Phenol, isopropylated

Endpoint summary

Key value for chemical safety assessment

Genetic toxicity in vitro

Description of key information

QSAR assessment using the following models (from the VEGA QSAR suite) gives the following outcome for the reaction mass:

Mutagenicity (Ames test) CONSENSUS model 1.0.2: Prediction is NON-Mutagenic, the result appears reliable

Mutagenicity (Ames test) model (CAESAR) 2.1.13: Prediction is NON-Mutagenic, the result appears reliable

Mutagenicity (Ames test) model (SarPy/IRFMN) 1.0.7: Prediction is NON-Mutagenic, the result appears reliable

Mutagenicity (Ames test) model (ISS) 1.0.2: Prediction is NON-Mutagenic, the result appears reliable

Mutagenicity (Ames test) model (KNN/Read-Across) 1.0.0: Prediction is NON-Mutagenic, the result appears reliable

This result is anticipated on the basis that phenol is not mutagenic to bacteria under the conditions of the Ames test. However, phenol presents positive results in other mutagenicity studies, and hence Mutagen Cat 2, H341: Suspected of causing genetic defects is applied to the overall reaction mass on the basis of the phenol content within the overall product.

On the above basis, it is proposed that further investigation of the substance using the Ames test is not necessary, and the outcome may be predicted on the basis of the components themselves. 

Link to relevant study records

Reference

Endpoint:

in vitro gene mutation study in bacteria

Type of information:

(Q)SAR

Adequacy of study:

key study

Study period:

February 2020

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 adequate and reliable documentation / justification

Justification for type of information:

The substance is a multi-constituent substance of limited solubility. CLP classification is available for the individual components of the substance via REACH Annex VI harmonised classifications, REACH Registration dossiers or notifications to the CLP inventory. As such, it is deemed inappropriate to conduct additional testing on the reaction mass subject to this registration when the results may be predicted on the basis of the components themselves. QSAR assessment using the following models (from the VEGA QSAR suite) is used assess each component with the associated range of results reported.
• Mutagenicity (Ames test) CONSENSUS model 1.0.2
• Mutagenicity (Ames test) model (CAESAR) 2.1.13
• Mutagenicity (Ames test) model (SarPy/IRFMN) 1.0.7
• Mutagenicity (Ames test) model (ISS) 1.0.2
• Mutagenicity (Ames test) model (KNN/Read-Across) 1.0.0
The attached report details the applicability of the models.

Qualifier:

no guideline followed

Principles of method if other than guideline:

QSAR assessment using the following models (from the VEGA QSAR suite) is used assess each component with the associated range of results reported.
• Mutagenicity (Ames test) CONSENSUS model 1.0.2
• Mutagenicity (Ames test) model (CAESAR) 2.1.13
• Mutagenicity (Ames test) model (SarPy/IRFMN) 1.0.7
• Mutagenicity (Ames test) model (ISS) 1.0.2
• Mutagenicity (Ames test) model (KNN/Read-Across) 1.0.0
The attached report details the applicability of the models.

GLP compliance:

no

Type of assay:

bacterial reverse mutation assay

Specific details on test material used for the study:

Not applicable – QSAR Assessment

Target gene:

Not applicable – QSAR Assessment

Species / strain / cell type:

other: Not applicable – QSAR Assessment

Details on mammalian cell type (if applicable):

Not applicable – QSAR Assessment

Cytokinesis block (if used):

Not applicable – QSAR Assessment

Metabolic activation:

not applicable

Metabolic activation system:

Not applicable – QSAR Assessment

Test concentrations with justification for top dose:

Not applicable – QSAR Assessment

Vehicle / solvent:

Not applicable – QSAR Assessment

Untreated negative controls:

other: Not applicable – QSAR Assessment

Negative solvent / vehicle controls:

other: Not applicable – QSAR Assessment

True negative controls:

other: Not applicable – QSAR Assessment

Positive controls:

other: Not applicable – QSAR Assessment

Details on test system and experimental conditions:

The following assessment tools are utilised:

Mutagenicity (Ames test) CONSENSUS model (version 1.0.2)
Mutagenicity (Ames test) Consensus model, based on the predictions of the available VEGA mutagenicity models (Caesar, SarPy, ISS and KNN).

Mutagenicity (Ames test) model (CAESAR) (version 2.1.13)
QSAR classification model for Mutagenicity based on a Support Vector Machine combined by a set of ToxTree rules developed by Benigni/Bossa. The model extends the original CAESAR Mutagenicity model 1.0 developed by Politecnico di Milano, Italy. Reference to the original model are found on the CAESAR Project website: http://www.caesar-project.eu/ .

Mutagenicity (Ames test) model (SarPy/IRFMN) (version 1.0.7)
QSAR classification model for Mutagenicity based on a set of rules built with SarPy software. Developed by Istituto Mario Negri, Italy; SarPy software developed by Politecnico di Milano, Italy. Model developed inside the VEGA platform.

Mutagenicity (Ames test) model (ISS) (version 1.0.2)
Classification model for Mutagenicity (Ames test) based on Benigni-Bossa (Istituto Superiore di Sanità) rule set as implemented in ToxTree 2.6.

Mutagenicity (Ames test) model (KNN/Read-Across) (version 1.0.0)
KNN (Read-Across) model for Mutagenicity (Ames test) developed by Istituto di Ricerche Farmacologiche Mario Negri.

The report is appended below.

Rationale for test conditions:

The substance is a multi-constituent substance of limited solubility. CLP classification is available for the individual components of the substance via REACH Annex VI harmonised classifications, REACH Registration dossiers or notifications to the CLP inventory. As such, it is deemed inappropriate to conduct additional testing on the reaction mass subject to this registration when the results may be predicted on the basis of the components themselves. QSAR assessment using the following models (from the VEGA QSAR suite) is used assess each component with the associated range of results reported.
• Mutagenicity (Ames test) CONSENSUS model 1.0.2
• Mutagenicity (Ames test) model (CAESAR) 2.1.13
• Mutagenicity (Ames test) model (SarPy/IRFMN) 1.0.7
• Mutagenicity (Ames test) model (ISS) 1.0.2
• Mutagenicity (Ames test) model (KNN/Read-Across) 1.0.0

Evaluation criteria:

Not applicable – QSAR Assessment

Statistics:

Not applicable – QSAR Assessment

Key result

Species / strain:

other: Not applicable – QSAR Assessment

Metabolic activation:

not applicable

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

not determined

Vehicle controls validity:

not applicable

Untreated negative controls validity:

not applicable

True negative controls validity:

not applicable

Positive controls validity:

not applicable

Additional information on results:

In each model for each substance, overall results are as follows:

Mutagenicity (Ames test) CONSENSUS model 1.0.2: Prediction is NON-Mutagenic, the result appears reliable
Mutagenicity (Ames test) model (CAESAR) 2.1.13: Prediction is NON-Mutagenic, the result appears reliable
Mutagenicity (Ames test) model (SarPy/IRFMN) 1.0.7: Prediction is NON-Mutagenic, the result appears reliable
Mutagenicity (Ames test) model (ISS) 1.0.2: Prediction is NON-Mutagenic, the result appears reliable
Mutagenicity (Ames test) model (KNN/Read-Across) 1.0.0: Prediction is NON-Mutagenic, the result appears reliable

Remarks on result:

no mutagenic potential (based on QSAR/QSPR prediction)

Results for each component, utilising the VEGA QSAR suite model are as follows:

Chemical name	SMILES	Ames Test – all models
2-isopropylphenol EC no.: 201-852-8	CC(C)c1ccccc1O	Negative
Phenol EC no.: 203-632-7	Oc1ccccc1	Negative
p-isopropylphenol EC no.: 202-798-8	CC(C)c1ccc(O)cc1	Negative
2,4-diisopropylphenol EC no.: 220-906-1	CC(C)c1ccc(O)c(c1)C(C)C	Negative

Refer to appended output below.

Conclusions:

QSAR assessment using the following models (from the VEGA QSAR suite) gives the following outcome for the reaction mass:
Mutagenicity (Ames test) CONSENSUS model 1.0.2: Prediction is NON-Mutagenic, the result appears reliable
Mutagenicity (Ames test) model (CAESAR) 2.1.13: Prediction is NON-Mutagenic, the result appears reliable
Mutagenicity (Ames test) model (SarPy/IRFMN) 1.0.7: Prediction is NON-Mutagenic, the result appears reliable
Mutagenicity (Ames test) model (ISS) 1.0.2: Prediction is NON-Mutagenic, the result appears reliable
Mutagenicity (Ames test) model (KNN/Read-Across) 1.0.0: Prediction is NON-Mutagenic, the result appears reliable
This result is anticipated on the basis that phenol is not mutagenic to bacteria under the conditions of the Ames test. However, phenol presents positive results in other mutagenicity studies, and hence Mutagen Cat 2, H341: Suspected of causing genetic defects is applied to the overall reaction mass on the basis of the phenol content within the overall product.
On the above basis, it is proposed that further investigation of the substance using the Ames test is not necessary, and the outcome may be predicted on the basis of the components themselves.

Executive summary:

QSAR assessment using the following models (from the VEGA QSAR suite) gives the following outcome for the reaction mass:

Mutagenicity (Ames test) CONSENSUS model 1.0.2: Prediction is NON-Mutagenic, the result appears reliable

Mutagenicity (Ames test) model (CAESAR) 2.1.13: Prediction is NON-Mutagenic, the result appears reliable

Mutagenicity (Ames test) model (SarPy/IRFMN) 1.0.7: Prediction is NON-Mutagenic, the result appears reliable

Mutagenicity (Ames test) model (ISS) 1.0.2: Prediction is NON-Mutagenic, the result appears reliable

Mutagenicity (Ames test) model (KNN/Read-Across) 1.0.0: Prediction is NON-Mutagenic, the result appears reliable

This result is anticipated on the basis that phenol is not mutagenic to bacteria under the conditions of the Ames test. However, phenol presents positive results in other mutagenicity studies, and hence Mutagen Cat 2, H341: Suspected of causing genetic defects is applied to the overall reaction mass on the basis of the phenol content within the overall product.

On the above basis, it is proposed that further investigation of the substance using the Ames test is not necessary, and the outcome may be predicted on the basis of the components themselves. 

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (negative)

Genetic toxicity in vivo

Description of key information

No data available.

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

Mutagen Cat 2, H341: Suspected of causing genetic defects is applied to the overall reaction mass on the basis of the phenol content within the overall product.