 Guideline.Nonanoyl chloride in acetone /olive oil was applied to groups of mice for 3 consecutive days in various concentrations on the dorsum of both ears. On day 5 after the first application mice are injected intravenously with [³H]thymidine. Subsequently [³H]thymidine activity was measured as a function of isotope incorporation in the draining atricular lymph nodes. Chemicals, which provoke at least in one concentration, a 3-fold or greater increase in isotope incorporation compared with the vehicle controls are classified as potential sensitizers.Since the chemicalNonanoyl chloride (CAS no: 764-85-2) revealed sensitizing properties in this test, it was considered to be sensitizing in the Murine local lymph node assay.

 

 

The above results were further supported by Guinea pig maximisation test reported by the INVENTORY MULTITIERED ASSESSMENT AND PRIORITISATION (IMAP) NICNAS (2017) onstructurally similar read across substanceBenzoyl chloride (CAS no: 98-88-4) in three Hartley guinea pigs in accordance with OECD TG 406.The chemical was tested at 2 % and 5 % after determining the maximum non irritant concentration to the skin on three Freund's complete adjuvant (FCA) pretreated animals. For the challenge exposure, benzoyl chloride diluted to 5 % and 2 % with mineral oil was retained from the range finding study. In the control group, a slight cutaneous reaction was noted 24 hours after the patch was removed, which was then noted to reverse in less than 24 hours. In the tested group, the application of the chemical induced a slight to well defined erythema in 90 % of the animals. The reaction was noted to persist 48 hours after patch removal.Since the skin reactions were not cleared, the chemicalBenzoyl chloride (CAS no: 98-88-4) was considered to be sensitizing on three Hartley guinea pigs.

 

 

Thus on the basis of available data for thetarget chemical3-(2,2-dichloroethenyl)-2,2-dimethylcyclopropane-1-carbonyl chloride (CAS No: 52314-67-7) and its structurally similar read across substancesNonanoyl Chloride (CAS no: 764-85-2) and Benzoyl chloride (CAS no: 98-88-4),it can be concluded thatchemical 3-(2,2-dichloroethenyl)-2,2-dimethylcyclopropane-1-carbonyl chloride (CAS No: 52314-67-7) is able to cause skin sensitization and considered as skin sensitizer.Comparing the above annotations with the criteria of CLP regulation, it can be classified under the category “Skin Sensitizer”.

Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

The skin sensitization potential of test substance 3-(2,2-dichloroethenyl)-2,2-dimethylcyclopropane-1-carbonyl chloride (CAS No: 52314-67-7) and its structurally similar read across substancesNonanoyl Chloride (CAS no: 764-85-2) and Benzoyl chloride (CAS no: 98-88-4) were observed in various studies. From the results obtained from these studies it is concluded that the chemical 3-(2,2-dichloroethenyl)-2,2-dimethylcyclopropane-1-carbonyl chloride (CAS No: 52314-67-7) is likely to cause skin sensitization and hence can be classified as“Skin Sensitizer”.