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The dose makes the poison

Liang Chen1, John P Giesy2, Ping Xie3

  • 1Donghu 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.

The Science of the Total Environment
|December 3, 2017
PubMed

Insights

Microcystins (MCs) are toxins that may cause liver damage. A recent study on MC-LR carcinogenicity in mice used a flawed, low-dose experimental design, making its conclusions about cancer risk misleading.

Area of Science:

  • Environmental toxicology
  • Hepatotoxicity research
  • Carcinogenesis studies

Background:

  • Microcystins (MCs) are potent hepatotoxins, with MC-LR classified as a possible human carcinogen (Group 2B) by IARC.
  • Recent research questioned the carcinogenicity of long-term, low-dose MC-LR exposure in mice.
  • Established guidelines for MC-LR exposure exist, such as the WHO's provisional guideline value for drinking water.

Purpose of the Study:

  • Critically evaluate the experimental design and conclusions of a recent study on MC-LR and liver tumor development in mice.
  • Assess the validity of low-dose exposure claims regarding MC-LR carcinogenicity.
  • Highlight the need for further research with robust methodologies.

Main Methods:

  • Analysis of the experimental design, including dosage calculations and exposure durations.
  • Comparison of the study's exposure levels to established tolerable daily intake (TDI) and no-observed-adverse-effect levels (NOAEL).
  • Review of the interpretation of previous research cited in the criticized study.

Main Results:

  • The MC-LR dose used in the criticized study (0.15μg/kg/d) was approximately 270-fold lower than the NOAEL.
  • The exposure dose was significantly below levels expected to induce liver tumors or promote existing ones, even with long-term exposure.
  • The study likely underestimated inter-species variations in toxicokinetics and toxicodynamics between mice and humans.

Conclusions:

  • The conclusions of the recent "Hepatology Research" article are misleading due to a flawed experimental design and inadequate dosage.
  • Further well-designed studies are necessary to definitively determine the carcinogenic potential of microcystins in humans.
  • Clearer definitions of "low-dose" exposure ranges for MCs in both animals and humans are needed.
Keywords:
Equivalent dosesExperimental designInter-species variationsLow-doseMicrocystinTumor

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