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KMID : 1156220180440050468
Journal of Environmental Health Sciences
2018 Volume.44 No. 5 p.468 ~ p.479
Intra-tracheal Administration of the Disinfectant Chloromethylisothiazolinone/methylisothiazolinone (CMIT/MIT) in a Pregnant Mouse Model for Evaluating Causal Association with Stillbirth
Kang Byoung-Hun

Kim Min-Sun
Park Yeong-Chul
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 C57BL/6 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 LD50-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.
KEYWORD
Humidifier disinfectants , CMIT/MIT , developmental toxicity test , intra-tracheal instillation , stillbirth
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