Adverse health effects of humidifier disinfectants in Korea: lung toxicity of polyhexamethylene guanidine phosphate

Abstract

-Exposure to humidifier disinfectants was identified in 2011 as the potential cause of an outbreak of lung disease in Korea. It is estimated that over 8 million people have been exposed to humidifier disinfectants-chemicals added to the water used in humidifiers to prevent the growth of microorganisms-since their commercial introduction. The primary component of humidifier disinfectant products involved was polyhexamethylene guanidine phosphate (PHMG-P), a guanidine-based antimicrobial agent. Lesions observed in the lungs of patients were similar to those observed in laboratory animals exposed to PHMG-P. In this review, we outline the physicochemical and toxicological properties of PHMG-P, and introduce a putative mechanism for its lung toxicity based in large part on research findings to date.

Polyhexamethylene Guanidine Phosphate Damages Tight Junctions and the F-Actin Architecture by Activating Calpain-1 via the P2RX7/Ca2+ Signaling Pathway

“…Polyhexamethylene guanidine (PHMG) is a guanidine-based polymeric antimicrobial agent [11][12][13]. The major two derivatives of its salt, PHMG phosphate (PHMG-p) and PHMG hydrochloride, are widely used in detergents, paints, and swimming pools [14][15][16].…”

Polyhexamethylene guanidine phosphate induces IL-6 and TNF-α expression through JNK-dependent pathway in human lung epithelial cells

“…The cytokine-mediated inflammatory response is considered to play a crucial role in the progression of PHMGinduced pulmonary fibrosis (Kim et al, 2016(Kim et al, , 2018. Therefore, the exploration of the regulatory mechanisms underlying the inflammatory response is important to elucidate the mechanism of PHMG-induced lung injury.…”

“…Previous studies have suggested that the inflammatory response induced by PHMG is significantly associated with the development of pulmonary fibrosis (Song et al, 2014;Kim et al, 2016Kim et al, , 2018. Cytokines, which are proteins secreted by all kinds of cells, act as fundamental mediators between cells (Lacy and Stow, 2011;Arango Dugue and Descoteaux, 2014).…”

Letter to the Editor. Questionable information on poisonings by alcohol surrogates

“…The latter seems to be more probable as PHMG has no strong hepatotoxicity; its LD50, when administered orally, has been around 450 mg/kg for mice and 630 mg/kg for rats (Lachenmeier et al ., 2012) or somewhat higher, while the animals died with signs of injury to the nervous system (Asiedu-Gyekye et al ., 2014, 2015; Kondrashov, 1992; Tsisanova & Salomatin, 2010). Lung lesions due to PHMG used in household humidifiers have been reported (Kim et al ., 2016), but no reports on liver injury in humans have come to our attention.…”

“…The difference between LD50 estimates in rats for PHMG and PHMB by the same researchers in two consecutive studies was striking: 600 vs. 25.6 mg/kg (Asiedu-Gyekye et al ., 2014, 2015). Note that general toxicity of both substances is largely similar with LD50 values 500-600 mg/kg in rats when administered orally (Kim et al ., 2016). The question is whether the value 25.6 mg/kg (Asiedu-Gyekye et al ., 2015) could have resulted from added precaution due to information on the mass poisoning in Russia (Ostapenko et al ., 2011) cited by Asiedu-Gyekye et al .…”