Combining non-targeted high resolution mass spectrometry with effect-directed analysis to identify contaminants of emerging concern in the field of ecotoxicology: A systematic quantitative literature review

Methods for measuring environmental toxicity and identifying chemical toxicity drivers using non-targeted analysis (NTA) were reviewed in this systematic quantitative literature review. Effect-directed analysis (EDA) was used to assess sample toxicity and prioritise NTA sample analysis. The most common bioassays performed were estrogen, androgen and aryl hydrocarbon receptor assays, with many studies using test batteries. Across the 95 studies in this review, the toxicity could be explained (>75 %) for eight studies, four studies had toxicity endpoints explained and unexplained, and 38 studies had unexplained (<75 %) toxicity. The addition of NTA allowed for toxicity to be explained with a median of 47 % for TOX_non-target studies and 34 % for TOX_{target+non-target}, far higher than the 13 % median for TOX_target studies within this review. The outcomes of identification were affected by method factors including sample extraction, chromatography method, data acquisition and data processing. Method factors with the biggest potential to introduce selection bias were sample extraction and chromatography technique. These factors were characterised by a high representation of reverse phase liquid chromatography contributing to the selective exclusion of polar, highly polar and ionic compounds from sample analysis. This reduces compound identification and excludes unknown chemical contaminants from analysis. Not all studies reported the explained toxicity contribution of identified compounds, however it was evident that many compound features could not be identified using NTA processing software. There were severe limitations for liquid chromatography data compared to gas chromatography data with insufficient spectral library databases for spectra matching. This bottleneck is partially solved through the rise in in silico and retention time prediction software. Future work, including increasing spectral databases for liquid chromatography, use of less biased chromatography and sample preparation techniques and inclusion of EDA-NTA into risk assessment frameworks, will allow for better toxicity assessment of emerging contaminants.