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 Pregnant Mouse Model for Evaluating Causal Association with Stillbirth

가습기살균제 CMIT/MIT의 기도 점적투여를 통한 임신마우스의 사산에 대한 영향

  • Kang, Byoung-Hun (GLP Center & Dept. of Toxicity Assessment, Daegu Catholic University) ;
  • Kim, Min-Sun (College of Pharmacy, Sunchon National University) ;
  • Park, Yeong-Chul (GLP Center & Dept. of Toxicity Assessment, Daegu Catholic University)
  • 강병훈 (대구가톨릭대학교 GLP센터 & 화학물질독성평가학과) ;
  • 김민선 (순천대학교 약학대학 약학과) ;
  • 박영철 (대구가톨릭대학교 GLP센터 & 화학물질독성평가학과)
  • Received : 2018.09.20
  • Accepted : 2018.10.20
  • Published : 2018.10.28
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Abstract

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.

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