Ephedrine hydrochloride

Genetic toxicity: in vitro

Administrative data

Endpoint:

in vitro cytogenicity / chromosome aberration study in mammalian cells

Remarks:

Type of genotoxicity: chromosome aberration

Type of information:

migrated 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: see 'Remark'

Remarks:

Non-GLP non-guideline study, published, acceptable for assessment Read across from CAS 134-72-5 As the toxicity of (-)-Ephedrine- Hydrochloride is predominantly mediated by the alkaloid with its phenethylamine skeleton read across to Ephedrine sulfate has been done and is scientifically justified.

Data source

Reference

Reference Type:

publication

Title:

Chromosome Aberrations In Vitro Related to Cytotoxicity of Nonmutagenic Chemicals and Metabolic Poisons

Author:

Hilliard A.C.

Year:

1998

Bibliographic source:

Environmental and Molecular Mutagenesis 31 :316-326

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 473 (In Vitro Mammalian Chromosome Aberration Test)

GLP compliance:

not specified

Type of assay:

in vitro mammalian chromosome aberration test

Test material

Test material information

Constituent 1

Reference substance name:

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

EC Number:

205-154-4

EC Name:

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

Cas Number:

134-72-5

Molecular formula:

C10H15NO.1/2H2O4S

IUPAC Name:

2-(methylamino)-1-phenylpropan-1-ol sulfate (2:1) (salt)

Constituent 2

Reference substance name:

Ephedrine sulfate

IUPAC Name:

Ephedrine sulfate

Details on test material:

- Name: Ephedrine sulfate
- Supplier: Sigma, st. Lois. MO

Method

Target gene:

no data

Species / strain

Species / strain / cell type:

Chinese hamster Ovary (CHO)

Details on mammalian cell type (if applicable):

Cloned Chinese hamster ovary cells (CHO-W-BI) were cultured in Mc-Coy's 5a medium with 10% fetal calf serum, L-glutamine, and antibiotics

Additional strain / cell type characteristics:

not specified

Metabolic activation:

with and without

Metabolic activation system:

S9 mix from male SD rats induced with phenobarbital/ß-napthoflavone

Test concentrations with justification for top dose:

0 ; 6; 8 and 10 mM (corresponding to 0 ; 1.58 ; 2.11 and 2.63 mg/L),
with and without metabolic activation.

Vehicle / solvent:

- Vehicle/solvent used: water

Controls

Untreated negative controls:

not specified

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Details on test system and experimental conditions:

METHOD OF APPLICATION: in medium

DURATION
- Exposure duration: 3 h
- Expression time (cells in growth medium): 17 h
- Fixation time (start of exposure up to fixation or harvest of cells): 2-3 h before trypsonozation


SPINDLE INHIBITOR (cytogenetic assays): 0.1 µg/ML Colcemid
STAIN (for cytogenetic assays): Giemsa

NUMBER OF REPLICATIONS: no data

NUMBER OF CELLS EVALUATED: 200

DETERMINATION OF CYTOTOXICITY
- Method: other: cell count

For each treatment. 200 metaphase cells containing 19-23 chromosomes were scored for CHO cells and 100 cells containing 45-49 chromosomes were scored for TK6, unless aberration frequencies were high or few cells were available for analysis due to mitotic suppression .Gaps (achromatic region less than or equal to the width of a chromatid), polyploid and endoreduplicated cells, and pulverized chromosomes were noted but not included in structural aberration totals .

Evaluation criteria:

A test is considered positive if there is a statistically significant increase (P < 0 .05) over concurrent controls in the percentages of cells with chromosomal aberrations at two separate concentrations of test article, with about 50 % cytotoxicity, or a reproducible increase at one dose level .

Statistics:

The analysis is a pairwise comparison of the percentage of cells with aberrations a each dose level with the controls by Fisher's exact test, with the P values adjusted for multiple comparisons against a common control by the method of Dunnett [1955].

Results and discussion

Test results

Species / strain:

Chinese hamster Ovary (CHO)

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Vehicle controls validity:

valid

Untreated negative controls validity:

not specified

Positive controls validity:

valid

Additional information on results:

no data

Remarks on result:

other: strain/cell type: Chinese hamster Ovary (CHO-W-Bl)

Remarks:

Migrated from field 'Test system'.

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information):
negative