Toxicity and clearance study of silver nanoparticles in rats

Abstract

은나노의 항균작용은 가전제품, 의료관련 제품, 농약, 가정용품 등 그 활용범위가 광범위하게 적용되어 사용되고 있다. 하지만, 은나노의 인체에 미치는 독성과 생태계에 미치는 영향에 대해서는 여전히 논란이 많다. 본 연구는 56 nm 크기의 은나노와 60 nm 크기의 은나노를 랫드를 이용하여 28일 및 90일 반복경구독성시험을 각각 수행하였다. 수행된 시험은 경제협력개발기구 테스트 가이드 및 우수실험실관리기준에 따라 수행하였다. 암수 랫드는 4개의 군으로 구성되었으며, 경구투여 후 혈액생화학, 혈액학, 조직병리검사 및 은의 조직분포 등을 관찰하였다. 또한, 은나노 경구투여 후 조직 내 은 제거율을 확인하고자 암수 랫드를 3개군으로 구성하여, 10 nm 및 25 nm 크기의 은나노를 사용하여 28일 반복경구투여를 실시하였다. 암수 랫드의 alkaline phoshatase 와 cholesterol 의 현저한 용량의존적인 변화가 28일 및 90일 반복경구독성시험에서 관찰되었다. 은나노의 조직분포 확인 결과, 측정된 모든 장기에서 용량의존적인 축적이 관찰되었으며, 특히 암컷 신장에 축적된 은 농도는 수컷 신장과 비교하여 약 2배가량 높아, 성별차이에 의한 은나노의 축적이 28일 및 90일 반복경구독성시험에서 관찰되었다. 이와 같은 결과를 볼 때, 암수 랫드의 표적장기는 간으로 사료된다. 한편, 은 제거율 연구에서 측정된 대부분 장기의 은농도는 4개월간의 회복기간 동안 점진적으로 감소되었다. 하지만, 뇌 와 고환에 축적된 은 농도는 4개월의 회복기간 후에도 크게 감소되지 않았다. 이는 축적된 은나노가 조직으로부터 쉽게 배출이 되지 않는것을 의미하며, 본 연구에서는 biological barrier 가 은나노 제거율에 영향을 미칠 수 있을 것이라 사료되며 보다 많은 연구가 요구된다.

The antibacterial effect of silver nanoparticles has led to their extensive application in health, electronic, medicinal, pesticide, and home products. Silver nanoparticles, however, remain a controversial area of research with respect to their toxicity in biological and ecological systems. This study tested the oral toxicity in rats of 60 nm silver nanoparticles over a period of 28 days, and of 56 nm silver nanoparticles over a period of 90 days, according to Organization for Economic Cooperation and Development (OECD) test guidelines with Good Laboratory Practices (GLP) application. The male and female rats were divided into four groups. After their exposure to the silver nanoparticles, their blood biochemistry and hematology were investigated, and they were subjected to a histopathological examination and a silver distribution study. Moreover, to clarify the clearance of the tissue silver concentration after the oral exposure of the rats to the silver nanoparticles was stopped, the rats were assigned to three groups and given two silver nanoparticles with different sizes (10 and 25 nm) for 28 days. Some significant dose-dependent changes were found in the alkaline phosphatase and cholesterol values in either the male and female rats in the 28- and 90-day studies. The tissue distribution of the silver nanoparticles showed dose-dependent accumulation of silver content in all the examined tissues. In particular, a gender-related difference in the accumulation of silver nanoparticles was noted in the kidney, with a twofold increase in the female kidneys compared with the male kidneys in the 28- and 90-day studies. The target organ of the silver nanoparticles was found to have been the liver in both the male and female rats. In the clearance test, the tissue silver content of the most tissues in the exposed rats gradually decreased to some extent during four-month recovery period, which indicates clearance of the accumulated silver nanoparticles. In contrast, the tissue concentration of silver in the brain and testis was not cleared well even after the four-month recovery period, which indicates that the accumulated silver nanoparticles may not be easily transported out of the tissues. The results of this study suggest that the tissue with biological barriers such as blood-testis barrier and blood-brain barrier may play an important role in the clearance of silver nanoparticles from the respective tissues.