第一章：绪论Chapter 1: Introduction to Environmental Toxicology

教师： 刘汝涛教授

博导

山东大学环境科学与工程学院

《环境毒理学》

课程/Course Description:The purpose of this course is to give a good overview of environmental toxicology. The emphasis will be on the effects ofenvironmental pollutants on humans. It will cover important principles that govern why certain substances are environmental hazards. It will also cover basic toxicology allowing student tounderstand why substances are toxic and how toxicity is measuredin the laboratory and field. Specific substances relevant to this field of study will be discussed such as acid rain, ozone, organic nutrients, pesticides, metals, PCBs, and petroleum. Meantime, I will introduce you some environmental problems that happened in the world recently.

Toxicology*What is toxicology? The study of the effects

of poisons.

Poisonous substances are produced by plants, animals, or bacteria.

Phytotoxins/植物毒素

Zootoxins/动物性毒素

Bacteriotoxins

Toxicant - the specific poisonous chemical.Xenobiotic - man-made substance and/or produced by but not normally

found in the body.

IntroductionToxicology is arguably the oldest scientific discipline, as the

earliest humans had to recognize which plants were safeto eat.

Most exposure of humans to chemicals is via naturallyoccurring compounds consumed from food plants.

Humans are exposed to chemicals both inadvertently and deliberately. *

What is (environmental )toxicology?

• 1. the study of the adverse effects of xenobiotics(Casarett and Doull’s Toxicology)

• 2. the study of the harmful interactions between chemicals and biological systems. (J.A Timbrell’sToxicology)

• 3.the subject concerned with the study of the noxious effects of chemical substances on living systems. (John Timbrell’s Toxicology)

• 4. the study of the nature and the mechanism of toxic substances on living organisms and other biological systems.

4. Environmental toxicology is the study of the nature, properties, effects and detection of toxic substances in the environment and in any environmentally exposed species, including humans.

This course will provide the understanding of toxicology related to the environment. Fundamental concepts will be coveredincluding dose-response relationships, absorption of toxicants, distribution and storage of toxicants, biotransformation and elimination of toxicants, target organ toxicity, teratogenesis, mutagenesis, carcinogenesis and risk assessment. In the second part of the course, we will study the chemodynamics of contaminants in the environment including fate and transport. The course will examine chemicals of environmental interest and how they are tested and regulated. We will critically review case studies and special topics. I hope you enjoy the course.

History*

50- 400 A.D. - Romans used poisons forexecutions and assassinations暗杀.

The philosopher, Socrates, was executed using hemlock/从芹叶钩吻 制取的毒药 for teaching radical ideas to youths.

Avicenna (A.D. 980-1036) Islamic/伊斯兰教

authority on poisons and antidotes.1200 A.D. - Spanish rabbi Maimonides writes

first-aid book for poisonings,Poisons and Their Antidotes

• Swiss physician Paracelsus(1493-1541) credited with being

• “the father of modern toxicology.”

• “All substances are poisons: there is none which is not a poison. The right dose differentiates a poison from a remedy/药物.”

History*

表1-1 1854年7月8日至8月26日伦敦两个

供水公司供水区的霍乱死亡人数

供水公司 人口数 霍乱死亡人数 霍乱死亡率（‰）

Southwark 167654 644 5.0

Lambeth 19133 16 0.9

死亡病例发生

二、环境毒理学的研究对象、内容及方法

Object, content and method of environmental toxicology1. 对象：

环境污染危害的对象:

2. 主要任务:(1). 人体毒理。

(2). 生态毒理。

3. 环境毒理学的研究内容

4. 环境毒理学的研究方法

The Dose Makes the Poison*

An apparently nontoxic chemical can be toxic at high doses. (Too much of a good thing can be bad).

Highly toxic chemicals can be life saving when given in appropriate doses. (Poisons are not harmful at a sufficiently low dose).

环境毒理学的研究方法: (即研究方案的确定)

(1). 体内试验，也称为整体动物实验：

(2 )、体外实验法

(3). 环境分子毒理学：

(4). 医学流行病学的调查方法应用于环境理学的研究中：

地球目前的寿命是46亿岁，至于未来地球能存在多久，这还是一个未知数。

Our earth

20th Century

Rachel Carson - alarmed publicabout dangers of pesticides in the environment.

History*

Environmental toxicants (airand water pollutants) are substances harmful to the environment and to humans.

Environmental toxicants are both natural andman made.

Public perception理解 that man-made ones are more serious than natural ones - Reality: bothare serious.

5,000,000 yearly deaths worldwide due to bacterial toxicants (Salmonella, E. coli)

Occupational and Environmental Toxicology*

- Industrial chemical workers(1940-present)

Workers typically are exposed to a greater number of carcinogensfor longer periods of time.

Occupations with high risk of cancer :Health care workers, pharmaceutical and laboratory workers, refinery workers, rubber workers, furniture makers, and pesticide workers.

Occupational and Environmental Toxicology*

John Snow对伦敦霍乱的分析是流行病学发展史中重要的一页。

表1-1 1854年7月8日至8月26日伦敦两个供水公司供水区的霍乱死亡人数

供水公司 人口数 霍乱死亡人数 霍乱死亡率（‰）

Southwark 167654 644 5.0

Lambeth 19133 16 0.9

Modern Toxicology*

1961 - Society of Toxicology

1970s - EPA, FDA, and NIOSH

Exposure Concepts*

Exposure to chemicals may come from many sources:

– Environmental– Occupational– Therapeutic– Dietary– Accidental– Deliberate

本章部分参考文献:• 1. Migliaccio, E., Giorgio, M., Mele, S., et.al., The p66shc adaptor protein controls oxidative

stress response and life span in mammals, Nature, 1999, 402(18): 309-313

• 2. 刘宛，李培军，周启星等，环境污染条件下生物体内DNA损伤的生物标记物研究进展，应

用与环境生物学报，2005,11(2): 251-255

• 3. West J.D.,Marnett L.J., Endogenous Reactive Intermediates as Modulators of Cell Signaling and Cell Death, Chem. Res. Toxicol, 2006, Web Pulished (in press)

• 4. Upston J.M.,Niu X.W.,Brown A.J., et al., Disease Stage-Dependent Accumulation of Lipid and Protein Oxidation Products in Human Atherosclerosis, American Journal of Patbology，2002,160(2) :701-710

• 5. Levine R.L.,Stadtman E.R., Oxidative modification of proteins during aging, Experimental Gerontology, 2001,36:1495-1502

• 6. Osawa T.,Kato Y., Protective Role of Antioxdative Food Factors in Oxidative Stress Caused by Hyperglycemia, Ann. N.Y. Acad. Sci, 2005,1043:440-451

• 7.

山东“癌症村”肖家店村：2000年死亡人数17人，其中11人死于

癌症；2001年死亡人数16人，9人是癌症；2002年死亡人数17人，10人是癌症；2003年死亡人数19人，12人是癌症；2004年死亡21人，14人是癌症。村民指出，最近十几年来，上游莱

芜、泰安、宁阳等城市排放的污水不断增加，导致村边的大汶河

严重污染，并且其中的亚硝酸盐都严重超标。从此不仅他们村，

附近马家洼村、李店村的癌症患者都是越来越多 。

中国著名的癌症杀人村！

河南“癌症村”老观嘴村：从上世纪80年代起，邻县先后建起了

很多造纸厂，大都是个体企业或承包企业，这些企业有的排放的

工业废水不达标，有的甚至根本就没有排污净化设备，污水直接

排入河流，导致卫河严重污染。住在两岸的很多村民近年来纷纷

患上肠癌、食道癌、肝癌、胃癌等病，位于河渠交汇处的老观嘴

村情况尤为严重，近年来已有近百人患癌症相继死亡。

天津“癌症村”西堤头村：最近5年来200多人患有癌症，平均

年龄51岁，可怕的是，这些癌症患者都来自同一个乡镇相邻的两

个村庄--天津市西堤头镇西堤头村和刘快庄村。曾经被当地村民

们引以自豪的鱼塘，如今这些河渠两旁都挤满了各类化工企业，

河渠下面暗藏着一个个排污口，渠道内充斥着各种颜色各种气味

的工业废水、废渣，散发着刺鼻的臭味，而其中的一个排污口还

在肆无忌惮地排放着不知从哪个化工厂出来的黑水。

淮河支流诸多“癌症村”：坐落在淮河的支流沙颍河畔的东孙楼

村，280户人中有40多人患了食道癌；沙颍河畔的另一个村子黄孟

营村，10年来死亡的205人中，因癌症死亡的有106人；在淮河最

大支流沙颍河沿岸的河南省沈丘县，出现了多个“癌症高发村”，

当地村民纷纷高价购买桶装纯净水饮用，他们强烈要求政府对沙

颍河沿岸群众健康状况进行普查；沙颍河边一个叫黄孟营的村子

里,14年来已有114名村民因患癌症去世。

无锡“癌症村”广丰村：几年来因癌症去世的20余人，目前已查

出患癌症者有近30人，占了全镇癌症病人总数的60％以上。广

丰村周围都是化工厂，排放的工业废气味道十分难闻，横穿该

村的马家河浜成了石利新村2000户居民生活污水的聚集地，邻

近的液化气公司不断散发出的怪味，让人喘不过气。

面对这触目惊心的事实，人们不仅要问：是谁把田园牧歌般

的乡村，变成了“癌症杀人村”？难道经济的发展非要以牺牲环

境和人的生命为代价？

发展经济、兴建工厂，必然对环境产生一定的影响。但

是，如果开办的工厂企业，严重污染环境，甚至损害群众的生

命安全，这样的工厂企业，根本不该建设；已经建设和生产

的，应该坚决地关闭、停产！！

环境保护是我国的一项基本国策，防治环境污染和生态破

坏，合理开发利用自然资源，关系到国家的全局利益和长远发

展，我们再也不能干那种先污染、后治理的事情了！！！

思考题：

1. 什么是环境毒理学?

2. 环境毒理学的研究内容、研究方法有那些?

Please Note：*Slides are cited from Larry Johnson’s lecture document.Partnership for Environmental Educationand Rural health (PEER) Texas A & M University

All the information used in the lectures of Environmental Toxicology is Used for Teaching only, not for Any kind of Business Activities.