US EPA

7424299 

Journal Article 

The dose makes the poison 

Chen, L; Giesy, JP; Xie, P; , 

2018 

1 

Science of the Total Environment
ISSN: 0048-9697
EISSN: 1879-1026 

Elsevier B.V. 

621 

649-653 

English 

29197283 

10.1016/j.scitotenv.2017.11.218 

WOS:000424196800065 

https://linkinghub.elsevier.com/retrieve/pii/S004896971733276X
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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. 

Equivalent doses; Experimental design; Inter-species variations; Low-dose; Microcystin; Tumor; Carcinogens; Design of experiments; International cooperation; Mammals; Potable water; Statistics; Toxic materials; Equivalent dose; Inter-species variations; International agency for research on cancers; Low dose; Microcystins; No observed adverse effect levels; Tolerable daily intake; World Health Organization; Tumors; drinking water; microcystin LR; carcinogen; microcystin; dose-response relationship; experimental design; health risk; interspecific variation; toxin; tumor; Article; cancer risk; carcinogenicity; chemical carcinogenesis; concentration response; human; liver cancer; long term exposure; maximum tolerated dose; no-observed-adverse-effect level; nonhuman; priority journal; species difference; toxicity testing; toxicokinetics; animal; chemically induced; dose response; liver tumor; mouse; Animalia; Mus; Animals; Carcinogens; Dose-Response Relationship, Drug; Humans; Liver Neoplasms; Mice; Microcystins; No-Observed-Adverse-Effect Level; Species Specificity