Inability of GSTT1 to activate iodinated halomethanes to mutagens in Salmonella.

Drinking water disinfection by-products (DBPs), including the ubiquitous trihalomethanes (THMs), are formed during the treatment of water with disinfectants (e.g., chlorine, chloramines) to produce and distribute potable water. Brominated THMs (Br-THMs) are activated to mutagens via glutathione S-transferase theta 1 (GSTT1); however, iodinated THMs (I-THMs) have never been evaluated for activation by GSTT1. Among the I-THMs, only triiodomethane (iodoform) has been tested previously for mutagenicity in Salmonella and was positive (in the absence of GSTT1) in three strains (TA98, TA100, and BA13), all of which have error-prone DNA repair (pKM101). We evaluated five I-THMs (chlorodiiodomethane, dichloroiodomethane, dibromoiodomethane, bromochloroiodomethane, and triiodomethane) for mutagenicity in Salmonella strain RSJ100, which expresses GSTT1, and its homologue TPT100, which does not; neither strain has pKM101. We also evaluated chlorodiiodo-, dichloroiodo-, and dibromoiodo-methanes in strain TA100 +/- rat liver S9 mix; TA100 has pKM101. None was mutagenic in any of the strains. The I-THMs were generally more cytotoxic than their brominated and chlorinated analogues but less cytotoxic than analogous trihalonitromethanes tested previously. All five I-THMs showed similar thresholds for cytotoxicity at ~2.5 µmoles/plate, possibly due to release of iodine, a well-known antimicrobial. Although none of these I-THMs was activated by GSTT1, iodoform appears to be the only I-THM that is mutagenic in Salmonella, only in strains deficient in nucleotide excision repair (uvrB) and having pKM101. Given that only iodoform is mutagenic among the I-THMs and is generally present at low concentrations in drinking water, the I-THMs likely play little role in the mutagenicity of drinking water.

Efficacy of eye drops containing crosslinked hyaluronic acid and CoQ10 in restoring ocular health exposed to chlorinated water.

PURPOSE: A prospective, open-label study in 20 professional swimmers evaluated the efficacy and safety of an ophthalmic solution containing crosslinked hyaluronic acid, coenzyme Q10, and vitamin E TPGS in releasing eye irritation and restoring ocular surface damages after prolonged exposure to chlorinated water. METHODS: Individually, one eye was instilled with the ophthalmic solution and the other used as a comparator. Eye drops were self-administered three times a day for 2 months. Tear film breakup time (primary endpoint), Schirmer I test, beating of eyelashes/min, tear osmolarity, corneal and conjunctival staining with fluorescein, Ocular Surface Disease Index questionnaire, subject satisfaction, visual acuity (secondary endpoints), and Efron Grading Scale were evaluated at screening/baseline (V1), week 1 (V2), week 2 (V3), week 4 (V4), and week 8 (V5). RESULTS: After 2 months, breakup time test significantly improved in the treated eyes (+1.67 s) compared to control (-3.00 s) (p = 0.0002). Corneal and conjunctival surfaces of treated eyes recovered significantly compared to control eyes when assessed by fluorescein staining (p < 0.0001), Ocular Surface Disease Index (p < 0.05), and visual analog scale (p = 0.0348) scores. Improvements were also observed with Schirmer I test, beating of eyelashes, and tear osmolarity, despite without statistical significance. Efron Grading Scale was consistent with the other tests. The ocular tolerability was excellent. CONCLUSION: The adequate combination of crosslinked hyaluronic acid, coenzyme Q10, and vitamin E TPGS, contained in the ophthalmic solution VisuXL®, has been shown to protect ocular surface from potential damages originating from prolonged exposure to chlorinated water. VisuXL may represent a compelling treatment in other situations beyond dry eye syndrome.

Methemoglobinemia Caused by Portable Dialysis in the Critically Ill.

OBJECTIVE: To evaluate the root cause of a series of methemoglobinemia cases in a medical ICU. RESULTS: We report a sentinel case of methemoglobinemia that was associated with dialysis sessions using a portable dialysis unit in our hospital. This led to the identification of four additional patients who developed methemoglobinemia while undergoing portable dialysis. We determined that these episodes were caused by inadequate clearance of chloramine from the tap water used for portable dialysis. Introduction of larger capacity carbon filters into the portable dialysis systems resulted in no further cases of methemoglobinemia at our institution. CONCLUSIONS: Clinicians should be aware of municipal tap water as a potential cause of methemoglobinemia and monitor for excessive levels of oxidants in dialysis water sources. The capacity of the hemodialysis equipment to clear chloramine can vary as a function of external factors. Using a reliable test method to identify chloramines in the water prior to entering the hemodialysis equipment is essential.

Prick testing with chemicals in the diagnosis of occupational contact urticaria and respiratory diseases.

BACKGROUND: Little is known about the use of prick tests with chemicals in diagnosing occupational diseases. OBJECTIVE: To evaluate the use of prick tests in the diagnosis of occupational contact urticaria, asthma and rhinitis caused by chemicals (undertaken at the Finnish Institute of Occupational Health). MATERIAL AND METHODS: We retrospectively reviewed the patient and test files for the period 1 January 1991 to 31 May 2011. Prick tests were performed with chemical solutions and human serum albumin (HSA)-chemical conjugates. RESULTS: Positive prick test reactions to isocyanate-HSA conjugates were associated with isocyanate-specific IgE in all 20 patients, and 17 patients had a relevant occupational disease. Positive reactions to chloramine-T-HSA conjugates in 10 patients also indicated the presence of specific IgE, although occupational diseases were not always diagnosed. Eleven of 17 patients with positive reactions to persulfate solutions were diagnosed with an occupational disease. Methacrylates, colophonium-related substances, amine hardeners, ethanolamines, glutaraldehyde, glyoxal, pyrocatechol and ammonium thioglycolate did not elicit any relevant prick test reactions. No generalized reactions were detected. CONCLUSION: Prick tests can be safely used for diagnosing contact urticaria, asthma and rhinitis caused by isocyanates, chloramine-T, persulfates, and chlorhexidine, but the results should be carefully interpreted and related to clinical symptoms and other diagnostic tests.

Inhalation exposure to chloramine T induces DNA damage and inflammation in lung of Sprague-Dawley rats.

Chloramine T has been widely used as a disinfectant in many areas such as kitchens, laboratories and hospitals. It has been also used as a biocide in air fresheners and deodorants which are consumer products; however, little is known about its toxic effects by inhalation route. This study was performed to identify the subacute inhalation toxicity of chloramine T under whole-body inhalation exposure conditions. Male and female groups of rats were exposed to chloramine T at concentrations of 0.2, 0.9 and 4.0 mg/m³ for 6 hr/day, 5 days/week during 4 weeks. After 28-day repeated inhalation of chloramine T, there were dose-dependently significant DNA damage in the rat tissues evaluated and inflammation was histopathologically noted around the terminal airways of the lung in both genders. As a result of the expression of three types of antioxidant enzymes (SOD-2, GPx-1, PRX-1) in rat's lung after exposure, there was no significant change of all antioxidant enzymes in the male and female rats. The results showed that no observed adverse effect level (NOAEL) was 0.2 mg/m³ in male rats and 0.9 mg/m³ in female rats under the present experimental condition.

Effects of two water disinfectants (chloramine T and peracetic acid) on the epidermis and gills of Garra rufa used in human ichthyotherapy.

Doctor fish (Garra rufa) have recently been used for aesthetic purposes and as a medical treatment in patients with psoriasis (ichthyotherapy). For this particular kind of human therapy it is essential to guarantee adequate hygienic conditions for both people and fish. The aim of this study was to test two concentrations of water disinfectants, chloramine T and peracetic acid, on Garra rufa to ascertain possible exposure damage to the epidermis and gills. Fish were exposed to 2 mg/l and 10 mg/l of chloramine T and to 15 microl/l and 45 microl/l of peracetic acid in a 40-minute static bath up to six times a day for one week. The epidermis and gills were checked for histological changes and the number of epidermal mucous cells, club cells and taste buds were quantified; mucous cells were also characterized histochemically to detect alterations in mucin production. No mortality or severe histological changes were found in treated or control fish. Cell count showed a significant increase (p < 0.05) in mucous cells (mean 49.1 +/- 6.7 vs 37.0 +/- 13.1 of controls) in animals treated with peracetic acid independently of the dose. Club cell number showed a significant (p < 0.05) decrease in fish treated with 2 mg/l of chloramine T (mean 74.3 +/- 15.6) and with 45 microl/1 of peracetic acid (mean 78.17 +/- 10.5) compared to controls (mean 107.0 +/- 19.2). Histochemical evaluation of mucous cells did not reveal changes in mucin type in fish exposed to the two disinfectants. The results suggest a good tolerability of Garra rufa to the two disinfectants at the concentrations tested.

Monochloramine use for prevention of Legionella in hospital water systems.

Eradication of Legionella species from water distribution systems especially in hospital settings has proven to be challenging. Legionella species causes Legionnaire's disease that is a potentially fatal respiratory disease often acquired through the aerosolization of contaminated water. Monochloramine has been used successfully in the municipal water systems to eradicate Legionella and there is currently limited data to support its use in the hospital setting. This technology appears to be affordable, safe and effective at penetrating biofilm in water distribution systems.

Exercise but not mannitol provocation increases urinary Clara cell protein (CC16) in elite swimmers.

Elite swimmers have an increased risk of developing asthma, and exposure to chloramine is believed to be an important trigger factor. The aim of the present study was to explore pathophysiological mechanisms behind induced bronchoconstriction in swimmers exposed to chloramine, before and after swim exercise provocation as well as mannitol provocation. Urinary Clara cell protein (CC16) was used as a possible marker for epithelial stress. 101 elite aspiring swim athletes were investigated and urinary samples were collected before and 1 h after completed exercise and mannitol challenge. CC16, 11ß-prostaglandin (PG)F(2α) and leukotriene E(4) (LTE(4)) were measured. Urinary levels of CC16 were clearly increased after exercise challenge, while no reaction was seen after mannitol challenge. Similar to CC16, the level of 11ß-PGF(2α) was increased after exercise challenge, but not after mannitol challenge, while LTE(4) was reduced after exercise. There was no significant difference in urinary response between those with a negative compared to positive challenge, but a tendency of increased baseline levels of 11ß-PGF(2α) and LTE(4) in individuals with a positive mannitol challenge. The uniform increase of CC16 after swim exercise indicates that CC16 is of importance in epithelial stress, and may as such be an important pathogenic factor behind asthma development in swimmers. The changes seen in urinary levels of 11ß-PGF(2α) and LTE(4) indicate a pathophysiological role in both mannitol and exercise challenge.

When pure is not so pure: chloramine-related hemolytic anemia in home hemodialysis patients.

Worldwide, chloramines are used as the preferred disinfectant for city water supplies. Although they have distinct advantages compared with chlorine and are deemed harmless to the general population, hemodialysis (HD) patients are at risk from chloramine-induced hemolytic anemia. In recent years, this has been highlighted in regional dialysis units but not as frequently in the home HD group. We report on 2 home HD patients who succumbed to severe oxidative hemolysis due to high mains water chloramine concentrations. Both patients were extensively investigated for other cause of anemia before a definitive diagnosis was reached. Delays in diagnosing this uncommon condition can be costly in terms of significant morbidity and excessive usage of recombinant erythropoietin and blood transfusion. Prevention primarily involves enforcing strict water quality control and establishing regular communication with water supply boards and home HD patients. Double (inline) carbon filters should be installed in patient's homes as an effective means for removing high incoming chloramine concentrations.

[Asthma induced by chloramine T in nurses: case report]. / Asma da cloramina T nel personale sanitario: descrizione di un caso.

BACKGROUND: Chloramine T is used in hospitals as a disinfectant and for sterilization of endoscopy instruments. OBJECTIVES: A case of a nurse suffering from asthma due to Chloramine T is presented in order to focus attention on this occupational disease. METHODS AND RESULTS: The patient (male, 43 years) had been a nurse since 1993, working in various departments and operating rooms where he was exposed to glutaraldehyde and Chloramine T to disinfect surgical and endoscopy instruments. In 2007 he noticed the beginning of asthmatic reactions after exposure to the disinfectant. Skin tests with common allergens gave positive reactions and a skin test with Chloramine T gave a positive result. An inhalation test with glutaraldehyde gave negative results for both asthma and rhinitis. During the inhalation test with Chloramine T 0.5%, a significant biphasic decrease in FEVI was observed. The score of subjective symptoms for rhinitis was negative, CONCLUSIONS: The case confirms the current difficulty in diagnosing occupational asthma due to Chloramine T in health care workers, which is due to the frequent presence of late reactions and to exposure to several respiratory allergens and irritants in the workplace. The specific inhalation challenge is thus confirmed as the gold standard for the diagnosis of asthma induced by Chloramine T and in occupational asthma in general. It may very well be that the frequency of occupational asthma due to sensitization to Chloramine T in nurses is underestimated.

[Genotoxicity of drinking water during chlorine and chloramine disinfection and the influence of disinfection conditions using the umu-test].

In this study, the effects of disinfectant dosage, reaction time and the ratio of Cl2 to N of disinfectant on genotoxicity of effluent of ozone-biological activated carbon (O3-BAC) during chlorine or chloramine disinfection were investigated using umu-test. It was found that, the genotoxicity of effluent of O3-BAC before disinfection ranged from 20-70 ng/L, and it increased after disinfection by chlorine or chloramines. With the same reaction time(24 h), genotoxicity after chlorination (40-95 ng/L) was higher than that after chloramination (20-40 ng/L) under same initial dosage. For chlorination, with initial dosage increasing from 0 mg/L to 10 mg/L, genotoxicity increased firstly, and got the maximum value at about 0.5-1 mg/L dosage, then decreased and got the minimum value at about 3-5 mg/L dosage, and finally increased again. For chloramination, genotoxicity didn't change that much. With the dosage of 3 mg/L and reaction time increasing from 0 h to 72 h, no matter for chlorine or chloramines disinfection, genotoxicity of effluent of O3-BAC both increased firstly, and got the maximum value at about 2 h, then decreased and got the minimum value at about 18 h, and finally increased again, and genotoxicity after chlorine disinfection (83-120 ng/L) was higher than that after chloramines disinfection (20-62 ng/L) under same reaction time. Further more, effects of the different ratios of Cl2 to N of disinfectant on genotoxicity of effluent of O3-BAC were also studied. Results of this study demonstrate that under test conditions, chloramine disinfection is safer than chlorine disinfection in the aspect of genotoxicity for drinking water, and the changes of genotoxicity are different from those of total HAAs.

Ocular and respiratory symptoms among lifeguards at a hotel indoor waterpark resort.

OBJECTIVES: To determine the cause of eye and respiratory irritation symptoms among lifeguards at an indoor waterpark. METHODS: Investigators 1) performed environmental sampling for chloramine, endotoxin, and microbials; 2) administered symptom questionnaires; 3) reviewed ventilation system designs; and 4) reviewed water chemistry. RESULTS: Airborne trichloramine concentrations were found at levels reported to cause irritation symptoms in other studies. Some endotoxin concentrations were found at levels associated with cough and fever in previous studies. Exposed lifeguards were significantly more likely to report work-related irritation symptoms than unexposed individuals. The ventilation system may not have provided sufficient air movement and distribution to adequately capture and remove air contaminants at deck level. No water microbes were detected, and water chemistry met state standards. CONCLUSIONS: Indoor waterparks need to control water chemistry and ensure adequate air movement and distribution to control air contaminants and reduce health symptoms.

[Disinfection by-products reduction of combined disinfection by chlorine and monochloramines in distribution system].

Halogen disinfection by-products of four chlorined disinfection processes with long contact time in distribution system was compared in the work. These four disinfection processes are free chlorine, monochloramines, free chlorine disinfection in clearwelles while chloramines in distribution system, sequential chlorination disinfection with short-term free chlorine plus chloramines. According to the research, free chlorine generates most trihalomethanes (THMs) and haloacetic acids (HAAs) both in clearwells and distribution system, while monochloramines barely yield halogen DBPs. Free chlorine disinfection in clearwelles while chloramines in distribution system could reduce 9.6% of THMs and 42% of HAAs in 24 h contact time of distribution system compared with free chlorine. But free chlorine has contacted with water for 2 h in this process, halogen DBPs have been yielded substantially. Process of sequential chlorination disinfection could control DBPs more effectively due to keeping a short contact time of free chlorine and water. 48% of THMs and 72% of HAAs are reduced in 24h compared with free chlorine. In conclusion, sequential chlorination disinfection is a more effective disinfection process for controlling DBPs and water safety.

Dechlorination by ultraviolet radiation: a suitable alternative to activated carbon in dialysis water systems?

Chlorine-based products are widely used in the water supply industry, and the potential for adverse effects in the haemodialysis setting is well documented. To date, the most commonly used method of chlorine removal has been granular activated carbon filters. An increasingly popular method of dechlorination is the use of high intensity, broad-spectrum UV systems to reduce both free chlorine and combined chlorine compounds (chloramines) into easily removed by-products. UV radiation has been successfully used in the pharmaceutical and food industries to destroy free chlorine and/or chloramines present in water, and kill all known spoilage microorganisms including bacteria, viruses, yeasts and moulds (and their spores). This nonchemical method can offer significant advantages and benefits compared to conventional dechlorination technologies currently employed in dialysis water systems. Whilst UV treatment at 254 nm wavelength has been routinely used for disinfection purposes in dialysis water systems, this paper considers whether UV radiation can be used as an alternative to more traditional methods of chlorine removal.

Warning: an anemia outbreak due to chloramine exposure in a clean hemodialysis unit--an issue to be revisited.

In July 2004, an anemia outbreak was identified in our hemodialysis (HD) unit. The dialysate chloramine levels had risen from <0.1 mg/mL in May to 0.27 mg/mL in August 2004. Other parameters of water quality were within accepted standards. Hematocrit (Ht) and hemoglobin (Hb) returned to basal values after one month without changing recombinant human erythropoetin (rHuEpo) doses and with exchange of activated charcoal column. Chloramines (chlorine and ammonia) are used routinely to disinfect and sterilize potable water. High blood levels of chloramines are associated with hemolysis and rarely methemoglobinemia. Uremic patients have a decreased ability to withstand oxidative stress. It is postulated that their antioxidant capacity is reduced, yet the mechanism remains unclear. Patients on maintenance hemodialysis are vulnerable to chloramine toxicity if chloramines are inadequately removed from water.