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. 2020 May 2;8(2):33.
doi: 10.3390/toxics8020033.

A Phenotypic and Genotypic Evaluation of Developmental Toxicity of Polyhexamethylene Guanidine Phosphate Using Zebrafish Embryo/Larvae

Jeongah Song  1 , Kojo Eghan  2   3 , Sangwoo Lee  2 , Jong-Su Park  2 , Seokjoo Yoon  2   3 , Wittaya Pimtong  4 , Woo-Keun Kim  2   3
Affiliations

A Phenotypic and Genotypic Evaluation of Developmental Toxicity of Polyhexamethylene Guanidine Phosphate Using Zebrafish Embryo/Larvae

Jeongah Song et al. Toxics. .

Abstract

Polyhexamethylene guanidine-phosphate (PHMG-P), a guanidine-based cationic antimicrobial polymer, is an effective antimicrobial biocide, potent even at low concentrations. Due to its resilient bactericidal properties, it has been used extensively in consumer products. It was safely used until its use in humidifiers led to a catastrophic event in South Korea. Epidemiological studies have linked the use of PHMG-P as a humidifier disinfectant to pulmonary fibrosis. However, little is known about its harmful impacts other than pulmonary fibrosis. Thus, we applied a zebrafish embryo/larvae model to evaluate developmental and cardiotoxic effects and transcriptome changes using RNA-sequencing. Zebrafish embryos were exposed to 0.1, 0.2, 0.3, 0.4, 0.5, 1, and 2 mg/L of PHMG-P from 3 h to 96 h post fertilization. 2 mg/L of PHMG-P resulted in total mortality and an LC50 value at 96 h was determined at 1.18 mg/L. Significant developmental changes were not observed but the heart rate of zebrafish larvae was significantly altered. In transcriptome analysis, immune and inflammatory responses were significantly affected similarly to those in epidemiological studies. Our qPCR analysis (Itgb1b, TNC, Arg1, Arg2, IL-1β, Serpine-1, and Ptgs2b) also confirmed this following a 96 h exposure to 0.4 mg/L of PHMG-P. Based on our results, PHMG-P might induce lethal and cardiotoxic effects in zebrafish, and crucial transcriptome changes were linked to immune and inflammatory response.

Keywords: RNA sequencing; embryotoxicity; inflammation; polyhexamethylene guanidine-phosphate; pulmonary illness.

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Conflict of interest statement

The authors declare no conflicts of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results.

Figures

Figure 1
Figure 1
Survival (a) and hatching rate (b) of zebrafish embryos/larvae under polyhexamethylene guanidine-phosphate (PHMG-P) exposure (N = 10). Asterisks (*) denotes statistical significance (p < 0.05).
Figure 2
Figure 2
Morphological images of zebrafish embryos/larvae during embryogenesis under 0 to 2 mg/L PHMG-P exposure. N.A.: not available due to significant lethality.
Figure 3
Figure 3
Heart rate of zebrafish embryos/larvae at 24 hpf, 48 hpf, 72 hpf, and 96 hpf under PHMG-P exposure (N = 5). Asterisk (*) denotes statistical significance (p < 0.05).
Figure 4
Figure 4
Gene transcription changes of Itgb1b (A), TNC (B), Arg1 (C), Arg2 (D), IL-1β (E), Serpine-1 (F), and Ptgs2b (G) after 96 hpf PHMG-P exposure (N = 3). Asterisks (* and **) denotes statistical significance with p < 0.05 and p < 0.01, respectively.
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