• 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.

• Journal of Environmental Health Sciences
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• v.46 no.3
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• pp.312-323
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• 2020

Objective: This study aimed to summarize the physiochemical properties, toxicity, and legal regulation of chloromethylisothiazolinone (CMIT) and/or methylisothiazolinone (MIT), review the health effects caused by exposure to CMIT/MIT, and evaluate the individual association of lung injury with the use of humidifier disinfectants (HD) containing a mixture of CMIT and MIT. Method: A literature review was conducted by searching keywords such as CMIT, MIT, health effect, dermatitis, asthma, and lung injury, either singly or combined. Results: Both CMIT and/or MIT were found to be associated with the development of several types of adverse health effects. In particular, respiratory diseases including asthma, nasal symptoms, cough, and rhinitis were caused by the use of products including CMIT or/and MIT. The mixture of CMIT/MIT has been banned in cosmetics. As of the end of 2017, nine patients who were confirmed to have HD associated lung injury (HDLI) were found to have used only an HD brand containing CMIT and MIT. Their responses regarding the name of the HD used could be trustworthy based on the short duration of HD use (less than six months) before the onset of HDLI and frequent use of HD per day. Conclusion: According to the toxicity and HDLI cases, the use of HD containing CMIT and /or MIT can cause fatal lung injury. Further study with manufacturers' assistance is necessary in order to obtain more clear evidence on the causal relationship since HDLI cases are being reported continuously.

• 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.

• 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.46 no.3
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• pp.285-296
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• 2020

Objective: The objective of this study was to describe the characteristics of exposure to humidifier disinfectants (HDs) and their association with the presence of a person who experienced the adverse health effects in general households in Korea. Methods: During the month of December 2016, a nationwide online survey was conducted on adults over 20 years of age who had experience of using HDs. It provided information on exposure characteristics and the experience of health effects. The final survey respondents consisted of 1,555 people who provided information on themselves and their household members during the use of HD. Exposure characteristics at the household level included average days of HD use per week, average hours of HD use per day, the duration within which one bottle of HD was emptied, average input frequency of HD, amount of HD (cc) per one time used, and active ingredients of HD products (PHMG, CMIT/MIT, PGH, or others). The risk of the presence of a person who experienced adverse health effects in the household was evaluated by estimating odds ratios (ORs) and 95% confidence intervals (CIs) adjusted for monthly income and region using a multiple logistic regression model. Subgroup analyses were conducted for households with a child (≤7 years) and households with a newborn infant during HD use. Results: The level of exposure to HD tended to be higher for households with a child or newborn infant for several variables including average days of HD use per week (P<0.0001) and average hours of HD use per day (P<0.0001). The proportion of households in which there was at least one person who experienced adverse health effects such as rhinitis, asthma, pneumonia, atopy/skin disease, etc. was 20.6% for all households, 25.3% for households with children, and 29.9% for households with newborn infants. The presence of a person who experienced adverse health effects in the household was significantly associated with average hours of HD use per day (P_trend<0.001), duration within which one bottle of HD was emptied (P_trend<0.001), average input frequency of HD (P_trend<0.001), amount of HD per one use (P_trend=0.01), and use of HDs containing PHMG (OR=2.23, 95% CI=1.45-3.43). Similar results were observed in subgroup analyses. Conclusion: Our results suggest that level of exposure to HD tended to be higher for households with a child or newborn infant and that exposure to HD is significantly associated with the presence of a person who experienced adverse health effects in the household.

• Journal of Environmental Health Sciences
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• v.43 no.4
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• pp.247-256
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• 2017

Objectives: The deaths of Korean victims exposed to the disinfectant CMIT/MIT have remained unresolved. This is mainly due to a lack of concordance between the few available toxicity tests and the abundant epidemiological data, making it difficult to establish a cause-and-effect relationship. Therefore, this study was carried out to investigate any potential associations between CMIT/MIT exposure and death. Methods: Groups of experimental and control C57BL/6 mice were instilled (in the trachea) with chloromethylisothiazolinone/methylisothiazolinone (CMIT/MIT) using a visual instillobot. CMIT/MIT was instilled over a period of three days and eight weeks, respectively, to achieve acute and chronic exposures. A threshold dose-response model was applied for estimating the threshold level as one line of evidence for a causal association between CMIT/MIT and death. Results: An acute exposure of 1.2 mg ai/kg/day of CMIT/MIT was estimated to reflect the threshold for death. The dose-response curve with this threshold showed a very steep slope and a narrow range of CMIT/MIT exposures. The narrow range of CMIT/MIT exposures, in particular, indicated an evident boundary between survival and death, thus implicating a strong causal association. A similar threshold dose-response relationship observed following acute exposure was also seen following chronic exposure to CMIT/MIT. Airborne disinfectant exposure was visible as minimal or mild lung damage with no fibrosis, as shown by histopathological tests. However, many observations are considered to be functional respiratory tract or lung failure due to death, as observed in necropsies of the mice that died due to CMIT/MIT exposures. Conclusions: There are two strong lines of evidence for a causal association between death and CMIT/MIT exposure: 1) The threshold dose-response curve, with a very steep slope and a narrow range of CMIT/MIT exposures showing a visible boundary between survival and death; and 2) many cases of functional respiratory or lung failure.

• Journal of Conservation Science
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• v.33 no.4
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• pp.255-266
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• 2017

Chemically derived pesticides have been used to prevent biological damage to domestic cultural property. However, their use is gradually being restricted due to the harmful effects on the human body and environment. Therefore, there is a growing interest in the search for new antifungal biopharmaceuticals whose safety has been confirmed by toxicity evaluation through animal experiments. This paper presents methods of toxicity evaluation of natural biocides using Sprague-Dawley rats and New Zealand White (NZW) rabbits. Safety of the natural biocide extract of Asarum sieboldii was evaluated using single-dose oral and dermal toxicity tests in Sprague-Dawley rats, and eye and skin irritation tests in NZW rabbits. The extract has proven antimicrobial and insecticidal activities against wood-rotting fungi and termites. After single oral administration to rats, the $LD_{50}$ values were determined to be over 4,000 and 2,000 mg/kg for males and females, respectively. After single dermal administration to rats, the $LD_{50}$ values exceeded 10,000 mg/kg for both males and females. The extract was identified to be non-irritant to the rabbit eye, and only slightly irritant to the rabbit skin. In this study, we confirmed the safety of the A sieboldii extract through animal testing. Due to the harmfulness of humidifier disinfectants, focus is on the safety of chemical pesticides, and toxicity evaluation is suggested as the basic method for hazard evaluation.