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Key value for chemical safety assessment

Genetic toxicity in vitro

Description of key information

Key study: Read-across from experimental data on an analogue. Test method OECD Guideline 471. GLP study. The substance was not mutagenic in bacterial cells in-vitro.
Key study: Read-across from experimental data on an analogue. Test method OECD Guideline 473. GLP study. The substance was not clastogenic in mammalian cells in-vitro.
Key study: Read-across from experimental data on an analogue. Test method OECD Guideline 476. GLP study. The substance was not mutagenic in mammalian cells in-vitro.

Link to relevant study records

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Endpoint:
in vitro gene mutation study in bacteria
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Read-across from an analogue substance for which a guideline study (Klimish 1) is available.
Reason / purpose:
read-across source
Principles of method if other than guideline:
Read-across approach from data on an analogue substance.
Type of assay:
bacterial reverse mutation assay
Key result
Species / strain:
S. typhimurium TA 1535
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
no cytotoxicity
Vehicle controls validity:
valid
Untreated negative controls validity:
valid
Positive controls validity:
valid
Key result
Species / strain:
S. typhimurium TA 1537
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
no cytotoxicity
Vehicle controls validity:
valid
Untreated negative controls validity:
valid
Positive controls validity:
valid
Key result
Species / strain:
S. typhimurium TA 98
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
no cytotoxicity
Vehicle controls validity:
valid
Untreated negative controls validity:
valid
Positive controls validity:
valid
Key result
Species / strain:
S. typhimurium TA 100
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
no cytotoxicity
Vehicle controls validity:
valid
Untreated negative controls validity:
valid
Key result
Species / strain:
E. coli WP2 uvr A
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
no cytotoxicity
Vehicle controls validity:
valid
Untreated negative controls validity:
valid
Positive controls validity:
valid
Remarks on result:
other: Based on a read-across from an analogue substance.
Conclusions:
Based on read-across approach from analogue substance P0310, the substance P-1401 is considered to be non-mutagenic in this Salmonella typhimurium and Escherichia coli reverse mutation assay.
Executive summary:

Based on experimental results obtained in a study according to OECD 471 on analogue substance P0310 where the test item was considered to be non-mutagenic, the read-across approach is applied and the substance P-1401 is also considered to be non-mutagenic in the Salmonella typhimurium and Escherichia coli reverse mutation assay.

Endpoint:
in vitro cytogenicity / chromosome aberration study in mammalian cells
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Read-across from an analogue substance for which a guideline study (Klimish 1) is available.
Reason / purpose:
read-across source
Principles of method if other than guideline:
Read-across approach from data on an analogue substance.
Type of assay:
in vitro mammalian chromosome aberration test
Key result
Species / strain:
Chinese hamster lung fibroblasts (V79)
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
cytotoxicity
Remarks:
(In Experiment II, in the absence of S9 mix, the concentration showing clear cytotoxicity was not scorable for cytogenetic damage).
Vehicle controls validity:
valid
Positive controls validity:
valid
Remarks on result:
other: Based on a read-across from an analogue substance.
Conclusions:
Based on read-across approach from analogue substance P0310, the substance P-1401 is considered to be non-clastogenic in this chromosome aberration test with and without metabolic activation.
Executive summary:

Based on experimental results obtained in a study according to OECD 473 on analogue substance P0310 where the test item was considered to be non-clastogenic with and without metabolic activation, the read-across approach is applied and the substance P-1401 is also considered to be non-clastogenic with and without metabolic activation in the chromosome aberration test.

Endpoint:
in vitro gene mutation study in mammalian cells
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Read-across from an analogue substance for which a guideline study (Klimish 1) is available.
Reason / purpose:
read-across source
Principles of method if other than guideline:
Read-across approach from data on an analogue substance.
Type of assay:
mammalian cell gene mutation assay
Key result
Species / strain:
mouse lymphoma L5178Y cells
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
cytotoxicity
Remarks:
(Moderate cytotoxic effects indicated by a relative total growth of less than 50 % of survival in both parallel cultures were solely observed at the maximum concentration of 5300 μg/mL following 4 hours of treatment without metabolic activation).
Vehicle controls validity:
valid
Positive controls validity:
valid
Remarks on result:
other: Based on a read-across from an analogue substance.
Conclusions:
Based on read-across approach from analogue substance P0310, the substance P-1401 is considered to be non-mutagenic in the mouse lymphoma assay.
Executive summary:

Based on experimental results obtained in a study according to OECD 476 on analogue substance P0310 where the test item was considered to be non-mutagenic, the read-across approach is applied and the substance P-1401 is also considered to be non-mutagenic in the mouse lymphoma assay.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (negative)

Genetic toxicity in vivo

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Bacterial reverse mutation assay:

Key study: Read-across approach from experimental data on the analogue substance P0310. OECD Guideline 471 and EU method B.13/14. GLP study. In conclusion, it can be stated that during the described mutagenicity test and under the experimental conditions reported, the test item did not induce gene mutations by base pair changes or frameshifts in the genome of the strains used. Therefore, the test item is considered to be non-mutagenic in this Salmonella typhimurium and Escherichia coli reverse mutation assay.

Chromosomal aberrations:

Key study: Read-across approach from experimental data on the analogue substance P0310. OECD Guideline 473 and EU method B.10. GLP study. In conclusion, it can be stated that under the experimental conditions reported, the test item did not induce structural chromosome aberrations as determined by the chromosome aberration test in V79 cells (Chinese hamster cell line) in vitro. Therefore, the test item is considered to be non-clastogenic in this chromosome aberration test with and without S9 mix, when tested up to the highest required concentration in Experiment IA (with and without S9 mix), IB (with S9 mix), and Experiment II (with S9 mix) or to the highest scorable concentration in Experiment II (without S9 mix).

Gene mutation assay in mammalian cells:

Key study: Read-across approach from experimental data on the analogue substance P0310. OECD Guideline 476 and EU method B.17. GLP study. In conclusion it can be stated that during the mutagenicity test described and under the experimental conditions reported the test item did not induce mutations in the mouse lymphoma thymidine kinase locus assay using the cell line L5178Y in the absence and presence of metabolic activation. Therefore, the test item is considered to be non-mutagenic in this mouse lymphoma assay.

Justification for classification or non-classification

Based on the available information on genetic toxicity in vitro (bacterial reverse mutation assay, chromosome aberration and gene mutation in mammalian cells) the substance is considered to be negative for genetic toxicity, and therefore, the substance is not classified in accordance with CLP Regulation (EC) No. 1272/2008.