• Journal of Environmental Health Sciences
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• v.48 no.3
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• pp.183-194
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• 2022

Background: No study has examined the regulatory factors associated with fatal health problems due to the use of humidified disinfectants (HD) in South Korea. Objectives: This study aimed to identify and discuss the deficiencies and limitations found in the Toxic Chemical Control Acts (TCCA) that failed to prevent the health risk of chemicals in HD products. Methods: The South Korean TCCA was reviewed focusing on acts in operation from 1994 through the end of 2011, the period when HD was allowed in manufacturing and marketing. Results: The TCCA was the act intended to regulate the toxicity of chemicals in HD products. We found the TCCA to lack three key legal clauses which would have been essential to controlling the health risk of HD. First, there was the exemption of toxic and hazard testing for existing chemicals, including chloromethylisothiazolinone (CMIT), methylisothiazolinone (MIT), and benzalkonium chloride (BKC). Secondly, there were no articles requiring industry to provide animal inhalation test result for polymers such as polyhexamethylene guanidine (PHMG) and Oligo(2-)ethoxyethoxyethyl guanidine chloride (PGH). Finally, there was a lack of articles on examining the risk of products as well as on addressing changes in the usage of products. These articles were found to be generally provided in the US Toxic Substance Chemical Act (TSCA) and the EU Registration, Evaluation and Authorization of Chemicals (REACH). Conclusions: In conclusion, the Ministry of Environment of South Korea had not updated key articles for regulating hazardous chemicals, causing large-scale health problems due to HD which had been fundamentally addressed in chemical-related acts in other countries.

• Journal of Ginseng Research
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• v.13 no.2
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• pp.202-210
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• 1989

The effects of Ginseng saponins on the in vitro biosynthesis of prostaglandins were examined in order to identify the role of some Ginseng components on the regulation of arachidonic arid metabolism. The productions of prostaglandin $E_2$ (PG$E_2$), $F_2$ (PGF2), thromboxane $B_2$(TX$B_2$) and 6-ketoprostaglandin Fl (6-Keto-PGF1) from [3Hl-arachidonic acid were evaluatpf by radiochromatographic analysis with rabbit kidney microtome, human platelet homogenate and bovine aortic microsome. The amounts of the total prostaglandins produced by cyclooxygenase activity and malondialdehyde from arachidonic acid didn't show significant changes in the presence of Ginseng saponins. Both of panaxadiol and panaxatriol didn't affect the production of PG$E_2$ while the formations of PG$F_2$( and TX$B_2$( were nearkedly reduced and the production of prostacyclin was increased. The formation of TXBE was reduced by ginsenoside $Rb_2$, Rc, and Re, however the production of 6-Keto-PGF1 was increased dose dependently up to 1 mg/ml. Moreover, platelet aggregations induced by arachidonic acid and U46619 (9.11-methanepoxy PG$H_2$), TX$A_2$ mimetics, were also inhibited by three ginsenosides. The effect of G-Re on prostacyclin synthetase was inhibited by tranylcypromine, prostacyclin synthetase inhibitor. These results suggest that Ginseng saponins may not directly act on cyclooxygenase but affect on the divergent pathway from endoperoxide.

• Archives of Pharmacal Research
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• v.29 no.5
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• pp.375-383
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• 2006

The anti platelet effects of a novel guanidine derivative, KR-32570 ([5-(2-methoxy-5-chlorophenyl) furan-2-ylcarbonyl]guanidine), were investigated with an emphasis on the mechanisms underlying its inhibition of collagen-induced platelet aggregation. KR-32570 significantly inhibited the aggregation of washed rabbit platelets induced by collagen $(10{\mu}g/mL)$, thrombin (0.05 U/mL), arachidonic acid $(100{\mu}M)$, a thromboxane (TX) $A_2$ mimetic agent U46619 (9,11-dideoxy-9,11-methanoepoxy-prostaglandin $F_2,\;1{\mu}M$) and a $Ca^{2+}$ ATPase inhibitor thapsigargin $(0.5{\mu}M)$ ($IC_{50}$ values: $13.8{\pm}1.8,\;26.3{\pm}1.2,\;8.5{\pm}0.9,\;4.3{\pm}1.7\;and\;49.8{\pm}1.4{\mu}M$, respectively). KR-32570 inhibited the collagen-induced liberation of $[^3H]$arachidonic acid from the platelets in a concentration dependent manner with complete inhibition being observed at $50{\mu}M$. The $TXA_2$ synthase assay showed that KR-32570 also inhibited the conversion of the substrate $PGH_2$ to $TXB_2$ at all concentrations. Furthermore, KR-32570 significantly inhibited the $[Ca^{2+}]_i$ mobilization induced by collagen at $50{\mu}M$, which is the concentration that completely inhibits platelet aggregation. KR-32570 also decreased the level of collagen $(10{\mu}g/mL)$induced secretion of serotonin from the dense-granule contents of platelets, and inhibited the NHE-1-mediated rabbit platelet swelling induced by intracellular acidification. These results suggest that the antiplatelet activity of KR-32570 against collagen-induced platelet aggregation is mediated mainly by inhibiting the release of arachidonic acid, $TXA_2$ synthase, the mobilization of cytosolic $Ca^{2+}$ and NHE-1.

• Journal of Environmental Health Sciences
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• v.47 no.3
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• pp.193-204
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• 2021

Objectives: In January 2021, the former heads of the manufacturer SK Chemical and the vendor Aekyung were acquitted for manufacturing and selling humidifier disinfectant (HD) containing 5-chloro-2-methylisothiazol-3(2H)-one/2-methylisothiazol-3(2H)-one (CMIT/MIT). In this article, we analyzed the rationale used in this judgement in the light of scientific consideration. Methods: The sentencing document for the judgements was obtained from the Korea Supreme Court Service. In particular, the judgements made by the court related to the toxicological and individual association with HD perspectives were discussed based on scientific evidence. Results: The ruling stated that the necessary conditions for causality between CMIT/MIT and such diseases were not met based on the fact that asthma and lung damage were not found in the inhalation exposure animal experiments. The judgment overlooked the inevitable limitations of using animal experiments for verifying health effects in humans, which are often inconsistent with the observations in animals. Among 11 governmentaffirmed lung injury cases with CMIT/MIT usage, three patients' humidifier disinfectant-associated lung injury (HDLI) pathology proved that CMIT/MIT could cause lung injury similar to that caused by PHMG and PGH. In addition, five children showed decreased lung function related to damage caused by humidifier disinfectant exposure. Conclusions: We conclude that there is sufficient evidence supporting the assertion that HDs containing CMIT/MIT cause lung injuries, including asthma, contrary to the court's decision.

• Journal of Environmental Health Sciences
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• v.44 no.4
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• pp.301-314
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• 2018

Objectives: The aim of this study was to introduce the overall progress of exposure assessment to humidifier disinfectant (HD); to present participants' demographic characteristics, exposure characteristics to humidifier disinfectant, and exposure classification; and furthermore to compare those characteristics between survivors and non-survivors. Methods: An assessment of environmental exposure to HD was conducted using modified HD-specific questionnaires that had been previously validated. We analyzed the data from 4,482 participants who had been potentially exposed to HD and had registered with the KEITI (Korea Environmental Industry & Technology Institute) from September 2016 to May 2018 (the fourth survey). Environmental exposure assessments were performed as follows: 1) contact with participants, 2) environmental exposure assessment though face-to-face interviews, 3) assessment review and coding, and 4) exposure rating. Results: Overall, survivors made up 77.1% (3,457 subjects) and non-survivors made up 22.9% (1,025 subjects). When compared with the survivors, non-survivors had a higher proportion of subjects aged >60 years and subjects who answered as suffering lung damage and having purchased HD because it is "Beneficial to health" (p<0.05). For the exposure characteristics compared to survivors, non-survivors had a higher proportion of cases of distance from humidifier to face being less that one meter and the spray direction being toward the face (p<0.05). Overall, respondents who used the "Oxy Ssak Ssak New Gaseupgi Dangbun", "Aekyung Gaseupgi Mate", "Homeplus Gaseupgi Chungjungje", and "E-Mart Gaseupgi Salgyunje" products made up 66.1, 12.3, 4.0, and 3.6%, respectively, and 72.5% of respondents used products with PHMG as the active chemical. When compared with survivors, non-survivors had a higher proportion of use of "Oxy Ssak Ssak New Gaseupgi Dangbun" but a lower proportion of use of products with CMIT/MIT, PGH, or PHMG as the active chemical. Conclusions: This study provided demographic characteristics and exposure assessment for applicants who have been injured by HD. In spite of the limitations of performing past exposure assessment through a questionnaire survey, such as recall bias, useful results may be obtained by comparing survivors with non-survivors. Further studies such as the exposure rating method and so on are necessary to assess past exposure to HD.

• 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.