Bis[[R-(R*,S*)]-β-hydroxy-α-methylphenethyl)methylammonium] sulphate

Genetic toxicity: in vitro

Administrative data

Endpoint:

in vitro gene mutation study in bacteria

Remarks:

Type of genotoxicity: gene mutation

Type of information:

migrated information: read-across based on grouping of substances (category approach)

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: GLP compliant guideline study, available as unpublished report, restriction in design (no E.coli WP2 or S.typhimurium TA 102 used and only one positive control used to test efficacy of the S9-mix), but adequate for assessment

Data source

Reference

Reference 1

Reference Type:

study report

Title:

Unnamed

Year:

1991

Report date:

1991

Reference 2

Reference Type:

other: Amendment

Title:

Unnamed

Year:

1992

Report date:

1992

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 471 (Bacterial Reverse Mutation Assay)

Deviations:

yes

Remarks:

, no E.coli WP2 or S.typhimurium TA 102 used and only one positive control used to test efficacy of the S9-mix

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.13/14 (Mutagenicity - Reverse Mutation Test Using Bacteria)

Deviations:

yes

Remarks:

, no E.coli WP2 or S.typhimurium TA 102 used and only one positive control used to test efficacy of the S9-mix

GLP compliance:

yes

Type of assay:

bacterial reverse mutation assay

Test material

Test material information

Constituent 1

Reference substance name:

Pseudoephedrine hydrochloride

EC Number:

206-462-1

EC Name:

Pseudoephedrine hydrochloride

Cas Number:

345-78-8

IUPAC Name:

2-(methylamino)-1-phenylpropan-1-ol hydrochloride

Details on test material:

- Name of test material (as cited in study report): (+)-Pseudoephedrin-HCl
- Appearance: white crystals or powder
- Storage: room temperature (darkness)

Method

Target gene:

His-locus

Species / strain

Species / strain / cell type:

S. typhimurium TA 1535, TA 1537, TA 98 and TA 100

Additional strain / cell type characteristics:

not applicable

Metabolic activation:

with and without

Metabolic activation system:

Aroclor 1254-induced rat liver S9 mix

Test concentrations with justification for top dose:

20, 100, 500, 2500, 5000 µg/plate

Vehicle / solvent:

aqua dest.

Controls

Controls 1

Untreated negative controls:

yes

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Remarks:

10 µg/plate

Positive control substance:

other: 2-aminoanthracene

Remarks:

All strains with metabolic activation

Controls 2

Untreated negative controls:

yes

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Remarks:

5 µg/plate

Positive control substance:

other: N-methyl-N'-nitro-N-nitroso-guanidine

Remarks:

TA 100, TA 1535; without metabolic activation

Controls 3

Untreated negative controls:

yes

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Remarks:

10 µg/plate

Positive control substance:

other: 4-nitro-o-phenylendiamine

Remarks:

TA 98; without metabolic activation

Controls 4

Untreated negative controls:

yes

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Remarks:

100 µg/plate

Positive control substance:

9-aminoacridine

Remarks:

TA 1537; without metabolic activation

Details on test system and experimental conditions:

EXPERIMENT 1:
- METHOD OF APPLICATION: in agar (plate incorporation)
- DURATION: Exposure duration: 48 h
- NUMBER OF REPLICATIONS: 3 test plates per dose or per control
- DETERMINATION OF CYTOTOXICITY: reduced his- background growth

EXPERIMENT 2:
- METHOD OF APPLICATION: preincubation
- DURATION: Preincubation period: 20 min; Exposure duration: 48 h
- NUMBER OF REPLICATIONS: 3 test plates per dose or per control
- DETERMINATION OF CYTOTOXICITY: reduced his- background growth

Evaluation criteria:

In general, a substance to be characterized as positive in the Ames test has to fulfill the following requirements:
- doubling of the spontaneous mutation rate (control)
- dose-response relationship
- reproducibility of the results

Results and discussion

Test results

Species / strain:

S. typhimurium TA 1535, TA 1537, TA 98 and 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

Positive controls validity:

valid

Additional information on results:

TEST-SPECIFIC CONFOUNDING FACTORS
- Water solubility: complete solubility of the test substance

Remarks on result:

other: all strains/cell types tested

Remarks:

Migrated from field 'Test system'.

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information):
negative

It is concluded that there is no evidence of induction of gene mutations by the test substance and its metabolites in the four S. typhimurium strains used.

Executive summary:

In a GLP compliant bacterial mutagenicity test, performed according to OECD guideline 471, 4 Salmonella typhimurium strains (TA 1535, TA 1537, TA 98, and TA 100) were used to test the mutagenic potential of the test substance both with and without metabolic activation. One standard plate test and one preincubation test were performed. In both tests strains were exposed to 0, 20, 100, 500, 2500, and 5000 µg/plate. No precipitation of the test substance was found. No bacteriotoxic effect was observed. An increased in the number of his+ revertants was not observed in the standard plate test or in the preincubation test either without S9 mix or after the addition of a metabolizing system. It was therefore concluded that the test substance is not mutagenic under these experimental conditions.