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Invited Review

Toxicologic Pathology, 34:319–326, 2006


Copyright 
C by the Society of Toxicologic Pathology

ISSN: 0192-6233 print / 1533-1601 online


DOI: 10.1080/01926230600773958

Traditional Toxicity Documentation of Chinese Materia


Medica—An Overview
ALBERT Y. LEUNG

Phyto-Technologies, Inc., Woodbine, Iowa 51579, USA

ABSTRACT
Documentation of Chinese materia medica (CMM) dates back to around 1,100 BC when only dozens of drugs were first described. By the end of the
16th century, the number of drugs documented had reached close to 1,900. And by the end of the last century, published records of CMM have reached
12,800 drugs. The recorded traditional information includes toxicities, incompatibilities, cautions, precautions and contraindications. Thus, contrary
to a general misconception, toxicity data on Chinese herbs exist and are not meager. If consulted properly before embarking on a study of CMM, it will
save researchers much time and efforts and the frustration of not obtaining consistent or expected results. The history of documentation is reviewed
with examples of major classic and contemporary works highlighting and emphasizing the manner in which CMM toxicities have traditionally been
documented through clinical experience as opposed to most modern toxicity data that are based on animal experimentation.
Keywords. Chinese materia medica; Chinese herbs; traditional Chinese medicine; toxicity; history of Chinese medicine; toxicity documentation.

INTRODUCTION outside of China) be presented to interested researchers, pro-


Traditional Chinese medicine (TCM) is a well-established viding them with some basic information regarding the tradi-
system of healthcare with over 3,000 years of continuous doc- tional properties of these materials and their major differences
umentation. No other healthcare systems in the world (mod- from conventional drugs or botanicals intended for use solely
ern or ancient) can claim such a distinction. Among its various as raw materials for modern drug discovery and development.
aspects that include diagnostics, acupuncture, moxibustion, To properly evaluate traditional Chinese medicines for their
qigong exercises, tuina massage, and materia med- documented values that will lead to relevant and reproducible
ica, the last is probably the most important. Chinese mate- results, one must have some appreciation for how data on the
ria medica (CMM), often referred to simply as traditional properties and toxicities of Chinese traditional drugs have
Chinese herbs or traditional Chinese medicines, is impor- been generated and periodically revised over the past 3 mil-
tant not just to TCM in modern practice, it is also important lennia. This review attempts to provide some such informa-
to modern American healthcare, as an increasing number of tion. Its focus will be on information directly related to CMM
Americans is using it as an alternative therapeutic modal- as a whole, and not on any isolated chemical components.
ity to conventional drugs as well as in dietary supplements.
Although to date no systematic investigations have been con- INTERPRETATION AND ENGLISH TRANSLITERATION OF TCM
ducted on the efficacy and safety of CMM that reflect its true One of the most difficult, but essential, tasks in study-
toxicity and/or value as they relate to its long-documented lit- ing the safety and efficacy of CMM is the interpretation of
erature, it is simply a matter of time before such studies need its writings. These are often esoteric and cannot be easily
to be undertaken to protect the health of the American public equated to modern pharmacologic and medical terms. Once
and to provide them with truly alternative choices in their a term or concept is misinterpreted using modern terminol-
healthcare. For these reasons, it is imperative that the gen- ogy, without simultaneously providing the original charac-
eral facts regarding CMM documentation (hitherto still little ters describing it, the original meaning will not be conveyed
known to the modern scientific and medical communities and even may be lost, which would lead to wrong conclu-
sions and irreproducible results. A typical example is the
Chinese term/concept of qu feng , literally meaning “re-
Address correspondence to: Albert Y. Leung, Phyto-Technologies, Inc., moving wind or expelling wind,” but its true meaning has
107 Enterprise Drive, Woodbine, IA 51579, USA; e-mail: ayl@earthpower. something to do with “relieving rheumatic pain and the com-
com mon cold.” If a scientist who reads Chinese but does not
Abbreviations: CMM: Chinese materia medica, Chinese medicines,
Chinese herbs, Chinese drugs, Chinese herbal drugs; TCM: Traditional understand TCM intended to study a CMM with qu feng
Chinese medicine; Pharmacopoeia: Chinese Pharmacopoeia; Pharma- properties misinterpreted it as related to “flatulence,” the
copoeia of the People’s Republic of China. expected “anti-flatulence” result of the subject herb would
319
320 LEUNG TOXICOLOGIC PATHOLOGY

not be obtained. If this negative result were published without HISTORICAL BACKGROUND
providing the original Chinese characters (or at least a proper Chinese materia medica consists of drugs derived from
transliteration) for the indication or the property studied, no botanicals, minerals and animals, with the botanical ones
other researchers could reproduce the results. Consequently, making up the majority. It is a key and integral part of TCM,
while modern science has just started to discover the poten- which also includes other therapeutic modalities, as men-
tial of CMM and tries to validate its safety and efficacy, it tioned earlier. The use of CMM dates back several thousand
is important always to accompany modern interpretations of years. However, as evidence available to date shows, its writ-
TCM concepts with their original Chinese characters, or at ten documentation did not start until only around 1,100 B.C.
least a standardized transliteration of them. (Leung, 1990). Since then, information on Chinese herbs has
Over the past century, various methods of transliteration evolved from sketchy mentions in ballads and geographic
of Chinese characters have been used. The two best known works, to works devoted to disease treatment, and eventu-
are the Wade-Giles and Pinyin systems. The former domi- ally culminating in monumental works exclusively devoted
nated the TCM literature for many decades until the latter to individual CMM and their prescriptions. All these publica-
was widely adopted beginning in the 1980s. Currently, the tions contain information on safety, toxicity, incompatibility,
Pinyin system is the predominant one used worldwide ex- precaution, and caution. Major works spanning a 3,000-year
cept for the literature emanating from Taiwan. The Library period are highlighted in Table 1 (Leung, 1990, 2001).
of Congress and the National Library of Medicine still hold Due to the nature of CMM practice that relies totally on
a sizable amount of information in the Wade-Giles translit- direct clinical experience with humans over time, there are
eration. Because of this lack of uniformity in one of the most no precise toxicity data like those of modern pharmaceuticals
important tools in the description and interpretation of TCM, generated from animal and in vitro experimentation. Nor are
much confusion exists in the identities of CMM. This conse- there any data on enzyme inhibitors, receptor agonists, recep-
quently is a major source of irreproducible results in research tor antagonists, or the like, which are often used to describe
and clinical applications involving TCM that requires the in- mechanisms of action of chemicals, including toxic ones.
terpretation of traditional TCM concepts. What is available in traditional toxicity data includes general
In addition, as with other traditional and botanical information accumulated over time that ranges from decades
medicines, traditional Chinese drugs often have multiple to centuries, based on collective data from different accounts,
names. Some of these are traditional ones recorded in well- not from a single episode based on any particular herbal sam-
known herbals over many centuries. However, the majority ple from any particular locality. Such documentation can be
deals with vernacular names that vary from region to region. viewed as word-of-mouth, but it has been generally based
Sometimes numerous names apply to a single drug while on multiple occurrences vetted over time before it entered
other times a single name applies to multiple drugs. Thus,
even without the transliteration (Wade-Giles or Pinyin) is-
sues, correct identity of CMM is already a major problem. TABLE 1.—Examples of major works impacting Chinese materia medica.
And this is another major source of irreproducibility in CMM
research and modern clinical practice. Title Historial period Comments

For lack of a universally standardized system for nam- Shi Jing (Book of 1,100–600 BCBallads reflect everyday life
Ballads) during that period; mentions
ing Chinese herbal drugs, the standardized names (standard- plum, peach, and lycium
ized common names, Latin binomials, and Pinyin transliter- (wolfberry) as edible but
ations) in the Herbs of Commerce, 2nd Edition (McGuffin cang’erzi , xanthium
et al., 2000) for CMM are used in this review. Since it is the fruit (a common CMM for
sinusitis) as toxic
only authoritative work available with standardized names Shan Hai Jing 770–221 BC Ancient geographic text; mentions
for botanicals in commerce, it was adopted by the United (Mountain & Sea many common CMM,
Ballads) including the highly toxic mang
States Food and Drug Administration as an official standard
cao that is sometimes
for the labeling of botanical ingredients in dietary supple- confused with star anise
ments effective January 1, 2006 [21 CFR 101.4(h)]. How- Wu Shi Er Bing Fang 1065–771 BC First work dedicated to disease
ever, the FDA withdrew the Direct Final Rule on December (Rx for 52 Diseases) treatment with CMM; describes
>283 prescriptions for 52
28, 2005 after adverse comments by a Siberian ginseng com- diseases, involving 247 drugs
pany that objected to the new standard common name of Shennong Bencao Jing 100 BC–200 AD First work dedicated exclusively
(The Shennong to CMM, their sources,
“eleuthero” for “Siberian ginseng” used in this work, thus Herbal) properties, indications,
delaying its adoption as the labeling standard. Despite this incompatibilities, and
status, the book contains only about 500 Chinese botanicals, toxicities; describes 365 CMM,
classified into 3 categories
which are a small fraction of the over 12,800 known CMM based on properties
documented in the Chinese literature (Institute of Chinese Bencao Gangmu 1592–1596 AD Compiled by Li Shi-Zhen;
Materia Medica, 1996). Hence, for CMM that are not found in (Compendium of describes 1,892 drugs &
CMM) >11,000 prescriptions
the Herbs of Commerce but are quoted in this review, the com- Zhonghua Bencao (The 1999 Monumental work in 10 volumes;
mon standardized Pinyin names and/or the corresponding Chinese Herbal) documents ∼9,000 CMM, with
Latin binomials recorded in credible publications, including both traditional and modern
scientific data
recent Chinese Pharmacopoeias and major works compiled Zhongyi Fangji Da 1993–1997 Detailed description of >100,000
by joint efforts of major Chinese institutions are used (Phar- Cidian (Encyclopedia classic prescriptions recorded
macopoeia, 1963–2005; Pharmacopoeia of the People’s Re- of TCM Rx) through the centuries; in 11
volumes
public of China, 2000; Zhonghua Bencao, 1999; Luo, 2003).
Vol. 34, No. 4, 2006 CHINESE MATERIA MEDICA TOXICITY 321

the traditional literature. As a corollary, in the modern doc- extensive use today, few, if any, have more than 75 years of hu-
umentation of scientific research, any published report from man experience. In contrast, some of the Chinese medicines
a single source (laboratory, institution, or clinic) is only con- have been used in humans for several millennia, with docu-
sidered credible and the reported results valid when these mentation of their safety and toxicity for at least 3,000 years.
results are reproduced by others. In addition, as in the case with modern allopathic drugs, new
There are no uniform methods of assessing the toxic effects uses and toxicities continue to be discovered and recorded, al-
of herbs in general and CMM in particular. Modern scientific beit in Chinese, which makes these data generally unavailable
techniques may involve acute and subacute testing that have to the modern scientific and medical communities. Conse-
been devised for modern chemical drugs, and are thus not quently, there is a general belief among scientists and health-
readily applicable to multicomponent systems like CMM and care professionals that there are no toxicity or efficacy data of
foods. Hence, it is extremely difficult to predict the adverse any kind in CMM. But, that is not true. In fact, such data exist.
effects of herbs based simply on such evaluation of a toxic It’s just that they are not universally available in any major
chemical present in these herbs. Yet, such interpretative and non-Chinese literature or databases. In this review, attempts
extrapolative assessments are often used exclusively to de- will be made to present major publications, both classical
fine the toxic effects of CMM. Many of the recorded adverse and recent, some of which specifically deal with traditional
reactions thus far attributed to CMM in the modern litera- toxicity data of CMM. Although most are in Chinese, they
ture have been equivocal, due to problems inherent in current can be readily accessed and its relevant portions be translated
CMM research. These problems include dubious identity of by any reasonably knowledgeable Chinese-reading scholars
subject herbs, misappropriation of a single chemical for the or scientists, who need not conduct extensive research to dis-
total activity of an herb, and the bias of conventional medical cover these sources, as the basic information and approach
and pharmacological researchers, who undertake the studies will be provided in this review.
or report on the findings, albeit often unintentional. The most Many toxicity studies using modern scientific methods
notorious yet well-publicized and widely quoted “adverse have been conducted on CMM-related materials (isolated
effects” of “ginseng” is the classic report by Siegel (1979) chemicals, chemical fractions, extracts, etc.) over the past
which coined the term “ginseng abuse syndrome,” consist- 75 or so years. However, most toxicity data resulting from
ing of nervousness, insomnia, hypertension, skin rash, and these studies cannot be correlated to the traditional proper-
diarrhea. It is a typical example of how the use of dubious ties and indications of the intact CMM and thus may not be
test materials (in this case, commercial herb-powder capsules relevant to the traditional materials concerned. Reliance on
labeled as “ginseng”) combined with a lack of knowledge in such data will only serve the interest of conventional drug
CMM have produced and perpetuated a set of adverse reac- development efforts, which are not relevant to efforts to eval-
tions that may have nothing to do with any particular ginseng, uate and validate the safety and efficacy of traditional CMM
Asian (Panax ginseng C.A. Mey.) or American (Panax quin- as they have been known and documented over time.
quefolius L.), material(s) intended for that study.
Consequently, despite voluminous publications on ginseng BASIC DIFFERENCES BETWEEN CMM AND MODERN DRUGS
(identity seldom well-defined) over the past few decades, the In order to conduct meaningful toxicity studies on tradi-
traditional properties (including toxicity) and efficacy of ren- tional medicines that will generate reproducible results, it is
shen (Chinese or Korean ginseng) as it has been known, doc- important to consider the following facts:
umented and used over time, are still unclear, thus perpetuat- 1. The toxicity of traditional herbs or formulas is not the
ing the controversies on ginseng. Unfortunately, this problem same as that of their isolated chemicals.
extends beyond ginseng; yet, it is currently not widely rec- 2. The toxicity resulting from a use out of context cannot
ognized. always be attributed to the traditional medicine in question.
GENERAL MISCONCEPTIONS Most scientists conducting research in this field have been
To most modern scientists who have only taken a cursory trained in modern medical, pharmacological and/or pharma-
look without trying to understand it, CMM is commonly re- ceutical sciences. They are accustomed to viewing test ma-
garded as nonscientific and anecdotal. This is quite under- terials as pure chemicals with rather well-defined pharmaco-
standable because, over millennia, as part of TCM, CMM logic activities that are readily measurable using modern tech-
has developed into a complicated and, to many, esoteric sys- nologies. Their knowledge of these primarily single-entity
tem of theories and practice based primarily on empirical chemicals is accumulated over a relatively short period of
human experience. time (normally within a generation), where initial manage-
Unlike modern allopathic drugs, the efficacy and safety able animal data lead to much more complicated human use
of CMM cannot be readily verified in a short term with an- data. Consequently, it is difficult for most of them to accept
imal experimentation, because the two are inherently very human toxicity and efficacy data that seem to have come from
different systems of therapeutics. While the development of nowhere, with no easy traceability, and certainly not along
allopathic drugs starts with toxicity testing in animals be- the same path with which they are familiar. Considering that
fore moving on to human toxicity and efficacy studies, the few of these scientists have prior experience with CMM, it is
traditional development of CMM skipped the animal step understandable that there is much skepticism concerning its
and started with human experimentation right at the onset. toxicity data. However, it must be borne in mind, while pre-
The former may take a few to several years to establish their clinical toxicity data of modern drugs are fairly precise and
pre-approval or premarket safety and efficacy before actual primarily experimentally derived (e.g., via animal and/or in
human experimentation begins. Of all the modern drugs in vitro studies), their human toxicity data are mainly obtained
322 LEUNG TOXICOLOGIC PATHOLOGY

through actual human usage, which are much less defined, of recurrent heart attack and stroke. And, its toxicities over
and the accumulation of these human toxicity data only starts this period have been found to include gastrointestinal up-
after the drugs have been approved for clinical trials and later set, ulcer, and bleeding, as well as Reye’s syndrome, among
use in humans. And as long as a drug is in human use, accu- others. These toxic properties of aspirin have not been deter-
mulation of its toxicity data is an ongoing process which is mined by typical modern toxicologic studies required for any
not unlike what has happened with CMM, except that, with drug before its approval, but rather by clinical observations
CMM, the process, has started centuries to millennia earlier. and experience after it has been put in clinical use. This sce-
Furthermore, due to the inherent differences in the practice nario of documenting new properties (including toxicities)
of CMM as opposed to that of modern allopathic drug therapy, and new indications is basically the same as with Chinese
there are few or no parallels in many aspects between the two herbal medicines, except what has been observed and docu-
systems, including the following: mented in CMM has lasted much longer, most for centuries
r CMM practice is primarily empirical and holistic, while or millennia as opposed to only decades with most allopathic
modern drug therapy is experimental science-based and drugs.
targets specific symptoms and obvious disease-causative A typical example is the familiar herb, American ginseng
agents. (Panax quinquefolius), a native North American species. The
r CMM practice emphasizes prevention and restoring bal- Jesuits first introduced its root to China at the beginning of
ance that often are intangible, while modern medicine at- the 18th century, believing it was the same as Chinese gin-
tempts to treat what is scientifically obvious or tangible. seng. It was well received. However, within a period of only
r While modern drugs are mostly single chemicals that are a few decades, the Chinese found that it was not the same as
readily identified and quantified, CMM are multicompo- their own ginseng and documented this difference. They did
nent therapeutics whose strength is due to their unique this strictly based on organoleptic identification and human
combinations around which this whole therapeutic system clinical experience over time, without the help of modern tax-
is based. onomic botany or other modern scientific techniques used in
r While combination modern drug therapy only started a identification and quality control (chemical, spectral, chro-
few decades ago with cancer chemotherapy and later AIDS matographic, biochemical, etc.), nor the modern sciences of
treatment (e.g., anti-HIV cocktails), the practice of com- pharmacology. Thus, by the mid 1700s, American ginseng
bination therapy in CMM started at least 3,000 years ago, was first described in writings as a distinctly different ginseng
which has since evolved into a well-documented treatment than Chinese ginseng and later became a favorite of the Can-
system unique to TCM. tonese. American ginseng is known since then as a tonic with
cooling (as opposed to Chinese ginseng’s warming) proper-
Because of the many differences between modern phar- ties; and this fact has not changed for over two centuries. Now,
maceuticals and CMM, one would expect certain modern American ginseng is normally used in persons with excessive
methodologies (e.g., identifying and standardizing against yang who need a tonic to strengthen their resistance but can-
specific chemical markers) used in the evaluation of modern not tolerate yang medicines like Chinese ginseng, which may
drugs not appropriate for studying the toxicity, safety and/or aggravate the problems they may already have, caused by this
efficacy of these traditional medicines. Innovative method- imbalance. American ginseng is thus a different herbal drug
ologies that identify, characterize, and standardize CMM than Chinese or Asian ginseng. They are derived from dis-
holistically and with consistency, which correlate their physi- tinctly different yet closely related plant species. American
cal and chemical profiles with biological ones (e.g., genomic) ginseng was later botanically identified as Panax quinque-
to represent their well-documented traditional properties (in folius and Chinese, or Asian ginseng, as Panax ginseng. Al-
total) and indications will be more appropriate and useful. though both are tonics, they have some different indications.
Due to its cooling nature, American ginseng is used to reduce
THE DOCUMENTATION PROCESS fever while Chinese ginseng is seldom, if ever, traditionally
Despite its esoteric nature, the theory and practice of CMM used for this purpose. These traditional properties were first
is not illogical as most scientists believe. If one takes time observed and differentiated through organoleptic examina-
to learn some of its basics, one will find it continues to un- tion followed by human usage over time (in this case, rel-
dergo evolution as more and more human clinical experience atively short), before the 2 materials were finally subjected
is being accumulated. Not unlike modern single-component to the modern science of botany which made the physical
chemical drugs (though the longest of which being in use, differentiation between the 2 plants from which they are de-
such as aspirin and morphine, have only a history of less than rived. However, their more subtle, traditional pharmacologic
200 years), the safety and therapeutic properties of Chinese distinction still eludes modern science.
herbal medicines are continually being determined and up- The documentation of CMM toxicity is a dynamic process
dated as new human experiences are acquired. While the hu- that keeps updating and revising the record whenever new
man clinical experience with most modern allopathic drugs is data arise. The highly toxic nature of certain traditional drugs
relatively short (e.g., over decades), that of most CMM gen- was already known and started to be documented about 3,000
erally extends over centuries to millennia. Thus, aspirin may years ago. For example, among the drugs described in the
have initially been used as an analgesic in rheumatism, lum- Wu Shi Er Bing Fang (See Table 1), are the toxic wu tou
bago, and neuralgia in the early 1900s, human experiences (aconite), ban xia (Pinellia ternata root), and li lu (Veratrum
with it since then have expanded its properties and uses into nigrum root/rhizome), many of which are also provided with
other areas, including the most recent use in reducing the risk processing methods to reduce their toxicity.
Vol. 34, No. 4, 2006 CHINESE MATERIA MEDICA TOXICITY 323

In the Shennong Bencao Jing (Shennong Herbal), the drugs use of toxic medicines to treat illnesses were highly revered.
were classified into 3 therapeutic categories based on their And highly toxic traditional drugs such as Sichuan aconite
properties and relative toxicities. Despite the toxic nature of (both the main root called chuan wu, and the less toxic cured
some of the drugs being revised centuries later, most have lateral root called fu zi), chan su (toad venom), and miner-
remained unchanged. als containing arsenic (e.g., realgar or xiong huang), mercury
In the Bencao Gangmu (Compendium of Materia Medica), (e.g., mercuric sulfide or zhu sha), and lead (e.g., lead tetrox-
381 among its 1892 drugs are clearly described as toxic. ide or qian dan) are still routinely used by TCM physicians
In one of the most extensive modern records, the Zhongyao in China (Pharmacopoeia, 1963–2005). Poisoning or adverse
Da Cidian (Encyclopdia of Materia Medica), published in effects due to Chinese herbs are often caused by ignorance
1977, 495 of its 5,767 drugs are reported as toxic. In the and/or their inappropriate use. Because of the laxity in adher-
newly published Zhonghua Bencao (The Chinese Herbal), ing to truly traditional Chinese medical principles in train-
which contains monographs on 8,980 drugs, the number of ing modern-day TCM physicians (Fruehauf, 1999) and the
toxic drugs is not immediately apparent. However, in the misconception of modernized TCM, such adverse events are
Duyao Bencao (Toxic Drugs Herbal), a book that specifically bound to increase rapidly in the near future, further spurred on
deals with toxic traditional Chinese drugs published in 1993, by a misinformed public who frequently use these medicines
903 toxic drugs are described in detail. And according to its as dietary supplements, and outside of traditional practice.
editors, 55 of these toxic drugs were previously considered Consequently, before one starts evaluating any CMM for its
nontoxic in historical records. toxicity and efficacy, it is extremely important to consult the
There is much latitude in the determination of which Chi- classical traditional literature to assure that one does not miss
nese medicine is toxic and how severely so. Traditionally, some important toxicity information. This will not only save
toxic drugs are classified into 3 categories: highly toxic, toxic, time and money in one’s research efforts, but also avoid toxic
and slightly toxic. Depending on the authors and the peri- effects unnecessarily inflicted on human subjects or patients
ods in which the herbals were published, drugs considered if the recorded toxicities are known or the cautions and pre-
“highly toxic” by one author in a particular period might be cautions heeded by the investigators conducting the research.
considered only “toxic” by another. And certain drugs consid-
ered “nontoxic” might later be described as “slightly toxic.” ACCESS TO CMM TOXICITY DATA
Nonetheless, when a drug exhibited toxic effects over time, Major Classic Works with Toxicity Data
these effects were recorded. For example, in the Pharma- There are at least 300 major classic works on CMM,
copoeia of the People’s Republic of China (Pharmacopoeia, known commonly as ben cao ( ), published over the past
1963–2000), mylabris (Chinese cantharides) was changed 3,000 years. All of the major ones reviewed contain toxicity
from “toxic” in the 1963 edition to “highly toxic” in later information. The following 4 are selected as examples for this
editions (1977–1995), ginkgo seed from “slightly toxic” in review because they are the most important ones that provide
1963 and 1977 editions to “toxic” in the 1985–1995 editions, a historical perspective, as well as a sense of the scope of
herb-paris rhizome (chong lou) from “nontoxic” in the 1977 toxicity documentation of traditional Chinese drugs.
edition to “slightly toxic” in 1985–1995 editions, orostachys
herb (wa song) from “highly toxic” in the 1963 edition to The Shennong Bencao Jing (Shennong Herbal)
“nontoxic” in the 1977 edition, honeycomb (feng fang) from (ca. 100 BC–200 AD): This is the first work exclusively
“toxic” in 1963 to “slightly toxic” in 1977 and finally to “non- devoted to CMM, compiled during the period from 100 BC
toxic” in 1985–1995 editions, houttuynia herb (yu xing cao) to 200 AD. It is also the first that attempted a systematic
from “slightly toxic” in 1963 to “nontoxic” in 1977–1995 edi- classification of CMM based primarily on their toxicities.
tions, and omphalia (lei wan) from “slightly toxic” in 1963 Thus, its recorded 365 drugs of plant, animal, and mineral
to “nontoxic” in 1977–1995 editions. origins were divided into 3 categories:
So, the dynamic process of documentation continues since r Superior (120)-jun (monarch), nontoxic, suitable for
the Shennong Bencao Jing started the toxicity documentation long-term use
and classification 2,000 years ago. What are recorded as toxic r Medium (120)-chen (minister), can be toxic, depending
drugs only apply to those that have been found to be consis- on usage
tently toxic over time, when used in the traditional manner. r Inferior (125)-shi (envoy), toxic, for treating diseases
There are countless others that ordinarily are not toxic but
may be toxic if used outside of tradition or out of context. Despite the fact that the information on the toxicities and
These latter are the ones that are being increasingly known indications of the drugs was recorded 2,000 years ago, much
to produce adverse effects in recent years. of it is still valid. When used as traditionally prescribed, the
While documentation of the safety and adverse effects of toxic properties of these drugs, as classified, seem to have
herbs used in the West and those used in various ethnob- withstood the test of time.
otanical systems may be scanty, that of traditional Chinese Examples of common drugs/herbs grouped under the 3
drugs has been extensive and continuous since around 1100 categories include:
BC. In fact, except for some CMM commonly used as tonics, r Superior—Asian ginseng (renshen), licorice (gancao),
few traditional Chinese drugs (plant, animal, and mineral) reishi (lingzhi), chrysanthemum (juhua), astragalus
lack toxicity or safety records, including cautions and con- (huangqi), Job’s tears (yimi), sesame seed, lycium, schisan-
traindications for their use. Practitioners of TCM are taught dra, Chinese wild ginger (xixin, Asarum spp.), Chinese
to use toxic drugs that play an important role in TCM prac- salvia (danshen), etc. A review of the CMM in this cate-
tice. Historically, TCM physicians who were skilled in the gory shows that most items are still appropriately classified
324 LEUNG TOXICOLOGIC PATHOLOGY

here. For example, ginseng, astragalus, licorice, Job’s tears, work only covers about 1,900 Chinese drugs, out of a total
schisandra, and lycium to this day continue to be regarded of around 12,800 with well-documented records, it at least
as nontoxic and suitable for long-term use after a period of would allow Western researchers access, for the first time, to
more than 2,000 years a small portion of CMM toxicity data that has been buried
r Medium—Chinese ephedra (mahuang), kudzu root and thus mostly inaccessible for centuries.
(gegen), dried ginger, dong quai (danggui), zhuling, sea- Zhongyao Da Cidian (Encyclopedia of Chinese Materia
weed, zicao, Chinese skullcap (huangqin), epimedium, etc. Medica) (Jiangsu, 1977): This was the most
As expected, many of the drugs in this category can be toxic, comprehensive work in 1977 on CMM since the Bencao
especially if not used properly, such as mahuang.
r Inferior—Rhubarb, aconite (fuzi and wutou), mang cao Gangmu. It consists of 3 volumes and 3,518 pages, describ-
ing 5,767 traditional Chinese drugs, many in great detail.
(Illicium lanceolatum) platycodon, bletilla (baiji), pinnel- The modern botanical, chemical, pharmacological and clini-
lia (banxia), Japanese knotweed (huzhang), heal-all (xiaku- cal data included in this book are from the world literature up
cao), almond (xingren), peach pit (taoren), forsythia (lian- to and including 1972. The traditional information includes
qiao capsule), earthworm, arsenic sulfide (xionghuang), processing and properties (quality, taste, toxicity, cautions,
mercuric sulfide (zhusha), etc. Drugs classified under this precautions, etc.), among other historical data. A review of
group are supposed to be toxic and used for treating dis- historical and classic works on CMM, including this one has
eased conditions as opposed to those in the Superior cate- been published (Leung, 1990).
gory where they are used for health promotion and main-
tenance. Many of the drugs here can still be considered as Zhonghua Bencao (The Chinese Herbal)
toxic as they had been 2,000 years ago (e.g., aconite, mang (Zhonghua, 1999): This monumental work consists of
cao, xiong huang, etc.). However, over time, some have 10 volumes, totaling 9,282 pages, with 8,534 illustrations
been found to be nontoxic and have since been upgraded in and 8,980 CMM monographs. This herbal was compiled by
recent times (e.g., bletilla, forsythia capsule, platycodon). the Chinese State Administration of TCM involving over 500
scholars/experts from at least 60 academic and research in-
Bencao Gangmu (Compendium of Materia Medica) stitutions, and took 10 years to complete. For those who want
(ca. 1592–1596): This work is probably the best lesser details, there is also an abridged 2-volume version
known of all Chinese classic herbals. It was compiled by available. The modern literature covered is up to 1994. It is
Li Shi-Zhen who is generally considered as China’s greatest the most extensive documentation of CMM to date. An En-
herbalist. In this work, the number of CMM items described glish review of this work has been published (Leung, 2001).
had increased from 365 recorded in the Shennong Bencao More recently, as part of the same work, two separate vol-
Jing to close to 1,800 plus 11,100 prescriptions (Leung, umes dealing with ethnic CMM (Tibetan and Mongolia) have
1990). Over the past four centuries, parts of it have been also been published.
translated into numerous languages. The newest English ver- MAJOR CONTEMPORARY WORKS FOCUSED ON TOXICITIES
sion has recently been published, which was translated and OF CMM
compiled by Xi-Wen Luo (2003). This English version is in Modern works on CMM toxicity documentation are pri-
6 volumes, totaling over 4,400 pages. For the first time, a com- marily based on compilations of data generated from sources
plete translation of the Bencao Gangmu is available. A brief, unrelated to traditional CMM, especially those from isolated
but detailed, comparison of the description of a few drugs chemicals, unverified or improperly characterized materials,
in the English and Chinese versions by this reviewer has re- uses out of context, etc. These have been increasing exponen-
vealed a close-to-text and reasonably readable translation, tially during the past decade and are still continuing. Unfor-
with practically no obvious omissions or rationalization on tunately, they are not useful for the evaluation or validation
the part of the translator and editors. Pending further use and of the safety and efficacy of traditional CMM, but are only
review, it is safe to assume this English translation as equiv- relevant for use in the development of new chemical drugs
alent to the original Chinese version in scope and content. for specific indications unrelated to traditional practice. How-
In this work, among other categories described (prepa- ever, these data are so pervasive that it is sometimes difficult
ration, indications, prescriptions, etc.), the “Properties” to tell the data that are the result of premature scientific inter-
(quality and taste) category provides a brief description pretations or extrapolations by investigators (in an attempt to
of whether a drug is toxic, slightly toxic or nontoxic; it confirm traditional data) and those that are traditionally de-
also provides cautions and precautions as well as con- rived. The examples of contemporary works selected for this
traindications for some CMM items. Some of the drugs review are ones that are dedicated to toxic CMM based pri-
originally described in the Shennong Bencao Jing have been marily on data from historical sources and those continually
reclassified in this compendium from toxic to nontoxic and accumulated from ongoing TCM practice, along with a cer-
vice versa. For example, baiji or bletilla rhizome (toxic, tain amount of modern animal data that may or may not have
under the inferior category in the Shennong Bencao Jing) been extrapolated to apply to humans. As the main purpose
is described as nontoxic in this 16th-century work. And of this review is to provide as true a traditional perspective
xixin (Chinese wild ginger), formerly considered nontoxic as possible on CMM toxicity, only a handful of publications
is described here with cautions and incompatibilities with in scope have been found suitable for inclusion.
certain vegetables, meats and other herbs.
The English version has 8 appendices, including those for Duju Zhongyao Gujinyong (Toxic Chinese Materia Med-
English drug names, Latin binomials, drug names in Pinyin ica: Past and Present) (Yang, 1991): This
and Chinese, and list of classic works quoted. Although this 404-page work describes the history of toxic Chinese drugs,
Vol. 34, No. 4, 2006 CHINESE MATERIA MEDICA TOXICITY 325

the prevention and treatment of their toxic effects, etc., with over a 16-year period, many of the less popular and less ex-
detailed monographs on 435 CMM. tensively circulated ones have come to the fore and many of
Youdu Zhongcaoyao Da Cidian (Encyclopedia of Toxic the more prominent ones have also greatly expanded in scope
Chinese Materia Medica) (Guo, 1992): and content. The following are examples of some well-known
This work (853 pages) provides monographs on 503 tradi- ones:
tional drugs (420 botanical, 50 animal, 33 mineral) along r Zhongcaoyao (Chinese Traditional and Herbal Drugs)
with data on 1,300 formulas; rating of toxicity as “extremely
toxic” with lethal dose under 1g (22 drugs), “highly toxic” r Zhongchengyao (Chinese Patent Medicines)
with very close therapeutic to toxic doses (50 drugs), “toxic” r Zhongyaocai (Journal of Chinese Medicinal Materials)
with relatively close therapeutic to toxic doses (230 drugs),
and “slightly toxic” with big differences in therapeutic and r Shizhen Guoyi Guoyao (Lishizhen Medicine and Materia
toxic doses (201 drugs); some modern scientific data are pro-
Medica Research)
vided. r Shizhen Guoyao Yanjiu (Shizhen Journal of Traditional
Duyao Bencao (Toxic Drugs Herbal) (Yang, Chinese Medicine Research)
1993): This work (1,119 pages) describes in detail 903 r Zhongyiyao Xuebao (Acta Chinese Medicine and Pharma-
toxic traditional drugs (55 of which not previously considered cology)
toxic), including both traditional and modern data; a good r Zhongguo Zhongyao Zazhi (Chinese Journal of CMM)
source for a quick review of any CMM as to its recorded
toxicity, contraindications, cautions, precautions, and/or in- r Zhongguo Yiyao Xuebao (Chinese Journal of TCM and
compatibilities. Pharmacy)
r Beijing Zhongyiyao Daxue Xuebao (Journal of Beijing
Youdu Zhongyao Xiandai Yanjiu Yu Heliyingyong (Toxic
University of TCM)
Chinese Materia Medica: Modern Research and Appropri- r Chengdu Zhongyiyao Daxue Xuebao (Journal of Chengdu
ate Applications) (Du and Fang,
University of TCM)
2003): This work (1,029 pages) provides detailed mono- r Nanjing Zhongyiyao Daxue Xuebao (Journal of Nanjing
graphs on 98 toxic traditional drugs, describing them from
University of TCM)
both historical/traditional and modern scientific perspectives; r Shanghai Zhongyiyao Daxue Xuebao (Acta Universitatis
includes chemical (contamination by heavy metals, agricul-
tural chemicals, pesticides, etc.), pharmacologic and clinical Traditionis Medicalis Sinensis Pharmacologiaeque Shang-
hai)
practice data (including use of zhu sha (HgS) for epilepsy in r Zhongyi Zazhi (Journal of TCM)
children), etc. r Yaoxue Xuebao (Acta Pharmaceutica Sinica)
Xiandai Zhongyao Dulixue (Modern Toxicology of
Chinese Materia Medica) (Xia, 2005): This Traditional toxicity information reported (based on tra-
934-page work describes 1,462 commonly used traditional ditional clinical practice with CMM) can be found espe-
drugs that have been recorded with toxic or potential toxic cially in several dozen regional journals of TCM most of
effects, cautions, and/or precautions, in any publication (an- which have an annual index, with the best ones containing
cient or recent) on CMM. In addition to the usual information key words in Pinyin corresponding to their respective po-
on botanical sources, collection and processing, tastes and tential Chinese characters and the worst simply titles of the
quality, indications, dosages, etc., most monographs also pro- articles in that issue. In any case, it is not a major task to
vide information on historical toxicity data, chemical com- locate toxicity information if the journal resources are avail-
position, toxicology, and comments based on historical and able in a single location. However, few of the major insti-
modern data. Many also give methods and advice for prevent- tutions in the United States, including the National Library
ing toxic effects, including heat processing, processing with of Medicine, have such resources, as they concentrate on
other herbs, adherence to TCM tradition, and traditional rec- acquisitions of journal titles geared at conventional medical
ommended dosages, among others. Although there are some and pharmaceutical interests that typically avoid TCM, as re-
traditional toxicity data (obtained through TCM practice) in ported and practiced in the traditional manner in China for
the “Toxicology” section, most of the toxicity data were ex- the past 3,000 years. Some toxicity information may occa-
perimentally derived, based on literature from the 1985–2002 sionally appear in national journals like the Zhongyi Zazhi
period. Their relevance to the true nature of the respective (Journal of TCM, which has an English edition), but the
CMM cannot be ascertained without careful review of each chances of such information also appearing in the English
source cited, which would be a monumental task. Neverthe- version are rather small, because typically not all informa-
less, this work has both a Chinese drug index and an index tion in Chinese publications enters the translated version, not
for Latin binomials, which make it quite easy to access infor- only in this journal but also in other major works like the Chi-
mation. It is a good quick source of traditional CMM toxicity nese Pharmacopoeia (Pharmacopoeia, 2000), for whatever
information. reason.
At present, it is unfortunate that in order to access ongo-
NATIONAL AND REGIONAL JOURNALS OF TCM AND CMM ing traditionally acquired toxicity-data relevant to CMM, one
As a part of an earlier review of general TCM and CMM re- cannot rely on most existing English sources (e.g., databases,
sources, examples of numerous of the over 100 better-known institutions, books, and journals) due to the fact that most
journals mentioned were given (Leung, 1990). Since then, non-Chinese toxicity data are not due to the intact traditional
326 LEUNG TOXICOLOGIC PATHOLOGY

CMM but to their specific, presumed active chemical con- ence & Technology Translation Press, Tianjin.
stituents, which are generally irrelevant to the toxicity infor-
mation one seeks for any particular traditional intact CMM. Institute of Chinese Materia Medica, Chinese Academy of TCM, Eds.
However, if one is at least aware of this problem, one will (1996). Quanguo Zhongcaoyao Mingjian (Nationnal Records
be able to ask the right questions when engaging a special of Chinese Materia Medica), 3 Vols. People’s Health Publish-
ers, Beijing.
consultant’s help in accessing such information. It is hoped
this review can provide the reader with the basics for doing Jiangsu Institute of Modern Medicine (Jiangsu). (1977). Zhongyao
so. Da Cidian (Encyclopedia of Chinese Materia Medica), 3
SUMMARY Vols. Shanghai Scientific and Technical Press, Shanghai.

Contrary to the common belief among the scientific and


medical communities, traditional CMM toxicity data exists Leung, A. Y. (1990). Chinese medicinals. In: Advances in New Crops (J. Janick
and is well-documented in the Chinese literature for over and J. E. Simon, Eds.), pp. 499–510. Timber Press, Portland, Oregon.
3,000 years. However, only a minute fraction of this infor- [reprinted in HerbalGram, 23, 21 (1990)].
mation has been translated into English, making it extremely Leung, A. Y. (2001). The Chinese Herbal (Zhonghua Bencao). Leung’s (Chinese)
difficult for non-Chinese-reading scientists and other inter- Herb News Jan/Feb 30, 1–3. AYSL Corp., Glen Rock, NJ.
ested professionals to access such information. This situa- Luo, X. W. (2003). Bencao Gangmu (Compendium of Materia Med-
ica). Foreign Languages Press, Beijing. (English Translation).
tion is not likely to change as experts in CMM or TCM
who are proficient in English are dwindling instead of in- McGuffin, M., Kartesz, J. T., Leung, A. Y., and Tucker, A. O. (2000). Herbs of
creasing, due to the continued misguided direction in efforts Commerce. 2nd ed. American Herbal Products Association, Silver Spring,
of modernizing TCM which equates it to evaluating CMM MD.
for their presumed active principles. This has greatly hin- Pharmacopoeia of the People’s Republic of China (1963–2005; issues published
dered true research efforts in the evaluation of the safety during this period).
and efficacy of traditional CMM known for their traditional Pharmacopoeia of the People’ Republic of China (2000). English Version (2000).
values which have been well-tested and well-documented Chemical Industry Press, Beijing.
over time. It is hoped that the basic information provided Siegel, R. K. (1979). Ginseng abuse syndrome. JAMA 241, 1614–15.
in this review will allow researchers, who are interested Xia, L. Y., Ed. (2005). Xiandai Zhongyao Dulixue (Modern Toxi-
cology of Chinese Materia Medica) Modern Toxicology of Chi-
in CMM for their truly traditional values, to be aware of
nese Materia Medica. Tianjin Science and Technology Transla-
the deficiencies and pitfalls in relying on current English tion Press, Tianjin.
information on CMM toxicity and thus will start obtain-
ing the desired and relevant results they have long been Yang, C. L. (1991). Toxic Chinese Materia Medica: Past and Present.
seeking. Duju Zhongyao Gujinyong (Toxic Chinese Materia Medica:
Past and Present). Chinese Medical Science and Technology
REFERENCES Press, Beijing.
Du, G. Y., and Fang, W. X., Eds. (2003). Youdu Zhongyao Xiandai Yan-
jiu Yu Heliyingyong (Toxic Chinese Materia Medica: Modern Re- Yang, C. L. (1993). Toxic Drugs Herbal. Duyao Bencao (Toxic Drugs
search and Appropriate Applications). People’s Health Press, Beijing. Herbal). Chinese Medicine and Materia Medica Press, Beijing.

Zhonghua Bencao Editorial Committee, State Administration of Tra-


Fruehauf, H. (1999). Science, politics, and the making of ‘TCM’—Chinese ditional Chinese Medicine (Zhonghua). (1999). Zhonghua Ben-
medicine in crisis. J. Chin Med. 61, 6–14. cao (The Chinese Herbal), 10 Volumes. Shanghai Scientific and
Guo, X. Z., Ed. (1992). Youdu Zhongcaoyao Da Cidian (Ency- Technical Press, Shanghai,
clopedia of Toxic Chinese Materia Medica). Tianjin Sci-