Polyhexamethylene Guanidine Phosphate Research Articles

Respiratory Toxicity of Polyhexamethylene Guanidine Phosphate Exposure in Zebrafish

Humidifier disinfectants containing polyhexamethylene guanidine phosphate (PHMG-P) can induce pulmonary toxicity and has caused human casualties in South Korea since 2006. Thereby, the safety evaluation of household chemicals such as PHMG-P has garnered increased importance. However, many limitations, such as the lack of specialized facilities and animal welfare concerns associated with the use of murine models, persist. Zebrafish gills have high functional and structural similarity to mammalian lungs. Moreover, zebrafish are sensitive to toxic substances, resulting in changes in behavioral or ventilatory patterns. Based on these facts, in this study, we aimed to evaluate the pulmonary toxicity of PHMG-P in zebrafish. Zebrafish exposed to PHMG-P showed an increase in mRNA levels of inflammatory factors persisting for 28 days along with histopathologic changes in the gills. An exposure time-dependent alteration in infiltration of inflammatory cells and destruction of gill lamellae was observed. In addition, an increase in mRNA levels of fibrosis factors was observed in gills exposed to PHMG-P for 28 days, as assessed by collagen staining with Masson's trichrome. These results supported the cellular level results. Taken together, our results reveal pulmonary toxic effects of PHMG-P and suggest useful markers for evaluating pulmonary toxicity.

Protective Effects of Nintedanib against Polyhexamethylene Guanidine Phosphate-Induced Lung Fibrosis in Mice.

Nintedanib (NDN), a tyrosine kinase inhibitor, has been shown to have anti-tumor, anti-inflammatory, and anti-fibrotic effects in several reports. We investigated the protective effects of NDN against polyhexamethylene guanidine phosphate (PHMG)-induced lung fibrosis in mice. The following three experimental groups were evaluated: (1) vehicle control; (2) PHMG (1.1 mg/kg); and (3) PHMG & NDN (60 mg/kg). PHMG induced pulmonary inflammation and fibrosis by intratracheal instillation in mice. In contrast, NDN treatment effectively alleviated the PHMG induced lung injury, and attenuated the number of total cells and inflammatory cells in the bronchoalveolar lavage fluid, including the fibrotic histopathological changes, and also reduced the hydroxyproline content. NDN also significantly decreased the expression of inflammatory cytokines and fibrotic factors, and the activation of the NLRP3 inflammasome in lung tissues. These results suggest that NDN may mitigate the inflammatory response and development of pulmonary fibrosis in the lungs of mice treated with PHMG.

Oleanolic acid acetate attenuates polyhexamethylene guanidine phosphate-induced pulmonary inflammation and fibrosis in mice

Oleanolic acid acetate (OAA), triterpenoid compound isolated from Vigna angularis (azuki bean), has been revealed anti-inflammatory in several studies. We investigated the effects of OAA against polyhexamethylene guanidine phosphate (PHMG-P)-induced pulmonary inflammation and fibrosis in mice. OAA treatment effectively alleviated PHMG-P-induced lung injury, including the number of total and differential cell in BAL fluid, histopathological lesions and hydroxyproline content in a dose dependent manner. Moreover, OAA treatment significantly decreased the elevations of IL-1β, IL-6, TNF-α, TGF-β1, and fibronectin, and the activation of the NOD-like receptor family, pyrin domain containing 3 (NLRP3) inflammasome in the lungs of PHMG-P-treated mice. Cytokines are known to be key modulators in the inflammatory responses that drive progression of fibrosis in injured tissues. The activation of NLRP3 inflammasome has been reported to be involved in induction of inflammatory cytokines. These results indicate that OAA may mitigate the inflammatory response and development of pulmonary fibrosis in the lungs of mice treated with PHMG-P.

Time course of polyhexamethyleneguanidine phosphate-induced lung inflammation and fibrosis in mice

Pulmonary fibrosis is a chronic progressive disease with unknown etiology and has poor prognosis. Polyhexamethyleneguanidine phosphate (PHMG-P) causes acute interstitial pneumonia and pulmonary fibrosis in humans when it exposed to the lung. In a previous study, when rats were exposed to PHMG-P through inhalation for 3 weeks, lung inflammation and fibrosis was observed even after 3 weeks of recovery. In this study, we aimed to determine the time course of PHMG-P-induced lung inflammation and fibrosis. We compared pathological action of PHMG-P with that of bleomycin (BLM) and investigated the mechanism underlying PHMG-P-induced lung inflammation and fibrosis. PHMG-P (0.9 mg/kg) or BLM (1.5 mg/kg) was intratracheally administered to mice. At weeks 1, 2, 4 and 10 after instillation, the levels of inflammatory and fibrotic markers and the expression of inflammasome proteins were measured. The inflammatory and fibrotic responses were upregulated until 10 and 4 weeks in the PHMG-P and BLM groups, respectively. Immune cell infiltration and considerable collagen deposition in the peribronchiolar and interstitial areas of the lungs, fibroblast proliferation, and hyperplasia of type II epithelial cells were observed. NALP3 inflammasome activation was detected in the PHMG-P group until 4 weeks, which is suspected to be the main reason for the persistent inflammatory response and exacerbation of fibrotic changes. Most importantly, the pathological changes in the PHMG-P group were similar to those observed in humidifier disinfectant-associated patients. A single exposure of PHMG-P led to persistent pulmonary inflammation and fibrosis for at least 10 weeks.

MicroRNA regulatory networks reflective of polyhexamethylene guanidine phosphate-induced fibrosis in A549 human alveolar adenocarcinoma cells

Polyhexamethylene guanidine phosphate (PHMG-phosphate), an active component of humidifier disinfectant, is suspected to be a major cause of pulmonary fibrosis. Fibrosis, induced by recurrent epithelial damage, is significantly affected by epigenetic regulation, including microRNAs (miRNAs). The aim of this study was to investigate the fibrogenic mechanisms of PHMG-phosphate through the profiling of miRNAs and their target genes. A549 cells were treated with 0.75 μg/mL PHMG-phosphate for 24 and 48 h and miRNA microarray expression analysis was conducted. The putative mRNA targets of the miRNAs were identified and subjected to Gene Ontology analysis. After exposure to PHMG-phosphate for 24 and 48 h, 46 and 33 miRNAs, respectively, showed a significant change in expression over 1.5-fold compared with the control. The integrated analysis of miRNA and mRNA microarray results revealed the putative targets that were prominently enriched were associated with the epithelial-mesenchymal transition (EMT), cell cycle changes, and apoptosis. The dose-dependent induction of EMT by PHMG-phosphate exposure was confirmed by western blot. We identified 13 putative EMT-related targets that may play a role in PHMG-phosphate-induced fibrosis according to the Comparative Toxicogenomic Database. Our findings contribute to the comprehension of the fibrogenic mechanism of PHMG-phosphate and will aid further study on PHMG-phosphate-induced toxicity.

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

Polyhexamethylene guanidine phosphate (PHMG) is an antimicrobial biocide that causes severe lung injury accompanied with inflammation and subsequent fibrosis. Cytokines mediate the inflammatory response, leading to fibrosis in injured tissues. PHMG is known to induce the expression of various cytokines in vitro and in vivo. In the present study, we investigated the involvement of three MAPK subfamilies (JNK, p38 MAPK, and ERK) in PHMG-induced cytokine expression in A549 human lung epithelial cells. Our in vivo and in vitro data indicated that PHMG induced an increase in mRNA expression of IL-6 and TNF-α, and enhanced the phosphorylation of JNK, p38 MAPK, and ERK. Further, we investigated the involvement of MAPKs in PHMG-induced mRNA expression of IL-6 and TNF-α using JNK, p38 MAPK, and ERK inhibitors in A549 cells. Pre-treatment with the JNK inhibitor but not the p38 MAPK or ERK inhibitor, significantly attenuated the PHMG-induced mRNA expression of IL-6 and TNF-α. These results suggest that the activation of JNK is involved at least partially in the induction of IL-6 or TNF-α expression by PHMG in A549 cells.

Toxic responses to polyhexamethylene guanidine phosphate in cytoplasmic organelles

In Korea, lung disease of children and pregnant women associated with humidifier disinfectant use has become a major concern. A common sterilizer is polyhexamethylene guanidine (PHMG), a member of the guanidine family of antiseptics. This study was done to elucidate the putative cytotoxic effect of PHMG and the PHMG-mediated altered gene expression in human alveolar epithelial A549 cells in vitro. Cell viability analyses revealed the potent cytotoxicity of PHMG, with cell death evident at as low as 5 μg/mL. Death was dose- and time-dependent, and was associated with formation of intracellular reactive oxygen species, and apoptosis significantly, at even 2 μg/mL concentration. The gene expression profile in A549 cells following 24 h exposure to 5 μg/mL of PHMG was investigated using DNA microarray analysis. Changes in gene expression relevant to the progression of cell death included induction of genes related to apoptosis, autophagy, fibrosis, and cell cycle. However, the expressions of genes encoding antioxidant and detoxifying enzymes were down-regulated or not affected. The altered expression of selected genes was confirmed by quantitative reverse transcription-polymerase chain reaction and Western blot analyses. The collective data suggest that PHMG confers cellular toxicity through the generation of intracellular reactive oxygen species and alteration of gene expression.

Synthesis and characterization of arginine-NIPAAm hybrid hydrogel as wound dressing: In vitro and in vivo study.

Despite the zwitterionic characteristic and biocompatible property of arginine based hydrogels, the brittle behavior and non-transparency still remain as a significant problem for wound dressing. Furthermore promoting the antibacterial property of the zwitterionic hydrogel is also necessary to prevent the bacterial colonization and subsequent wound infection. Therefore, we created a hybrid hydrogel combined methacrylate arginine (M-Arg) and N-isopropyl acrylamide (NIPAAm). NIPAAm improves transparency and mechanical property as well as acts as a temperature-response drug release system. Additionally, chlorhexidine (CHX) was preloaded into the hydrogels and polyhexamethylene guanidine phosphate (PHMG) was grafted on the hydrogel surface, respectively, which make the hydrogel useful as a favorable antibacterial dressing. The hybrid hydrogel has a combination effect of biocompatibility, environmentally responsive transformation behavior, biodegradability, anti-protein adsorption and antimicrobial properties. This report proposes the preparation of P(M-Arg/NIPAAm) hydrogel that has a great potential for wound healing.

Effects of polyhexamethylene guanidine phosphate on human gingival fibroblasts

Objective: Polyhexamethylene guanidine phosphate (PHMG-P) was compared to chlorhexidine (CHX) in order to determine potential cytotoxic and immune-modulatory effects on human gingival fibroblasts.Materials and methods: Cytotoxic effects of PHMG-P and CHX on human gingival fibroblasts were assessed using cell viability assay at various time points and concentrations. The effects of PHMG-P and CHX on the secretion of prostaglandin (PG) E2, interleukin (IL)-6, IL-8 and matrix metalloproteinase (MMP)-1 by non-stimulated or IL-1β stimulated fibroblasts were evaluated by enzyme-linked immunosorbent assays.Results: PHMG-P concentration 0.00009% led to the total loss of fibroblast viability within 24 h, whereas inhibition of fibroblast viability by CHX occurred at significantly higher concentrations of 0.0009% (p < .001). Short-term exposure to 0.005% PHMG-P led to loss of fibroblast viability after 5 min, whilst cells exposed to 0.005% CHX survived 30 min of treatment (p < .001). IL-1β stimulation induced an inflammatory response with a significant increase in the secretion of PGE2, IL-6, IL-8 and MMP-1. Treatment of IL-1β stimulated fibroblasts in combination with PHMG-P or CHX at concentrations of 0.000045 or 0.0.00009% resulted in significantly decreased PGE2, IL-6, IL-8 and MMP-1 levels. PHMG-P or CHX alone did not affect the baseline secretion of PGE2, IL-6, IL-8 or MMP-1 by gingival fibroblasts.Conclusions: Cytotoxic effects on gingival fibroblasts were triggered by both PHMG-P and CHX at concentrations below those used in clinical practice. The tested antiseptics did not cause inflammation and reduced IL-1β-induced secretion of inflammatory mediators and collagenase by gingival fibroblasts, which suggests anti-inflammatory properties.

Types of household humidifier disinfectant and associated risk of lung injury (HDLI) in South Korea

From 2002 through 2015, hundreds of people died of fatal lung injuries associated with the use of humidifier disinfectants (HDs) in Korea. Several chemical disinfectants used for household humidifiers were later clinically confirmed to cause HD-associated lung injury (HDLI). The aim of this study is to evaluate the registered lung disease cases and to compare the distribution of HDLI patients, including deaths, by HD use characteristics including types of HD and HD brands categorized by age group. A total of 530 registered were clinically examined through two rounds of investigations conducted from July 2013 until April 2015. Information on HD use was obtained from a structured questionnaire and home investigations. Approximately one-half of the patients (n=221) were clinically confirmed to be associated with the use of HDs. Pregnant women (n=35, 16%) and pre-school children≤6years old (n=128, 58%) accounted for most of the HD-associated lung injury patients (n=163, 74%). Sixty-seven percent of HDLI patients developed HDLI after less than one year of HD use. HD products containing polyhexamethylene guanidine phosphate (PHMG) were the most frequently used among confirmed HDLI patients (n=123, 55.7%), followed by oligo (2-(2-ethoxy) ethoxyethyl guanidinium (PGH) (n=24, 10.9%) and a mixture of chloromethylisothiazolinone (CMIT) and methylisothiazolinone (MIT) (n=3, 1.4%). Other HDs did not appear to be linked to HDLI. The majority of the HDLI patients (n=85, 38.5%) was found to use only Oxy Saksak® products containing PHMG. The development of HDLI was clinically found to be associated with the use of several HD products containing PHMG and PGH, and to lesser extent, CMIT/MIT.

Analysis of genomic responses in a rat lung model treated with a humidifier sterilizer containing polyhexamethyleneguanidine phosphate

The antimicrobial biocide polyhexamethyleneguanidine (PHMG) phosphate is the main ingredient in the commercially available humidifier disinfectant. PHMG phosphate-based humidifier disinfectants can cause pulmonary fibrosis and induce inflammatory and fibrotic responses both in vivo and in vitro. However, toxicological mechanisms including genomic alterations induced by inhalation exposure to PHMG phosphate have not been elucidated. Therefore, this study evaluated the toxicological effects of the PHMG phosphate-containing humidifier disinfectant. We used DNA microarray to identify global gene expression changes in rats treated with PHMG phosphate-containing humidifier disinfectant for 4 weeks and 10 weeks. Functional significance of differentially expressed genes (DEGs) was estimated by gene ontology (GO) analysis. Four weeks post-exposure, 320 and 392 DEGs were identified in female and male rats, respectively (>2-fold, p<0.05). Ten weeks post-exposure, 1290 and 995 DEGs were identified in females and males, respectively. Of these, 119 and 556 genes overlapped between females and males at 4 weeks and 10 weeks, respectively, post-PHMG phosphate exposure. In addition, 21 genes were upregulated and 4 genes were downregulated in response to PHMG phosphate in a time-dependent manner. Thus, we predict that changes in genomic responses could be a significant molecular mechanism underlying PHMG phosphate toxicity. Further studies are required to determine the detailed mechanism of PHMG phosphate-induced pulmonary toxicity.

In vitro inflammatory effects of polyhexamethylene biguanide through NF-κB activation in A549 cells

Polyhexamethylene biguanide (PHMB) is a member of the polymeric guanidine family, which is used as a biocide and preservative in industrial, medicinal, and consumer products. Some studies reported that polyhexamethylene guanidine phosphate, which is also a member of the guanidine family, induced severe inflammation and fibrosis in the lungs. However, limited studies have evaluated the pulmonary toxicity of PHMB associated with inflammatory responses. The aim of this study was to elucidate the inflammatory responses and its mechanisms induced by PHMB in lung cells. A549 cells exposed to PHMB showed decreased viability, reactive oxygen species (ROS) generation, inflammatory cytokine secretion, and nuclear factor kappa B (NF-κB) activation. The cells showed dose-dependent cytotoxicity and slight generation of ROS. PHMB triggered inflammatory cytokine secretion and NF-κB activation by modulating the degradation of IκB-α and the accumulation of nuclear p65. TNF-α plays important roles in IL-8 expression as well as NF-κB activation. Moreover, IL-8 production induced by PHMB was completely suppressed by a NF-κB inhibitor, but not by a ROS scavenger. In conclusion, we suggest that PHMB induces the inflammatory responses via the NF-κB signaling pathway.

Humidifier disinfectant lung injury, how do we approach the issues?

A large portion of the Korean population has been exposed to toxic humidifier disinfectants (HDs), and considering that the majority of the victims are infants, the magnitude of the damage is expected to be considerably larger than what has currently been revealed. The current victims are voicing problems caused by various diseases, including but not limited to lung, upper respiratory tract, cardiovascular, kidney, musculoskeletal, eye, and skin diseases, etc. However, there has been difficulty in gaining validation for these health problems and identifying causal relationships due to lack of evidence proving that toxic HD is the specific causes of extrapulmonary diseases such as allergic rhinitis. Furthermore, the victims and bereaved families of the HD case have not received any support for psychological distress such as post-traumatic stress disorder, depression, feelings of injustice, and anger caused by the trauma. In addition, because the underlying mechanisms of the toxic materials within the HDs such as polyhexamethylene guanidine phosphate, poly(oxyalkylene guanidine) hydrochloride, chloromethylisothiazolinone/methylisothiazolinone have yet to be determined, the demand for information regarding the HD issue is growing. The victims of the HD cases require support that goes beyond financial aid for medical costs and living expenses. There is a desperate need for government-led integrated support centers that provide individualized support through health screenings; in other words, we need an integrated facility that provides the appropriate social support to allow the victims to recover their physical and mental health, so as to well prepare them to return to a normal life. The implementation of such a plan requires not only the close cooperation between those departments already directly involved such as the Ministry of Environment and the Ministry of Health and Welfare, but also active support on a national scale from pan-governmental consultative bodies.

Carbon nanotube-filled intumescent multilayer nanocoating on cotton fabric for enhancing flame retardant property

Abstract In this work, hybrid organic-inorganic film of polyhexamethylene guanidine phosphate (PHMGP)/one kind of industrially available fluorescent whitening agents (VBL)-MWNTs was built via layer-by-layer assembly technique to protect cotton fabric from fire. The UV–vis spectra and the TEM images confirm that VBL could improve the dispersibility of MWNTs in water. Attenuated total reflection Fourier transform infrared spectroscopy and scanning electron microscopy prove that the PHMGP and VBL-MWNTs are successfully incorporated into the cotton fabric. Compared to the control fabric, the thermal stability, flame retardancy and residue chars of the coated fabrics are improved with the bilayer number increasing, which were assessed by thermo-gravimetric analysis, microscale combustibility experiments, vertical and horizontal flammability tests, respectively. The enhancements are ascribed to both the physical barrier effect of MWNTs and the intumescent flame retardant of PHMGP and VBL.

Unique nanobrick wall nanocoating for flame-retardant cotton fabric via layer-by-layer assembly technique

Unique quadlayer assembly film of polyhexamethylene guanidine phosphate (PHMGP)/ammonium polyphosphate (APP)/PHMGP/α-zirconium phosphate (α-ZrP) was constructed on cotton fabric to achieve excellent flame-retardant modification. X-ray diffraction and attenuated total reflection Fourier transform infrared spectroscopy confirmed that PHMGP, APP, and α-ZrP grew linearly in the layer-by-layer assembly process. Thermogravimetric analysis was carried out to assess the thermal stability of the coated fabric, and the relevant results showed that cotton fabric were effectively protected by the assembly coating during burning. The microscale combustion calorimetry results indicated that the coated fabric showed smaller values of the peak heat release rate and total heat release than the uncoated one. Characterizations of burning behaviors of all fabrics in vertical configuration revealed that the nanobrick wall coating obviously decreased the burning time, thoroughly eliminated the afterglow phenomenon, and significantly enhanced the residue char left after burning. Moreover, the unique nanobrick wall coating provides an enhanced flame-retardant effect as compared to the PHMGP/APP, PHMGP/α-ZrP and APP coatings. The scanning electron micrograph and Fourier transform infrared spectra of the residue chars revealed that the excellent flame retardancy of the coated cotton was attributed to the catalytic charring of the intumescent component and the protection of the unique nanobrick wall as an reinforced barrier layer during burning.

가습기 살균제 폐 손상 피해자의 살균제 노출 특성 -태아와 임산부 노출을 중심으로 -

In South Korea, many cases of humidifier disinfectant-associated lung injury (HDLI) have been reported among people who used humidifier products containing humidifier disinfectant (HD). The objective of this study is to characterize exposure to HD among a total of 221 HDLI patients who used HD. Information and data on the HDs used were collected through a structured questionnaire and home environmental investigations. The conditions of these 221 HDLI patients were clinically confirmed to be caused by the use of HD. Children aged under 5 years old made up the highest proportion of HDLI cases (n=125, 56.6 %), followed by pregnant women (n=35, 15.8%). Forty-three percent (n=95) of the victims died. There were three cases of fetuses and 35 pregnant women among the victims. The number of HDLI patients who used only the Oxy Saksak brand of HD was found to be 85 (38.5%), followed by the HD brands Cefu (n=24, 10.9%), Lottemart Wiselect (n=9, 4.1%) and Aekyung (n=3). Patients who exclusively used HD brands containing polyhexamethylene guanidine phosphate (PHMG) (n=13, 55.7%) as an active ingredient made up the largest share, followed by those who exclusively used HD containing only oligo(2-(2-ethoxy) ethoxyethyl guanidinium (PGH) (n=24, 10.9%) and by those who only used a mixture of chloromethylisothiazolinone (CMIT) and methylisothiazolinone (MIT) (n=3, 1.4%). HD products containing PHMG were found to be the most commonly used among the confirmed HDLI patients. Three exposed fetuses who never used HD after birth developed lung injuries, indicating a probability of exposure to HD during gestation. All HDLI patients responded that they used HD while sleeping and for longer than 10 hours per day. In conclusion, the development of HDLI was clinically found to be associated with the use of several HD products containing PHMG, PGH and CMIT/MIT.

가습기 살균제 피해자 호흡기로 흡입된 가습기 살균제 양 추정 - 호흡기 외부(external) 및 내부 노출(internal exposure) 추정 방법과 사례 -

In South Korea, many cases of humidifier disinfectant-associated lung injury (HDLI) have been reported among people who used humidifier products containing humidifier disinfectant (HD). The objectives of this study are to estimate both airborne HD concentration in the room where HD was used and the amount of humidifier disinfectant absorbed into the respiratory system. Information and data on the HDs were collected using a structured questionnaire and home environmental investigations include the volume of HD (ml) and hours used per day, concentration of disinfectants contained in the HD brand (<TEX>${\mu}g/ml$</TEX>), volume of the room (<TEX>$m^3$</TEX>), assumed ventilation rate (<TEX>$m^3/hr$</TEX>) and breathing rate assumed (<TEX>$m^3/hr$</TEX>). We used children aged under five years old as a sample and estimated both airborne HD concentrations and amount of HD absorbed into the respiratory system. The estimated airborne concentration of HD in the room ranged from 68 to <TEX>$369{\mu}g/m^3$</TEX> for PHMG (polyhexamethylene guanidine phosphate) and from 16 to <TEX>$239{\mu}g/m^3$</TEX> for PGH (oligo (2-(2-ethoxy) ethoxyethyl guanidine). The amount of HD absorbed in the respiratory system per day was estimated to range from 227 to <TEX>$1,225{\mu}g$</TEX> for PHMG and from 53 to <TEX>$794{\mu}g$</TEX> for PGH. In conclusion, a great amount of HD was likely absorbed into respiratory system, likely beyond the level of the capacity of the immune system to remove the HD absorbed.

Boron-containing intumescent multilayer nanocoating for extinguishing flame on cotton fabric

Sodium polyborate (SPB) has been employed with polyhexamethylene guanidine phosphate (PHMGP) to compose a nitrogen-phosphorus-boron intumescent coating on cotton fabric via a layer-by-layer (LBL) technique for obtaining excellent flame retardancy. The infrared spectra and atomic emission spectra indicate that the PHMGP-SPB multilayer grows gradually during the assembly process. Thermogravimetric analysis results show that the residue char of cotton is greatly enhanced after treatment with the LBL coating, which has a high char forming effect on cellulose during testing. The micro-calorimeter test finds that the assembly coating drastically decreases the peak heat release rate and total heat release of cotton fabric as a result of the catalytic charring effect. Cotton’s burning behavior is monitored by the flammability test, and the results show that ten bilayer (BL) coating with only 7.5 wt% can completely extinguish the flame on cotton samples. The oxygen index test reveals that the limiting oxygen index (LOI) of cotton samples is substantially increased by introducing the LBL coating. When the BL increases to 20, the LOI value reaches up to 41. The residual char after burning is analyzed by scanning electron microscope and infrared spectroscopy, and the results show the the LBL coating has an intumescent flame-retardant effect on cotton.

Humidifier Disinfectants Are a Cause of Lung Injury among Adults in South Korea: A Community-Based Case-Control Study.

BackgroundsAn outbreak of lung injury among South Korean adults was examined in a hospital-based case-control study, and the suspected cause was exposure to humidifier disinfectant (HD). However, a case-control study with community-dwelling controls was needed to validate the previous study’s findings, and to confirm the exposure-response relationship between HD and lung injury.MethodsEach case of lung injury was matched with four community-dwelling controls, according to age (±3 years), sex, residence, and history of childbirth since 2006 (for women). Environmental risk factors, which included type and use of humidifier and HD, were investigated using a structured questionnaire during August 2011. The exposure to HD was calculated for both cases and controls, and the corresponding risks of lung injury were compared.ResultsAmong 28 eligible cases, 16 patients agreed to participate, and 60 matched controls were considered eligible for this study. The cases were more likely to have been exposed to HD (odds ratio: 116.1, 95% confidence interval: 6.5–2,063.7). All cases were exposed to HDs containing polyhexamethyleneguanidine phosphate, and the risk of lung injury increased with the cumulative exposure, duration of exposure, and exposure per day.ConclusionsThis study revealed a statistically significant exposure-response relationship between HD and lung injury. Therefore, continuous monitoring and stricter evaluation of environmental chemicals’ safety should be conducted.

Safety study, anti-inflammatory and antioxidant action of drug caramel with polyhexamethylene guanidine phosphate

Background: Among the new antiseptic medicines, most meeting modern requirements in terms of treatment of microbial invasion are one of the leading positions occupied by the polymeric guanidine compound. Polyhexamethylene guanidine phosphate (PHMGP) has a wide spectrum of antimicrobial activity and practical absence of toxicity. We have developed a new dosage form caramel “Guamel'” with the active pharmaceutical ingredient. Methods: on white rats of both sexes were studied parameters of acute toxicity and irritant dosage form caramel “Guamel'”, as well as anti-inflammatory and antioxidant effects. Results: It was found that the PHMGP developed drug caramel does not have skin-resorptive and allergenic action. Study of acute toxicity on white rats showed harmlessness studied dosage form PHMGP. It was found that a single oral administration to laboratory animals in drug caramel maximum allowable amount and cutaneous application does not lead to death during a 48 hour period of observation, does not cause visible changes in the basic physiological processes and does not affect the function of vital organs. On carrageenan model of inflammation it proved that the drug caramel with PHMGP exhibits anti-inflammatory effect, such a superior drug-referent Septolete. It is also found to have developed in preparation of antioxidant activity in the inhibition of oxidative protein modifications also significantly superior to the reference drug. Conclusions: The developed dosage form caramel “Guamel'” for external use of the safety performance meets the requirements for such drugs. The developed dosage form caramel “Guamel'” exhibits high anti-inflammatory and antioxidant activity, which is the force exceeds the reference value. All of this is experimental rationale for the industrial production of this dosage form caramel “Guamel'”.