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BackgroundPreservatives are often necessary components of commercial products. Large-scale North American studies on preservative allergy are limited.ObjectiveTo evaluate demographics, positive patch test reactions (PPTRs), clinical relevance, and trends for preservatives tested by the North American Contact Dermatitis Group.MethodsWe conducted a retrospective cross-sectional analysis of North American Contact Dermatitis Group patch testing results of preservatives from 1994 through 2016.ResultsA total of 50,799 patients were tested; 11,338 (22.3%) had a PPTR to at least 1 preservative. The most frequent reactions were to methylisothiazolinone 0.2% aqueous (aq) (12.2%), formaldehyde 2% aq (7.8%), formaldehyde 1% aq (7.8%), quaternium-15 2% petrolatum (pet) (7.7%), and methyldibromo glutaronitrile/phenoxyethanol 2% pet (5.1%). Paraben mix 12% pet (1%), iodopropynyl butylcarbamate 0.1% pet (0.4%), benzyl alcohol 1% pet (0.3%), and phenoxyethanol 1% pet (0.2%) had the lowest PPTRs. Linear regression analysis of preservatives tested showed that only methylchloroisothiazolinone/methylisothiazolinone 0.01% aq (parameter estimate, 0.42; 95% CI, 0.17-0.66; P

Background: Most occupational skin disease (OSD) is caused by contact dermatitis which affects workplace productivity, quality of life (QoL) and is associated with a substantial economic burden. We report on whether there have been any emerging workplace allergens identified over the past six years. Methods: A retrospective study was performed using de-identified data obtained from patients assessed at our Occupational Dermatology Clinic in Melbourne, Victoria, Australia from 2017 to 2022. Patch-testing was performed to identify allergens causing allergic contact dermatitis (ACD). Results: Of a total of 657 patch-tested patients, ACD (151/298, 50.3%) was the most common diagnosis in those with significant work-related skin conditions,. The top occupational groups affected were healthcare workers (HCW) (29%; 45/151), trade workers (25.2%; 38/151) and health-and-beauty workers (13.2%; 20/151). The most common allergens were rubber chemicals, particularly thiurams. The next most common were the preservatives such as methylchloroisothiazolinone (MCI) and methylisothiazolinone (MI). Conclusion: Rubber chemicals remain the most common occupational allergens followed by MCI and MI. HCW were the largest affected occupational group. Despite occasional case reports of new allergens, no major change in the causes of OCD was detected. Where possible, workplaces should provide allergen-free products to reduce the risk of developing ACD. [ABSTRACT FROM AUTHOR]

Isothiazolinone preservatives (methylisothiazolinone (MIT) and methylchloroisothiazolinone (CMIT) are commonly used in cosmetics, industrial and household products. However, these isothiazolinone derivatives are known to cause allergic contact dermatitis. Hence, a sensitive, accurate, and reliable method for the detection of these compounds is thus warranted. The study aims to analyze concentrations of MIT and CMIT by high performance liquid chromatography. The analytical method used for quantification of MIT and CMIT in cosmetic products (leave-on-baby wet wipes) complies with the validation acceptance criteria (international standards ISO 5725, EU25 European Union for cosmetic regulations). MIT and CMIT were extracted and analyzed in leave-on baby wet-wipes collected from different stores in Riyadh city. Extraction was performed by ultrasonication of the samples, solid-phase extraction, and liquid-liquid extraction. Ten (10) µL of the sample was injected into the HPLC system and samples were analyzed with a mixture of acetic acid and methanol (80:20 v/v) in an isocratic mode. The flow rate was maintained at 1 mL/min. UV detection was performed at 274 nm. The results demonstrated recoveries between 90 and 106%, measurement uncertainty of C +/− 0.4% for methylisothiazolinone and C +/− 0.03% for methylchloroisothiazolinone, repeatability limit (r = 0.2%) and intermediate precision limit; R = 2% and R2 of 0.9996. [ABSTRACT FROM AUTHOR]

The electrochemical properties of methylisothiazolinone (MIT), the most widely used preservative, were investigated by cyclic (CV) and differential pulse voltammetry (DPV) to develop a new method for its determination. To our knowledge, this is the first demonstration of a voltammetric procedure for the determination of MIT on a boron-doped diamond electrode (BDDE) in a citrate–phosphate buffer (C-PB) environment. The anodic oxidation process of methylisothiazolinone, which is the basis of this method, proved to be diffusion-controlled and proceeded with an irreversible two-electron exchange. The radical cations, as unstable primary products, were converted in subsequent chemical reactions to sulfoxides and sulfones, and finally to more stable final products. Performed determinations were based on the DPV technique. A linear calibration curve was obtained in the concentration range from 0.7 to 18.7 mg L−1, with a correlation coefficient of 0.9999. The proposed procedure was accurate and precise, allowing the detection of MIT at a concentration level of 0.24 mg L−1. It successfully demonstrated its suitability for the determination of methylisothiazolinone in household products without the need for any separation steps. The proposed method can serve as an alternative to the prevailing chromatographic determinations of MIT in real samples. [ABSTRACT FROM AUTHOR]

In recent years, personal care products (PCPs) have surfaced as a novel class of pollutants due to their release into wastewater treatment plants (WWTPs) and receiving environments by sewage effluent and biosolid-augmentation soil, which poses potential risks to non-target organisms. Among PCPs, there are preservatives that are added to cosmetics for protection against microbial spoilage. This paper presents a review of the occurrence in different environmental matrices, toxicological effects, and mechanisms of microbial degradation of four selected preservatives (triclocarban, chloroxylenol, methylisothiazolinone, and benzalkonium chloride). Due to the insufficient removal from WWTPs, cosmetic preservatives have been widely detected in aquatic environments and sewage sludge at concentrations mainly below tens of µg L-1. These compounds are toxic to aquatic organisms, such as fish, algae, daphnids, and rotifers, as well as terrestrial organisms. A summary of the mechanisms of preservative biodegradation by micro-organisms and analysis of emerging intermediates is also provided. Formed metabolites are often characterized by lower toxicity compared to the parent compounds. Further studies are needed for an evaluation of environmental concentrations of preservatives in diverse matrices and toxicity to more species of aquatic and terrestrial organisms, and for an understanding of the mechanisms of microbial degradation. The research should focus on chloroxylenol and methylisothiazolinone because these compounds are the least understood. [ABSTRACT FROM AUTHOR]

The degradation of various preservatives used in the cosmetics industry, including five parabens and their most employed substitute, methylisothiazolinone (MIT), was investigated. A mild photo-Fenton process was applied using low iron concentrations (5 mg/L) at a pH of five, instead of the traditional acidic value of three. At these conditions, the paraben degradation was very low after one hour of reaction and it was necessary to present humic-like substances (HLS) acting as iron chelators to improve the process. Values obtained when MIT was treated were very low, also in the presence of HLS, indicating that their complexing effect was not acting properly. When MIT was added to the mixture of parabens an inhibitory effect was found in the presence of HLS. A possible complex between iron and MIT was suggested and the studies of hydrogen peroxide consumption and Job's plot technique confirmed this hypothesis. Evidence of the formation of this inactive complex, so far never reported, will be essential in future work when dealing with this compound using Fenton processes. Furthermore, this fact points out the importance of using mixtures of model contaminants instead of a single one or a group of the same family, since their ability to form active or inactive complexes with iron can strongly change the behavior of the whole system. [ABSTRACT FROM AUTHOR]

5-Chloro-2-methyl-4-isothiazolin-3-one (CMIT) and 2-methyl-4-isothiazolin-3-one (MIT) used as preservatives in various products, including humidifier disinfectants, presents substantial health hazards. This research delves into the toxicological assessments of CMIT/MIT in the respiratory system using animal models. Through the synthesis of radiolabeled [14C]CMIT and [14C]MIT, we investigated the biological uptake and in vivo behaviors of CMIT/MIT in the respiratory tissues following intratracheal exposure. Quantitative whole-body autoradiography (QWBA) revealed significant persistence of CMIT/MIT in lung tissue. In addition, radio high-performance liquid chromatography (radio-HPLC) with tandem mass spectrometry (LC-MS/MS) was employed for metabolite profiling and identification. Notably, around 28% of the radiolabel was retained in tissue after the extraction step, suggesting covalent binding of CMIT/MIT and their metabolites with pulmonary biomolecules. This observation demonstrates the propensity of the electrophilic isothiazolinone ring in CMIT/MIT to undergo chemical interactions with biothiols in proteins and enzymes, fostering irreversible alterations of biomolecules. Such accumulations of transformations could result in direct toxicity at both cellular and organ levels. Additionally, the detection of metabolites, including a MIT dimer conjugated with glutathione (GSH), as analyzed by mass spectrometry indicates the possible reduction of cellular GSH levels and subsequent oxidative stress. This investigation offers an in-depth insight into the toxic mechanisms of CMIT/MIT, underlying their capability to engage in complex formations with biomacromolecules and induce pronounced respiratory toxicity. These results highlight the imperative for stringent safety assessments of these chemicals, advocating for improved public health and safety measures in the use of chemicals. [Display omitted] • The radiolabeled CMIT and MIT were synthesized using radioactive carbon (14C). • The SUV of CMIT/MIT in lung was determined to be 6.01 after 0.083 h post exposure. • In the analysis of metabolites, the parent structures of CMIT/MIT were not observed. • Some metabolites were found to be conjugated with glutathione. • Approximately 28% of the radiolabel was bound to pulmonary biomolecules. [ABSTRACT FROM AUTHOR]

A variety of isothiazolinone-containing small molecules have been registered and used as chemical additives in many household products. However, their biodistribution and potential harmful effects on human health, especially respiratory effects, were not yet identified in sufficient detail. The purpose of this study was to investigate whether a biocide comprising a mixture of chloromethylisothiazolinone (CMIT) and methylisothiazolinone (MIT) could reach the lungs and induce lung injury when exposure occurs by two administration routes involving the respiratory tract: intratracheal and intranasal instillation. To investigate the biodistribution of CMIT/MIT, we quantified the uptake of 14C-labeled CMIT/MIT in experimental animals for up to seven days after intratracheal and intranasal instillation. In the toxicity study, lung injury was assessed in mice using total inflammatory cell count in bronchoalveolar lavage fluid (BALF) and lung histopathology. The results of the biodistribution study indicated that CMIT/MIT were rapidly distributed throughout the respiratory tract. Using quantitative whole-body autoradiogram analysis, we confirmed that following intranasal exposure, CMIT/MIT reached the lungs via the respiratory tract (nose–trachea–lung). After 5 min post intratracheal and intranasal instillation, the amount of radiotracer ([14C]CMIT/MIT) in the lungs was 2720 ng g−1 and 752 ng g−1 tissue, respectively, and lung damage was observed. A higher amount of the radiotracer resulted in higher toxicity. Both intratracheal and intranasal instillation of CMIT/MIT increased inflammatory cell counts in the BALF and induced injuries in the alveoli. The frequency and the severity scores of injuries caused by intratracheal instillation were approximately-four to five times higher than those induced by intranasal instillation. Therefore, we concluded that CMIT/MIT could reach the lungs following nasal and intratracheal exposure and cause lung injuries, and the extent of injury was dependent on the exposure dose.

Isothiazolinones, used as preservative, are known to be skin sensitizers. Although cosmetics represent their main source, occupational exposure may be a significant origin of eczema. While allergic eczema related to these derivates have been reported in a number of professional sectors, their presence in the same workplace was not common. Isothiazolinones are commonly known as skin sensitizers in both domestic and workplace areas. Rubber manufacturing should be considered as a possible occupational exposure to isothiazolinones. This consideration will facilitate further declaration and recognition of allergic dermatitis related to these substances in this specific workplace. [ABSTRACT FROM AUTHOR]

Abstract Isothiazolinones, used as preservative, are known to be skin sensitizers. Although cosmetics represent their main source, occupational exposure may be a significant origin of eczema. While allergic eczema related to these derivates have been reported in a number of professional sectors, their presence in the same workplace was not common.

Methylisothiazolinone (MI) is commonly used as a preservative in personal care products and is a frequent cause of allergic contact dermatitis. Wepresent a patient with allergic contact dermatitis caused by MI in hair care products and discuss this allergen to bring attention to this common cause ofcontact dermatitis, and to highlight its frequent use in hair care products. If allergy to MI is suspected, testing should be performed to this individual preservative, as testing solely for the combination preservative,methylisothiazolinone/methylchloroisothiazolinone (Kathon CG®), may miss many cases of MI allergy.

Isothiazolinone preservatives (methylisothiazolinone (MIT) and methylchloroisothiazolinone (CMIT) are commonly used in cosmetics, industrial and household products. However, these isothiazolinone derivatives are known to cause allergic contact dermatitis. Hence, a sensitive, accurate, and reliable method for the detection of these compounds is thus warranted. The study aims to analyze concentrations of MIT and CMIT by high performance liquid chromatography. The analytical method used for quantification of MIT and CMIT in cosmetic products (leave-on-baby wet wipes) complies with the validation acceptance criteria (international standards ISO 5725, EU25 European Union for cosmetic regulations). MIT and CMIT were extracted and analyzed in leave-on baby wet-wipes collected from different stores in Riyadh city. Extraction was performed by ultrasonication of the samples, solid-phase extraction, and liquid-liquid extraction. Ten (10) µL of the sample was injected into the HPLC system and samples were analyzed with a mixture of acetic acid and methanol (80:20 v/v) in an isocratic mode. The flow rate was maintained at 1 mL/min. UV detection was performed at 274 nm. The results demonstrated recoveries between 90 and 106%, measurement uncertainty of C +/− 0.4% for methylisothiazolinone and C +/− 0.03% for methylchloroisothiazolinone, repeatability limit (r = 0.2%) and intermediate precision limit; R = 2% and R2 of 0.9996.

Background Isothiazolinones are preservatives which are present in cosmetics, household chemicals and many other industrial products. Initially, a mixture of methylchloroisothiazolinone and methylisothiazolinone (MCI/MI – Kathon CG) was used, and then, from the beginning of the 21st century, only methylisothiazolinone. Due to a significant increase in the number of contact dermatitis caused by allergy to this compound, it was withdrawn from leave-on cosmetics, and its concentration in rinse-off cosmetics was reduced. The aim of the study was to analyze the incidence of contact allergy to isothiazolinones among patients in the Nofer Institute of Occupational Medicine, Łódź, the intensification of patch test results and hypersensitivity depending on the occupation, and to assess the contribution of immediate allergy to the occurrence of that hypersensitivity. Material and Methods In a group of 1137 patients (832 females and 305 males) with suspected contact dermatitis, diagnosed in 2014–2018, patch tests series including methylchloroisothiazolinone/methylisothiazolinone (0.01%) and methylisothiazolinone (0.2%), produced by Chemotechnique Diagnostics, Sweden, were performed. In a group of 29 individuals with contact allergy to isothiazolinones, prick tests with methylisothiazolinone (0.001%, 0.01%, 0.1%, 1%) (Sigma-Aldrich, Germany) were conducted. Results Of the 1137 subjects, 95 (8.3%) were allergic to isothiazolinones, slightly more often females – 71 (8.5%) than males – 24 (7.9%). In total, 150 positive patch tests with isothiazolinones (13.2%) were obtained. The number of positive results with methylisothiazolinone alone (7.8%) was higher than the number with methylisothiazolinone from Kathon CG (5.4%). Among the subjects sensitized to methylisothiazolinone alone strongly positive patch tests (+++) concerned 60.7%. In the female group, office workers (42.3%) and medical staff (18.3%) predominated, and in the male group – locksmiths, turners, mechanics and similar ones (45.8%), and construction workers (25.0%). Prick tests with methylisothiazolinone were negative, and they became positive after 3–5 h. Conclusions Isothiazolinones, particularly methylisothiazolinone, are significant causal factors of contact allergy, including that of occupational origin. They have strongly allergenic properties, and in patch tests they often give very severe inflammatory reactions. The issue of the role of immediate allergy in the pathogenesis of isothiazolinones sensitization requires further research. Med Pr. 2020;71(5):603–11

The electrochemical properties of methylisothiazolinone (MIT), the most widely used preservative, were investigated by cyclic (CV) and differential pulse voltammetry (DPV) to develop a new method for its determination. To our knowledge, this is the first demonstration of a voltammetric procedure for the determination of MIT on a boron-doped diamond electrode (BDDE) in a citrate–phosphate buffer (C-PB) environment. The anodic oxidation process of methylisothiazolinone, which is the basis of this method, proved to be diffusion-controlled and proceeded with an irreversible two-electron exchange. The radical cations, as unstable primary products, were converted in subsequent chemical reactions to sulfoxides and sulfones, and finally to more stable final products. Performed determinations were based on the DPV technique. A linear calibration curve was obtained in the concentration range from 0.7 to 18.7 mg L−1, with a correlation coefficient of 0.9999. The proposed procedure was accurate and precise, allowing the detection of MIT at a concentration level of 0.24 mg L−1. It successfully demonstrated its suitability for the determination of methylisothiazolinone in household products without the need for any separation steps. The proposed method can serve as an alternative to the prevailing chromatographic determinations of MIT in real samples.

The degradation of various preservatives used in the cosmetics industry, including five parabens and their most employed substitute, methylisothiazolinone (MIT), was investigated. A mild photo-Fenton process was applied using low iron concentrations (5 mg/L) at a pH of five, instead of the traditional acidic value of three. At these conditions, the paraben degradation was very low after one hour of reaction and it was necessary to present humic-like substances (HLS) acting as iron chelators to improve the process. Values obtained when MIT was treated were very low, also in the presence of HLS, indicating that their complexing effect was not acting properly. When MIT was added to the mixture of parabens an inhibitory effect was found in the presence of HLS. A possible complex between iron and MIT was suggested and the studies of hydrogen peroxide consumption and Job’s plot technique confirmed this hypothesis. Evidence of the formation of this inactive complex, so far never reported, will be essential in future work when dealing with this compound using Fenton processes. Furthermore, this fact points out the importance of using mixtures of model contaminants instead of a single one or a group of the same family, since their ability to form active or inactive complexes with iron can strongly change the behavior of the whole system.

A myasthenic crisis denotes a severe exacerbation of myasthenia gravis, leading a patient to enter a life-threatening state due to progressing muscle weakness that ultimately results in respiratory failure. A crisis can require intubation, mechanical ventilation, and additional critical care to prevent further decompensation and potentially death. Numerous well-documented precipitating factors exist, such as infections, surgery, stress, and various medications. We present the case of a 43-year-old woman recently diagnosed with myasthenia gravis who has experienced two myasthenic crises since diagnosis without evident triggers such as surgery, changes in medication, or infection. Following an unremarkable initial diagnostic test and continued treatment for the crisis, we sought additional information from the patient's family member at the bedside. We were informed that two weeks prior to both times of crisis with intubation, the patient had dyed her hair blue. The common chemical component in the two different hair dyes used was methylisothiazolinone, which is suspected to have contributed to the exacerbation of the patient's myasthenia gravis. As more evidence for new precipitating factors of myasthenic crises develops, it is crucial for physicians to quickly identify signs and symptoms of a crisis so appropriate intervention can occur in a time-sensitive manner. In addition, myasthenia gravis patients should be made aware to be cautious of precipitating factors of a crisis, including but not limited to new beauty products., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2024, Gomez Rosado et al.)

Background: Preservatives are widely used in personal and industrial products. Frequent and sustained exposure to preservatives can cause contact allergy. Objective: We investigated the prevalence of contact allergic reactions to common preservatives in Taiwan over a 20-year period. Methods: A retrospective analysis was conducted among patients with allergic contact dermatitis who underwent patch testing at our clinic between 1996 and 2015. Patients who showed positive reactions to preservatives were enrolled. The location of the reaction, likely source of the allergen, and patient occupation, sex, and age were recorded. Thirteen common preservatives, including methylchloroisothiazolinone/methylisothiazolinone (MCI/MI), MI, formaldehyde (FA), paraben mix, and quaternium-15, were investigated. Results: Of 757 enrolled patients, 151 showed at least one positive reaction to preservatives. Allergy to MCI/MI (12.5%), the most frequent allergen in the standard series, showed a steeply increasing trend over time. FA (4.8%) and paraben mix (2.1%) were the next common allergens. Cosmetic products were the most common source of exposure (63.6%), while hairdressers and massage therapists were most commonly associated with occupational contact dermatitis. A sharp increase of sensitivity to MCI/MI was observed after 2006 and that of allergy to MI after 2013. Conclusions: In Taiwan, the prevalence of contact allergy to MCI/MI, MI, and parabens has increased in recent years. Individuals who are frequently exposed to cosmetic products should consider precautions against sensitization.

Background: The epidemiological surveillance of contact dermatitis is one of the objectives of the Spanish Registry of Research in Contact Dermatitis and Cutaneous Allergy. Knowing whether the prevalence of positive tests to the different allergens changes over time is important for this monitoring process., Objectives: To describe the various temporary trends in allergen positivity in the GEIDAC standard series from 2018 through December 31, 2022., Methods: This was a multicenter, observational trial of consecutive patients analyzed via patch tests as part of the study of possible allergic contact dermatitises collected prospectively within the Spanish Registry of Research in Contact Dermatitis and Cutaneous Allergy. The data was analyzed using 2 statistical tests: one homogeneity test (to describe the changes seen over time) and one trend test (to see whether the changes described followed a linear trend)., Results: A total of 11327 patients were included in the study. Overall, the allergens associated with a highest sensitization were nickel sulfate, methylisothiazolinone, cobalt chloride, methylchloroisothiazolinone/methylisothiazolinone, and fragrance mix i. A statistically significant decrease was found in the percentage of methylisothiazolinone positive tests across the study years with an orderly trend., Conclusions: Although various changes were seen in the sensitizations trends to several allergens of the standard testing, it became obvious that a high sensitization to nickel, methylchloroisothiazolinone/methylisothiazolinone and fragrances mix i remained. Only a significant downward trend was seen for methylisothiazolinone., (Copyright © 2023 AEDV. Publicado por Elsevier España, S.L.U. All rights reserved.)

The disposal of reverse osmosis (RO) concentrate (ROC) is a critical challenge impeding the application of RO-based wastewater reclamation. Herein, we proposed an enhanced biotreatment approach for the simultaneous removal of nitrogen, phosphorous, hardness, and methylisothiazolinone (MIT) from ROC by suspended-solid phase cultivation of Scenedesmus sp. LX1. Repeated carrier addition, guided by the developed optimal carrier addition model, efficiently enhanced algal growth and contaminant removal through dynamically controlling the suspended algal density by cell attachment. The maximum algal growth rate (212.2 mg/(L∙d)) increased by 41% compared with the control, and the time needed for reaching the maximum algal biomass (906.7 mg/L) was shortened by 1 d, attributing to the mitigation of density restriction. 91.8% of nitrogen (30.2 mg/L) was removed with 5.5 mg/(L∙d) accelerating removal rate, and phosphate (3.7 mg/L) was completely removed within 1 d. Hardness precursors calcium and inorganic carbon were also removed in large amounts, 268.4 and 128.2 mg/L, respectively. Moreover, suspended-solid phase cultivation significantly mitigated the growth inhibition caused by MIT toxicity, enabled the algae to completely biodegrade MIT of extremely high concentrations (4.7 mg/L and 11.4 mg/L) in a short time. Our results demonstrate the feasibility of suspended-solid phase algal cultivation for simultaneously and effectively removing multiple main contaminants from ROC.

Background/Objective: Since 2005, there has been a significant increase in contact allergy to methylisothiazolinon (MI)/methylchloroisothiazolinone (MCI) incidences in European countries, but there has been no documented large-scale studies of such incidences in Taiwan. Methods: From 1987 to 2015, a total of 2590 patients received patch testing in our Contact Dermatitis Clinic. Analyzed were patients with positive reactions to MI/MCI (Kathon CG) in patch testing and with suspected allergy to MI/MCI. Results: Among the total 2590 patients, 2388 received patch testing during 1987–2005, while 202 received patch testing during 2006–2015. Because Kathon CG was not routinely patch tested for all patients from 1987 to 2005, the incidence of contact allergy to MI/MCI was thus corrected to 3/145 (2.1%) for this time period. After 2005, there were 11 patients (11/202, 5.4%) who showed positive reactions to MI/MCI. Amongst the 14 patients who showed positive reactions to MI/MCI, 12 of them were females (85.7%). The majority of the lesions was located on the hands (10 patients, 71.4%), along with the face (3 patients, 21.4%). Interestingly, 6 patients (42.9%) who showed positive reactions to MI/MCI were associated with contact allergy to essential oils, and five of them were aromatherapists. Conclusion: According to our study, the incidence of MI/MCI contact allergy in a referral center in Taiwan was 5.4%. A trend of increasing incidence of contact allergy to MI/MCI was noted after 2005, which is consistent with the findings in Europe. Allergic contact dermatitis to MI/MCI should be suspected in patients who have eczema on the hands and face, especially those who are aromatherapists.

Methylisothiazolinone (MIT) is widely used in daily chemicals, fungicides, and other fields and its toxicity has posed a threat to water system and human health. In this study, ultraviolet (UV)/trichloroisocyanuric acid (TCCA), which belongs to advanced oxidation processes (AOP), was adopted to degrade MIT. Total chlorine attenuation detection proved that TCCA has medium UV absorption and a strong quantum yield (0.49 mol E−1). At a pH of 7.0, 93.5% of MIT had been decontaminated after 60 min in UV/TCCA system (k obs = 4.4 × 10−2 min−1, R2 = 0.978), which was much higher than that in the UV alone system and TCCA alone system, at 65% (1.7 × 10−2 min−1, R2 = 0.995) and 10% (1.8 × 10−3 s−1, R2 = 0.915), respectively. This system also behaved well in degrading other five kinds of contaminants. Tert-butanol (TBA) and carbonate (CO 3 2−) were separately used in quenching experiments, and the degradation efficiency of MIT decreased by 39.5% and 46.5% respectively, which confirmed that HO• and reactive chlorine species (RCS) were dominant oxidants in UV/TCCA system. With TCCA dosage increasing in a relatively low concentration range (0.02–0.2 mM) and pH decreasing, the effectiveness of this AOP system would be strengthened. The influences of coexisting substances (Cl−, SO 4 2−, CO 3 2−, NO 2 − and NO 3 −) were explored. MIT degradation pathways were proposed and sulfur atom oxidation and carboxylation were considered as the dominant removal mechanisms of MIT. Frontier orbital theory and Fukui indexes of MIT were employed to further explore the degradation mechanism. [Display omitted] • Total chlorine attenuation detection proved TCCA has a strong quantum yield. • UV/TCCA system was superior than UV or TCCA alone system to remove MIT. • Impacts of water matrix were investigated in UV/TCCA system on MIT removal. • Theoretical calculation was used to confirm possible MIT degradation pathways. [ABSTRACT FROM AUTHOR]

This study evaluates the behavioral characteristics of components (methylisothiazolinone (MIT) and chloromethylisothiazolinone (CMIT)) contained in disinfectant solutions when they convert to liquid aerosols. The analytical method for MIT and CMIT quantitation was established and optimized using sorbent tube/thermal desorber-gas chromatography-mass spectrometry system; their behavioral characteristics are discussed using the quantitative results of these aerosols under different liquid aerosol generation conditions. MIT and CMIT showed different behavioral characteristics depending on the aerosol mass concentration and sampling time (sampling volume). When the disinfectant solution was initially aerosolized, MIT and CMIT were primarily collected on glass filter (MIT = 91.8 ± 10.6% and CMIT = 90.6 ± 5.18%), although when the generation and filter sampling volumes of the aerosols increased to 30 L, the relative proportions collected on the filter decreased (MIT = 79.0 ± 12.0% and CMIT = 39.7 ± 8.35%). Although MIT and CMIT had relatively high vapor pressure, in liquid aerosolized state, they primarily accumulated on the filter and exhibited particulate behavior. Their relative proportions in the aerosol were different from those in disinfectant solution. In the aerosol with mass concentration of ≤5 mg m−3, the relative proportion deviations of MIT and CMIT were large; when the mass concentration of the aerosol increased, their relative proportions constantly converged at a lower level than those in the disinfectant solution. Hence, it can be concluded that the behavioral characteristics and relative proportions need to be considered to perform the quantitative analysis of the liquid aerosols and evaluate various toxic effects using the quantitative data.

Disinfectants including polyhexamethylene guanidine phosphate (PHMG) and mixtures of chloromethylisothiazolinone/ methylisothiazolinone (CMIT/MIT) have been widely used in Korea to prevent microbial growth in the humidifier water, which triggered an outbreak of serious respiratory diseases. In addition to the respiratory syndrome, disease-related symptoms including liver toxicity, asthma, and skin allergies were also found after extensive survey of people exposed to the humidifier disinfectants (HDs). In this study, eye irritation tests were performed based on the Organization for economic co-operation and development (OECD) test guidelines 492 using EpiOcularTM which is a tissue model of reconstructed human cornea-like epithelium. As results, the raw materials of PHMG (26% as active ingredient) and CMIT/MIT (1.5% as active ingredient) were classified under UN globally harmonized system of classification and labeling of chemical (GHS) category 1 or category 2. However, aqueous dilutions of raw materials such as market products of HDs that contain 0.13% of PHMG and 0.03% of CMIT/MIT or further dilutions of the market products for humidifier that contain 0.0013% of PHMG and 0.0003% of CMIT/MIT were classified under any category, which suggested absence of eye irritation at the test concentration.

Patch tests are often used in safety evaluations to identify the substance causing skin irritation, but the same substance can sometimes give positive or negative results depending on the test conditions. Here, we investigated differences in the skin penetration of two test compounds under different application conditions. We studied the effects of the anionic surfactant sodium dodecyl sulfate (SDS) and the nonionic surfactant polysorbate 80 (PS) on skin penetration of the preservatives methylisothiazolinone (MT) and methylchloroisothiazolinone (MCT), which are used in cosmetics such as shampoos. The skin permeation of MT was enhanced by SDS but was unchanged by PS. Skin impedance decreased in the presence of SDS whereas PS had the same effect as the control aqueous solution, suggesting that SDS reduction of the barrier function of skin affects the permeation of MT, a hydrophilic drug. Application of a mixture of MCT and MT in the presence of SDS did not affect the skin permeation of MCT whereas the permeation of MT was enhanced by SDS, indicating that the skin permeation of MCT is less affected by SDS than is MT. Thus, attention should be paid to the possible effect of co-solutes, especially hydrophilic drugs.

• MIT was electrochemical degraded by a Ti/SnO 2 -Sb 2 O 3 /α, β-PbO 2 electrode. • Electrochemical treatment required low energy consumption and no chemical addition. • 68.8% of electrons that used for MIT oxidation was utilized to mineralize MIT into CO 2. • The sulfur atom can be oxidized into SO 4 2− and separated from MIT ring structure. Methylisothiazolinone (2-methyl-4-isothiazolin-3-one) (MIT) is a commonly used biocide in wastewater treatment processes. Residual MIT in wastewater leads to high environmental risks and toxicity. The degradation of MIT via electrochemical oxidation, including kinetics, energy efficiency, oxidation mechanism and degradation pathway, was investigated in this study. Findings from energy and cost evaluation by using electrochemical technology were compared with those of other technologies. Experimental results indicate that electrolyte, current density and initial concentration can significantly affect MIT degradation. The lowest electrical energy per order was less than 3.85 kWh m−3 when NaCl was used as the electrolyte. Electrochemical degradation is advantageous because it can be easily applied without adding chemicals into wastewater and has relative low costs. The oxygen evolution, production of recalcitrant byproducts, and the mass transfer limitation resulted in the decrease of instantaneous current efficiency and mineralization current efficiency. Electron efficiency analysis demonstrated that 68.8% of the electrons used for MIT oxidation were effectively utilized to mineralize MIT into CO 2. The proportion of direct and indirect oxidation of MIT during electrochemical degradation was quantitatively determined as 37.7% and 62.3%, respectively. HO was the most effective species for MIT degradation. MIT degradation pathway was proposed, in which the C C bond in MIT was broken down. C 3 H 7 NOS and C 3 H 7 NO 4 were detected, indicating the occurrence of ring opening reaction. Sulfur was oxidized into SO 4 2− and cleaved from C 3 H 7 NOS. [ABSTRACT FROM AUTHOR]

Background: Preservatives are widely used in personal and industrial products. Frequent and sustained exposure to preservatives can cause contact allergy. Objective: We investigated the prevalence of contact allergic reactions to common preservatives in Taiwan over a 20-year period. Methods: A retrospective analysis was conducted among patients with allergic contact dermatitis who underwent patch testing at our clinic between 1996 and 2015. Patients who showed positive reactions to preservatives were enrolled. The location of the reaction, likely source of the allergen, and patient occupation, sex, and age were recorded. Thirteen common preservatives, including methylchloroisothiazolinone/methylisothiazolinone (MCI/MI), MI, formaldehyde (FA), paraben mix, and quaternium-15, were investigated. Results: Of 757 enrolled patients, 151 showed at least one positive reaction to preservatives. Allergy to MCI/MI (12.5%), the most frequent allergen in the standard series, showed a steeply increasing trend over time. FA (4.8%) and paraben mix (2.1%) were the next common allergens. Cosmetic products were the most common source of exposure (63.6%), while hairdressers and massage therapists were most commonly associated with occupational contact dermatitis. A sharp increase of sensitivity to MCI/MI was observed after 2006 and that of allergy to MI after 2013. Conclusions: In Taiwan, the prevalence of contact allergy to MCI/MI, MI, and parabens has increased in recent years. Individuals who are frequently exposed to cosmetic products should consider precautions against sensitization. [ABSTRACT FROM AUTHOR]

Currently available toxicity data on humidifier disinfectants are primarily limited to polyhexamethylene guanidine phosphate-induced lung fibrosis. We, therefore, investigated whether the sterilizer component Kathon, which is a mixture of chloromethylisothiazolinone and methylisothiazolinone, induces fibrotic lung injury following direct lung exposure in an animal model. Mice were intratracheally instilled with either the vehicle or Kathon. Differential cell counts, cytokine analysis, and histological analysis of lung tissue were then performed to characterize the injury features, and we investigated whether Kathon altered fibrosis-related gene expression in lung tissues via RNA-Seq and bioinformatics. Cell counting showed that Kathon exposure increased the proportion of macrophages, eosinophils, and neutrophils. Moreover, T helper 2 (Th2) cytokine levels in the bronchoalveolar lavage were significantly increased in the Kathon groups. Histopathological analysis revealed increased perivascular/alveolar inflammation, eosinophilic cells, mucous cell hyperplasia, and pulmonary fibrosis following Kathon exposure. Additionally, Kathon exposure modulated the expression of genes related to fibrotic inflammation, including the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) signaling pathway, extracellular signal regulated kinase (ERK)1 and ERK2 cascade, extracellular matrix (ECM)-receptor interaction pathway, transforming growth factor beta receptor signaling pathway, cellular response to tumor necrosis factor, and collagen fibril organization. Our results suggest that Kathon exposure is associated with fibrotic lung injury via a Th2-dependent pathway and is thus a possible risk factor for fibrosis.

Methylisothiazolinone (MI) is one of the most used preservatives in shampoos and also one of the most effective. A preservative mixture known as Kathon™ CG is commercially available. It contains 5-chloro-2-methyl-4-isothiazolin-3-one (CMI) and 2-methyl-4-isothiazolin-3-one (MI) (3:1) and stabilizers. The aim of this study is to evaluate the influence of formulation factors in the quantification and stability of isothiazolinones in shampoos. Two shampoo bases containing Kathon™ CG as a preservative were prepared. Some ingredients that are at risk of interfering with the preservative stability were added to these formulations. The preservative was quantified by HPLC-DAD (High-performance liquid chromatography with a diode-array detector) after preparation of the formulation and after storage at room temperature and at 40 °C. The addition of magnesium silicate proved to be essential for the breakdown of the interaction between the matrix and the analytes in the extraction procedure. The content of CMI/MI decreased right after preparation indicating that immediate interactions between CMI/MI and the ingredients may have occurred after preparation resulting in a decrease in the preservative concentration. Detrimental interactions between the ingredients, regarding the stability of the isothiazolinones were detected immediately after preparation and over time resulting in the reduction of CMI/MI concentration in these cosmetic shampoos.

Background: Preservatives present in cosmetics and other industrial products can cause allergic contact dermatitis. The aim of the study was to assess the frequency of allergy to selected preservatives in consecutive patients examined due to contact dermatitis in the Nofer Institute of Occupational Medicine, Łódź, and to establish whether individuals sensitized to formaldehyde react simultaneously to formaldehyde releasers. Material and Methods: A group of 405 patients (308 females and 97 males) was examined in 2011–2013. In all participants patch tests with a series of 13 preservatives (paraben mix, formaldehyde, Quaternium 15, chloromethylisothiazolinone/methylisothiazolinone mix, methyldibromoglutaronitrile, diazolidinyl urea, imidazolidinyl urea, DMDM hydantoin, 2-bromo-2-nitropropane-1,3-diol, iodopropynyl butylcarbamate, benzalkonium chloride, sodium metabisulfite, produced by Chemotechnique Diagnostics, Sweden) were performed. Results: Of the 405 patients 74 (including 52 females) showed positive results of patch tests. Contact allergy to at least 1 preservative was noted in 47 (11.6%) patients, including 34 (11%) females and 13 (13.4%) males. Methylisothiazolinone proved to be the most frequent sensitizer – 4.7% (5.2% females, 3.1% males) while parabens, 2-bromo-2-nitropropane-1,3-diol and imidazolidinyl urea (0.2%) were found to be the least frequent. Fourteen (3.4%) participants, 10 women and 4 men, were allergic to formaldehyde and/or formaldehyde releasers. In 11 (78.6%) of them monovalent hypersensitivity was observed. In 13 (3.2% of the examined group) patients allergy to preservatives might have been of occupational origin. Conclusions: Preservatives, particularly isothiazolinones, are significant causal factors of allergic contact dermatitis, including occupational cases. Individuals sensitized to formaldehyde may react simultaneously to formaldehyde releasers, however, such reactions are relatively rare. Med Pr 2015;66(3):327–332

Numerous mechanisms have been postulated to play an important role in the pathogenesis of poikiloderma of Civatte (PC), including chronic exposure to ultraviolet radiation, menopause-related hormonal changes, contact hypersensitivity and genetic predisposition. Herein, we report a case of contact sensitization to fragrances and commonly used preservatives, methylchloroisothiazolinone and methylisothiazolinone, also widely known as Kathon CG, in a post-menopausal woman with PC, who denied excessive sun exposure and a family history. After abstaining from the use of her personal care products containing the documented allergens, not only the itching and burning symptoms, but also the cutaneous changes appeared to improve partially. This report underlines the possible influence of contact hypersensitivity in the pathogenesis of PC.

Methylisothiazolinone (MIT) has been widely used to control bacterial growth in reverse osmosis (RO) systems. However, MIT's toxicity on microalgae should be determined because residual MIT is concentrated into RO concentrate (ROC) and might have a severe impact on microalgae-based ROC treatment. This study investigated the tolerance of Scenedesmus sp. LX1 to MIT and revealed the mechanism of algal growth inhibition and toxicity resistance. Scenedesmus sp. LX1 was inhibited by MIT with a half-maximal effective concentration at 72 h (72 h-EC 50 ) of 1.00 mg/L, but the strain recovered from the inhibition when its growth was not completely inhibited. It was observed that this inhibition's effect on subsequent growth was weak, and the removal of MIT was the primary reason for the recovery. Properly increasing the initial algal density significantly shortened the adaptation time for accelerated recovery in a MIT-containing culture. Photosynthesis damage by MIT was one of the primary reasons for growth inhibition, but microalgal cell respiration and adenosine triphosphate (ATP) synthesis were not completely inhibited, and the algae were still alive even when growth was completely inhibited, which was notably different from observations made with bacteria and fungi. The algae synthesized more chlorophyll, antioxidant enzymes of superoxide dismutase (SOD) and catalase (CAT), and small molecules, such as reduced glutathione (GSH), to resist MIT poisoning. The microalgae-based process could treat the MIT-containing ROC, since MIT was added for only several hours a week in municipal wastewater reclamation RO processes, and the MIT average concentration was considerably lower than the maximum concentration that algae could tolerate. [ABSTRACT FROM AUTHOR]

Contact allergy to preservatives is an important public health problem. Ideally, new substances should be evaluated for the risk on skin sensitisation before market entry, for example by using a quantitative risk assessment (QRA) as developed for fragrances. As a proof-of-concept, this QRA was applied to the preservative methylisothiazolinone (MI), a common cause of contact allergy. MI is used in different consumer products, including personal care products (PCPs) and household cleaning products (HCPs). Aggregate exposure to MI in PCPs and HCPs was therefore assessed with the Probabilistic Aggregated Consumer Exposure Model (PACEM). Two exposure scenarios were evaluated: scenario 1 calculated aggregate exposure on actual MI product concentrations before the restricted use in PCPs and scenario 2 calculated aggregate exposure using the restrictions for MI in PCPs. The QRA for MI showed that in scenarios 1 and 2, the proportion of the population at risk for skin sensitisation is 0.7% and 0.5%, respectively. The restricted use of MI in PCPs does not seem very effective in lowering the risk on skin sensitization. To conclude, it is important to consider aggregate exposure from the most important consumer products into consideration in the risk assessment. [ABSTRACT FROM AUTHOR]

Background/Objective Since 2005, there has been a significant increase in contact allergy to methylisothiazolinon (MI)/methylchloroisothiazolinone (MCI) incidences in European countries, but there has been no documented large-scale studies of such incidences in Taiwan. Methods From 1987 to 2015, a total of 2590 patients received patch testing in our Contact Dermatitis Clinic. Analyzed were patients with positive reactions to MI/MCI (Kathon CG) in patch testing and with suspected allergy to MI/MCI. Results Among the total 2590 patients, 2388 received patch testing during 1987–2005, while 202 received patch testing during 2006–2015. Because Kathon CG was not routinely patch tested for all patients from 1987 to 2005, the incidence of contact allergy to MI/MCI was thus corrected to 3/145 (2.1%) for this time period. After 2005, there were 11 patients (11/202, 5.4%) who showed positive reactions to MI/MCI. Amongst the 14 patients who showed positive reactions to MI/MCI, 12 of them were females (85.7%). The majority of the lesions was located on the hands (10 patients, 71.4%), along with the face (3 patients, 21.4%). Interestingly, 6 patients (42.9%) who showed positive reactions to MI/MCI were associated with contact allergy to essential oils, and five of them were aromatherapists. Conclusion According to our study, the incidence of MI/MCI contact allergy in a referral center in Taiwan was 5.4%. A trend of increasing incidence of contact allergy to MI/MCI was noted after 2005, which is consistent with the findings in Europe. Allergic contact dermatitis to MI/MCI should be suspected in patients who have eczema on the hands and face, especially those who are aromatherapists. [ABSTRACT FROM AUTHOR]

Chloromethylisothiazolinone (MCI) and methylisothiazolinone (MI) have been widely used as preservatives in cosmetics, household products and industrial products since the late 1970s. First cases of contact allergy to the MCI/MI combination were noted in 1980–1982 in Sweden. Then, a significant increase in the frequency of sensitization to these compounds was observed in many European centers. The increase has been stopped by the introduction of legislation on their maximum concentrations in consumer and industrial products in Europe and in some non-European countries. But approval of the use of MI alone without limits in industrial products (from 2000) and at a maximum concentration of 100 ppm in cosmetics (from 2005) resulted in an unprecedented increase in the number of individuals sensitized to this compound. Allergic contact dermatitis due to MI occurs in both adults and children. It is often manifested by severe symptoms, which may be also induced by airborne exposure. The most important sources of sensitization include cosmetic products and paints. To counteract the increasing problem of contact allergy epidemic to MI, the recommendations have been developed, suggesting the ban on the use of MI in “leave-on” cosmetics and maximum concentration of 15 ppm in “rinse-off” products. These recommendations are likely to be implemented in 2014. Med Pr 2014;65(4):543–554

A history of allergies doubles the risk of vulvodynia—a chronic pain condition of unknown etiology often accompanied by increases in numbers of vulvar mast cells. We previously established the biological plausibility of this relationship in mouse models where repeated exposures to the allergens oxazolone or dinitrofluorobenzene on the labiar skin or inside the vaginal canal of ND4 Swiss Webster outbred mice led to persistent tactile sensitivity and local increases in mast cells. In these models, depletion of mast cells alleviated pain. While exposure to cleaning chemicals has been connected to elevated vulvodynia risk, no single agent has been linked to adverse outcomes. We sensitized female mice to methylisothiazolinone (MI)—a biocide preservative ubiquitous in cosmetics and cleaners—dissolved in saline on their flanks, and subsequently challenged them with MI or saline for ten consecutive days in the vaginal canal. MI-challenged mice developed persistent tactile sensitivity, increased vaginal mast cells and eosinophils, and had higher serum Immunoglobulin E. Therapeutic and preventive intra-vaginal administration of Δ9-tetrahydrocannabinol reduced mast cell accumulation and tactile sensitivity. MI is known to cause skin and airway irritation in humans, and here we provide the first pre-clinical evidence that repeated MI exposures can also provoke allergy-driven genital pain.

Methylisothiazolinone (MI), along with Kathon™ CG (methylchloroisothiazolinone/MI), are widely used preservatives to prevent bacterial overgrowth in aqueous solutions of various types of cosmetic, household, and industrial products. Because of its high sensitising power and widespread use, MI is currently one of the most common causes of allergic contact dermatitis, both in our private lives and in the occupational field. As it was thought that MI had less sensitivity capacity, it started to be commercialised separately, and a new epidemic of sensitisation to these preservatives has been observed in recent years. MI should be included separately in the standard patch testing series. Also, the use of isothiazolinones should be revised, and legislative measures from the competent authorities should be implemented in order to resolve this problem.

Methylisothiazolinone (MIT) is a common biocide used in cosmetic and industrial settings. Studies have demonstrated that MIT is a human sensitizer, to the extent that in 2013 MIT was named allergen of the year. Recently, we showed that MIT exposure in Xenopus laevis (the African clawed frog) inhibits wound healing and tail regeneration. However, it is unknown whether MIT affects these processes in other animals. Here, we investigated the effects of MIT exposure in planaria—non-parasitic freshwater flatworms able to regenerate all tissues after injury. Using a common research strain of Dugesia japonica , we determined that intact planarians exposed to 15 μM MIT displayed both neuromuscular and epithelial-integrity defects. Furthermore, regenerating (head and tail) fragments exposed to 15 μM MIT failed to close wounds or had significantly delayed wound healing. Planarian wounds normally close within 1 h after injury. However, most MIT-exposed animals retained open wounds at 24 h and subsequently died, and those few animals that were able to undergo delayed wound healing without dying exhibited abnormal regeneration. For instance, head regeneration was severely delayed or inhibited, with anterior structures such as eyes failing to form in newly produced tissues. These data suggest that MIT directly affects both wound healing and regeneration in planarians. Next, we investigated the ability of thiol-containing antioxidants to rescue planarian wound closure during MIT exposure. The data reveal both n -acetyl cysteine and glutathione were each able to fully rescue MIT inhibition of wound healing. Lastly, we established MIT toxicity levels by determining the LC 50 of 5 different planarian species: D. japonica, Schmidtea mediterranea , Girardia tigrina, Girardia dorotocephala, and Phagocata gracilis . Our LC 50 data revealed that concentrations as low as 39 μM (4.5 ppm) are lethal to planarians, with concentrations of just 5 μM inhibiting wound healing, and suggest that phylogeny is predictive of species toxicity levels. Together these results indicate MIT may have broad wound healing effects on aquatic species in general and are not limited to X. laevis alone. Future studies should investigate the impact of MIT on wound healing in other organisms, including non-aquatic organisms and mammals. [ABSTRACT FROM AUTHOR]

The South African clawed frog, Xenopus laevis , has a strong history as a suitable model for environmental studies. Its embryos and transparent tadpoles are highly sensitive to the environment and their developmental processes are well described. It is also amenable for molecular studies. These characteristics enable its use for rapid identification and understanding of exposure-induced defects. To investigate the consequences of chemical exposure on aquatic animals, Xenopus laevis embryos and tadpoles were exposed to the biocide, methylisothiazolinone (MIT). Frog tadpoles exposed to MIT following tail amputation lost their natural regenerative ability. This inhibition of regeneration led to a failure to regrow tissues including the spinal cord, muscle, and notochord. This MIT-dependent regenerative defect is due to a failure to close the amputation wound. A wound healing assay revealed that while untreated embryos close their wounds within one day after injury, MIT-treated animals maintained open wounds that did not reduce in size and caused lethality. Concomitant exposure of MIT with chemicals containing thiol groups such as glutathione and N-acetyl cysteine restored normal wound healing and regeneration responses in tadpoles. Together these results indicate that exposure to MIT impairs developmental wound repair and tissue regeneration in Xenopus laevis . Thus, this study reveals new aspects of MIT activity and demonstrates that Xenopus laevis is a well-suited model for facilitating future research into chemical exposure effects on injury responses. [ABSTRACT FROM AUTHOR]

A total of 221 patients were evaluated to be humidifier disinfectant associated with lung injury (HDLI) through two rounds of programs through April 2015. The humidifier disinfectant (HD) brands most often associated with HDLI were found to be Oxy (n=151, 68 %) and Cefu (n=26, 17 %). Polyhexamethylene guanidine used for disinfectant for four types of HD brands including Oxy was found to be associated with the highest number of HDLI cases (n=188). Further programs are operating to identify various health effects including lung injury which may be associated with the use of HD. Not only national agencies, but also pertinent environmental health societies should cooperate in the necessary investigations so that this tragedy can be properly addressed and future incidents concerning chemicals and chemical-containing products can be prevented.