課程大綱

課程資訊

課程名稱

呼吸毒理學概論
Fundamentals of Inhalation Toxicology

開課學期

101-2

授課對象

公共衛生學院職業醫學與工業衛生研究所

授課教師

鄭尊仁

課號

OMIH7038

課程識別碼

841 M1690

班次

學分

全/半年

半年

必/選修

選修

上課時間

星期二7,8(14:20~16:20)

上課地點

公衛212

備註

總人數上限：25人

Ceiba 課程網頁

http://ceiba.ntu.edu.tw/1012IT

課程簡介影片

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課程概述

本課程對象為公衛學院環衛所與職衛所及其他相關系所對呼吸毒理有興趣之碩士及博士班研究生。上課方式包括講演與討論及實驗課程，內容包括呼吸暴露系統的建立與監測、呼吸道生物學、呼吸道對吸入物質的毒理反應等。

課程目標

使學生瞭解呼吸毒理基本原理，作為呼吸毒理研究的基礎。

課程要求

課前閱讀指定教材及上課參與討論。

預期每週課後學習時數

Office Hours

指定閱讀

2013呼吸毒理學課程大綱

教科書："Inhalation Studies: Foundations and Techniques", Second Edition, Edited by
Robert F. Phalen. Informa Healthcare, 2008

2/19.簡介
Michael A. Dorato. 1990. Overview of Inhalation Toxicology. Environmental Health Perspectives Vol. 85, pp. 163-170.

2/26. 微粒產生及監測
Phalen. Ch3,4

3/5. 氣體產生及監測
討論：比較微粒及氣體產生及監測之異同
Phalen, Ch3,4

3/5. 暴露系統
討論：比較全身及鼻部暴露之優缺點，參觀暴露腔
Phalen, Ch5

3/12. 報告：奈米微粒暴露系統
比較不同奈米產生儀器
1. Manabu Shimada. 2009.Development and Evaluation of an Aerosol Generation and Supplying System for Inhalation Experiments of Manufactured Nanoparticles. Environ. Sci. Technol 43, 5529–5534
2. 李曜全.可控制奈米微粒產生技術開發.2008.勞工安全衛生研究季刊第17卷第2期第153-162頁
3. Jun Ho Ji et al.2007.Long-Term Stability Characteristics of Metal Nanoparticle Generator Using Small Ceramic Heater for Inhalation Toxicity Studies. Inhalation Toxicology, 19:745-751
4. Philip Demokritou et al.2010. Development and characterization of a Versatile Engineered Nanomaterial Generation System (VENGES) suitable for toxicological studies. Inhalation Toxicology,22(S2):107-116.

3/26, 4/02 實驗
Meng Ho, Kuen-Yuh Wu, Hung-Min Chein, Lung-Chi Chen, Tsun-Jen Cheng (2011, Nov). Pulmonary toxicity of inhaled nanoscale and fine zinc oxide particles: Mass and surface area as exposure metric. Inhalation Toxicology, 23(14): 947–956.

4/16. 呼吸道結構與功能（包括沈積清除等防衛機轉）
討論：比較人類與動物結構之異同
Phalen. Ch2

4/23. 毒性測試
Phalen. Ch6

4/30大氣微粒呼吸毒理研究
1. Cheng TJ*, Hwang JS, Wang PY, Tsai CF, Chen CY, Lin SH, Chan CC. Effects of concentrated ambient particles on heart rate and blood pressure in pulmonary hypertensive rats. Environ Health Perspect 2003;111:147-50. (SCI)
2. Cheng TJ*, Kao HP, Chan CC, Chang WP. Effects of ozone on DNA single-strand breaks and 8-oxoguanine formation in A549 cells. Environ Res 2003;93:279-84. (SCI)
3. Lei YC, Chan CC, Wang PY, Lee CT, Cheng TJ*. Effects of Asian dust event particles on inflammation markers in peripheral blood and bronchoalveolar lavage in pulmonary hypertensive rats. Environ Res 2004;95:71-6. (SCI)
4. Chang CC, Hwang JS, Chan CC, Wang PY, Cheng TJ*. Effects of concentrated ambient particles on heart rate, blood pressure, and cardiac contractility in spontaneously hypertensive rats. Inhal Toxicol 2004;16:421-9. (SCI)
5. Lei YC, Chen MC, Chan CC, Wang PY, Cheng TJ*. Effect of concentrated ambient particles on airway responsiveness and pulmonary inflammation in pulmonary hypertensive rats. Inhal Toxicol 2004;16:785-792. (SCI)
6. Lei YC, Hwang JS, Chan CC, Lee CT, Cheng TJ*. Enhanced oxidative stress and endothelial dysfunction in streptozotocin-diabetic rats exposed to fine particles. Environ Res 2005;99:335-43. (SCI)
7. Chang CC, Hwang JS, Chan CC, Wang PY, Cheng TJ*. Effects of concentrated ambient particles on heart rate variability in spontaneously hypertensive rats. J Occup Health 2005;47:471-80. (SCI).
8. Chang CC, Hwang JS, Chan CC, Cheng TJ*. Interaction effects of ultrafine carbon black with iron and nickel on heart rate variability in spontaneously hypertensive rats. Environ Health Perspect 2007;115:1020-7 (SCI).
9. Chang CC, Hwang JS, Chan CC, Wang PW, Cheng TJ*. Effects of concentrated ambient particles on heart rate, blood pressure, and cardiac contractility in spontaneously hypertensive rats during a dust storm event. Inhal Toxicol 2007;19:973-8 (SCI).

5/7奈米微粒呼吸毒理研究：
1. Meng Ho, Kuen-Yuh Wu, Hung-Min Chein, Lung-Chi Chen, Tsun-Jen Cheng (2011, Nov). Pulmonary toxicity of inhaled nanoscale and fine zinc oxide particles: Mass and surface area as exposure metric. Inhalation Toxicology, 23(14): 947–956.

2. Hsiao-Chi Chuang, Hung-Tzu Juan, Yuan-Horng Yan, Tzu-Hsuen Yuan, Jyh-Seng Wang, Hao-Cheng Chen, Yaw-Huei Hwang, Chii-Hong Lee, Tsun-Jen Cheng. Cardiopulmonary toxicity of pulmonary exposure to occupationally-relevant zinc oxide nanoparticles.

3. Hsiao-Chi Chuang, Ta-Chih Hsiao, Cheng-Kuan Wu, Hui-Hsien Chang, Chii-Hong Lee, Chih-Cheng Chang, Tsun-Jen Cheng: Allergenicity and toxicology of inhaled silver nanoparticles in allergen provocation mice models

5/14 報告：呼吸毒理期刊
大氣微粒濃縮的原理及毒性研究
1. Constantinos Sioutas et al. 1995. A technique to expose animals to concentrated fine ambient aerosols. Environment Health Perspectives, 103:172-177
2. Polina Maciejczyk, Mianhua Zhong, Qian Li, Judy Xiong,Christine Nadziejko, and Lung Chi Chen. 2005Effects of Subchronic Exposures to Concentrated Ambient Particles (CAPs) in Mice: II. The Design of a CAPs Exposure System for Biometric Telemetry Monitoring. Inhalation Toxicology, 17:189–197
3. Qinghua Sun et al.2005. Long-term Air Pollution Exposure and Acceleration of Atherosclerosis and Vascular Inflammation in an Animal Model. JAMA, 294(23):3003-3010

奈米呼吸毒理研究
1. Yasuo Morimoto et al.2010. Inflammogenic effect of well-characterized fullerenes in inhalation and intratracheal instillation studies. Particle and Fibre Toxicology, 7:4
2. Gi Soo Kang et al. 2011. Long-term inhalation exposure to nickel nanoparticles exacerbated atherosclerosis in a susceptible mouse model. Environment Health Perspectives, 119(2):176-181
3. William S et al.2005. Comparing Inhaled Ultrafine versus Fine Zinc Oxide Particles in Healthy Adults. American Journal of Respiratory and Critical Care Medicine vol 171
4. Scott C. Wesselkamper et al. 2001. Development of pulmonary tolerance in mice exposed to zinc oxide fumes. Toxicological Science 60,144-151

奈米銀呼吸毒理研究：
1. Ji JH et al.2007. A twenty eight- day inhalation toxicity study of silver nanoparticles in Sprague-Dawley rats. Inhal Toxicol ;19:857–71
2. Jae Hyuck Sung et al. 2008. Lung function changes in Sprague-Dawley rats after prolonged inhalation exposure to silver nanoparticles. Inhal Toxicol;20: 567–74
3. Jae Hyuck Sung et al. 2009. Subchronic Inhalation Toxicity of Silver Nanoparticles. Toxicological Sciences, 108(2),452-461
4. Jae Hyuck Sung et al. 2010. Acute inhalation toxicity of silver nanoparticles . Toxicology and Industrial Health; 27(2) 149–154

動物實驗倫理(動物實驗準則)
Society of Toxicology . 1999.Guiding Principles in the Use of Animals in Toxicology

氣管灌注；
討論：比較呼吸及氣管灌注暴露方法
1. Joseph D Brain et al.1975. Pulmonary distribution of particles given by intratracheal instillation or by aerosol inhalation. Environmental Research 11,13-33
2. B K J. Leong et al.1998. Quantitative morphometric analysis of pulmonary deposition of aerosol particles inhaled via intratracheal nebulization, intratracheal instillation or nose-only inhalation in rats. J. Appl. Toxicol. 18, 149–160
3. Yasuo Oka et al. 2006.A reliable method for Intratracheal Instillation of Materials to the Entire Lung in Rats. J Toxicol Pathol. 19:107-109.

參考書目

a. ”Concepts in Inhalation Toxicology.” Edited by R.O McClellan and R.F
Henderson 2nd edition.1995, Taylor and Francis, Washington, DC
b. "Methods in Inhalation Toxicology", Edited by
Robert F. Phalen. CRC Press, 1997

評量方式
(僅供參考)

No.	項目	百分比	說明
1.	期末口頭及書面報告	40%
2.	期中考	40%
3.	上課參與及報告	20%

課程進度

週次	日期	單元主題
第1週	02/19	Introduction
第2週	02/26	Generation and characterization of aerosols (Ch 3,4)黃盛修老師
第3週	03/05	Generation and monitoring of gas (Ch 3,4) 討論:比較微粒及氣體產生及監測之異同 Methods for Exposing Subjects (Ch 5) 討論:比較全身及鼻部暴露之優缺點
第4週		報告：比較不同奈米產生儀器
第5週	03/19	停課（院評鑑）
第6週	03/26	儀器原理簡介 Laboratory (nanoparticles generation）
第7週	04/02	Laboratory (nanoparticles generation )
第8週	04/09	Midterm
第9週	04/16	Morphology of the respiratory tract and function (Ch2) 討論:比較人類與動物結構之異同
第10週	04/23	Toxicity testing (Ch6)
第11週	04/30	Inhalation toxicity of air pollution
第12週	05/07	Inhalation toxicity of nanoparticles
第13週	05/14	報告：呼吸毒理期刊論文及比較呼吸及氣管灌注暴露方法 Ethics of animal research Laboratory and Safety
第14週	05/21	Laboratory (intratracheal instillation and lavage; staining and scoring)
第15週	05/28	Laboratory (intratracheal instillation and lavage; staining and scoring)
第16週	06/04	Laboratory (lung function)
第17週	06/11	Oral presentation
第18週	06/18	Final