Metabolomic Investigations of the Temporal Effects of Exposure to Pharmaceuticals and Personal Care Products and Their Mixture in the Eastern Oyster (Crassostrea virginica)

• Published in: Environmental toxicology and chemistry Vol. 39; no. 2; pp. 419 - 436
• Main Authors: Brew, David W., Black, Marsha C., Santos, Marina, Rodgers, Jackson, Henderson, W. Matthew
• Format: Journal Article
• Language: English
• Published: United States Blackwell Publishing Ltd 01-02-2020
• Subjects: Adductor muscle; Amino acids; Aquaculture; Biological effects; Biomarkers; Consumer products; Contaminants; Cosmetics industry; Crassostrea virginica; Depuration; Diphenhydramine; Discriminant analysis; Exposure; Fatty acids; Fluoxetine; Gas chromatography; Gas chromatography‐mass spectrometry; Indigenous species; Intermediates; Keystone species; Krebs cycle; Mass spectrometry; Mass spectroscopy; Metabolic pathways; Metabolism; Metabolites; Metabolomics; Mixtures; Mollusks; Muscles; Organic chemistry; Osmotic stress; Oxidative metabolism; Oxidative stress; Oyster physiology; Oysters; Personal care products; Personal grooming; Pharmaceuticals; Physiological effects; Trajectory analysis; Tricarboxylic acid cycle; Metabolomics; Personal care products; Oyster physiology; Gas chromatography-mass spectrometry; Mixtures; Pharmaceuticals
• ISSN: 0730-7268; 1552-8618
• DOI: 10.1002/etc.4627

The eastern oyster (Crassostrea virginica) supports a large aquaculture industry and is a keystone species along the Atlantic seaboard. Native oysters are routinely exposed to a complex mixture of contaminants that increasingly includes pharmaceuticals and personal care products (PPCPs). Unfortunately, the biological effects of chemical mixtures on oysters are poorly understood. Untargeted gas chromatography‐mass spectrometry metabolomics was utilized to quantify the response of oysters exposed to fluoxetine, N,N‐diethyl‐meta‐toluamide, 17α‐ethynylestradiol, diphenhydramine, and their mixture. Oysters were exposed to 1 µg/L of each chemical or mixture for 10 d, followed by an 8‐d depuration period. Adductor muscle (n = 14/treatment) was sampled at days 0, 1, 5, 10, and 18. Trajectory analysis illustrated that metabolic effects and class separation of the treatments varied at each time point and that, overall, the oysters were only able to partially recover from these exposures post‐depuration. Altered metabolites were associated with cellular energetics (i.e., Krebs cycle intermediates), as well as amino acid metabolism and fatty acids. Exposure to these PPCPs also affected metabolic pathways associated with anaerobic metabolism, osmotic stress, and oxidative stress, in addition to the physiological effects of each chemical's postulated mechanism of action. Following depuration, fewer metabolites were altered, but none of the treatments returned them to their initial control values, indicating that metabolic disruptions were long‐lasting. Interestingly, the mixture did not directly cluster with individual treatments in the scores plot from partial least squares discriminant analysis, and many of its affected metabolic pathways were not well predicted from the individual treatments. The present study highlights the utility of untargeted metabolomics in developing exposure biomarkers for compounds with different modes of action in bivalves. Environ Toxicol Chem 2020;39:419–436. © 2019 SETAC