• Journal of Environmental Health Sciences
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• v.46 no.2
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• pp.224-231
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• 2020

Objective: The objectives of this study are to update the information on the characteristics of humidifier disinfectant (HD) usage with HD associated health problems and to discuss the role of HD exposure assessment in the national program to monitor health problems in patients with HD associated diseases. Method: A total of 201 HD associated patients who registered to undergo clinical examination at Kangbuk Samsung Hospital was interviewed to acquire their responses regarding several HD use characteristics, including type of HD brands used, HD use duration, average daily HD use hours, and the volume of the room in which HD was used. The responses of the HD associated patients to HD use-related questions were compared between responses in the lung injury investigation and this study. Results: The responses of HD associated patients in this study were found to be different from those in the lunginjury investigation. In particular, some of the patients who had not answered in the lung-injury investigation were able to answer thanks to assistance from the investigator in this study. For their responses regarding the name of the most commonly used HD brand, the number of patients who did not answer (N=11) was reduced to eight in this study. Significant changes in the responses of study subjects to questions related to HD use were achieved through the interview in this study. Conclusion: This study found significant changes in the responses regarding HD use characteristics. HD exposure assessment should be included in the program in order to allow surveillance of HD associated health problems.

• Journal of Environmental Health Sciences
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• v.49 no.3
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• pp.159-168
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• 2023

Background: An ongoing environmental exposure assessment of humidifier disinfectants (HDs) has been conducted since November 2011 among individuals who experienced HD exposure-related adverse health effects. It is being performed in order to determine and quantify exposure to humidifier disinfectants in victims and their families. To date, the assessment has encompassed Cycles I-to-V. There is no report summarizing the characteristics of the subjects from the overall cycles. Objectives: We intended to examine the individual characteristics related to demographics, HD usage, and HD exposure using integrated data from Cycles I-to-V of the environmental exposure assessment of HDs and the changes with the cycles. Methods: We included 7,543 individuals who participated in Cycles I-to-V of the environmental exposure assessment of HDs. We summarized the participants' characteristics regarding their demographics (e.g., sex, education level, and age), HD usage history (e.g., product name, ingredient, and frequency of HD use), and HD exposure (e.g., daily time of HD use, cumulative time of HD use, and exposure intensity). In addition, their characteristics were compared across the cycles of the exposure assessment. Results: Among the 7,543 participants from Cycles I-to-V, there were more male participants than females (51.05% overall), except for Cycles I and III. Across all cycles, a higher proportion of survivors was observed than deceased individuals. While PHMG was the most prevalent ingredient in HDs throughout all the cycles, its proportion gradually decreased over the course of the examination cycles. Participants in Cycle I reported longer daily times of HD use compared to those in the subsequent cycles. On the other hand, cumulative time of HD use was shorter in the earlier cycles than in the later cycles. Conclusions: Using the integrated data from the full cycles of the environmental exposure assessment, this study identified changes in demographic characteristics as well as the HD exposure characteristics between the participants across different cycles.

• Journal of Environmental Health Sciences
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• v.44 no.5
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• pp.468-479
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• 2018

Objectives: Recently, a report was published that the humidifier disinfectant CMIT/MIT did not cause developmental toxicity and was not detected in systemic circulation as a result of an inhalation toxicity test. Therefore, this study was carried out to investigate any associations between CMIT/MIT exposure and developmental toxicity using the in vivo apical toxicity test method. Methods: Groups of pregnant ICR mice were instilled in the trachea with chloromethylisothiazolinone/methylisothiazolinone (CMIT/MIT) using a visual instillobot over a period of seven days from days 11 to 17 days post-coitum. For the in vivo apical toxicity test method, an $LD_{50}$-based dose-range finding model was applied to decide the dose range for inducing developmental toxicity. Results: Among the groups of 0, 0.1, 0.5, 1.0, and 1.5 mg ai/kg/day CMIT/MIT, the exposure groups of 0.5 mg and 1.0 ai/kg/day CMIT/MIT were estimated to reflect the thresholds for the stillbirth and death of pregnant mice, respectively. The groups of 0.5, 1.0, and 1.5 mg ai/kg/day CMIT/MIT induced stillbirth rates of 2.57, 10, and 53.8%, respectively. Another exposure group of 0.75 mg ai/kg/day CMIT/MIT did not induce any deaths of pregnant mice and resulted in a stillbirth rate of 8% in only one of six pregnant mice. Conclusions: CMIT/MIT can induce stillbirth in pregnant mice. It was also concluded that CMIT/MIT moves through the pulmonary circulation system and then continues on through systemic circulation and the placenta. There is a possibility of stillbirth and other health causalities in humans beyond the lungs caused by CMIT/MIT exposure.

• Journal of Korean Society of Occupational and Environmental Hygiene
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• v.29 no.1
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• pp.13-20
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• 2019

Objective: This study was performed to propose a domestic occupational exposure limit(OEL) following a health hazard assessment, calculation of a non-carcinogenicity reference concentration worker($RfC_{worker}$) value, and examination of international agencies' exposure limits. It also recommends legal management within the Occupational Safety and Health Act for PHMG-Phosphate(CAS No. 89697-78-9), It is a humidifier disinfectant that generated many lung injuries. Methods: We have investigated the recommendation or guidelines of foreign OEL for PHMG-Phosphate and the actual state of legal management in Korea. To examine the procedures and methods for recommendation OEL. Toxicological hazard and health hazard classifications were examined and a non-carcinogenicity $RfC_{worker}$ value was calculated for PHMG-Phosphate. An OEL and the necessity of legal management were recommended as well. Results and Conclusions: The OEL for PHMG-Phosphate is recommended to be $0.01mg/m^3$. The recommended OEL is close to 10 times the RfCworker value of $0.000833mg/m^3$ calculated from the chemical dose-response hazard assessment, which is a 2017 study. The CMIT/MIT(3:1) mixture, which was a social issue as a humidifier disinfectant substance, was also exposed to the same ratio in March 2018, establish the OEL. It is recommended to establish OEL for PHMG-Phosphate to prevent worker health hazards and for chemical safety management.

• Environmental Analysis Health and Toxicology
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• v.31
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• pp.19.1-19.7
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• 2016

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

• Journal of Environmental Health Sciences
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• v.45 no.3
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• pp.273-284
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• 2019

Objective: This study was performed to estimate the number of those who used humidifier disinfectants (HDs) and experienced health effects from exposure to HDs in Korea between 1994 and 2011. Methods: A nationwide interview survey was conducted for the representative sample to identify the proportion of those who used HDs among the general population (n=3,001). Another online survey was conducted for those exposed to HDs to find the proportion of those who experienced health effects among those who were exposed to HDs (n=3,993). Statistics for population size by region and year (1994-2011) were used to estimate the cumulative number of those exposed to HDs and those who experienced health effects. In terms of the proportion of those exposed to HDs, those less than 30 years of age were excluded due to an issue related to information bias. Various approaches for estimation included the capture-recapture method for estimation of those who experienced health effects. Results: The cumulative proportion of those exposed to HDs was 6.7% among the general population, and the proportion of those who experienced health effects among those who were exposed to HDs was 13.9%. Based on these factors, it was estimated that 3.5 to 4.0 million people were exposed to HDs and 350 to 400 thousand experienced health effects at least requiring visiting a hospital. Conclusion: It is suggested that a nationwide representative sample may be essential for population size estimation of those exposed to environmental risk factors and of those who experienced health effects.

• Journal of Environmental Health Sciences
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• v.45 no.1
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• pp.71-81
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• 2019

Objectives: The lung injuries by exposure to the humidifier disinfectants (HDs) were reported in 2011, Korea. For the HD victims, environmental exposure level and clinical diagnosis were conducted to determine the levels of damage by HDs. Methods: The exposure assessment to the HDs from 1st to 4th questionnaire surveys were carried out for 5,245 victims. And the affecting factors of exposure levels were analyzed by characterizing exposure and demographic information. By using of exposure concentration and cumulative time, exposure levels were classified and compared by percentage of clinical diagnosis classes. The high exposure and low clinical diagnosis rating groups, and low exposure and high clinical diagnosis rating groups were analyzed to overcome the limitation of past exposure assessment such as recall bias. Results: Among the all applicants damaged by the humidifier disinfectants, survivors were 4,028 and the dead were 1,217. And male and female were 2,675, and 2,547, respectively. In case of occurrence age of lung disease, under 10 years was majority age group (1,536) and followed by thirties (917). Pregnant women and fetuses were 339 and 439, respectively. And the damages by exposure to the HDs were concentrated on these susceptible populations in groups with low exposure and high clinical diagnosis rating. On the other hand, the groups classified by high exposure and low clinical diagnosis rating were shown different characterization. Conclusions: The questionnaire survey on past exposure may be uncertain due to recall bias. However, the relationship between classified exposure levels and clinical diagnosis ratings might be shown positive correlation if the exposure assessment errors were analyzed and controlled.

• Journal of Environmental Health Sciences
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• v.46 no.3
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• pp.335-343
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• 2020

Objectives: The Korean Ministry of Environment has identified cases of people suspected of suffering lung disease potentially caused by polyhexamethylene guanidine (PHMG) used in humidifier disinfectants (HDs). Exposure assessment for the HDs was conducted using a questionnaire during face-to-face interview. The main purposes of this study were to develop a methodology to effectively classify levels of exposure to HDs based on a questionnaire. Methods: We first identified the overall participants' exposure characteristics by HD exposure levels; Second, we selected misclassified subjects and investigated characteristics of overestimated and underestimated subjects, focusing on exposure cases to PHMG-containing HDs. An inhalation reference concentration (RfC) for PHMG was produced on the basis of inhalation toxicity values. We made a cross-tabulation of the exposure classes (Exposure classes 1-to-4) by clinical classes based on the RfC. When the value of the exposure class minus the clinical class was 0 or 1, we assumed these were true values. When the value was ≥2 and ≤ -2, we assigned these cases to the overestimation group and underestimation group, respectively. Results: The overestimated group may have already recovered and responded excessively due to psychological anxiety or in order to receive compensation. On the other hand, relatively high mortality rates and surrogate responses for those under 10 years of age may have resulted in inaccurate exposure assessment for underestimated groups. For the characteristics of exposure, it was shown that for the underestimated group, the exposure was relatively weaker than the overestimated group, even though a high overall clinical rating was determined. Conclusions: This study may suggest ways to reduce bias and overcome the limitations of current HD exposure assessment.

• Journal of Environmental Health Sciences
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• v.48 no.6
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• pp.324-330
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• 2022

Background: Lung injuries due to exposure to humidifier disinfectants (HDs) were reported in 2011 in South Korea. As a result of the government's epidemiological investigation and toxicity test study, it was found that HDs caused health damage such as lung disease. Objectives: The purpose of this study was to classify HD exposure ratings and analyze the affecting factors that could identify the relationship with lung disease. Methods: Exposure assessment for HDs was conducted using a questionnaire during face-to-face interviews with the applicants. Ratings of high exposure (Class 1) and low exposure (Class 2) were cross-tabulated with clinical ratings (acceptable and unacceptable). Logistic regression analysis was carried out by setting the clinical rating of lung disease as a dependent variable and the socio-demographic and exposure characteristics obtained through the questionnaire as independent variables. Results: The concentration in air of polyhexamethylene guanidine (PHMG) was 71.96±107.47 ㎍/m³, and the exposure concentration was 15.21±23.28 ㎍/m³ . The exposure rating was overestimated with 97.1% of affected subjects having high exposure using margin of exposure (MOE), but only 9.9% matching the clinical class. In the overestimated group, it could be explained by the fact that the exposure time was long and the subjects had already recovered from damage symptoms. As a result of logistic regression analysis, ten variables were found to be significant influencing factors. Conclusions: A new exposure rating could be calculated based on the MOE, and factors affecting lung disease could be estimated through comparative evaluation with the clinical rating.

• Journal of Environmental Health Sciences
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• v.49 no.3
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• pp.169-177
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• 2023

Background: The Korea Centers for Disease Control and Prevention (KCDC) has identified cases of people suspected of suffering lung disease potentially caused by chloromethylisothiazolinone/methylisothiazolinone (CMIT/MIT) used in humidifier disinfectants (HDs). The Korean Ministry of Environment (MoE) epidemiological investigation and toxicity test study found that HDs caused health damage such as asthma and lung disease. Objectives: The main purposes of this study were to classify the HD exposure rating and to analyze the exposure characteristics that affect exposure to CMIT/MIT HDs. Methods: The exposure characteristics and socio-demographic characteristics of victim participants using CMIT/MIT HDs were investigated through questionnaires. An inhalation no observed adverse effect level (NOAEL) for CMIT/MIT was produced based on inhalation toxicity values. Exposure ratings (class 1~class 2) were cross-tabulated with clinical ratings (acceptable~unacceptable). A correlation analysis was conducted with the main exposure characteristics that affect the exposure concentration of CMIT/MIT HDs. Results: The concentration in indoor air of CMIT/MIT was 8.75±25.40 ㎍/m³, and the exposure concentration was 2.30±6.29 ㎍/m³. The CMIT/MIT exposure rating of 67 participants with high exposures of not more than MOE 100 were evaluated as 14.5%, while the damage participants who matched the clinical rating made up 4.5%. The exposure concentration of CMIT/MIT showed a positive correlation with the daily usage amount and usage frequency, and a negative correlation with volume of the indoor environment. Conclusions: A new exposure rating could be suggested and calculated based on the MOE, and the factors affecting the exposure concentration could be identified.