Veterinary MedicineEnvironmental SciencesToxicologyAnalytical ToxicologyAquatic ToxicologyEnvironmental ToxicologyEnvironmental HepatotoxicantsEnvironmental HepatotoxinsFreshwater ToxicologyHepatotoxicity MechanismsMarine BiotoxinsChronic Exposure AssessmentLiquid Chromatography-mass SpectrometryLiquid Chromatography-mass Spectrometry AnalysisLiquid Chromatography-mass Spectrometry Method DevelopmentMicrocystin HepatotoxicityMicrocystin ToxicologySerum Alanine AminotransferaseSerum Biomarkers
Microcystins are the most common cyanotoxins in eutrophic freshwaters, have caused mass human intoxications such as the 1996 Caruaru dialysis deaths, yet no direct evidence of their presence in human tissues had been reported. This study aimed to develop an improved LC‑MS cleanup protocol to detect microcystins in human serum and to evaluate whether chronic exposure at or above the WHO tolerable daily intake could be associated with liver injury. The authors applied a refined sample cleanup followed by liquid chromatography‑mass spectrometry to quantify microcystins in fishermen’s serum samples. Microcystins were detected in 1/87 fishermen’s serum (average 0.39 ng ml⁻¹), corresponding to daily intakes of 2.2–3.9 µg MC‑LRₑq, and serum levels correlated positively with liver enzymes, indicating a risk of hepatocellular damage from chronic exposure.
Hepatotoxic microcystins (MCs) are the most commonly reported cyanotoxins in eutrophic freshwaters. In 1996, human intoxications by MCs caused deaths of 76 patients at Caruaru dialysis centers in Brazil. So far, there have been no direct evidences of MC occurrence in human tissue in consequence of exposure to MC. In this study, we improved cleanup procedures for detecting MCs in serum sample using liquid chromatography-mass spectrometry, and confirmed for the first time the presence of MCs in serum samples (average 0.39 ng/ml, which amounts to ca. 1/87 of the concentrations found in tissue samples of the Caruaru victims) of fishermen at Lake Chaohu. Daily intake by the fishermen was estimated to be in the range of 2.2–3.9 μg MC-LReq, whereas the provisional World Health Organization tolerable daily intake (TDI) for daily lifetime exposure is 0.04 μg/kg or 2–3 μg per person. Moreover, statistical analysis showed closer positive relationships between MC serum concentrations and concentrations of alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, and lactate dehydrogenase than between the MC concentrations and other biochemical indicators. Thus, the data raise the question whether extended exposure in the range of the TDI or up to a factor of 10 above it may already lead to indication of liver damage. The results also demonstrate a risk of health effects from chronic exposure to MCs at least for populations with high levels of exposure, like these fishermen.
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Fatal microcystin intoxication in haemodialysis unit in Caruaru, Brazil
Shideh Pouria, Armèle Dornelas de Andrade, José Etham de Lucena Barbosa et al. · The Lancet · 1998 · 809 citations
Medicine, Nephrology, Toxicology +14
Yoshio Ueno, Satoshi Nagata, Tomoaki Tsutsumi et al. · Carcinogenesis · 1996 · 750 citations · Full text