Human exposure to polyhexamethylene guanidine phosphate from humidifiers in residential settings: Cause of serious lung disease

Abstract

Exposure to the humidifier disinfectant, polyhexamethylene guanidine phosphate (PHMG), in mists generated from ultrasonic humidifiers was studied in a simulation chamber and apartment rooms. PHMG is suspected as a causative agent of lung disease in Korea residences. In the simulation-chamber study, the amount of disinfectant discharged from three different ultrasonic humidifiers was measured. Mists generated at 1, 2, and 4 times the recommended amount of disinfectant were sampled with an impinger, and the effect of relative humidity (RH) on airborne disinfectant concentration was studied by changing RH from 60%-70% to 90%-100%. In addition, particle size distribution (PSD) in mists was measured by scanning mobility particle sizer (SMPS), aerodynamic particle sizer (APS), and Mastersizer. In the apartment study, mists generated from ultrasonic humidifiers were sampled for 6 h in small and large rooms during fall ( n = 10) and winter ( n = 15). In the simulation study, the humidifiers discharged 205 ± 24.6 ml/h of mist at maximum capacity. Concentrations of airborne disinfectant increased with increasing concentration of disinfectant. RH affected airborne disinfectant concentration in the chamber, with increasing concentration with increasing RH. Below RH 70%, no airborne PHMG was detected. PHMG-containing mists generated from ultrasonic humidifier showed various sizes ranging from 149-157 nm to 690-740 nm to larger than 5.4 µm by SMPS, APS, and Mastersizer, respectively. Surface area mean diameter measured by Mastersizer ranged from 5.39 µm to 5.72 µm. In the apartment study conducted during the fall, the geometric mean (GM) and geometric standard deviation (GSD) and arithmetic mean (AM) and standard deviation (SD) of airborne PHMG concentration were 3.22 + 5.13 µg/m and 8.26 ± 12.18 µg/m, respectively. In the winter, GM + GSD and AM ± SD of airborne PHMG concentration were 0.21 + 2.11 µg/m and 0.35 ± 0.62 µg/m, respectively. RH and temperature in the apartment rooms for fall and winter were 22.5 ± 1.7°C, 74.5 ± 15.6% and 22.0 ± 2°C, 51.1 ± 12.9%, respectively. Different RHs in the fall and winter resulted in very different airborne concentrations of disinfectant in the apartment rooms. Exposure levels and PSD of mists generated from ultrasonic humidifiers in apartments are not sufficient to conclude that PHMG causes lung disease in Korean residences.

Polyurethanes from Hydrophobic Elastic Materials to Hydrogels with Potent Nonleaching Biocidal and Antibiofilm Activity

“…As shown in Figure , the dramatic drop in cell viability was recorded for the physical blend of PHMG and PPU. The observed toxicity is attributed to the leaching of the unbonded PHMG oligomers into the culture medium, and its adverse effect on humans cells. , Indeed, the highly water-soluble characteristic of PHMG is responsible for its leaching and subsequent uptake by both cell membranes and bacteria, leading to cell toxicity and biocidal activity in a dissolved form. The chemical anchoring of PHMG to the UPU backbone at the proper concentration provided copolymers with excellent selectivity for killing bacteria over mammalian cells, as proved from the biocidal activity and MTT assay.…”

Health Effects Associated With Humidifier Disinfectant Use: A Systematic Review for Exploration

“…Forty-eight published studies using non-human animal subjects or in vitro toxicology studies were included in the review ( Table 3 ). 16 39 40 41 42 43 44 60 61 62 63 64 65 66 67 68 69 70 71 72 73 74 75 76 77 78 79 80 81 82 83 84 85 86 87 88 89 90 91 92 93 94 95 96 97 98 99 100 To investigate the hazardous effects of humidifier disinfectants, in vitro studies were performed using various cell lines, and toxicity tests were performed using several animal models. Cytotoxicity, lung fibrosis, and pulmonary genotoxicity due to PHMG exposure were described as a consequence of toxicity testing undertaken shortly after HDLI was reported.…”

“… 39 Although controversial, experimental tests revealed that when a humidifier disinfectant was sprayed, it could be deposited in the lungs. 40 60 61 62 The incidence of HDLI increased with the estimated exposure concentration and the distance to the humidifier in an investigation conducted on a group of subjects who were using humidifier disinfectants. 10 41 42 63 Even though an HDLI outbreak resulted in a substantial number of deaths, the effects were reversible in some people who were exposed to the humidifier disinfectant.…”

Characteristics of a new respiratory syndrome associated with the use of a humidifier disinfectant: humidifier disinfectant-related respiratory syndrome (HDRS)

“…A rodent study has reported that intratracheal instillation or inhalation of PHMG phosphate induces severe lung inflammation and fibrosis, similar to the pathological features in affected humans [7][8][9]. The aerosol form of PHMG (nano-sized PHMG) that is released by humidifiers can penetrate and accumulate deep in the lungs [10]. The analysis of the pathological, radiological and clinical features of HDLI cases, and lung histopathology of HD-exposed experimental animals, led to the refinement of the diagnostic criteria for HDLI in 2013 [11,12] (Tables 1 and 2).…”