Developmental Toxicity and Thyroid Endocrine Disruption of Polyhexamethylene Guanidine Hydrochloride and Humidifier Disinfectant in Zebrafish Larvae

Suhyun Park,Kyunghee Ji,Hyojin Kim

doi:10.3390/app11114884

Abstract

Polyhexamethylene guanidine (PHMG), a major component of humidifier disinfectants (HDs), is responsible for the outbreak of pulmonary diseases in pregnant women and children in South Korea. This study aims to characterize the developmental toxicity and thyroid endocrine disruption of Vegetable Home Cleanup HD and its main component, PHMG-hydrochloride (PHMG-H), in zebrafish embryo/larvae after a 7-d exposure. Acute lethality, development, whole-body thyroid hormones, and transcription of genes related to the hypothalamus-pituitary-thyroid axis were investigated. Zebrafish embryos exposed to the actual-use concentration (0.6%) of HD exhibited significant embryo coagulation and larval mortality. The concentration of triiodothyronine (T3) was significantly high in fish exposed to 0.4 mg/L PHMG-H, accompanied by the downregulation of the tshβ gene. These results suggest a feedback mechanism for the regulation of increased T3 levels. Significant decrease of thyroxine (T4) concentration, increase of T3/T4 ratio, and upregulation of the deio2 gene in fish exposed to PHMG-H suggested that there was an increase in the active T3 due to the catalysis of outer ring deiodination. Future research is required to determine the factors that contribute to the differences in toxicity between the two counter ions of PHMG.

Highlights

Polyhexamethylene guanidine (PHMG), a guanidine-based cationic biocide, is an antimicrobial agent that acts on a broad spectrum of bacteria, viruses, and fungi [1]
In South Korea, it is commonly used as a major component of household humidifier disinfectants (HDs) by mixing it with water in the humidifier reservoir in order to prevent the growth of microorganisms [5]
Malformation rate was significantly increased in embryo exposed to 0.4 mg/L PHMG-H (Figure 1B), showing morphological changes such as pronounced yolk sac edema and spinal curvature

Summary

Introduction

Polyhexamethylene guanidine (PHMG), a guanidine-based cationic biocide, is an antimicrobial agent that acts on a broad spectrum of bacteria, viruses, and fungi [1]. PHMG has been widely used as an antiseptic in medicine, cotton fabric, and the food industry [2,3]. This compound has been registered as a disinfectant of medical devices by the Food and. PHMG-P induced pulmonary injuries in zebrafish, including inflammation, histological changes, and fibrosis [10]. Previous zebrafish study confirmed that the cationic nature is considered to be one of the main causes of PHMG-P-induced cytotoxicity [11]. The adverse developmental effects of two HDs (Oxy® and Wiselect) and their major component, that is PHMG-P, are associated with thyroid endocrine disruption in zebrafish embryo/larvae [12]. PHMG-hydrochloride (PHMG-H), another derivative of PHMG, was considered to be involved in the outbreak [9]; there is limited information on its properties, such as its content or toxicity in HD

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