Exposure to humidifier disinfectants induces developmental effects and disrupts thyroid endocrine systems in zebrafish larvae

Abstract

Humidifier disinfectants have been widely used in Korea to prevent the growth of microorganisms in humidifier water. However, their use has been banned since 2011 after epidemiological studies reported humidifier disinfectant induced lung injury. In the present study, the developmental effects of exposure to two humidifier disinfectants (Oxy® and Wiselect) and their main component, polyhexamethylene guanidine (PHMG)-phosphate, were investigated in zebrafish embryos/larvae for seven days. The effects on triiodothyronine (T3) and thyroxine (T4) hormones, reactive oxygen species (ROS) generation, antioxidant enzyme activities, and changes in expression of the genes related to the hypothalamus-pituitary-thyroid (HPT) axis and oxidative stress were also investigated. Zebrafish embryos exposed to the highest concentration (amounts recommended for use by the manufacturers) of all tested humidifier disinfectants showed an increase in embryo coagulation, leading to death without hatching. Exposure to Oxy® and Wiselect resulted in significantly decreased body length, increased ROS generation and antioxidant enzyme activities, decreased T4, and up-regulated genes related to the HPT axis (trh, trβ, and tpo) and oxidative damage (sod2 and gpx1b). The humidifier disinfectants and PHMG-phosphate could induce oxidative stress and disrupt thyroid hormone systems in zebrafish, leading to developmental retardation when used at sub-lethal concentrations. Potential effects of long-term exposure to humidifier disinfectants and mixture effects of several major components deserve further investigation.