Ephedrine hydrochloride

Endpoint summary

Additional information

Ames Test:

In an Ames Test, the read across substance (+)-Pseudoephedrin-HCl (CAS No. 345-78-8) was tested for its mutagenic potential based on the ability to induce point mutations in selected loci of several bacterial strains, (Salmonella typhimurium: TA 1535, TA 100, TA 1537, TA 98). The dose range of the test item was 20 µg - 5000 µg/plate. The standard plate test and preincubation test - both with and without metabolic activation (liver S9 mix from induced rats) - were performed.

A biologically relevant increase in the number of his+ or trp+ 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. The test substance is not mutagenic in Salmonella typhimurium under test conditions chosen in this study.

CA :

In a mammalian cell cytogenetics chromosome aberration assay (Hilliard, 1998) CHO cell cultures were exposed to Ephedrine sulfate at concentrations of 0 ; 6 ; 8 and 10 mM with and without metabolic activation for 3 hours and were examined for structural chromosome changes after 20 hours. In both independent experiments, neither a significant nor a biologically relevant increase in the number of cells carrying structural chromosomal aberrations was observed after treatment with the test item. Thus, Ephedrine sulfate was negative in two aberration tests with and without S-9 activation in CHO cells. Moderate cytotoxicity up to the maximum dose of 10 mM was observed.

MLA:

In a mouse lymphoma assay (McGregor, 1988) , using the L5178Y thymidine kinase locus the mutagenic potential of the read across substance (-)-Ephedrine was tested at concentrations of 1.5 - 450 µg/mL without metabolic activation. The study demonstrated that the test substance was inactive and showed no mutagenic potential.

In further supporting studies concenrning genetic toxicity (Ishidate, 1993: CA ; Zeiger, 1998: Ames test ; Matthews, 1993: BALB/c3T3 transformation) no positive test results were described with the test item or the read across substance Ephedrine sulfate.

Justification for selection of genetic toxicity endpoint
No study was selected, since all tests were negative.

Short description of key information:
As the toxicity of (-)-Ephedrine- Hydrochloride is predominantly mediated by the alkaloid with its phenethylamine skeleton read across to Ephedrine sulphate, DL-Ephedrine-HCl or (+)-Ephedrine-HCl has been done and is scientifically justified.

The read across substances (+)-Pseudoephedrin-HCl (CAS No. 345-78-8), Ephedrine sulfate (CAS 134-72-5) and (-)-Ephedrine (CAS 299-42-3) were tested in three in vitro studies (Ames test, CA, MLA). All tests were negative.

Endpoint Conclusion: No adverse effect observed (negative)

Justification for classification or non-classification

Based on the results of the genetic toxicity studies, the test substance was not classified according to Regulation (EC) No 1272/2008 and Directive 67/548/EC (DSD).