The dose makes the poison. 2018

Liang Chen, and John P Giesy, and Ping Xie
Donghu Experimental Station of Lake Ecosystems, State Key Laboratory of Freshwater Ecology and Biotechnology, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan 430072, China; University of Chinese Academy of Sciences, Beijing 100049, China. Electronic address: chan91@yeah.net.

Some microcystins (MCs) might cause hepatotoxicity in animals and humans. MC-LR is also a tumor promoter and a suspect carcinogen. In 2010, the International Agency for Research on Cancer (IARC) classified MC-LR as a possible human carcinogen (Group 2B). Recently, an article entitled "Long-term, low-dose exposure to microcystin toxin does not increase the risk of liver tumor development or growth in mice" was published in Hepatology Research by Meaghan Labine and Gerald Y. Minuk. However, the experimental design was flawed and the conclusion is misleading. 1μg/L MC-LR in drinking water is the provisional guideline value established by the World Health Organization (WHO) for humans in 1998, based on a tolerable daily intake (TDI) of 0.04μg/kg body mass (BM). Assuming the mice drink 1.5mL/10g BM of water per day, the exposure dose would be 0.15μg/kg/d BM, about 270-fold less than 40μg/kg/d, the no-observed-adverse-effect level (NOAEL). Thus, the dose of MC-LR was too small and "unlikely to result in liver tumor development or enhance existing tumor growth", even with a long-term (28weeks) exposure. Presumably, they didn't consider inter-species variations between mice and humans, including toxicokinetics and toxicodynamics. Ranges of "low-dose" MCs for animals and humans should be defined. Also, the authors misunderstood or misrepresented several previous studies. Before drawing final conclusions on the carcinogenicity of MCs, further well-designed experiments are warranted.

UI MeSH Term Description Entries
D008113 Liver Neoplasms Tumors or cancer of the LIVER. Cancer of Liver,Hepatic Cancer,Liver Cancer,Cancer of the Liver,Cancer, Hepatocellular,Hepatic Neoplasms,Hepatocellular Cancer,Neoplasms, Hepatic,Neoplasms, Liver,Cancer, Hepatic,Cancer, Liver,Cancers, Hepatic,Cancers, Hepatocellular,Cancers, Liver,Hepatic Cancers,Hepatic Neoplasm,Hepatocellular Cancers,Liver Cancers,Liver Neoplasm,Neoplasm, Hepatic,Neoplasm, Liver
D002273 Carcinogens Substances that increase the risk of NEOPLASMS in humans or animals. Both genotoxic chemicals, which affect DNA directly, and nongenotoxic chemicals, which induce neoplasms by other mechanism, are included. Carcinogen,Oncogen,Oncogens,Tumor Initiator,Tumor Initiators,Tumor Promoter,Tumor Promoters,Initiator, Tumor,Initiators, Tumor,Promoter, Tumor,Promoters, Tumor
D004305 Dose-Response Relationship, Drug The relationship between the dose of an administered drug and the response of the organism to the drug. Dose Response Relationship, Drug,Dose-Response Relationships, Drug,Drug Dose-Response Relationship,Drug Dose-Response Relationships,Relationship, Drug Dose-Response,Relationships, Drug Dose-Response
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D013045 Species Specificity The restriction of a characteristic behavior, anatomical structure or physical system, such as immune response; metabolic response, or gene or gene variant to the members of one species. It refers to that property which differentiates one species from another but it is also used for phylogenetic levels higher or lower than the species. Species Specificities,Specificities, Species,Specificity, Species
D051379 Mice The common name for the genus Mus. Mice, House,Mus,Mus musculus,Mice, Laboratory,Mouse,Mouse, House,Mouse, Laboratory,Mouse, Swiss,Mus domesticus,Mus musculus domesticus,Swiss Mice,House Mice,House Mouse,Laboratory Mice,Laboratory Mouse,Mice, Swiss,Swiss Mouse,domesticus, Mus musculus
D052998 Microcystins Cyclic heptapeptides found in MICROCYSTIS and other CYANOBACTERIA. Hepatotoxic and carcinogenic effects have been noted. They are sometimes called cyanotoxins, which should not be confused with chemicals containing a cyano group (CN) which are toxic. Cyanoginosins
D019055 No-Observed-Adverse-Effect Level The highest dosage administered that does not produce toxic effects. NOAEL,No-Observed-Effect Level,Acceptable Daily Intake,Tolerable Daily Intake,Acceptable Daily Intakes,Daily Intake, Acceptable,Daily Intake, Tolerable,Daily Intakes, Acceptable,Daily Intakes, Tolerable,Intake, Acceptable Daily,Intake, Tolerable Daily,Intakes, Acceptable Daily,Intakes, Tolerable Daily,Level, No-Observed-Adverse-Effect,Level, No-Observed-Effect,Levels, No-Observed-Adverse-Effect,Levels, No-Observed-Effect,No Observed Adverse Effect Level,No Observed Effect Level,No-Observed-Adverse-Effect Levels,No-Observed-Effect Levels,Tolerable Daily Intakes

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