1-methyl-3-phenylpropylamine

Endpoint summary

Key value for chemical safety assessment

Genetic toxicity in vitro

Description of key information

Prediction model based estimation and data from read across chemical have been reviewed to determine the mutagenic nature of 1-methyl-3-phenylpropylamine (22374-89-6). The studies are as mentioned below

Gene mutation toxicity was predicted for 1-methyl-3-phenylpropylamine using the battery approach from Danish QSAR database (2018). The study assumed the use of Salmonella typhimurium bacteria in the Ames test. The end point for gene mutation has been modeled 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 by Danish QSAR for1-methyl-3-phenylpropylamine is negative and hence the chemical is predicted to classify as a gene mutant in vitro.

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 for test substance. In the study conducted by Mortelmans et al in 1986,test chemical was examined for its ability to cause mutagenic changes when tested in five strains of the bacteria Salmonella typhimurium, specifically, TA 1535, TA 1537, TA97, TA 98 and TA 100 through the preincubation assay method. The test was conducted both in the presence and absence of metabolic activation using rat and hamster liver derived S-9 mix, over a range of doses, from 0 to 10000 ug/plate. Based on the results of this study, the test substance was not considered to be mutagenic under the conditions of this test.

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 for target substance.  The test substance did not induce mutagenicity in an Ames assay conducted on S. typhimurium TA 1535, TA 1537, TA 98, TA 100 and TA 102 strains with and without rat liver S9 activation. Although positive response is observed in some strains, there were also no apparent trends discernible that would suggest a change in mutagenic activity caused by the addition of the ingredients. Hence the test chemical cannot be classified as mutagenic

Link to relevant study records

Reference

Endpoint:

in vitro gene mutation study in bacteria

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

data from handbook or collection of data

Justification for type of information:

Data for the target chemical is summarized based on the structurally similar read across chemicals

Reason / purpose for cross-reference:

other: Prediction

Reason / purpose for cross-reference:

read-across source

Reason / purpose for cross-reference:

read-across source

Qualifier:

according to guideline

Guideline:

other: As mention below

Principles of method if other than guideline:

WoE derived based on the predicted data for the target chemical and experimental data from structurally and functionally similar read across chemicals

GLP compliance:

not specified

Type of assay:

bacterial reverse mutation assay

Target gene:

Histidine

Species / strain / cell type:

S. typhimurium, other:

Details on mammalian cell type (if applicable):

Not applicable

Additional strain / cell type characteristics:

not specified

Species / strain / cell type:

S. typhimurium, other: TA 1535, TA 1537, TA 98,TA 97 and TA 100

Details on mammalian cell type (if applicable):

Not applicable

Additional strain / cell type characteristics:

not specified

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:

not specified

Metabolic activation system:

not specified

Test concentrations with justification for top dose:

1; No data
2;0,10,100,1000 and 10000ug/plate.
3;five doses up to 5 mg mainstream smoke condensate (MSC)/plate

Vehicle / solvent:

1;No data
2;water or DMSO
3;water or DMSO

Untreated negative controls:

not specified

Negative solvent / vehicle controls:

not specified

True negative controls:

not specified

Positive controls:

not specified

Untreated negative controls:

yes

Negative solvent / vehicle controls:

yes

True negative controls:

not specified

Positive controls:

yes

Positive control substance:

sodium azide

other: 4-nitro-o-phenylenediamine-Used with metabolic activation for strain TA 98 9-aminoacridine- Used with metabolic activation for strains TA 97 and TA 1537 2-aminoanthracene-Used with all strains with rat and hamster liver metabolic activation systems.

Untreated negative controls:

yes

Negative solvent / vehicle controls:

yes

True negative controls:

not specified

Positive control substance:

sodium azide

methylmethanesulfonate

Details on test system and experimental conditions:

1.No data
2.Details on test system and conditions
METHOD OF APPLICATION: in medium; in agar (plate incorporation); preincubation; in suspension; as impregnation on paper disk: preincubation

DURATION
- Preincubation period: 20 minutes
- Exposure duration: 48 hours
- Expression time (cells in growth medium):No data available
- Selection time (if incubation with a selection agent): :No data available
- Fixation time (start of exposure up to fixation or harvest of cells): :No data available

SELECTION AGENT (mutation assays): :No data available
SPINDLE INHIBITOR (cytogenetic assays): :No data available
STAIN (for cytogenetic assays): :No data available

NUMBER OF REPLICATIONS: : All assays were repeated no less than one week after completion of the initial test.

NUMBER OF CELLS EVALUATED: :No data available

DETERMINATION OF CYTOTOXICITY
- Method: mitotic index; cloning efficiency; relative total growth; other: Toxicity was evidenced by one or more of the following phenomena: appearance of his- pinpoint colonies, reduced numbers of revertant colonies per plate or thinning or absence of the bacterial lawn.

OTHER EXAMINATIONS:
- Determination of polyploidy: :No data available
- Determination of endoreplication: :No data available
- Other: :No data available

OTHER: At least one toxic dose was incorporated into the first mutagenicity test, the repeat test(s) occasionally had the doses adjusted so that an apparent toxic dose was not reached.
3.METHOD OF APPLICATION: in agar (plate incorporation)
For plating, approximately 10(8) bacteria suspended in 100 ml culture medium, 120 ml of the MSC dissolved in DMSO or DMSO alone, 500 ml S9 mix or 0.1 mol/l phosphate buffer, pH 7.4, were added to 2 ml of top agar supplemented with histidine and biotin (0.05 nmol each). The components were mixed and spread evenly on minimal glucose agar plates. After the top agar hardened, the plates were incubated in the dark at 361C for 44–48 h. The number of His+ revertant colonies was determined with an automatic colony counter. In all experiments several negative and positive strain-specific and S9-specific control substances were assayed concurrently.

Rationale for test conditions:

Not specified

Evaluation criteria:

1. No data
2.Mutagenic response: a dose-related, reproducible increase in the number of revertants over background, even if the increase was less than twofold.
Nonmutagenic response: when no increase in the number of revertants was elicited
Questionable response: when there was an absence of a clear cut dose related increase in revertants, when the dose related increase in revertants was not reproducible or when the response was of insufficient magnitude to support a determination of mutagenicity.
3.The normal mutagenic response to MSC is characterized by a linear increase in the number of revertants as the amount of MSC is increased. This is followed by a leveling or decrease in response due to toxicity.

Statistics:

1.No data
2.Not specified
3.The mutagenic response reported here was calculated as the slope (revertants/mg TPM) of the linear portion of the dose–response curve fitted with Poisson-weights to the data. A single slope was calculated for each of the four batches.

Species / strain:

S. typhimurium, other:

Metabolic activation:

not specified

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

Species / strain:

S. typhimurium, other: TA 1535, TA 1537, TA 98,TA 97 and TA 100

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

not specified

Vehicle controls validity:

valid

Untreated negative controls validity:

not specified

Positive controls validity:

valid

Species / strain:

S. typhimurium, other: TA98, TA100, TA102, TA1535 and TA1537

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

not specified

Vehicle controls validity:

valid

Untreated negative controls validity:

not specified

Positive controls validity:

valid

Remarks on result:

other: No mutagenic effect were observed based on prediction

Conclusions:

Gene mutation toxicity study for 1-methyl-3-phenylpropylamine (22374-89-6) as predicted using data from read across chemicals for Salmonella typhimurium bacterial strains in the presence and absence of S9 metabolic activation system is negative and hence the chemical is not likely to classify as a gene mutant in vitro.

Executive summary:

Genetic mutation in vitro;

Prediction model based estimation and data from read across chemical have been reviewed to determine the mutagenic nature of 1-methyl-3-phenylpropylamine (22374-89-6). The studies are as mentioned below

Gene mutation toxicity was predicted for 1-methyl-3-phenylpropylamine using the battery approach from Danish QSAR database (2018). The study assumed the use of Salmonella typhimurium bacteria in the Ames test. The end point for gene mutation has been modeled 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 by Danish QSAR for1-methyl-3-phenylpropylamine is negative and hence the chemical is predicted to classify as a gene mutant in vitro.

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 for test substance. In the study conducted by Mortelmans et al in 1986,test chemical was examined for its ability to cause mutagenic changes when tested in five strains of the bacteria Salmonella typhimurium, specifically, TA 1535, TA 1537, TA97, TA 98 and TA 100 through the preincubation assay method. The test was conducted both in the presence and absence of metabolic activation using rat and hamster liver derived S-9 mix, over a range of doses, from 0 to 10000 ug/plate. Based on the results of this study, the test substance was not considered to be mutagenic under the conditions of this test.

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 for target substance.  The test substance did not induce mutagenicity in an Ames assay conducted on S. typhimurium TA 1535, TA 1537, TA 98, TA 100 and TA 102 strains with and without rat liver S9 activation. Although positive response is observed in some strains, there were also no apparent trends discernible that would suggest a change in mutagenic activity caused by the addition of the ingredients. Hence the test chemical cannot be classified as mutagenic

Based on the data available for the target chemical and its read across substance and applying weight of evidence1-methyl-3-phenylpropylamine (22374-89-6) does not exhibit gene mutation in vitro . Hence the test chemical is not likely to classify as a gene mutant in vitro.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (negative)

Genetic toxicity in vivo

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Genetic mutation in vitro;

Prediction model based estimation and data from read across chemical have been reviewed to determine the mutagenic nature of 1-methyl-3-phenylpropylamine (22374-89-6). The studies are as mentioned below

Gene mutation toxicity was predicted for 1-methyl-3-phenylpropylamine using the battery approach from Danish QSAR database (2018). The study assumed the use of Salmonella typhimurium bacteria in the Ames test. The end point for gene mutation has been modeled 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 by Danish QSAR for1-methyl-3-phenylpropylamine is negative and hence the chemical is predicted to classify as a gene mutant in vitro.

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 for test substance. In the study conducted by Mortelmans et al in 1986,test chemical was examined for its ability to cause mutagenic changes when tested in five strains of the bacteria Salmonella typhimurium, specifically, TA 1535, TA 1537, TA97, TA 98 and TA 100 through the preincubation assay method. The test was conducted both in the presence and absence of metabolic activation using rat and hamster liver derived S-9 mix, over a range of doses, from 0 to 10000 ug/plate. Based on the results of this study, the test substance was not considered to be mutagenic under the conditions of this test.

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 for target substance.  The test substance did not induce mutagenicity in an Ames assay conducted on S. typhimurium TA 1535, TA 1537, TA 98, TA 100 and TA 102 strains with and without rat liver S9 activation. Although positive response is observed in some strains, there were also no apparent trends discernible that would suggest a change in mutagenic activity caused by the addition of the ingredients. Hence the test chemical cannot be classified as mutagenic

Based on the data available for the target chemical and its read across substance and applying weight of evidence1-methyl-3-phenylpropylamine (22374-89-6) 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 above annotation and CLP criteria the target chemical 1-methyl-3-phenylpropylamine (22374-89-6) does not exhibit gene mutation in vitro . Hence the test chemical is not likely to classify as a gene mutant in vitro.