A Preliminary Safety Evaluation of Polyhexamethylene Guanidine Hydrochloride (original) (raw)
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Toxicological assessment of polyhexamethylene biguanide for water treatment
Interdisciplinary Toxicology, 2015
Polyhexamethylene biguanide (PHMB) is an antiseptic with antiviral and antibacterial properties used in a variety of products including wound care dressings, contact lens cleaning solutions, perioperative cleansing products, and swimming pool cleaners. There are regulatory concerns with regard to its safety in humans for water treatment. We decided to assess the safety of this chemical in Sprague-Dawley rats. PHMB was administered in a single dose by gavage via a stomach tube as per the manufacturer’s instruction within a dose range of 2 mg/kg to 40 mg/kg. Subchronic toxicity studies were also conducted at doses of 2 mg/kg, 8 mg/kg and 32 mg/kg body weight and hematological, biochemical and histopathological findings of the major organs were assessed. Administration of a dose of 25.6 mg/kg,
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Water Research, 2006
It is well known that water disinfection through chlorination causes the formation of a mixture of disinfection by-products (DBPs), many of which are genotoxic and carcinogenic. To demonstrate the formation of such compounds, a pilot water plant supplied with water from Lake Trasimeno was set up at the waterworks of Castiglione del Lago (PG, Italy). The disinfectants, continuously added to prefiltered lake water flowing into three different basins, were sodium hypochlorite, chlorine dioxide and peracetic acid, an alternative disinfectant used until now for disinfecting waste waters, but not yet studied for a possible use in drinking water treatment. The aim of this study was to evaluate the formation during the disinfection processes of some toxic compounds that could explain the genotoxic effects of drinking waters. Differently treated waters were concentrated by solid-phase adsorption on silica C 18 columns and toxicity was assessed in a line of human hepatoma cells (HepG2), a metabolically competent cellular line very useful for human risk evaluation. The seasonal variability of the physical-chemical water characteristics (AOX, UV 254 nm, potential formation of THM, pH and temperature) made indispensable experimentation with water samples taken during the various seasons. Autumn waters cause greater toxicity compared to those of other seasons, in particular dilution of the concentrate at 0.5 l equivalent of disinfected waters with chlorine dioxide and peracetic acid causes a 55% reduction in cellular vitality while the cellular vitality is over 80% with the all other water concentrates. Moreover it is very interesting underline that non-cytotoxic quantities of the autumnal water concentrates cause, after 2 h treatment, a decrease in GSH and a statistically significant increase in oxygen radicals, while after prolonged treatment (24 h) cause a GSH increase, without variations in the oxygen radical content. This phenomenon could be interpreted as the cellular adaptation response to an initial oxidative stress.
Lethal and sub lethal effects of the biocide chlorhexidine on aquatic organisms
Ecotoxicology, 2013
Chlorhexidine is among the most used biocides in Europe, however its toxicity to aquatic organisms is scarcely known. The main objective of this study was to assess the lethal and sub lethal effects of chlorhexidine digluconate (ChD) on four aquatic model organisms: the bacteria Vibrio fischeri, the algae Pseudokirchneriella subcapitata, the crustacean Daphnia magna and the embryos of the fish Danio rerio. ChD was very toxic to algae and crustaceans, with a 72 h-EC50 of 62.2 lg/l and a 48 h-EC50 of 45.0 lg/l, respectively. Toxicity to fish embryos and the bacteria was lower, with a 96 h-EC50 of 804.0 lg/l and a 15 min-EC50 of 1,694.0 lg/l, respectively. Concerning sub lethal effects on D. magna (feeding inhibition) a 6 h-EC50 of 503.7 lg/l was obtained. In fish, ChD caused developmental abnormalities, namely alterations in the amniotic fluid (48 h-EC20 of 753.6 lg/l) and early hatching. Moreover, enzymatic biomarkers on fish embryos showed an induction of cholinesterase activity in all ChD tested concentrations (80-900 lg/l). The catalase activity was also induced at the highest concentration tested (900 lg/l) whereas no changes were observed for glutathione-S-transferase and lactate dehydrogenase activities. The toxicity of ChD to the algae and crustacean raises concerns about its potential effects in aquatic food webs, since these organisms are in the base of trophic chains, and highlights the need for further studies on ChD toxicity to aquatic organisms.
Journal of Medical Microbiology, 2008
Polyhexamethylene guanidine hydrochloride (PHMGH), an antimicrobial biocide of the guanidine family, was tested for efficacy against quality-control strains of Staphylococcus aureus, Pseudomonas aeruginosa, Salmonella choleraesuis, meticillin-resistant S. aureus (MRSA) and Escherichia coli. Bactericidal activity against S. aureus, P. aeruginosa and Salmonella choleraesuis was determined using the official methods of analysis of the Association of Official Analytical Chemists, with modifications as recommended by the Canadian General Standards Board. For MRSA and E. coli, the MIC and minimal bactericidal concentration were determined using the broth dilution technique. The experiments were carried out at 20 6C under a range of conditions including varying PHMGH concentration (0.001-0.1 %), contact time (0.5-10 min) and water type (distilled, tap and hard water). The phenol coefficient values determined with S. aureus, Salmonella choleraesuis and P. aeruginosa were 7.5, 6.1 and 5, respectively. No matter what type of water was used to make the dilutions, PHMGH killed MRSA and E. coli at concentrations as low as 0.04 and 0.005 % (w/v), respectively, within 1.5 min. The mode of action of PHMGH was elucidated by transmission electron microscopy: the cell envelope was broken, resulting in cell content leakage into the medium. The ultimate aim of this study was to show that PHMGH can be used as an odourless, colourless, non-corrosive and harmless disinfectant for hospital and household facilities.
Occurrence of disinfection by-products in swimming pools and the estimated resulting cytotoxicity
Science of The Total Environment, 2019
64 disinfection by-products (DBPs) investigated in Australian pools • First report of bromochloroacetaldehyde and bromodichloroacetaldehyde in pools • First investigation of N-nitrosamines in a brominated pool • Up to 64% of the total molar DBP concentration consisted of chloral hydrate. • Over 90% of the total calculated chronic cytotoxicity was due to chloral hydrate.
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 lg/mL. Death was dose-and time-dependent, and was associated with formation of intracellular reactive oxygen species, and apoptosis significantly, at even 2 lg/mL concentration. The gene expression profile in A549 cells following 24 h exposure to 5 lg/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.
In vitro toxicity of surface water disinfected by different sequential treatments
Water Research, 2009
The in vitro toxicity of extracts of Hanjiang water disinfected by different sequential treatments was evaluated. Hanjiang water was disinfected using ozone, chloride dioxide or chlorine as the primary disinfectant followed by chlorine as the secondary disinfectant. HepG 2 cells were exposed to extracts corresponding to concentrations of 0.2, 1, 5, 25 and 125 mL water/mL medium. Compared with control, HepG 2 cells exposed to extracts of raw water and all disinfected water for 24 h increased oxidative stress level, DNA damage and micronuclei frequency, and decreased cell viability. Water disinfected by Cl 2 þ Cl 2 had the highest DNA double-strand breaks. All disinfected water and raw water increased micronuclei frequency via clastogenic and aneugenic effects. Oxidative stress induced DNA strand breaks and micronuclei frequency and therefore reduced cell viability either in disinfected water or raw water. Compared with raw water, water after disinfection increased DNA strand breaks, decreased cell viability and changed oxidative stress potential. Compared with chlorination, sequential treatment using O 3 or ClO 2 as primary disinfectant followed by chlorine disinfection reduced chlorinated by-products, DNA double-strand breaks and cell viability, but did not decrease micronuclei frequency and other DNA damage such as DNA single-strand break, alkali liable sites and incomplete excision sites. Sequential treatments did not significantly reduce in vivo toxicity of disinfected Hanjiang water.
Drowning in Disinfection Byproducts? Assessing Swimming Pool Water
Environmental Science & Technology, 2007
Disinfection is mandatory for swimming pools: public pools are usually disinfected by gaseous chlorine or sodium hypochlorite and cartridge filters; home pools typically use stabilized chlorine. These methods produce a variety of disinfection byproducts (DBPs), such as trihalomethanes (THMs), which are regulated carcinogenic DBPs in drinking water that have been detected in the blood and breath of swimmers and of nonswimmers at indoor pools. Also produced are halogenated acetic acids (HAAs) and haloketones, which irritate the eyes, skin, and mucous membranes; trichloramine, which is linked with swimmingpool-associated asthma; and halogenated derivatives of UV sun screens, some of which show endocrine effects. Precursors of DBPs include human body substances, chemicals used in cosmetics and sun screens, and natural organic matter. Analytical research has focused also on the identification of an additional portion of unknown DBPs using gas chromatography (GC)/mass spectrometry (MS) and liquid chromatography (LC)/MS/MS with derivatization. Children swimmers have an increased risk of developing asthma and infections of the respiratory tract and ear. A 1.6-2.0-fold increased risk for bladder cancer has been associated with swimming or showering/bathing with chlorinated water. Bladder cancer risk from THM exposure (all routes combined) was greatest among those with the GSTT1-1 gene. This suggests a mechanism involving distribution of THMs to the bladder by dermal/inhalation exposure and activation there by GSTT1-1 to mutagens. DBPs may be reduced by engineering and behavioral means, such as applying new oxidation and filtration methods, reducing bromide and iodide in the source water, increasing air circulation in indoor pools, and assuring the cleanliness of swimmers. The positive health effects gained by swimming can be increased by reducing the potential adverse health risks.
Assessment Of Bromochloroacetonitrile Formed As A Disinfection Byproduct in an HaCaT Cells
Bromochloroacetonitrile is a disinfection byproduct of water chlorination. We investigated, the cytotoxic effects of bromochloroacetonitrile in human keratinocyte cells. Cells were exposed to 5–80 µM bromochloroacetonitrile for 24 and 48 h. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and Lactate Dehydrogenase Leakage assays was used to evaluate cytotoxic effects. The changes in cellular Reactive Oxygen Species was determined. In addition, the effect of bromochloroacetonitrile on wound healing in cell culture was investigated by the scratch test. Concentration and time-dependent cytotoxicity was observed. Increasing concentrations of bromochloroacetonitrile have been observed to induce reactive oxygen species assay production in human keratinocyte cells. It was determined that concentrations of 5, 10 and 20 µM of bromochloroacetonitrile did not have a negative effect on wound healing, but when toxic concentrations of 40, 60 and 80 µM were increased, it had a slowing ...
2014
The introduction of drinking water disinfection greatly reduced the incidence of waterborne diseases. However, the reaction between disinfectants and natural or synthetic organic matter in the source water can lead to an unintended consequence which is the formation of drinking water disinfection by-products (DBPs). Many DBPs are mutagenic, cytotoxic, genotoxic, carcinogenic, or teratogenic. Studies on the molecular mechanisms of toxic effects induced by DBPs, and the overall toxicity of DBP complex mixtures are limited. The objectives of this dissertation were to i) analyze the occurrence and comparative toxicity of the emerging haloacetaldehyde (HAL) DBPs, ii) investigate the molecular mechanism of DBPinduced toxicity by the haloacetic acids (HAAs), iii) develop a single well microplate-based ATPprotein assay as a novel toxicity metric for DBPs, iv) investigate the occurrence and in vitro mammalian cell toxicity of DBPs in European drinking water samples collected from the site where epidemiological studies on reproductive outcomes were being conducted (HIWATE), and v) determine the impact of iodinated X-ray contrast media (ICM) in the source water and the type of disinfectant on the overall toxicity of DBP mixtures. From this study, iodoacetaldehyde was identified as a new DBP and ten HALs induced in vitro cytotoxicity and genotoxicity in Chinese hamster ovary (CHO) cells. HALs were the second most cytotoxic DBP class among six DBP chemical classes reported in the literature. Three mono-halogenated HAAs (monoHAA) including chloroacetic acid, bromoacetic acid, and iodoacetic acid induced ATP depletion in CHO cells, and cellular ATP levels was recovered when they were simultaneously treated with pyruvate. The magnitude of monoHAA-mediated ATP depletion highly correlated with the iii monoHAA-induced inhibition kinetics of GAPDH and with diverse measurements of toxicity including cytotoxicity, genotoxicity, mutagenicity and teratogenicity published in the literature. A novel single well microplate-based ATP-protein assay was developed and with this assay, monoHAAs showed the greatest reduction in ATP levels while diHAAs showed a moderate reduction with higher concentration ranges. TriHAAs induced increases in ATP levels. The occurrence and in vitro mammalian cell toxicity of DBPs in the HIWATE study was investigated. The cytotoxic potency index values significantly correlated with the total number of identified DBPs and also with the concentration of 21 target DBPs. The genotoxic potency index values were not correlated with either of these metrics or with any DBP chemical class. In the ICM study, Iopamidol generated an enhanced level of CHO cell cytotoxicity and genotoxicity after disinfection, and the relative Iopamidol-mediated increase in toxicity was greater when chloramines was used as the disinfectant compared with chlorine. Four other ICMs (Iopromide, Iohexol, Diatrizoate and Iomeprol) expressed some cytotoxicity over the control, and expressed higher cytotoxicity when chlorinated. Only Iohexol enhanced genotoxicity compared to the chlorinated source water. iv ACKNOWLEDGEMENT "... He said to me, "My grace is sufficient for you, for my power is made perfect in weakness." Therefore, I will boast all the more gladly about my weaknesses, so that Christ's power may rest on me.-2 Corinthians 12:9-" Heavenly Father, I give you thanks with all my heart. You are my solid rock, my fortress and my shepherd. My Ph.D. journey would not have been possible without the support and encouragement of so many people around me. First of all, I would like to express my deepest appreciation to my advisor, Professor Michael Plewa for his inspiration and guidance throughout my graduate study. I thank Dr. Elizabeth Wagner for all her help and guidance in the laboratory. I would also like to thank my doctoral committee members, Professor Benito Mariñas, Professor Jodi Flaws and Professor Susan Richardson, for their intellectual comments and encouragement. I thank my friends and colleagues in Dr. Plewa's laboratory group. Thank you, Yukako Komaki, Justin Pals, Jennifer Osiol and Azra Dad for your thoughtful comments, discussions and encouragements and for being a wonderful friend for me. I am very thankful to my family for their unending love and care. Mom, Dad, and Michaela, I love you all so much.