Pentene, 2,4,4-trimethyl-, sulfurized

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 Pentene, 2, 4, 4-trimethyl-, sulfurized. 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. Pentene, 2, 4, 4-trimethyl-, sulfurized did 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 is predicted to not likely classify as a gene mutant in vitro.

Based on the predicted result it can be concluded that Pentene, 2, 4, 4-trimethyl-, sulfurized 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

Remarks:

Type of genotoxicity: gene mutation

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 prediction database and the supporting QMRF report has been attached

Qualifier:

according to guideline

Guideline:

other: Refer below principle

Principles of method if other than guideline:

Prediction is dosne using OECD QSAR Toolbox version 3.3

GLP compliance:

not specified

Type of assay:

bacterial reverse mutation assay

Specific details on test material used for the study:

- Name of test material: Pentene, 2, 4, 4-trimethyl-, sulfurized
- EC name: Pentene, 2,4,4-trimethyl-, sulfurized
- Molecular formula: C24H50S8
- Molecular weight: 594.141 g/mole (As in Chem exper)
- Substance type: Organic
- Physical state: No data available
- Purity: No data

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):

No data

Additional strain / cell type characteristics:

not specified

Cytokinesis block (if used):

No data

Metabolic activation:

with

Metabolic activation system:

S9 metabolic activation system

Test concentrations with justification for top dose:

No data

Vehicle / solvent:

No data

Untreated negative controls:

not specified

Negative solvent / vehicle controls:

not specified

True negative controls:

not specified

Positive controls:

not specified

Positive control substance:

not specified

Details on test system and experimental conditions:

No data

Rationale for test conditions:

No data

Evaluation criteria:

The plates were evaluated for a dose dependent increase in the number of revertants/plate

Statistics:

No data

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:

No data

The prediction was based on dataset comprised from the following descriptors: "Gene mutation"
Estimation method: Takes highest mode value from the 6 nearest neighbours
Domain  logical expression:Result: In Domain

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

Domain logical expression index: "a"

Referential boundary: The target chemical should be classified as Alkane branched with quaternary carbon OR Sulfide, poly OR tert-Butyl by Organic Functional groups ONLY

Domain logical expression index: "b"

Referential boundary: The target chemical should be classified as Alkane branched with quaternary carbon OR Overlapping groups OR Sulfide, poly OR tert-Butyl by Organic Functional groups (nested) ONLY

Domain logical expression index: "c"

Referential boundary: The target chemical should be classified as Alkane branched with quaternary carbon OR Overlapping groups OR Sulfide, poly OR tert-Butyl 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 Disulfide [-SS-] OR Suflur, di- or poly suflur attach [S] OR Tertiary Carbon by Organic functional groups (US EPA) ONLY

Domain logical expression index: "e"

Referential boundary: The target chemical should be classified as Sulfenic acid derivative by Organic functional groups, Norbert Haider (checkmol)

Domain logical expression index: "f"

Referential boundary: The target chemical should be classified as No alert found by DNA binding by OASIS v.1.3

Domain logical expression index: "g"

Referential boundary: The target chemical should be classified as AN2 OR AN2 >> Schiff base formation by aldehyde formed after metabolic activation OR AN2 >> Schiff base formation by aldehyde formed after metabolic activation >> Geminal Polyhaloalkane Derivatives OR AN2 >> Shiff base formation for aldehydes OR AN2 >> Shiff base formation for aldehydes >> Geminal Polyhaloalkane Derivatives OR Non-covalent interaction OR Non-covalent interaction >> DNA intercalation OR Non-covalent interaction >> DNA intercalation >> DNA Intercalators with Carboxamide Side Chain OR Non-covalent interaction >> DNA intercalation >> Fused-Ring Nitroaromatics OR Radical OR Radical >> Generation of ROS by glutathione depletion (indirect) OR Radical >> Generation of ROS by glutathione depletion (indirect) >> Haloalkanes Containing Heteroatom OR Radical >> Radical mechanism via ROS formation (indirect) OR Radical >> Radical mechanism via ROS formation (indirect) >> Conjugated Nitro Compounds OR Radical >> Radical mechanism via ROS formation (indirect) >> Fused-Ring Nitroaromatics OR Radical >> Radical mechanism via ROS formation (indirect) >> Geminal Polyhaloalkane Derivatives OR Radical >> Radical mechanism via ROS formation (indirect) >> p-Substituted Mononitrobenzenes OR SN1 OR SN1 >> Nucleophilic attack after reduction and nitrenium ion formation OR SN1 >> Nucleophilic attack after reduction and nitrenium ion formation >> Conjugated Nitro Compounds OR SN1 >> Nucleophilic attack after reduction and nitrenium ion formation >> Fused-Ring Nitroaromatics OR SN1 >> Nucleophilic attack after reduction and nitrenium ion formation >> p-Substituted Mononitrobenzenes OR SN2 OR SN2 >> Acylation involving a leaving group  OR SN2 >> Acylation involving a leaving group  >> Geminal Polyhaloalkane Derivatives OR SN2 >> Acylation involving a leaving group after metabolic activation OR SN2 >> Acylation involving a leaving group after metabolic activation >> Geminal Polyhaloalkane Derivatives OR SN2 >> Alkylation, direct acting epoxides and related OR SN2 >> Alkylation, direct acting epoxides and related >> Epoxides and Aziridines OR SN2 >> DNA alkylation OR SN2 >> DNA alkylation >> Alkylphosphates, Alkylthiophosphates and Alkylphosphonates OR SN2 >> DNA alkylation >> Vicinal Dihaloalkanes OR SN2 >> Internal SN2 reaction with aziridinium and/or cyclic sulfonium ion formation (enzymatic) OR SN2 >> Internal SN2 reaction with aziridinium and/or cyclic sulfonium ion formation (enzymatic) >> Vicinal Dihaloalkanes OR SN2 >> Nucleophilic substitution at sp3 Carbon atom OR SN2 >> Nucleophilic substitution at sp3 Carbon atom >> Haloalkanes Containing Heteroatom OR SN2 >> Nucleophilic substitution at sp3 carbon atom after thiol (glutathione) conjugation OR SN2 >> Nucleophilic substitution at sp3 carbon atom after thiol (glutathione) conjugation >> Geminal Polyhaloalkane Derivatives by DNA binding by OASIS v.1.3

Domain logical expression index: "h"

Referential boundary: The target chemical should be classified as No alert found by DNA binding by OECD

Domain logical expression index: "i"

Referential boundary: The target chemical should be classified as 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 OR Michael addition >> P450 Mediated Activation to Quinones and Quinone-type Chemicals >> Hydroquinones OR SN1 OR SN1 >> Iminium Ion Formation OR SN1 >> Iminium Ion Formation >> Aliphatic tertiary amines OR SN1 >> Nitrenium Ion formation OR SN1 >> Nitrenium Ion formation >> Aromatic nitro OR SN1 >> Nitrenium Ion formation >> Primary aromatic amine OR SN1 >> Nitrenium Ion formation >> Tertiary aromatic amine OR SN2 OR SN2 >> Direct Acting Epoxides and related OR SN2 >> Direct Acting Epoxides and related >> Sulfuranes OR SN2 >> SN2 at an sp3 Carbon atom OR SN2 >> SN2 at an sp3 Carbon atom >> Aliphatic halides by DNA binding by OECD

Domain logical expression index: "j"

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

Domain logical expression index: "k"

Referential boundary: The target chemical should be classified as Low reactive OR Low reactive >> N-substituted aromatic amides OR Low reactive >> Organic disulfides by DPRA Lysine peptide depletion

Domain logical expression index: "l"

Referential boundary: The target chemical should be classified as No alert found by Protein binding by OASIS v1.3

Domain logical expression index: "m"

Referential boundary: The target chemical should be classified as Acylation OR Acylation >> Ester aminolysis OR Acylation >> Ester aminolysis >> Amides OR SN1 OR SN1 >> Nucleophilic substitution (SN1) on alkyl (aryl) mercury cations OR SN1 >> Nucleophilic substitution (SN1) on alkyl (aryl) mercury cations >> Mercury compounds  by Protein binding by OASIS v1.3

Domain logical expression index: "n"

Referential boundary: The target chemical should be classified as Group 14 - Carbon C AND Group 16 - Sulfur S by Chemical elements

Domain logical expression index: "o"

Referential boundary: The target chemical should be classified as Group 1 - Alkali Earth Li,Na,K,Rb,Cs,Fr OR Group 14 - Metalloids Si,Ge OR Group 14 - Metals Sn,Pb OR Group 15 - Nitrogen N OR Group 15 - Phosphorus P OR Group 16 - Oxygen O OR Group 17 - Halogens Cl OR Group 17 - Halogens F OR Group 17 - Halogens F,Cl,Br,I,At by Chemical elements

Domain logical expression index: "p"

Referential boundary: The target chemical should be classified as Not bioavailable by Lipinski Rule Oasis ONLY

Domain logical expression index: "q"

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

Domain logical expression index: "r"

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

Domain logical expression index: "s"

Parametric boundary:The target chemical should have a value of log Kow which is >= 7.7

Domain logical expression index: "t"

Parametric boundary:The target chemical should have a value of log Kow which is <= 15.6

Conclusions:

Pentene, 2, 4, 4-trimethyl-, sulfurized did not induce gene mutation in Salmonella typhimurium strains TA 1535, TA 1537, TA 98, TA 100 and TA 102 in the presence of S9 metaboliic activation system and hence is predicted to not likely 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 Pentene, 2, 4, 4-trimethyl-, sulfurized. 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. Pentene, 2, 4, 4-trimethyl-, sulfurized did 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 is predicted to not likely classify as a gene mutant in vitro.

Based on the predicted result it can be concluded that Pentene, 2, 4, 4-trimethyl-, sulfurized 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

Gene mutation in vitro:

Prediction model based estimation for the target chemical and data from read across have been reviewed to determine the mutagenic nature of

Pentene, 2, 4, 4-trimethyl-, sulfurized. The summary of the studies reviewed is 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 Pentene, 2, 4, 4-trimethyl-, sulfurized. 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. Pentene, 2, 4, 4-trimethyl-, sulfurized did 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 is predicted to not likely classify as a gene mutant in vitro.

In another study mentioned (U. S. Environmental protection Agency, 2000) an in-vitro gene toxicity test, Salmonella typhimurium TA98, TA100, TA1535, TA1537, TA1538 bacterial cells were exposed to Pentene, 2, 4, 4-trimethyl-, sulfurized in the concentration of 0, 0.01, 0.03, 0.1, 0.3 and 1 µL/plate with and without metabolic activation. Plate incorporation assay was performed with three replicate assay plates. The mean number of his- revertants/plate was calculated for each concentration and strain.The results showed that there was no significant evidence of mutation in any of the Salmonella strains in the quantitative mutagenesis assay in the presence or absence of metabolic activation. Pentene, 2, 4, 4-trimethyl-, sulfurized is non mutagenic at a concentration of 0, 0.01, 0.03, 0.1, 0.3 and 1 µL/plate in Salmonella typhimurium strains TA98, TA100, TA1535, TA1537, TA1538.

Gene mutation toxicity study was performed by Zeiger et al ( Environmental and Molecular Mutagenesis, 1992) to determine the mutagenic nature of structurally and functionally read across chemical n-Eicosane (RA CAS no 112 -95 -8; IUPAC name: Icosane). The study was performed usingSalmonella typhimurium strainsTA97, TA98, TA100, TA1535, TA1537 in the presence and absence of S9 metabolic activation system. The chemical was dissolved in acetone and used at dose levels of 0, 100, 333, 1000, 3333 or 1000 µg/plate by the preincubation method. The plates were preincubated for 20 mins and the exposure duration was 48 hrs. Concurrent solvent and positive control chemicals were included in the study. n- Eicosane did notinduce gene mutation in Salmonella typhimurium strainsTA97, TA98, TA100, TA1535, TA1537 in the presence and absence of S9 metabolic activation system and hence is not likely to classify as a gene mutant in vitro.

Prival et al (Mutation research, 1991) performed gene mutation toxicity study to determine the mutagenic nature of another structurally and functionally similar read across chemical Candelilla wax (RA CAS no 8006 -44 -8). Plate incorporation assay was performed and the test chemical was used at dose level of 0.033, 0.10, 0.33, 1.0, 3.3 or 10 mg per plate.All platings were performed in duplicate and all tests were.The plates were observed for a dose dependent increase in the number of revertants/plate. Concurrent positive control chemicals were also included in the study. Test results were considered valid only if the positive control compounds induced increases in mutant counts to at least twice background. Another experiment to check for the possibility for the presence of histidine in the test substance was also performed but it was found that Candellila wax does not contain histidine in it. Candelilla wax failed to induce mutation in S. typhimurium strains TA98, TA100, TA1535, TA1537 and TA1538 and E. coli strain WP2 both in the presence and absence of S9 metabolic activation system and hence is not likely to classify as a gene mutant in vitro.

Based on the information available for the target chemical and its read across, Pentene, 2, 4, 4-trimethyl-, sulfurized does not exhibit gene mutation in vitro. Hence the chemical is not likely to classify as a gene mutant in vitro as per the criteria mentioned in CLP regulation.

Justification for classification or non-classification

Based on the information available for the target chemical and its read across, Pentene, 2, 4, 4-trimethyl-, sulfurized does not exhibit gene mutation in vitro. Hence the chemical is not likely to classify as a gene mutant in vitro as per the criteria mentioned in CLP regulation.