Comprehensive analysis of adverse outcome pathway, potency, human exposure supports carcinogenicity of polyhexamethylene guanidine phosphate in lung cancer DOI Creative Commons
Yong Joo Park, Ha Ryong Kim,

Jun Woo Kim

et al.

Ecotoxicology and Environmental Safety, Journal Year: 2024, Volume and Issue: 287, P. 117222 - 117222

Published: Nov. 1, 2024

In this study, we investigated the potential mechanisms by which polyhexamethylene guanidine phosphate (PHMG-p), a known respiratory irritant, may contribute to lung cancer development. Using adverse outcome pathway (AOP) framework, analyzed established databases (such as AOP-Wiki) and employed AI tools (AOP-helpFinder) identify key events (KEs) associated with carcinogenesis. Our analysis indicates that chronic inhalation of PHMG-p triggers non-genotoxic pathway, characterized cell membrane disruption, inflammation, oxidative stress, point departure (POD) 0.0018 mg/m³, suggesting carcinogenic potential. Additionally, human exposure assessment revealed most claimants were exposed levels exceeding estimated reference concentration (RfC) 0.018 µg/m³. While downstream KEs, such DNA damage, mutation, proliferation, require further investigation, our findings, supported AOP framework potency assessments, strongly suggest could induce in individuals affected humidifier disinfectants. These results underscore importance comprehensive risk approach for evaluating carcinogenicity PHMG-p.

Language: Английский

Comparative toxicogenomics database’s 20th anniversary: update 2025 DOI Creative Commons
Allan Peter Davis,

Thomas C. Wiegers,

Daniela Sciaky

et al.

Nucleic Acids Research, Journal Year: 2024, Volume and Issue: 53(D1), P. D1328 - D1334

Published: Oct. 10, 2024

For 20 years, the Comparative Toxicogenomics Database (CTD; https://ctdbase.org) has provided high-quality, literature-based curated content describing how environmental chemicals affect human health. Today, CTD includes over 94 million toxicogenomic connections relating chemicals, genes/proteins, phenotypes, anatomical terms, diseases, comparative species, pathways and exposures. In this 20th year anniversary update, we reflect on CTD's remarkable growth provide an overview of increased data new features, including enhancements to curation workflow (e.g. exposure tool expanded use natural language processing), added functionality improvements Tetramers Pathway View tools) significant upgrades software infrastructure. Linking lab-based core with real-world via controlled vocabularies facilitates analysis across entire health continuum, from molecular toxicological mechanisms population level, vice versa. The 'prototype database' originally described in 2004 evolved into a premier, sophisticated, highly cited well-engineered knowledgebase discoverybase that is utilized by scientists worldwide design testable hypotheses about

Language: Английский

Citations

15
A new approach for risk assessment of pulmonary toxicants: a preliminary study using didecyldimethylammonium chloride DOI

Jun Woo Kim,

Yu Bin Han,

Kyu Hyuck Chung

et al.

Environmental Science and Pollution Research, Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 13, 2024

Language: Английский

Citations

0
Pulmonary Surfactant Biogenesis Blockage Mediated Polyhexamethylene Guanidine Disinfectant Induced Pulmonary Fibrosis DOI
Xin Li,

Jianzhong Zhang,

Mingyue Wang

et al.

Journal of Hazardous Materials, Journal Year: 2024, Volume and Issue: 480, P. 136307 - 136307

Published: Oct. 30, 2024

Language: Английский

Citations

0
Comprehensive analysis of adverse outcome pathway, potency, human exposure supports carcinogenicity of polyhexamethylene guanidine phosphate in lung cancer DOI Creative Commons
Yong Joo Park, Ha Ryong Kim,

Jun Woo Kim

et al.

Ecotoxicology and Environmental Safety, Journal Year: 2024, Volume and Issue: 287, P. 117222 - 117222

Published: Nov. 1, 2024

In this study, we investigated the potential mechanisms by which polyhexamethylene guanidine phosphate (PHMG-p), a known respiratory irritant, may contribute to lung cancer development. Using adverse outcome pathway (AOP) framework, analyzed established databases (such as AOP-Wiki) and employed AI tools (AOP-helpFinder) identify key events (KEs) associated with carcinogenesis. Our analysis indicates that chronic inhalation of PHMG-p triggers non-genotoxic pathway, characterized cell membrane disruption, inflammation, oxidative stress, point departure (POD) 0.0018 mg/m³, suggesting carcinogenic potential. Additionally, human exposure assessment revealed most claimants were exposed levels exceeding estimated reference concentration (RfC) 0.018 µg/m³. While downstream KEs, such DNA damage, mutation, proliferation, require further investigation, our findings, supported AOP framework potency assessments, strongly suggest could induce in individuals affected humidifier disinfectants. These results underscore importance comprehensive risk approach for evaluating carcinogenicity PHMG-p.

Language: Английский

Citations

0