Critical window of exposure of CMIT/MIT with respect to developmental effects on zebrafish embryos: Multi-level endpoint and proteomics analysis

Nivedita Chatterjee, Hyunho Lee, Jiwan Kim, Doeun Kim, Sangkyu Lee, Jinhee Choi

Research output: Contribution to journalArticlepeer-review

13 Scopus citations

Abstract

Systemic toxicity, particularly, developmental defects of humidifier disinfectant chemicals that have caused lung injuries in Korean children, remains to be elucidated. This study evaluated the mechanisms of the adverse effects of 5-chloro-2-methyl-4-isothiazoline-3-one/2methyl-4-isothiazolin-3-one (CMIT/MIT), one of the main biocides of the Korean tragedy, and identify the most susceptible developmental stage when exposed in early life. To this end, the study was designed to analyze several endpoints (morphology, heart rate, behavior, global DNA methylation, gene expressions of DNA methyl-transferases (dnmts) and protein profiling) in exposed zebrafish (Danio rerio) embryos at various developmental stages. The results showed that CMIT/MIT exposure causes bent tail, pericardial edema, altered heart rates, global DNA hypermethylation and significant alterations in the locomotion behavior. Consistent with the morphological and physiological endpoints, proteomics profiling with bioinformatics analysis suggested that the suppression of cardiac muscle contractions and energy metabolism (oxidative phosphorylation) were possible pivotal underlying mechanisms of the CMIT/MIT mediated adverse effects. Briefly, multi-level endpoint analysis indicated the most susceptible window of exposure to be ≤ 6 hpf followed by ≤ 48 hpf for CMIT/MIT. These results could potentially be translated to a risk assessment of the developmental exposure effects to the humidifier disinfectants.

Original languageEnglish
Article number115784
JournalEnvironmental Pollution
Volume268
DOIs
StatePublished - 1 Jan 2021

Keywords

  • CMIT/MIT
  • Critical window of exposure
  • DNA methylation
  • Developmental cardiac functional defects
  • Locomotion behavior
  • Proteomics

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