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

Endpoint summary

Key value for chemical safety assessment

Genetic toxicity in vitro

Description of key information

Based on the prediction done using the OECD QSAR toolbox version 3.3 with log kow as the primary descriptor and considering the five closest read across substances, gene mutation was predicted for 3-(2,2-dichloroethenyl)-2,2-dimethylcyclopropane-1-carbonyl chloride (52314-67-7). The study assumed the use of Salmonella typhimurium strains TA 1535, TA 1537, TA 98, TA 100 and TA 102 with and without S9 metabolic activation system. 3-(2,2-dichloroethenyl)-2,2-dimethylcyclopropane-1-carbonyl chloride was predicted to not induce gene mutation in Salmonella typhimurium strains TA 1535, TA 1537, TA 98, TA 100 and TA 102 in the presence and absence of S9 metabolic activation system and hence, according to the prediction made, it is not likely to classify as a gene mutant in vitro.

Based on the predicted result it can be concluded that the substance is considered to not toxic as per the criteria mentioned in CLP regulation.

Link to relevant study records

Reference

Endpoint:

in vitro gene mutation study in bacteria

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 the supporting QMRF report has been attached.

Qualifier:

according to guideline

Guideline:

other: As mention below

Principles of method if other than guideline:

Prediction is done using OECD QSAR Toolbox version 3.3, 2017

GLP compliance:

not specified

Type of assay:

bacterial reverse mutation assay

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

Target gene:

Histidine

Species / strain / cell type:

S. typhimurium TA 1535, TA 1537, TA 98, TA 100 and TA 102

Details on mammalian cell type (if applicable):

Not applicable.

Additional strain / cell type characteristics:

not specified

Cytokinesis block (if used):

not specified

Metabolic activation:

with

Metabolic activation system:

S9 metabolic activation

Test concentrations with justification for top dose:

not specified

Vehicle / solvent:

not specified

Untreated negative controls:

not specified

Negative solvent / vehicle controls:

not specified

True negative controls:

not specified

Positive controls:

not specified

Details on test system and experimental conditions:

not specified

Rationale for test conditions:

not specified

Evaluation criteria:

Prediction was done considering a dose dependent increase in the number of revertants/plate.

Statistics:

not specified

Species / strain:

S. typhimurium, other: TA 1535, TA 1537, TA 98, TA 100 and TA 102

Metabolic activation:

with

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

not specified

Vehicle controls validity:

not specified

Untreated negative controls validity:

not specified

Positive controls validity:

not specified

Additional information on results:

not specified

Remarks on result:

other: No mutagenic effect were observed

The prediction was based on dataset comprised from the following descriptors: "Gene mutation"
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" )  and ("j" and "k" )  )

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 Acyl halide OR Alkenyl halide OR Cycloalkane by Organic Functional groups ONLY

Domain logical expression index: "c"

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

Domain logical expression index: "d"

Referential boundary: The target chemical should be classified as Aliphatic Carbon [CH] OR Aliphatic Carbon [-CH2-] OR Aliphatic Carbon [-CH3] OR Carbonyl, aliphatic attach [-C(=O)-] OR Chlorine, olefinic attach [-Cl] OR Miscellaneous sulfide (=S) or oxide (=O) OR Olefinic carbon [=CH- or =C<] OR Tertiary Carbon by Organic functional groups (US EPA) ONLY

Domain logical expression index: "e"

Referential boundary: The target chemical should be classified as Acyl chloride OR Acyl halide OR Carbonic acid derivative OR Carboxylic acid derivative OR CO2 derivative (general) OR Halogen derivative by Organic functional groups, Norbert Haider (checkmol) ONLY

Domain logical expression index: "f"

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

Domain logical expression index: "g"

Referential boundary: The target chemical should be classified as Aliphatic Carbon [CH] AND Aliphatic Carbon [-CH2-] AND Aliphatic Carbon [-CH3] AND Carbonyl, aliphatic attach [-C(=O)-] AND Chlorine, olefinic attach [-Cl] AND Miscellaneous sulfide (=S) or oxide (=O) AND Olefinic carbon [=CH- or =C<] AND Tertiary Carbon by Organic functional groups (US EPA) ONLY

Domain logical expression index: "h"

Referential boundary: The target chemical should be classified as Acyl chloride AND Acyl halide AND Carbonic acid derivative AND Carboxylic acid derivative AND CO2 derivative (general) AND Halogen derivative by Organic functional groups, Norbert Haider (checkmol) ONLY

Domain logical expression index: "i"

Similarity boundary:Target: CC1(C)C(C=C(Cl)Cl)C1C(=O)Cl
Threshold=10%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization

Domain logical expression index: "j"

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

Domain logical expression index: "k"

Parametric boundary:The target chemical should have a value of log Kow which is <= 4.72

Conclusions:

3-(2,2-dichloroethenyl)-2,2-dimethylcyclopropane-1-carbonyl chloride (52314-67-7) was predicted to not induce gene mutation in Salmonella typhimurium strains TA 1535, TA 1537, TA 98, TA 100 and TA 102 in the presence of S9 metabolic activation system and hence, according to the prediction made, it is not likely to classify as a gene mutant in vitro.

Executive summary:

Based on the prediction done using the OECD QSAR toolbox version 3.3 with log kow as the primary descriptor and considering the five closest read across substances, gene mutation was predicted for 3-(2,2-dichloroethenyl)-2,2-dimethylcyclopropane-1-carbonyl chloride (52314-67-7). The study assumed the use of Salmonella typhimurium strains TA 1535, TA 1537, TA 98, TA 100 and TA 102 with S9 metabolic activation system. 3-(2,2-dichloroethenyl)-2,2-dimethylcyclopropane-1-carbonyl chloride was predicted to not induce gene mutation in Salmonella typhimurium strains TA 1535, TA 1537, TA 98, TA 100 and TA 102 in the presence of S9 metabolic activation system and hence, according to the prediction made, it is not likely to classify as a gene mutant in vitro.

Based on the predicted result it can be concluded that the substance is considered to not toxic as per the criteria mentioned in CLP regulation.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (negative)

Genetic toxicity in vivo

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Prediction model based estimation and data from read across chemical have been reviewed to determine the mutagenic nature of3-(2,2-dichloroethenyl)-2,2-dimethylcyclopropane-1-carbonyl chloride (52314-67-7). The studies are as mentioned below

Based on the prediction done using the OECD QSAR toolbox version 3.3 with log kow as the primary descriptor and considering the five closest read across substances, gene mutation was predicted for 3-(2,2-dichloroethenyl)-2,2-dimethylcyclopropane-1-carbonyl chloride (52314-67-7). The study assumed the use of Salmonella typhimurium strains TA 1535, TA 1537, TA 98, TA 100 and TA 102 with and without S9 metabolic activation system. 3-(2,2-dichloroethenyl)-2,2-dimethylcyclopropane-1-carbonyl chloride was predicted to not induce gene mutation in Salmonella typhimurium strains TA 1535, TA 1537, TA 98, TA 100 and TA 102 in the presence and absence of S9 metabolic activation system and hence, according to the prediction made, it is not likely to classify as a gene mutant in vitro.

Based on the predicted result it can be concluded that the substance is considered to not toxic as per the criteria mentioned in CLP regulation.

Gene mutation toxicity was predicted for 3-(2,2-dichloroethenyl)-2,2-dimethylcyclopropane-1-carbonyl chloride (52314-67-7) using the battery approach from Danish QSAR database (2017). The study assumed the use of Salmonella typhimurium bacteria in the Ames test. The end point for gene mutation has been modelled in the Danish QSAR using the three software systems Leadscope, CASE Ultra and SciQSAR. Based on predictions from these three systems, a fourth and overall battery prediction is made. The battery prediction is made using the so called Battery algorithm. With the battery approach it is in many cases possible to reduce “noise” from the individual model estimates and thereby improve accuracy and/or broaden the applicability domain.

Gene mutation toxicity study as predicted by3-(2,2-dichloroethenyl)-2,2-dimethylcyclopropane-1-carbonyl chloride is negative and hence the chemical is predicted to not classify as a gene mutant in vitro.

In a study for structurally and functionally similar read across chemical, Gene mutation toxicity study was performed by National Institute of Technology and Evaluation (Japan chemicals collaborative knowledge database , 2017)to determine the mutagenic nature ofCyclohexene (110-83-8). The read across substances share high similarity in structure and log kow .Therefore, it is acceptable to derive information on mutation from the analogue substance. Cyclohexene was assessed for its possible mutagenic potential. For this purpose Bacterial reverse mutation assay was performed according toGuidelines for Screening Mutagenicity Testing of Chemicals (Chemical Substances Control Law of Japan) and OECD Test Guideline 471 on Salmonella typhimurium TA100, TA1535, TA98, TA1537 and Escherichiacoli WP2 uvrA. The test material was exposed in the presence and absence of S9 at different concentration. No mutagenic effects were observed in any strain. Therefore Cyclohexene was considered to be non mutagenic in the presence and absence of metabolic activation. Hence test substance cannot be classified as gene mutant in vitro.

 

In a study for structurally and functionally similar read across chemical, Gene mutation toxicity study was performed by Errol Zeigeret.al. (Environmental and Molecular Mutagenesis, 1992) to determine the mutagenic nature of Methyl cyclopentane (96-37-7). The read across substances share high similarity in structure and log kow .Therefore, it is acceptable to derive information on mutation from the analogue substance. Methyl cyclopentane was assessed for its possible mutagenic potential. For this purpose Bacterial reverse mutation assay was performedon Salmonella typhimuriumTA97, TA98, TA100 and TA1535. The test material was exposed in the presence and absence of S9 at concentration of0, 3.3-333µg/plate byPreincubation method. No mutagenic effects were observed in any strain. Therefore Methyl cyclopentane was considered to be non mutagenic in the presence and absence of metabolic activation. Hence test substance cannot be classified as gene mutant in vitro.

Based on the data available for the target chemical and its read across substance and applying weight of evidence of 3-(2,2-dichloroethenyl)-2,2-dimethylcyclopropane-1-carbonyl chloride (52314-67-7) does not exhibit gene mutation in vitro. Hence the test chemical is not likely to classify as a gene mutant in vitro.

Justification for classification or non-classification

Thus based on the above annotation and CLP criteria for the target chemical . 3-(2,2-dichloroethenyl)-2,2-dimethylcyclopropane-1-carbonyl chloride (52314-67-7) does not exhibit gene mutation in vitro. Hence the test chemical is not likely to classify as a gene mutant in vitro.