Cytotoxicity and genotoxicity of clothianidin in human lymphocytes with or without metabolic activation system

Zülal Atlı Şekeroğlu1, Vedat Şekeroğlu1, Ebru Uçgun1

  • 1a Department of Molecular Biology and Genetics, Faculty of Science and Letters , Ordu University , Ordu , Turkey.

Insights

Clothianidin (CHN) exhibits cytotoxic and genotoxic effects on human lymphocytes without metabolic activation. However, CHN and its metabolites showed no significant genotoxicity when tested with the human metabolic activation system (S9 mix).

Area of Science:

  • Toxicology
  • Genetics
  • Environmental Science

Background:

  • Clothianidin (CHN) is a widely used neonicotinoid insecticide.
  • Limited research exists on the cytotoxic and genotoxic impacts of CHN and its metabolites in human cells.
  • Understanding these effects is crucial for assessing environmental and human health risks.

Purpose of the Study:

  • To investigate the cytotoxic and genotoxic potential of CHN and its metabolites.
  • To evaluate these effects in human lymphocyte cultures with and without a metabolic activation system (S9 mix).
  • To utilize chromosomal aberration (CA) and micronucleus (MN) tests for comprehensive assessment.

Main Methods:

  • Human peripheral blood lymphocytes were cultured and treated with varying concentrations of CHN (25, 50, 100 µg/ml).
  • Treatments were conducted in the presence (3h) and absence (48h) of the S9 mix.
  • Cytotoxicity and genotoxicity were assessed using mitotic index (MI), nuclear division index (NDI), chromosomal aberration (CA), and micronucleus (MN) assays.

Main Results:

  • CHN induced significant cytotoxic and genotoxic effects in the absence of S9 mix, evidenced by decreased MI and NDI, and increased CA and MN formation.
  • In the presence of S9 mix, CHN did not significantly induce cytotoxicity or genotoxicity.
  • These findings suggest that CHN's direct action, rather than its metabolites, is responsible for the observed genotoxic effects under these experimental conditions.

Conclusions:

  • Clothianidin demonstrates cytotoxic, cytostatic, and genotoxic potential in human lymphocytes, particularly without metabolic activation.
  • Metabolites of CHN did not exhibit significant genotoxicity under the tested experimental conditions.
  • The study highlights the importance of metabolic activation in evaluating the toxicological profile of insecticides like CHN.

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