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

not be obtained. If this negative result were published without
providing the original Chinese characters (or at least a proper
transliteration) for the indication or the property studied, no
other researchers could reproduce the results. Consequently,
while modern science has just started to discover the poten-
tial of CMM and tries to validate its safety and efficacy, it
is important always to accompany modern interpretations of
TCM concepts with their original Chinese characters, or at
least a standardized transliteration of them.
Over the past century, various methods of transliteration
of Chinese characters have been used. The two best known
are the Wade-Giles and Pinyin systems. The former domi-
nated the TCM literature for many decades until the latter
was widely adopted beginning in the 1980s. Currently, the
Pinyin system is the predominant one used worldwide ex-
cept for the literature emanating from Taiwan. The Library
of Congress and the National Library of Medicine still hold
a sizable amount of information in the Wade-Giles translit-
eration. Because of this lack of uniformity in one of the most
important tools in the description and interpretation of TCM,
much confusion exists in the identities of CMM. This conse-
quently is a major source of irreproducible results in research
and clinical applications involving TCM that requires the in-
terpretation of traditional TCM concepts.
In addition, as with other traditional and botanical
medicines, traditional Chinese drugs often have multiple
names. Some of these are traditional ones recorded in well-
known herbals over many centuries. However, the majority
deals with vernacular names that vary from region to region.
Sometimes numerous names apply to a single drug while
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.
And this is another major source of irreproducibility in CMM
research and modern clinical practice.
HISTORICAL BACKGROUND
Chinese materia medica consists of drugs derived from
botanicals, minerals and animals, with the botanical ones
making up the majority. It is a key and integral part of TCM,
which also includes other therapeutic modalities, as men-
tioned earlier. The use of CMM dates back several thousand
years. However, as evidence available to date shows, its writ-
ten documentation did not start until only around 1,100 B.C.
(Leung, 1990). Since then, information on Chinese herbs has
evolved from sketchy mentions in ballads and geographic
works, to works devoted to disease treatment, and eventu-
ally culminating in monumental works exclusively devoted
to individual CMM and their prescriptions. All these publica-
tions contain information on safety, toxicity, incompatibility,
precaution, and caution. Major works spanning a 3,000-year
period are highlighted in Table 1 (Leung, 1990, 2001).
Due to the nature of CMM practice that relies totally on
direct clinical experience with humans over time, there are
no precise toxicity data like those of modern pharmaceuticals
generated from animal and in vitro experimentation. Nor are
there any data on enzyme inhibitors, receptor agonists, recep-
tor antagonists, or the like, which are often used to describe
mechanisms of action of chemicals, including toxic ones.
What is available in traditional toxicity data includes general
information accumulated over time that ranges from decades
to centuries, based on collective data from different accounts,
not from a single episode based on any particular herbal sam-
ple from any particular locality. Such documentation can be
viewed as word-of-mouth, but it has been generally based
on multiple occurrences vetted over time before it entered
TABLE 1.—Examples of major works impacting Chinese materia medica.
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
the traditional literature. As a corollary, in the modern doc-
umentation of scientific research, any published report from
a single source (laboratory, institution, or clinic) is only con-
sidered credible and the reported results valid when these
results are reproduced by others.
There are no uniform methods of assessing the toxic effects
of herbs in general and CMM in particular. Modern scientific
techniques may involve acute and subacute testing that have
been devised for modern chemical drugs, and are thus not
readily applicable to multicomponent systems like CMM and
foods. Hence, it is extremely difficult to predict the adverse
effects of herbs based simply on such evaluation of a toxic
chemical present in these herbs. Yet, such interpretative and
extrapolative assessments are often used exclusively to de-
fine the toxic effects of CMM. Many of the recorded adverse
reactions thus far attributed to CMM in the modern litera-
ture have been equivocal, due to problems inherent in current
CMM research. These problems include dubious identity of
subject herbs, misappropriation of a single chemical for the
total activity of an herb, and the bias of conventional medical
and pharmacological researchers, who undertake the studies
or report on the findings, albeit often unintentional. The most
notorious yet well-publicized and widely quoted “adverse
effects” of “ginseng” is the classic report by Siegel (1979)
which coined the term “ginseng abuse syndrome,” consist-
ing of nervousness, insomnia, hypertension, skin rash, and
diarrhea. It is a typical example of how the use of dubious
test materials (in this case, commercial herb-powder capsules
labeled as “ginseng”) combined with a lack of knowledge in
CMM have produced and perpetuated a set of adverse reac-
tions that may have nothing to do with any particular ginseng,
Asian (Panax ginseng C.A. Mey.) or American (Panax quin-
quefolius L.), material(s) intended for that study.
Consequently, despite voluminous publications on ginseng
(identity seldom well-defined) over the past few decades, the
traditional properties (including toxicity) and efficacy of ren-
shen (Chinese or Korean ginseng) as it has been known, doc-
umented and used over time, are still unclear, thus perpetuat-
ing the controversies on ginseng. Unfortunately, this problem
extends beyond ginseng; yet, it is currently not widely rec-
ognized.
GENERAL MISCONCEPTIONS
To most modern scientists who have only taken a cursory
look without trying to understand it, CMM is commonly re-
garded as nonscientific and anecdotal. This is quite under-
standable because, over millennia, as part of TCM, CMM
has developed into a complicated and, to many, esoteric sys-
tem of theories and practice based primarily on empirical
human experience.
Unlike modern allopathic drugs, the efficacy and safety
of CMM cannot be readily verified in a short term with an-
imal experimentation, because the two are inherently very
different systems of therapeutics. While the development of
allopathic drugs starts with toxicity testing in animals be-
fore moving on to human toxicity and efficacy studies, the
traditional development of CMM skipped the animal step
and started with human experimentation right at the onset.
The former may take a few to several years to establish their
pre-approval or premarket safety and efficacy before actual
human experimentation begins. Of all the modern drugs in
321
extensive use today, few, if any, have more than 75 years of hu-
man experience. In contrast, some of the Chinese medicines
have been used in humans for several millennia, with docu-
mentation of their safety and toxicity for at least 3,000 years.
In addition, as in the case with modern allopathic drugs, new
uses and toxicities continue to be discovered and recorded, al-
beit in Chinese, which makes these data generally unavailable
to the modern scientific and medical communities. Conse-
quently, there is a general belief among scientists and health-
care professionals that there are no toxicity or efficacy data of
any kind in CMM. But, that is not true. In fact, such data exist.
It’s just that they are not universally available in any major
non-Chinese literature or databases. In this review, attempts
will be made to present major publications, both classical
and recent, some of which specifically deal with traditional
toxicity data of CMM. Although most are in Chinese, they
can be readily accessed and its relevant portions be translated
by any reasonably knowledgeable Chinese-reading scholars
or scientists, who need not conduct extensive research to dis-
cover these sources, as the basic information and approach
will be provided in this review.
Many toxicity studies using modern scientific methods
have been conducted on CMM-related materials (isolated
chemicals, chemical fractions, extracts, etc.) over the past
75 or so years. However, most toxicity data resulting from
these studies cannot be correlated to the traditional proper-
ties and indications of the intact CMM and thus may not be
relevant to the traditional materials concerned. Reliance on
such data will only serve the interest of conventional drug
development efforts, which are not relevant to efforts to eval-
uate and validate the safety and efficacy of traditional CMM
as they have been known and documented over time.
BASIC DIFFERENCES BETWEEN CMM AND MODERN DRUGS
In order to conduct meaningful toxicity studies on tradi-
tional medicines that will generate reproducible results, it is
important to consider the following facts:
1. The toxicity of traditional herbs or formulas is not the
same as that of their isolated chemicals.
2. The toxicity resulting from a use out of context cannot
always be attributed to the traditional medicine in question.
Most scientists conducting research in this field have been
trained in modern medical, pharmacological and/or pharma-
ceutical sciences. They are accustomed to viewing test ma-
terials as pure chemicals with rather well-defined pharmaco-
logic activities that are readily measurable using modern tech-
nologies. Their knowledge of these primarily single-entity
chemicals is accumulated over a relatively short period of
time (normally within a generation), where initial manage-
able animal data lead to much more complicated human use
data. Consequently, it is difficult for most of them to accept
human toxicity and efficacy data that seem to have come from
nowhere, with no easy traceability, and certainly not along
the same path with which they are familiar. Considering that
few of these scientists have prior experience with CMM, it is
understandable that there is much skepticism concerning its
toxicity data. However, it must be borne in mind, while pre-
clinical toxicity data of modern drugs are fairly precise and
primarily experimentally derived (e.g., via animal and/or in
vitro studies), their human toxicity data are mainly obtained
322 LEUNG
through actual human usage, which are much less defined,
and the accumulation of these human toxicity data only starts
after the drugs have been approved for clinical trials and later
use in humans. And as long as a drug is in human use, accu-
mulation of its toxicity data is an ongoing process which is
not unlike what has happened with CMM, except that, with
CMM, the process, has started centuries to millennia earlier.
Furthermore, due to the inherent differences in the practice
of CMM as opposed to that of modern allopathic drug therapy,
there are few or no parallels in many aspects between the two
systems, including the following:
r CMM practice is primarily empirical and holistic, while
modern drug therapy is experimental science-based and
targets specific symptoms and obvious disease-causative
agents.
r CMM practice emphasizes prevention and restoring bal-
ance that often are intangible, while modern medicine at-
tempts to treat what is scientifically obvious or tangible.
r While modern drugs are mostly single chemicals that are
readily identified and quantified, CMM are multicompo-
nent therapeutics whose strength is due to their unique
combinations around which this whole therapeutic system
is based.
r While combination modern drug therapy only started a
few decades ago with cancer chemotherapy and later AIDS
treatment (e.g., anti-HIV cocktails), the practice of com-
bination therapy in CMM started at least 3,000 years ago,
which has since evolved into a well-documented treatment
system unique to TCM.
Because of the many differences between modern phar-
maceuticals and CMM, one would expect certain modern
methodologies (e.g., identifying and standardizing against
specific chemical markers) used in the evaluation of modern
drugs not appropriate for studying the toxicity, safety and/or
efficacy of these traditional medicines. Innovative method-
ologies that identify, characterize, and standardize CMM
holistically and with consistency, which correlate their physi-
cal and chemical profiles with biological ones (e.g., genomic)
to represent their well-documented traditional properties (in
total) and indications will be more appropriate and useful.
THE DOCUMENTATION PROCESS
Despite its esoteric nature, the theory and practice of CMM
is not illogical as most scientists believe. If one takes time
to learn some of its basics, one will find it continues to un-
dergo evolution as more and more human clinical experience
is being accumulated. Not unlike modern single-component
chemical drugs (though the longest of which being in use,
such as aspirin and morphine, have only a history of less than
200 years), the safety and therapeutic properties of Chinese
herbal medicines are continually being determined and up-
dated as new human experiences are acquired. While the hu-
man clinical experience with most modern allopathic drugs is
relatively short (e.g., over decades), that of most CMM gen-
erally extends over centuries to millennia. Thus, aspirin may
have initially been used as an analgesic in rheumatism, lum-
bago, and neuralgia in the early 1900s, human experiences
with it since then have expanded its properties and uses into
other areas, including the most recent use in reducing the risk
TOXICOLOGIC PATHOLOGY
of recurrent heart attack and stroke. And, its toxicities over
this period have been found to include gastrointestinal up-
set, ulcer, and bleeding, as well as Reye’s syndrome, among
others. These toxic properties of aspirin have not been deter-
mined by typical modern toxicologic studies required for any
drug before its approval, but rather by clinical observations
and experience after it has been put in clinical use. This sce-
nario of documenting new properties (including toxicities)
and new indications is basically the same as with Chinese
herbal medicines, except what has been observed and docu-
mented in CMM has lasted much longer, most for centuries
or millennia as opposed to only decades with most allopathic
drugs.
A typical example is the familiar herb, American ginseng
(Panax quinquefolius), a native North American species. The
Jesuits first introduced its root to China at the beginning of
the 18th century, believing it was the same as Chinese gin-
seng. It was well received. However, within a period of only
a few decades, the Chinese found that it was not the same as
their own ginseng and documented this difference. They did
this strictly based on organoleptic identification and human
clinical experience over time, without the help of modern tax-
onomic botany or other modern scientific techniques used in
identification and quality control (chemical, spectral, chro-
matographic, biochemical, etc.), nor the modern sciences of
pharmacology. Thus, by the mid 1700s, American ginseng
was first described in writings as a distinctly different ginseng
than Chinese ginseng and later became a favorite of the Can-
tonese. American ginseng is known since then as a tonic with
cooling (as opposed to Chinese ginseng’s warming) proper-
ties; and this fact has not changed for over two centuries. Now,
American ginseng is normally used in persons with excessive
yang who need a tonic to strengthen their resistance but can-
not tolerate yang medicines like Chinese ginseng, which may
aggravate the problems they may already have, caused by this
imbalance. American ginseng is thus a different herbal drug
than Chinese or Asian ginseng. They are derived from dis-
tinctly different yet closely related plant species. American
ginseng was later botanically identified as Panax quinque-
folius and Chinese, or Asian ginseng, as Panax ginseng. Al-
though both are tonics, they have some different indications.
Due to its cooling nature, American ginseng is used to reduce
fever while Chinese ginseng is seldom, if ever, traditionally
used for this purpose. These traditional properties were first
observed and differentiated through organoleptic examina-
tion followed by human usage over time (in this case, rel-
atively short), before the 2 materials were finally subjected
to the modern science of botany which made the physical
differentiation between the 2 plants from which they are de-
rived. However, their more subtle, traditional pharmacologic
distinction still eludes modern science.
The documentation of CMM toxicity is a dynamic process
that keeps updating and revising the record whenever new
data arise. The highly toxic nature of certain traditional drugs
was already known and started to be documented about 3,000
years ago. For example, among the drugs described in the
Wu Shi Er Bing Fang (See Table 1), are the toxic wu tou
(aconite), ban xia (Pinellia ternata root), and li lu (Veratrum
nigrum root/rhizome), many of which are also provided with
processing methods to reduce their toxicity.
Vol. 34, No. 4, 2006 CHINESE MATERIA MEDICA TOXICITY
In the Shennong Bencao Jing (Shennong Herbal), the drugs
were classified into 3 therapeutic categories based on their
properties and relative toxicities. Despite the toxic nature of
some of the drugs being revised centuries later, most have
remained unchanged.
In the Bencao Gangmu (Compendium of Materia Medica),
381 among its 1892 drugs are clearly described as toxic.
In one of the most extensive modern records, the Zhongyao
Da Cidian (Encyclopdia of Materia Medica), published in
1977, 495 of its 5,767 drugs are reported as toxic. In the
newly published Zhonghua Bencao (The Chinese Herbal),
which contains monographs on 8,980 drugs, the number of
toxic drugs is not immediately apparent. However, in the
Duyao Bencao (Toxic Drugs Herbal), a book that specifically
deals with toxic traditional Chinese drugs published in 1993,
903 toxic drugs are described in detail. And according to its
editors, 55 of these toxic drugs were previously considered
nontoxic in historical records.
There is much latitude in the determination of which Chi-
nese medicine is toxic and how severely so. Traditionally,
toxic drugs are classified into 3 categories: highly toxic, toxic,
and slightly toxic. Depending on the authors and the peri-
ods in which the herbals were published, drugs considered
“highly toxic” by one author in a particular period might be
considered only “toxic” by another. And certain drugs consid-
ered “nontoxic” might later be described as “slightly toxic.”
Nonetheless, when a drug exhibited toxic effects over time,
these effects were recorded. For example, in the Pharma-
copoeia of the People’s Republic of China (Pharmacopoeia,
1963–2000), mylabris (Chinese cantharides) was changed
from “toxic” in the 1963 edition to “highly toxic” in later
editions (1977–1995), ginkgo seed from “slightly toxic” in
1963 and 1977 editions to “toxic” in the 1985–1995 editions,
herb-paris rhizome (chong lou) from “nontoxic” in the 1977
edition to “slightly toxic” in 1985–1995 editions, orostachys
herb (wa song) from “highly toxic” in the 1963 edition to
“nontoxic” in the 1977 edition, honeycomb (feng fang) from
“toxic” in 1963 to “slightly toxic” in 1977 and finally to “non-
toxic” in 1985–1995 editions, houttuynia herb (yu xing cao)
from “slightly toxic” in 1963 to “nontoxic” in 1977–1995 edi-
tions, and omphalia (lei wan) from “slightly toxic” in 1963
to “nontoxic” in 1977–1995 editions.
So, the dynamic process of documentation continues since
the Shennong Bencao Jing started the toxicity documentation
and classification 2,000 years ago. What are recorded as toxic
drugs only apply to those that have been found to be consis-
tently toxic over time, when used in the traditional manner.
There are countless others that ordinarily are not toxic but
may be toxic if used outside of tradition or out of context.
These latter are the ones that are being increasingly known
to produce adverse effects in recent years.
While documentation of the safety and adverse effects of
herbs used in the West and those used in various ethnob-
otanical systems may be scanty, that of traditional Chinese
drugs has been extensive and continuous since around 1100
BC. In fact, except for some CMM commonly used as tonics,
few traditional Chinese drugs (plant, animal, and mineral)
lack toxicity or safety records, including cautions and con-
traindications for their use. Practitioners of TCM are taught
to use toxic drugs that play an important role in TCM prac-
tice. Historically, TCM physicians who were skilled in the
323
use of toxic medicines to treat illnesses were highly revered.
And highly toxic traditional drugs such as Sichuan aconite
(both the main root called chuan wu, and the less toxic cured
lateral root called fu zi), chan su (toad venom), and miner-
als containing arsenic (e.g., realgar or xiong huang), mercury
(e.g., mercuric sulfide or zhu sha), and lead (e.g., lead tetrox-
ide or qian dan) are still routinely used by TCM physicians
in China (Pharmacopoeia, 1963–2005). Poisoning or adverse
effects due to Chinese herbs are often caused by ignorance
and/or their inappropriate use. Because of the laxity in adher-
ing to truly traditional Chinese medical principles in train-
ing modern-day TCM physicians (Fruehauf, 1999) and the
misconception of modernized TCM, such adverse events are
bound to increase rapidly in the near future, further spurred on
by a misinformed public who frequently use these medicines
as dietary supplements, and outside of traditional practice.
Consequently, before one starts evaluating any CMM for its
toxicity and efficacy, it is extremely important to consult the
classical traditional literature to assure that one does not miss
some important toxicity information. This will not only save
time and money in one’s research efforts, but also avoid toxic
effects unnecessarily inflicted on human subjects or patients
if the recorded toxicities are known or the cautions and pre-
cautions heeded by the investigators conducting the research.
ACCESS TO CMM TOXICITY DATA
Major Classic Works with Toxicity Data
There are at least 300 major classic works on CMM,
known commonly as ben cao ( ), published over the past
3,000 years. All of the major ones reviewed contain toxicity
information. The following 4 are selected as examples for this
review because they are the most important ones that provide
a historical perspective, as well as a sense of the scope of
toxicity documentation of traditional Chinese drugs.
The Shennong Bencao Jing (Shennong Herbal)
(ca. 100 BC–200 AD): This is the first work exclusively
devoted to CMM, compiled during the period from 100 BC
to 200 AD. It is also the first that attempted a systematic
classification of CMM based primarily on their toxicities.
Thus, its recorded 365 drugs of plant, animal, and mineral
origins were divided into 3 categories:
r Superior (120)-jun (monarch), nontoxic, suitable for
long-term use
r Medium (120)-chen (minister), can be toxic, depending
on usage
r Inferior (125)-shi (envoy), toxic, for treating diseases
Despite the fact that the information on the toxicities and
indications of the drugs was recorded 2,000 years ago, much
of it is still valid. When used as traditionally prescribed, the
toxic properties of these drugs, as classified, seem to have
withstood the test of time.
Examples of common drugs/herbs grouped under the 3
categories include:
r Superior—Asian ginseng (renshen), licorice (gancao),
reishi (lingzhi), chrysanthemum (juhua), astragalus
(huangqi), Job’s tears (yimi), sesame seed, lycium, schisan-
dra, Chinese wild ginger (xixin, Asarum spp.), Chinese
salvia (danshen), etc. A review of the CMM in this cate-
gory shows that most items are still appropriately classified
324 LEUNG
here. For example, ginseng, astragalus, licorice, Job’s tears,
schisandra, and lycium to this day continue to be regarded
as nontoxic and suitable for long-term use after a period of
more than 2,000 years
r Medium—Chinese ephedra (mahuang), kudzu root
(gegen), dried ginger, dong quai (danggui), zhuling, sea-
weed, zicao, Chinese skullcap (huangqin), epimedium, etc.
As expected, many of the drugs in this category can be toxic,
especially if not used properly, such as mahuang.
r Inferior—Rhubarb, aconite (fuzi and wutou), mang cao
(Illicium lanceolatum) platycodon, bletilla (baiji), pinnel-
lia (banxia), Japanese knotweed (huzhang), heal-all (xiaku-
cao), almond (xingren), peach pit (taoren), forsythia (lian-
qiao capsule), earthworm, arsenic sulfide (xionghuang),
mercuric sulfide (zhusha), etc. Drugs classified under this
group are supposed to be toxic and used for treating dis-
eased conditions as opposed to those in the Superior cate-
gory where they are used for health promotion and main-
tenance. Many of the drugs here can still be considered as
toxic as they had been 2,000 years ago (e.g., aconite, mang
cao, xiong huang, etc.). However, over time, some have
been found to be nontoxic and have since been upgraded in
recent times (e.g., bletilla, forsythia capsule, platycodon).
Bencao Gangmu (Compendium of Materia Medica)
(ca. 1592–1596): This work is probably the best
known of all Chinese classic herbals. It was compiled by
Li Shi-Zhen who is generally considered as China’s greatest
herbalist. In this work, the number of CMM items described
had increased from 365 recorded in the Shennong Bencao
Jing to close to 1,800 plus 11,100 prescriptions (Leung,
1990). Over the past four centuries, parts of it have been
translated into numerous languages. The newest English ver-
sion has recently been published, which was translated and
compiled by Xi-Wen Luo (2003). This English version is in
6 volumes, totaling over 4,400 pages. For the first time, a com-
plete translation of the Bencao Gangmu is available. A brief,
but detailed, comparison of the description of a few drugs
in the English and Chinese versions by this reviewer has re-
vealed a close-to-text and reasonably readable translation,
with practically no obvious omissions or rationalization on
the part of the translator and editors. Pending further use and
review, it is safe to assume this English translation as equiv-
alent to the original Chinese version in scope and content.
In this work, among other categories described (prepa-
ration, indications, prescriptions, etc.), the “Properties”
(quality and taste) category provides a brief description
of whether a drug is toxic, slightly toxic or nontoxic; it
also provides cautions and precautions as well as con-
traindications for some CMM items. Some of the drugs
originally described in the Shennong Bencao Jing have been
reclassified in this compendium from toxic to nontoxic and
vice versa. For example, baiji or bletilla rhizome (toxic,
under the inferior category in the Shennong Bencao Jing)
is described as nontoxic in this 16th-century work. And
xixin (Chinese wild ginger), formerly considered nontoxic
is described here with cautions and incompatibilities with
certain vegetables, meats and other herbs.
The English version has 8 appendices, including those for
English drug names, Latin binomials, drug names in Pinyin
and Chinese, and list of classic works quoted. Although this
TOXICOLOGIC PATHOLOGY
work only covers about 1,900 Chinese drugs, out of a total
of around 12,800 with well-documented records, it at least
would allow Western researchers access, for the first time, to
a small portion of CMM toxicity data that has been buried
and thus mostly inaccessible for centuries.
Zhongyao Da Cidian (Encyclopedia of Chinese Materia
Medica) (Jiangsu, 1977): This was the most
comprehensive work in 1977 on CMM since the Bencao
Gangmu. It consists of 3 volumes and 3,518 pages, describ-
ing 5,767 traditional Chinese drugs, many in great detail.
The modern botanical, chemical, pharmacological and clini-
cal data included in this book are from the world literature up
to and including 1972. The traditional information includes
processing and properties (quality, taste, toxicity, cautions,
precautions, etc.), among other historical data. A review of
historical and classic works on CMM, including this one has
been published (Leung, 1990).
Zhonghua Bencao (The Chinese Herbal)
(Zhonghua, 1999): This monumental work consists of
10 volumes, totaling 9,282 pages, with 8,534 illustrations
and 8,980 CMM monographs. This herbal was compiled by
the Chinese State Administration of TCM involving over 500
scholars/experts from at least 60 academic and research in-
stitutions, and took 10 years to complete. For those who want
lesser details, there is also an abridged 2-volume version
available. The modern literature covered is up to 1994. It is
the most extensive documentation of CMM to date. An En-
glish review of this work has been published (Leung, 2001).
More recently, as part of the same work, two separate vol-
umes dealing with ethnic CMM (Tibetan and Mongolia) have
also been published.
MAJOR CONTEMPORARY WORKS FOCUSED ON TOXICITIES
OF CMM
Modern works on CMM toxicity documentation are pri-
marily based on compilations of data generated from sources
unrelated to traditional CMM, especially those from isolated
chemicals, unverified or improperly characterized materials,
uses out of context, etc. These have been increasing exponen-
tially during the past decade and are still continuing. Unfor-
tunately, they are not useful for the evaluation or validation
of the safety and efficacy of traditional CMM, but are only
relevant for use in the development of new chemical drugs
for specific indications unrelated to traditional practice. How-
ever, these data are so pervasive that it is sometimes difficult
to tell the data that are the result of premature scientific inter-
pretations or extrapolations by investigators (in an attempt to
confirm traditional data) and those that are traditionally de-
rived. The examples of contemporary works selected for this
review are ones that are dedicated to toxic CMM based pri-
marily on data from historical sources and those continually
accumulated from ongoing TCM practice, along with a cer-
tain amount of modern animal data that may or may not have
been extrapolated to apply to humans. As the main purpose
of this review is to provide as true a traditional perspective
as possible on CMM toxicity, only a handful of publications
in scope have been found suitable for inclusion.
Duju Zhongyao Gujinyong (Toxic Chinese Materia Med-
ica: Past and Present) (Yang, 1991): This
404-page work describes the history of toxic Chinese drugs,
Vol. 34, No. 4, 2006 CHINESE MATERIA MEDICA TOXICITY
the prevention and treatment of their toxic effects, etc., with
detailed monographs on 435 CMM.
Youdu Zhongcaoyao Da Cidian (Encyclopedia of Toxic
Chinese Materia Medica) (Guo, 1992):
This work (853 pages) provides monographs on 503 tradi-
tional drugs (420 botanical, 50 animal, 33 mineral) along
with data on 1,300 formulas; rating of toxicity as “extremely
toxic” with lethal dose under 1g (22 drugs), “highly toxic”
with very close therapeutic to toxic doses (50 drugs), “toxic”
with relatively close therapeutic to toxic doses (230 drugs),
and “slightly toxic” with big differences in therapeutic and
toxic doses (201 drugs); some modern scientific data are pro-
vided.
Duyao Bencao (Toxic Drugs Herbal) (Yang,
1993): This work (1,119 pages) describes in detail 903
toxic traditional drugs (55 of which not previously considered
toxic), including both traditional and modern data; a good
source for a quick review of any CMM as to its recorded
toxicity, contraindications, cautions, precautions, and/or in-
compatibilities.
Youdu Zhongyao Xiandai Yanjiu Yu Heliyingyong (Toxic
Chinese Materia Medica: Modern Research and Appropri-
ate Applications) (Du and Fang,
2003): This work (1,029 pages) provides detailed mono-
graphs on 98 toxic traditional drugs, describing them from
both historical/traditional and modern scientific perspectives;
includes chemical (contamination by heavy metals, agricul-
tural chemicals, pesticides, etc.), pharmacologic and clinical
practice data (including use of zhu sha (HgS) for epilepsy in
children), etc.
Xiandai Zhongyao Dulixue (Modern Toxicology of
Chinese Materia Medica) (Xia, 2005): This
934-page work describes 1,462 commonly used traditional
drugs that have been recorded with toxic or potential toxic
effects, cautions, and/or precautions, in any publication (an-
cient or recent) on CMM. In addition to the usual information
on botanical sources, collection and processing, tastes and
quality, indications, dosages, etc., most monographs also pro-
vide information on historical toxicity data, chemical com-
position, toxicology, and comments based on historical and
modern data. Many also give methods and advice for prevent-
ing toxic effects, including heat processing, processing with
other herbs, adherence to TCM tradition, and traditional rec-
ommended dosages, among others. Although there are some
traditional toxicity data (obtained through TCM practice) in
the “Toxicology” section, most of the toxicity data were ex-
perimentally derived, based on literature from the 1985–2002
period. Their relevance to the true nature of the respective
CMM cannot be ascertained without careful review of each
source cited, which would be a monumental task. Neverthe-
less, this work has both a Chinese drug index and an index
for Latin binomials, which make it quite easy to access infor-
mation. It is a good quick source of traditional CMM toxicity
information.
NATIONAL AND REGIONAL JOURNALS OF TCM AND CMM
As a part of an earlier review of general TCM and CMM re-
sources, examples of numerous of the over 100 better-known
journals mentioned were given (Leung, 1990). Since then,
325
over a 16-year period, many of the less popular and less ex-
tensively circulated ones have come to the fore and many of
the more prominent ones have also greatly expanded in scope
and content. The following are examples of some well-known
ones:
r Zhongcaoyao (Chinese Traditional and Herbal Drugs)
r Zhongchengyao (Chinese Patent Medicines)
r Zhongyaocai (Journal of Chinese Medicinal Materials)
r Shizhen Guoyi Guoyao (Lishizhen Medicine and Materia
Medica Research)
r Shizhen Guoyao Yanjiu (Shizhen Journal of Traditional
Chinese Medicine Research)
r Zhongyiyao Xuebao (Acta Chinese Medicine and Pharma-
cology)
r Zhongguo Zhongyao Zazhi (Chinese Journal of CMM)
r Zhongguo Yiyao Xuebao (Chinese Journal of TCM and
Pharmacy)
r Beijing Zhongyiyao Daxue Xuebao (Journal of Beijing
University of TCM)
r Chengdu Zhongyiyao Daxue Xuebao (Journal of Chengdu
University of TCM)
r Nanjing Zhongyiyao Daxue Xuebao (Journal of Nanjing
University of TCM)
r Shanghai Zhongyiyao Daxue Xuebao (Acta Universitatis
Traditionis Medicalis Sinensis Pharmacologiaeque Shang-
hai)
r Zhongyi Zazhi (Journal of TCM)
r Yaoxue Xuebao (Acta Pharmaceutica Sinica)
Traditional toxicity information reported (based on tra-
ditional clinical practice with CMM) can be found espe-
cially in several dozen regional journals of TCM most of
which have an annual index, with the best ones containing
key words in Pinyin corresponding to their respective po-
tential Chinese characters and the worst simply titles of the
articles in that issue. In any case, it is not a major task to
locate toxicity information if the journal resources are avail-
able in a single location. However, few of the major insti-
tutions in the United States, including the National Library
of Medicine, have such resources, as they concentrate on
acquisitions of journal titles geared at conventional medical
and pharmaceutical interests that typically avoid TCM, as re-
ported and practiced in the traditional manner in China for
the past 3,000 years. Some toxicity information may occa-
sionally appear in national journals like the Zhongyi Zazhi
(Journal of TCM, which has an English edition), but the
chances of such information also appearing in the English
version are rather small, because typically not all informa-
tion in Chinese publications enters the translated version, not
only in this journal but also in other major works like the Chi-
nese Pharmacopoeia (Pharmacopoeia, 2000), for whatever
reason.
At present, it is unfortunate that in order to access ongo-
ing traditionally acquired toxicity-data relevant to CMM, one
cannot rely on most existing English sources (e.g., databases,
institutions, books, and journals) due to the fact that most
non-Chinese toxicity data are not due to the intact traditional
326 LEUNG
CMM but to their specific, presumed active chemical con-
stituents, which are generally irrelevant to the toxicity infor-
mation one seeks for any particular traditional intact CMM.
However, if one is at least aware of this problem, one will
be able to ask the right questions when engaging a special
consultant’s help in accessing such information. It is hoped
this review can provide the reader with the basics for doing
so.
SUMMARY
Contrary to the common belief among the scientific and
medical communities, traditional CMM toxicity data exists
and is well-documented in the Chinese literature for over
3,000 years. However, only a minute fraction of this infor-
mation has been translated into English, making it extremely
difficult for non-Chinese-reading scientists and other inter-
ested professionals to access such information. This situa-
tion is not likely to change as experts in CMM or TCM
who are proficient in English are dwindling instead of in-
creasing, due to the continued misguided direction in efforts
of modernizing TCM which equates it to evaluating CMM
for their presumed active principles. This has greatly hin-
dered true research efforts in the evaluation of the safety
and efficacy of traditional CMM known for their traditional
values which have been well-tested and well-documented
over time. It is hoped that the basic information provided
in this review will allow researchers, who are interested
in CMM for their truly traditional values, to be aware of
the deficiencies and pitfalls in relying on current English
information on CMM toxicity and thus will start obtain-
ing the desired and relevant results they have long been
seeking.
REFERENCES
Du, G. Y., and Fang, W. X., Eds. (2003). Youdu Zhongyao Xiandai Yan-
jiu Yu Heliyingyong (Toxic Chinese Materia Medica: Modern Re-
search and Appropriate Applications). People’s Health Press, Beijing.
Fruehauf, H. (1999). Science, politics, and the making of ‘TCM’—Chinese
medicine in crisis. J. Chin Med. 61, 6–14.
Guo, X. Z., Ed. (1992). Youdu Zhongcaoyao Da Cidian (Ency-
clopedia of Toxic Chinese Materia Medica). Tianjin Sci-
TOXICOLOGIC PATHOLOGY
ence & Technology Translation Press, Tianjin.
Institute of Chinese Materia Medica, Chinese Academy of TCM, Eds.
(1996). Quanguo Zhongcaoyao Mingjian (Nationnal Records
of Chinese Materia Medica), 3 Vols. People’s Health Publish-
ers, Beijing.
Jiangsu Institute of Modern Medicine (Jiangsu). (1977). Zhongyao
Da Cidian (Encyclopedia of Chinese Materia Medica), 3
Vols. Shanghai Scientific and Technical Press, Shanghai.
Leung, A. Y. (1990). Chinese medicinals. In: Advances in New Crops (J. Janick
and J. E. Simon, Eds.), pp. 499–510. Timber Press, Portland, Oregon.
[reprinted in HerbalGram, 23, 21 (1990)].
Leung, A. Y. (2001). The Chinese Herbal (Zhonghua Bencao). Leung’s (Chinese)
Herb News Jan/Feb 30, 1–3. AYSL Corp., Glen Rock, NJ.
Luo, X. W. (2003). Bencao Gangmu (Compendium of Materia Med-
ica). Foreign Languages Press, Beijing. (English Translation).
McGuffin, M., Kartesz, J. T., Leung, A. Y., and Tucker, A. O. (2000). Herbs of
Commerce. 2nd ed. American Herbal Products Association, Silver Spring,
MD.
Pharmacopoeia of the People’s Republic of China (1963–2005; issues published
during this period).
Pharmacopoeia of the People’ Republic of China (2000). English Version (2000).
Chemical Industry Press, Beijing.
Siegel, R. K. (1979). Ginseng abuse syndrome. JAMA 241, 1614–15.
Xia, L. Y., Ed. (2005). Xiandai Zhongyao Dulixue (Modern Toxi-
cology of Chinese Materia Medica) Modern Toxicology of Chi-
nese Materia Medica. Tianjin Science and Technology Transla-
tion Press, Tianjin.
Yang, C. L. (1991). Toxic Chinese Materia Medica: Past and Present.
Duju Zhongyao Gujinyong (Toxic Chinese Materia Medica:
Past and Present). Chinese Medical Science and Technology
Press, Beijing.
Yang, C. L. (1993). Toxic Drugs Herbal. Duyao Bencao (Toxic Drugs
Herbal). Chinese Medicine and Materia Medica Press, Beijing.
Zhonghua Bencao Editorial Committee, State Administration of Tra-
ditional Chinese Medicine (Zhonghua). (1999). Zhonghua Ben-
cao (The Chinese Herbal), 10 Volumes. Shanghai Scientific and
Technical Press, Shanghai,