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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 3.4 with log kow as the primary descriptor and considering the five closest read across substances, gene mutation was predicted for Poly(oxy-1,2-ethanediyl), alpha-(4-nonylphenyl)-omega-hydroxy-, branched (EC name: 4-Nonylphenol, branched, ethoxylated). The study assumed the use of Salmonella typhimurium strain TA100 with S9 metabolic activation system. Poly(oxy-1,2-ethanediyl), alpha-(4-nonylphenyl)-omega-hydroxy-, branched (EC name: 4-Nonylphenol, branched, ethoxylated) failed to induce mutation in Salmonella typhimurium strain TA100 with S9 metabolic activation system and hence is predicted to not classify for gene mutation 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
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 OECD QSAR toolbox version 3.4 and the supporting QMRF report has been attached
Qualifier:
equivalent or similar to
Guideline:
other: Refer below principle
Principles of method if other than guideline:
Prediction is done using QSAR Toolbox version 3.4
GLP compliance:
not specified
Type of assay:
bacterial reverse mutation assay
Specific details on test material used for the study:
- Name of test material : Poly(oxy-1,2-ethanediyl), alpha-(4-nonylphenyl)-omega-hydroxy-, branched
- EC name: 4-Nonylphenol, branched, ethoxylated
- Molecular formula : C23H40O5
- Molecular weight : 396.63 g/mol
- Substance type: Organic
Target gene:
Histidine
Species / strain / cell type:
S. typhimurium TA 100
Details on mammalian cell type (if applicable):
Not applicable
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 observed for a dose dependent increase in the number of revertants/plate
Statistics:
No data
Species / strain:
S. typhimurium TA 100
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 ("k" and ( not "l") )  )  and ("m" and "n" )  )

Domain logical expression index: "a"

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

Domain logical expression index: "b"

Referential boundary: The target chemical should be classified as Alcohol AND Alkane, branched with tertiary carbon AND Alkyl arenes AND Aryl AND Ether by Organic Functional groups

Domain logical expression index: "c"

Referential boundary: The target chemical should be classified as Alcohol AND Alkyl arenes AND Ether AND Overlapping groups by Organic Functional groups (nested)

Domain logical expression index: "d"

Referential boundary: The target chemical should be classified as Aliphatic Carbon [CH] AND Aliphatic Carbon [-CH2-] AND Aliphatic Carbon [-CH3] AND Aromatic Carbon [C] AND Hydroxy, aliphatic attach [-OH] AND Olefinic carbon [=CH- or =C<] AND Oxygen, aliphatic attach [-O-] AND Oxygen, one aromatic attach [-O-] AND Tertiary Carbon by Organic functional groups (US EPA)

Domain logical expression index: "e"

Referential boundary: The target chemical should be classified as Alcohol AND Alkylarylether AND Aromatic compound AND Dialkylether AND Ether AND Hydroxy compound AND Primary alcohol 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.1.4

Domain logical expression index: "g"

Referential boundary: The target chemical should be classified as AN2 OR AN2 >>  Michael-type addition, quinoid structures OR AN2 >>  Michael-type addition, quinoid structures >> Flavonoids OR AN2 >>  Michael-type addition, quinoid structures >> Quinones and Trihydroxybenzenes OR AN2 >> Michael-type addition on alpha, beta-unsaturated carbonyl compounds OR AN2 >> Michael-type addition on alpha, beta-unsaturated carbonyl compounds >> Four- and Five-Membered Lactones OR AN2 >> Nucleophilic addition reaction with cycloisomerization OR AN2 >> Nucleophilic addition reaction with cycloisomerization >> Hydrazine Derivatives OR AN2 >> Shiff base formation after aldehyde release OR AN2 >> Shiff base formation after aldehyde release >> Specific Acetate Esters OR Non-covalent interaction OR Non-covalent interaction >> DNA intercalation OR Non-covalent interaction >> DNA intercalation >> Bleomycin and Structurally Related Compounds OR Non-covalent interaction >> DNA intercalation >> Coumarins OR Non-covalent interaction >> DNA intercalation >> DNA Intercalators with Carboxamide and Aminoalkylamine Side Chain OR Non-covalent interaction >> DNA intercalation >> Quinones and Trihydroxybenzenes 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) >> Anthrones OR Radical >> Radical mechanism via ROS formation (indirect) >> Bleomycin and Structurally Related Compounds OR Radical >> Radical mechanism via ROS formation (indirect) >> Conjugated Nitro Compounds OR Radical >> Radical mechanism via ROS formation (indirect) >> Coumarins OR Radical >> Radical mechanism via ROS formation (indirect) >> Flavonoids OR Radical >> Radical mechanism via ROS formation (indirect) >> Hydrazine Derivatives OR Radical >> Radical mechanism via ROS formation (indirect) >> Quinones and Trihydroxybenzenes OR Radical >> ROS formation after GSH depletion (indirect) OR Radical >> ROS formation after GSH depletion (indirect) >> Haloalcohols OR SN1 OR SN1 >> Nucleophilic attack after carbenium ion formation OR SN1 >> Nucleophilic attack after carbenium ion formation >> Specific Acetate Esters OR SN1 >> Nucleophilic attack after reduction and nitrenium ion formation OR SN1 >> Nucleophilic attack after reduction and nitrenium ion formation >> Conjugated Nitro Compounds OR SN2 OR SN2 >> Acylation OR SN2 >> Acylation >> Specific Acetate Esters OR SN2 >> Alkylation by epoxide metabolically formed after E2 reaction OR SN2 >> Alkylation by epoxide metabolically formed after E2 reaction >> Haloalcohols OR SN2 >> Alkylation, direct acting epoxides and related OR SN2 >> Alkylation, direct acting epoxides and related >> Epoxides and Aziridines OR SN2 >> Alkylation, nucleophilic substitution at sp3-carbon atom OR SN2 >> Alkylation, nucleophilic substitution at sp3-carbon atom >> Haloalkanes Containing Heteroatom OR SN2 >> Alkylation, ring opening SN2 reaction OR SN2 >> Alkylation, ring opening SN2 reaction >> Four- and Five-Membered Lactones OR SN2 >> Direct acting epoxides formed after metabolic activation OR SN2 >> Direct acting epoxides formed after metabolic activation >> Coumarins OR SN2 >> Direct nucleophilic attack on diazonium cation OR SN2 >> Direct nucleophilic attack on diazonium cation >> Hydrazine Derivatives 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 >> Specific Acetate Esters by DNA binding by OASIS v.1.4

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 azo OR SN1 >> Nitrenium Ion formation >> Tertiary aromatic amine by DNA binding by OECD

Domain logical expression index: "j"

Referential boundary: The target chemical should be classified as Has superfragment AND OCCOR{*} by Superfragments ONLY

Domain logical expression index: "k"

Referential boundary: The target chemical should be classified as Not known precedent reproductive and developmental toxic potential by DART scheme v.1.0

Domain logical expression index: "l"

Referential boundary: The target chemical should be classified as Alkoxy propanol derivatives OR Di-substituted hydrocarbons (24a) OR Di-substituted hydrocarbons (24b) OR Known precedent reproductive and developmental toxic potential by DART scheme v.1.0

Domain logical expression index: "m"

Parametric boundary:The target chemical should have a value of log Kow which is >= -1.76

Domain logical expression index: "n"

Parametric boundary:The target chemical should have a value of log Kow which is <= 8.47

Conclusions:
Poly(oxy-1,2-ethanediyl), alpha-(4-nonylphenyl)-omega-hydroxy-, branched failed to induce mutation in Salmonella typhimurium strain TA100 in the presence of S9 metabolic activation system and hence is predicted to not classify as a gene mutant in vitro.
Executive summary:

Based on the prediction done using the OECD QSAR toolbox version 3.4 with log kow as the primary descriptor and considering the five closest read across substances, gene mutation was predicted for Poly(oxy-1,2-ethanediyl), alpha-(4-nonylphenyl)-omega-hydroxy-, branched (EC name: 4-Nonylphenol, branched, ethoxylated). The study assumed the use of Salmonella typhimurium strain TA100 with S9 metabolic activation system. Poly(oxy-1,2-ethanediyl), alpha-(4-nonylphenyl)-omega-hydroxy-, branched (EC name: 4-Nonylphenol, branched, ethoxylated) failed to induce mutation in Salmonella typhimurium strain TA100 with S9 metabolic activation system and hence is predicted to not classify for gene mutation 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

Gene toxicity in vitro:

Prediction model based estimation and data from read across chemicals have been reviewed and summarized to determine the mutagenic nature of Poly(oxy-1,2-ethanediyl), alpha-(4-nonylphenyl)-omega-hydroxy-, branched (EC name: 4-Nonylphenol, branched, ethoxylated):

Based on the prediction done using the OECD QSAR toolbox version 3.4 with log kow as the primary descriptor and considering the five closest read across substances, gene mutation was predicted for Poly(oxy-1,2-ethanediyl), alpha-(4-nonylphenyl)-omega-hydroxy-, branched (EC name: 4-Nonylphenol, branched, ethoxylated). The study assumed the use of Salmonella typhimurium strain TA100 with S9 metabolic activation system. Poly(oxy-1,2-ethanediyl), alpha-(4-nonylphenyl)-omega-hydroxy-, branched (EC name: 4-Nonylphenol, branched, ethoxylated) failed to induce mutation in Salmonella typhimurium strain TA100 with S9 metabolic activation system and hence is predicted to not classify for gene mutation in vitro.

In a study for read across with 70 -80% structural similarity, Gene mutation toxicity study was performed (J check, 2017) to evaluate the mutagenic nature of Polyoxyethylene p-nonylphenyl ether (RA CAS no 9016 -45 -9; EC name: Nonylphenol, ethoxylated). The test was performed as per the OECD guideline 471 using S. typhimurium TA 1535, TA 1537, TA 98 and TA 100 and E. coli WP2 uvr A with and without of S9 mix at dose levels of 0, 156, 313, 625, 1250, 2500, 5000 µg/plate. Concurrent solvent and positive controls were included in the study. Polyoxyethylene p-nonylphenyl ether failed to induce mutation in S. typhimurium TA 1535, TA 1537, TA 98 and TA 100 and E. coli WP2 uvr A in the presence and absence of S9 mix and hence is not likely to classify as a gene mutant in vitro.

Mutagenicity study was also conducted by Meyer et al ( Pharmacology & Toxicology, 1988) using Salmonella typhimurium strains TA 1535, TA 1537, TA 100 and TA 98 for Nonoxynol 9 (CAS no 26027 -38 -3; EC anme: 4-Nonylphenol, ethoxylated; 50 -60% structurally similar) by the Ames test protocol. It was tested at a concentration of 0, 40, 200, 1000, 5000 and 25000 µg/plate with and without S9 metabolic activation system. In all tests performed without metabolic activation, no mutagenic effects were seen. The same picture was seen in the tests using metabolic activation, except for the test in S. typhimurium strain TA 98 where the number of revertants was elevated 30% after 1000 pg/plate. The highest dose tested exerted a marked toxic effect. However, the increased number of revertants observed in strain TA-98 after metabolic activation did not indicate a clear-cut mutagenic response of NP-9, as the increase was considerably less than 100%. The test compound Nonoxynol 9 is not mutagenic to the Salmonella typhimurium strains TA 1535, TA 1537, TA 100 and TA 98 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 weight of evidence data summarized, Poly(oxy-1,2-ethanediyl), alpha-(4-nonylphenyl)-omega-hydroxy-, branched is not likely to exhibit genetic toxicity. Thus, the chemical is not classified as a genetic toxicant as per as per the criteria mentioned in CLP regulation.

Justification for classification or non-classification

Based on the weight of evidence data summarized, Poly(oxy-1,2-ethanediyl), alpha-(4-nonylphenyl)-omega-hydroxy-, branched (CAS no 127087 -87 -0;

EC name: 4-Nonylphenol, branched, ethoxylated) is not likely to exhibit genetic toxicity. Thus, the chemical is not classified as a genetic toxicant as per as per the criteria mentioned in CLP regulation.