나노입자 흡입시험을 위한 노출시스템 개발 및 성능평가

Abstract

나노 입자에 대한 인체 유해성 평가를 위한 흡입독성 평가방법으로는 나노물질의 노출방법에 따라 전신노출방식(whole-body exposure system)과 비부노출방식(nose-only exposure system)이 있다. 전신노출방식은 챔버내의 rat 또는 mouse 등의 시험 동물에 시험물질을 전신노출시켜 물질의 독성을 평가하는 방법이다. 비부노출방식은 비부에 직접 미량의 시험 물질 노출하는 방법이다. 본 연구에서는 전신노출방식 챔버에서 동물의 breathing zone에서의 시험물질 농도 균질성을 확보하기 위해 다중노즐시스템을 적용하였다. 그 결과 다중노즐시스템을 적용한 챔버가 공간상의 균일도가 향상됨을 확인하였다. 비부노출방식 챔버의 경우 분사 노즐에서 노출되는 유량의 편차가 작도록 설계하였다. 이는 수치적 모사와 실제 노출유량의 측정으로 OECD 흡입독성시험 가이드라인에 적합함을 확인하였다. 비부노출 평가에서 가장 중요한 포트(port)간의 편차가 OECD 흡입독성시험 Guideline에 적합함을 확인하였다. 흡입독성 시험시 동물에게 노출되도록 정해진 농도를 정확하고 빠르게 도달하고 유지하는 것이 매우 중요하다. 이를 위하여 에어로졸 유량을 직접 정확히 조절하는 방식을 적용하여 농도부분배기를 개발하였다. 개발된 분배기는 농도의 공비에 따른 농도의 구배가 이루어 짐을 확인하였고 시간에 따른 변화를 확인하였다. 평가 결과 독성평가에 적합함을 확인하였다.|The methods of inhalation toxicity that evaluate the safety of nanoparticles on human healthy can be divided by the means of exposure: Whole-body exposure system and nose-only exposure system. The whole-body exposure system is the method of assessing the toxicity of the test substance by settling the test animals, such as rats or mice, in the exposure chamber and exposing the substance over the entire body. The nose-only exposure system is the method that exposes a tiny amount of test substance directly to the nose of the test animals. In order for this study to secure the high uniformity in the concentration of the test substance at the animal breathing zone in the whole-body exposure chamber, the multi-nozzle system is applied. As a result of the application of the multi-nozzle system, it is verified that the concentration uniformity has been increased. The nose-only exposure chamber is designed to reduce the variation of flow rate among the injection nozzles. It is verified that the chamber design is in compliance with OECD Inhalation test guideline by measurement of the actual flow rate and the numerical analysis. The variation among the ports, which is the most important aspect of nose-only exposure study, is verified in compliance with OECD Inhalation test guideline. To expose the substance to the test animals during the exposure study, it is crucial that the test substance reaches the target concentration quickly and maintains the concentration accurately. For this reason, a concentration dispenser, which can directly and accurately control aerosol flow rate, has been developed. This equipment has verified the following aspects, the concentration gradient according to dilution ratio and concentration variation over the time.; The methods of inhalation toxicity that evaluate the safety of nanoparticles on human healthy can be divided by the means of exposure: Whole-body exposure system and nose-only exposure system. The whole-body exposure system is the method of assessing the toxicity of the test substance by settling the test animals, such as rats or mice, in the exposure chamber and exposing the substance over the entire body. The nose-only exposure system is the method that exposes a tiny amount of test substance directly to the nose of the test animals. In order for this study to secure the high uniformity in the concentration of the test substance at the animal breathing zone in the whole-body exposure chamber, the multi-nozzle system is applied. As a result of the application of the multi-nozzle system, it is verified that the concentration uniformity has been increased. The nose-only exposure chamber is designed to reduce the variation of flow rate among the injection nozzles. It is verified that the chamber design is in compliance with OECD Inhalation test guideline by measurement of the actual flow rate and the numerical analysis. The variation among the ports, which is the most important aspect of nose-only exposure study, is verified in compliance with OECD Inhalation test guideline. To expose the substance to the test animals during the exposure study, it is crucial that the test substance reaches the target concentration quickly and maintains the concentration accurately. For this reason, a concentration dispenser, which can directly and accurately control aerosol flow rate, has been developed. This equipment has verified the following aspects, the concentration gradient according to dilution ratio and concentration variation over the time.