{"title":"“More toxic than thought!”","authors":"R. Fotler, D.R. Dietrich","doi":"10.1016/j.cotox.2025.100542","DOIUrl":null,"url":null,"abstract":"<div><div>Climate change enhances the formation and duration of toxin producing cyanobacterial blooms. Although toxins, e.g. Microcystins (MC), and their maximum levels in drinking water (1μg MC-LR<sub>equiv.</sub>/Liter) and foodstuffs are regulated and controlled, the basis for this regulation is questionable. Nearly all governmental regulations rely on WHO guidance values (GV) that were derived from an <em>in vivo</em> mouse study using a single MC congener (MC-LR). However cellular uptake (and thus toxicity) is governed by organic anion transporting polypeptides (OATPs), whereby rodents and humans differ drastically with regard to the expression and transport affinity and capacity of OATPs, and thus mice appear less susceptible to MC. Accordingly, the current questionable GVs provided by WHO must be replaced <em>ad interim</em> with a Toxicity Equivalence Factor (TEF) approach, whereby as a consequence current GVs need to be lowered by at least a factor 22 as shown here. The latter would result in a GV for drinking water of 0.045μg MC-LR<sub>equiv.</sub>/Liter to ensure safety of humans. As not all MC congeners can be tested, a new assessment approach using modern toxicology methods e.g. <em>in vitro</em> and <em>in silico</em> tools including artificial intelligence approaches must be undertaken to better characterize risks from exposure to toxic.</div></div>","PeriodicalId":93968,"journal":{"name":"Current opinion in toxicology","volume":"43 ","pages":"Article 100542"},"PeriodicalIF":4.6000,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Current opinion in toxicology","FirstCategoryId":"1085","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S2468202025000269","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
引用次数: 0
Abstract
Climate change enhances the formation and duration of toxin producing cyanobacterial blooms. Although toxins, e.g. Microcystins (MC), and their maximum levels in drinking water (1μg MC-LRequiv./Liter) and foodstuffs are regulated and controlled, the basis for this regulation is questionable. Nearly all governmental regulations rely on WHO guidance values (GV) that were derived from an in vivo mouse study using a single MC congener (MC-LR). However cellular uptake (and thus toxicity) is governed by organic anion transporting polypeptides (OATPs), whereby rodents and humans differ drastically with regard to the expression and transport affinity and capacity of OATPs, and thus mice appear less susceptible to MC. Accordingly, the current questionable GVs provided by WHO must be replaced ad interim with a Toxicity Equivalence Factor (TEF) approach, whereby as a consequence current GVs need to be lowered by at least a factor 22 as shown here. The latter would result in a GV for drinking water of 0.045μg MC-LRequiv./Liter to ensure safety of humans. As not all MC congeners can be tested, a new assessment approach using modern toxicology methods e.g. in vitro and in silico tools including artificial intelligence approaches must be undertaken to better characterize risks from exposure to toxic.