Journal of Environmental Health Sciences (한국환경보건학회지)

Korean Society of Environmental Health (한국환경보건학회)
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Intra-tracheal Administration of the Disinfectant Chloromethylisothiazolinone/methylisothiazolinone (CMIT/MIT) in a Mouse Model to Evaluate a Causal Association with Death

마우스의 기도 내 점적을 통한 가습기살균제 CMIT/MIT와 사망 간의 원인적 연관성에 관한 연구

  • Kim, Hayoung (GLP Center & Dept. of Toxicity Assessment, Daegu Catholic University) ;
  • Chung, Yonghyun (Occupational Safety and Health Research Institute) ;
  • Park, Yeongchul (GLP Center & Dept. of Toxicity Assessment, Daegu Catholic University)
  • 김하영 (대구가톨릭대학교 GLP센터 & 화학물질독성평가학과) ;
  • 정용현 (산업안전보건연구원) ;
  • 박영철 (대구가톨릭대학교 GLP센터 & 화학물질독성평가학과)
  • Received : 2017.07.20
  • Accepted : 2017.08.10
  • Published : 2017.08.28
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Abstract

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.

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