A Phenotypic and Genotypic Evaluation of Developmental Toxicity of Polyhexamethylene Guanidine Phosphate Using Zebrafish Embryo/Larvae
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 us...
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2020-05-01
|
| Series: | Toxics |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2305-6304/8/2/33 |
| _version_ | 1797568929032306688 |
|---|---|
| author | Jeongah Song Kojo Eghan Sangwoo Lee Jong-Su Park Seokjoo Yoon Wittaya Pimtong Woo-Keun Kim |
| author_facet | Jeongah Song Kojo Eghan Sangwoo Lee Jong-Su Park Seokjoo Yoon Wittaya Pimtong Woo-Keun Kim |
| author_sort | Jeongah Song |
| collection | DOAJ |
| description | 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 LC<sub>50</sub> 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. |
| first_indexed | 2024-03-10T20:03:55Z |
| format | Article |
| id | doaj.art-c976103749264c96b2396988d482b838 |
| institution | Directory Open Access Journal |
| issn | 2305-6304 |
| language | English |
| last_indexed | 2024-03-10T20:03:55Z |
| publishDate | 2020-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Toxics |
| spelling | doaj.art-c976103749264c96b2396988d482b8382023-11-19T23:22:29ZengMDPI AGToxics2305-63042020-05-01823310.3390/toxics8020033A Phenotypic and Genotypic Evaluation of Developmental Toxicity of Polyhexamethylene Guanidine Phosphate Using Zebrafish Embryo/LarvaeJeongah Song0Kojo Eghan1Sangwoo Lee2Jong-Su Park3Seokjoo Yoon4Wittaya Pimtong5Woo-Keun Kim6Jeonbuk Department of Inhalation Research, Korea Institute of Toxicology, Jeongeup 56212, KoreaDepartment of Predictive Toxicology, Korea Institute of Toxicology, Daejeon 34114, KoreaDepartment of Predictive Toxicology, Korea Institute of Toxicology, Daejeon 34114, KoreaDepartment of Predictive Toxicology, Korea Institute of Toxicology, Daejeon 34114, KoreaDepartment of Predictive Toxicology, Korea Institute of Toxicology, Daejeon 34114, KoreaNano Environmental and Health Safety Research Team, National Nanotechnology Center, National Science and Technology Development Agency, Pathum Thani 12120, ThailandDepartment of Predictive Toxicology, Korea Institute of Toxicology, Daejeon 34114, KoreaPolyhexamethylene 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 LC<sub>50</sub> 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.https://www.mdpi.com/2305-6304/8/2/33polyhexamethylene guanidine-phosphateRNA sequencinginflammationembryotoxicitypulmonary illness |
| spellingShingle | Jeongah Song Kojo Eghan Sangwoo Lee Jong-Su Park Seokjoo Yoon Wittaya Pimtong Woo-Keun Kim A Phenotypic and Genotypic Evaluation of Developmental Toxicity of Polyhexamethylene Guanidine Phosphate Using Zebrafish Embryo/Larvae Toxics polyhexamethylene guanidine-phosphate RNA sequencing inflammation embryotoxicity pulmonary illness |
| title | A Phenotypic and Genotypic Evaluation of Developmental Toxicity of Polyhexamethylene Guanidine Phosphate Using Zebrafish Embryo/Larvae |
| title_full | A Phenotypic and Genotypic Evaluation of Developmental Toxicity of Polyhexamethylene Guanidine Phosphate Using Zebrafish Embryo/Larvae |
| title_fullStr | A Phenotypic and Genotypic Evaluation of Developmental Toxicity of Polyhexamethylene Guanidine Phosphate Using Zebrafish Embryo/Larvae |
| title_full_unstemmed | A Phenotypic and Genotypic Evaluation of Developmental Toxicity of Polyhexamethylene Guanidine Phosphate Using Zebrafish Embryo/Larvae |
| title_short | A Phenotypic and Genotypic Evaluation of Developmental Toxicity of Polyhexamethylene Guanidine Phosphate Using Zebrafish Embryo/Larvae |
| title_sort | phenotypic and genotypic evaluation of developmental toxicity of polyhexamethylene guanidine phosphate using zebrafish embryo larvae |
| topic | polyhexamethylene guanidine-phosphate RNA sequencing inflammation embryotoxicity pulmonary illness |
| url | https://www.mdpi.com/2305-6304/8/2/33 |
| work_keys_str_mv | AT jeongahsong aphenotypicandgenotypicevaluationofdevelopmentaltoxicityofpolyhexamethyleneguanidinephosphateusingzebrafishembryolarvae AT kojoeghan aphenotypicandgenotypicevaluationofdevelopmentaltoxicityofpolyhexamethyleneguanidinephosphateusingzebrafishembryolarvae AT sangwoolee aphenotypicandgenotypicevaluationofdevelopmentaltoxicityofpolyhexamethyleneguanidinephosphateusingzebrafishembryolarvae AT jongsupark aphenotypicandgenotypicevaluationofdevelopmentaltoxicityofpolyhexamethyleneguanidinephosphateusingzebrafishembryolarvae AT seokjooyoon aphenotypicandgenotypicevaluationofdevelopmentaltoxicityofpolyhexamethyleneguanidinephosphateusingzebrafishembryolarvae AT wittayapimtong aphenotypicandgenotypicevaluationofdevelopmentaltoxicityofpolyhexamethyleneguanidinephosphateusingzebrafishembryolarvae AT wookeunkim aphenotypicandgenotypicevaluationofdevelopmentaltoxicityofpolyhexamethyleneguanidinephosphateusingzebrafishembryolarvae AT jeongahsong phenotypicandgenotypicevaluationofdevelopmentaltoxicityofpolyhexamethyleneguanidinephosphateusingzebrafishembryolarvae AT kojoeghan phenotypicandgenotypicevaluationofdevelopmentaltoxicityofpolyhexamethyleneguanidinephosphateusingzebrafishembryolarvae AT sangwoolee phenotypicandgenotypicevaluationofdevelopmentaltoxicityofpolyhexamethyleneguanidinephosphateusingzebrafishembryolarvae AT jongsupark phenotypicandgenotypicevaluationofdevelopmentaltoxicityofpolyhexamethyleneguanidinephosphateusingzebrafishembryolarvae AT seokjooyoon phenotypicandgenotypicevaluationofdevelopmentaltoxicityofpolyhexamethyleneguanidinephosphateusingzebrafishembryolarvae AT wittayapimtong phenotypicandgenotypicevaluationofdevelopmentaltoxicityofpolyhexamethyleneguanidinephosphateusingzebrafishembryolarvae AT wookeunkim phenotypicandgenotypicevaluationofdevelopmentaltoxicityofpolyhexamethyleneguanidinephosphateusingzebrafishembryolarvae |