Analysis of drugs and pharmaceuticals in the environment is typically performed with non-chiral chromatographic techniques. The environmental risks posed by chiral compounds analysed in this way must therefore be assumed to be independent of chirality, meaning that each enantiomer is equally potent in toxicity and long-lived in stability. This manuscript examines the degradation of each of the four isomers of ephedrine in river simulating microcosms and links this to toxicity data obtained by exposing three different organisms (D. magna, P. subcapitata and T. thermophila) to each of the isomers individually. Microcosms showed that significant degradation only occurred in biotic conditions and that only two isomers (1R,2S-(-)-ephedrine, 1S,2S-(+)-pseudoephedrine) degraded significantly over a period of fourteen days. This is concerning because at least one of the non-degraded isomers (1S,2R-( +)-ephedrine) has been observed in wastewater effluent, which discharges directly into rivers, meaning these isomers could be persistent in the environment. We also observed formation of 1S,2R-(+)-ephedrine in single isomer 1R,2S-(-)-ephedrine river simulating microcosms. Human liver microsome assays and mass spectrometry based data mining revealed that 1S,2R-(+)-ephedrine is not human derived but it could be formed as a results of microbial metabolic processes. Across all three organisms tested the persistent isomers (1S,2R-(+)-ephedrine and 1R,2R-(-)-pseudoephedrine) were more toxic than those that undergo degradation; meaning that if these isomers are entering or formed in the environment they might represent a potentially hazardous contaminant.