Shengkai DING, Qing GUO, Qianqian LIU, Xinyang LIU, Yuanyuan YE, Yazhen SHANG*

1. Institute of Traditional Chinese Medicine, Chengde Medical College; Key Research Laboratory of Anti-dementia of Traditional Chinese Medicine, Hebei Province; Key Laboratory of Traditional Chinese Medicine Research and Development of Hebei Province, Chengde 067000, China; 2. The Fourth Hospital of Shijiazhuang, Shijiazhuang 050011, China

Abstract With the wide application of traditional Chinese medicine in the world, the related reports on the toxicity of traditional Chinese medicine are increasing, which makes the safety of traditional Chinese medicine receive wide attention. This paper analyzes the toxicity of traditional Chinese medicine with a fair and scientific attitude, in order to promote the benign and sustainable development of traditional Chinese medicine.

Key words Traditional Chinese medicine, Toxicity

1 Introduction

As the quintessence of China, traditional Chinese medicine has a broad and profound connotation. Some people said that the subject of traditional Chinese medicine can be mastered by a small number of people, which shows that its content is wide and its meaning is profound. Traditional Chinese medicine has carried too much honor and history since ancient times, and it seems to be the embodiment of justice to save people from suffering. Especially in recent years, traditional Chinese medicine has been intentionally or unintentionally worn with "pure natural=non-toxic side effects=can rest assured to take the halo". Many people are unwilling to mention the toxicity of traditional Chinese medicine out of their love for the quintessence of the nation. Some traditional Chinese medicine manufacturers emphasize its efficacy and avoided talking about its toxic side effects. However, does traditional Chinese medicine really have no toxic side effects?

The answer is obviously no. In recent years, poisoning incidents related to traditional Chinese medicine have occurred at home and abroad. For example, weight loss of traditional Chinese medicine in Belgium caused many cases of kidney poisoning, Coptidis Rhizoma toxicity in Singapore, Minor Bupleurum Decoction poisoning events in Japan, drug-induced liver damage in Polygoni Multiflori Radix and kidney damage caused by Gentian Liver-Draining Pill[1-5],etc., these poisoning events of traditional Chinese medicine make people pay great attention to the safety of traditional Chinese medicine.

As the ancients said, "every medicine has its side effect."PlainQuestions70,GreatTreatiseontheFiveNormalRulessaid: "if you cure a disease with high toxicity, ten will go to its six; if you treat a disease with regular toxicity, ten will remove its seven; if you treat a disease with small toxicity, ten will remove its eight; if you treat a disease non-toxic, ten will go to its nine." There is a theory of "correcting deviation with deviation" in the theory of traditional Chinese medicine. Zhang Jingyue of the Ming Dynasty said inTheClassifiedClassic: "Medicine is the cure, but poison is the power. The so-called poisonous is based from the flavor bias. If the flavor is partial, the bait belongs to it, so it goes to the evil spirit of people." However, poison refers to the bias of drugs, and people get sick, and traditional Chinese medicine believes that it is caused by infection with evil qi, so the toxicity of traditional Chinese medicine is its properties, then how should we understand the "toxicity" of traditional Chinese medicine?

2 Whether the drug itself contains toxic ingredients

There is a difference in the concept of poison in ancient and modern Chinese medicine. There is no distinction between ancient medicine and poison, which is mixed as poison, and it is believed that all medicines for the treatment of diseases are poisons. The second poison also refers to the bias of the drug, and the third poison refers to the toxic and side effects of traditional Chinese medicine. As early asPlainQuestions70,GreatTreatiseontheFiveNormalRules, there are four kinds of theories: high toxicity, regular toxicity, small toxicity and non-toxic. The toxicity and classification standards of traditional Chinese medicine in the 2015 edition of thePharmacopoeiaofthepeople’sRepublicofChina(part I)[6]and the textbook Chinese Medicine[7]of colleges and universities are also divided into three levels: "high toxicity (10 kinds)", "toxic (42 kinds)" and "minor toxicity (31 kinds)". In modern times, drug toxicity is usually defined as the harm or harmful effects of drugs on the body, including acute, subacute, subchronic, chronic and special toxicity. The research contents of the interaction between toxic traditional Chinese medicine and the body include toxic manifestations, toxic mechanisms, toxic components, toxic target organs, toxicokinetics, poison control methods and clinical safe and rational application and so on[8]. At present, the toxicological research contents of traditional Chinese medicine mainly include describing toxicology, mechanism toxicology and management toxicology.

Modern medical scientists use chemical means to extract and separate toxic components from many traditional Chinese medicines, thus scientifically revealing the essence of drug "poison" and providing a scientific and reliable basis for determining the toxicity and non-toxicity of drugs. Drugs that do not contain toxic ingredients are harmless to the human body, such as Chinese Angelica, Phragmitis Rhizoma, honey and so on. And drugs containing toxic ingredients are harmful to the human body, that is, toxic products, such as Croton, arsenic and Mylabris. (Croton contains Croton toxin, arsenic contains arsenic, cantharidin in Mylabris,etc.)

3 Toxic relationship between traditional Chinese medicine and compound prescription

The prescription is related to the toxicity of the drug. Traditional Chinese medicine is the basic unit of the prescription, the so-called "prescription is made of medicine". In some cases, when the traditional Chinese medicine that makes up the prescription itself is toxic, the prescription it is composed of may also be toxic. At this point, the toxicity of the drug is consistent with that of the prescription, which is usually manifested as the toxicity intensity of the toxic drug and how much the drug tastes are closely related to the toxicity of the whole prescription. The prescription is separated from the toxicity of the drug. Although the prescription is composed of medicine, it is not equal to medicine. As the saying goes, "the completion of the prescription can not only make the medicine have all its nature, but also make the medicine lose its nature". In some cases, the traditional Chinese medicine that makes up the prescription is toxic, and it does not determine that the prescription it is composed of is also toxic. There are two situations in which the toxicity of the prescription is separated from that of the drug: First, the toxicity of single medicine is limited by the choice of compatibility, dosage or preparation, and the whole prescription is non-toxic or low toxic. It is mentioned inTheDivineHusbandman’sMateriaMedicaClassicthat "if it is poisonous and it is suitable for using. You cann’t use those who are mutual restraint and mutual detoxication. For example, in the compatibility of "mutual restraint" and "mutual detoxication" in "the compatibility of herbs"[9], one drug is used to reduce or eliminate the toxicity or side effects of another drug; on the contrary, if the compatibility or preparation is improper, it may lead to increased toxicity of the whole prescription or other toxicity that has nothing to do with the toxicity of a single traditional Chinese medicine. Second, the unreasonable compatibility of non-toxic traditional Chinese medicine may also make the whole prescription toxic or obvious side effects. Second, the unreasonable compatibility of non-toxic traditional Chinese medicine may also make the whole prescription toxic or obvious side effects. Some traditional Chinese medicine plants do not show toxicity, such as ginseng, which contains ginsenoside C has hemolytic effect, but ginsenoside A has anti-hemolytic effect, so ginseng does not show hemolytic effect. Some traditional Chinese medicines contain toxic ingredients, but due to the content of components and overall than the content of tiny, as a whole does not display the toxicity, such as: sweet almond, peach kernel, and so on, the toxicity of Chinese traditional medicine composition and its overall toxicity has inner link, namely have differences again, said general toxic drugs will contain toxic ingredients, and of drug toxicity, does not necessarily show toxic as a whole. Third, repeat use of similar drugs. Aconitine contained in aconitine such as Radix Aconiti, Radix Aconitum kusnezoffii, Radix Aconiti Lateralis Praeparata, Aconiti Brachypodi Radix,and other aconitine is very toxic, and these drugs contain aconitine alkaloids with cardiotoxicity[10].

4 Whether the dosage is appropriate

Although the toxic ingredients contained in some traditional Chinese medicines are toxic, they are also effective therapeutic ingredients. Diseases can be cured within the allowable dose, but excessive dosage can lead to poisoning. For example, in the 2015 edition of thePharmacopoeiaofthepeople’sRepublicofChina(ChP), the treatment dose of strychnine in Strychnos nux vomica is 0.78%-0.82%[6], which is used to treat rheumatism, but adult consumption of 5-10 mg can produce toxic reaction and 30 mg can lead to death. Another example: long-term use of traditional Chinese medicine containing aristolochic acid (such asAristolochiamanshuriensis, Asarum) and preparations (Gentian Liver-Draining Pill, Red-Abducting Pill) will cause aristolochic acid nephropathy and lead to renal failure[11]. In 2003, the China Food and Drug Administration(CFDA) can celled the medicinal standard ofAristolochiamanshuriensis. Such as: Bitter almond, 1 g raw bitter almond can produce 2.5 g hydrocyanic acid, and hydrocyanic acid is a highly toxic soup. Trace application can slightly inhibit the respiratory center and show the therapeutic effect of relieving cough and relieving asthma, while exceeding the dosage will have a toxic effect on the human body, even death, and the lethal dose is 0.05 g. According to this, it can be calculated that the maximum tolerance dose for adults to bitter almond is 20 g. It can be seen that the safe dosage of bitter almond is "non-toxic" when the safe dosage is between 10 and 20 g. More than 20 g is "toxic"[12-13]. In short, the drug dosage should not exceed the maximum tolerance of the human body. Only in this way can we ensure the safety and effectiveness of clinical medication.

The development of traditional Chinese medicine in China has a long history, and its application research in the global scope has received more and more attention. However, the toxicity of traditional Chinese medicine needs to be objectively and dialectically understood, the corresponding safety evaluation system should be established for reference to modern science and technology, and the safety evaluation research of traditional Chinese medicine should be strengthened. Such as a comprehensive and systematic summary of relevant literature, experimental verification of adverse reactions of traditional Chinese medicine, expanding the scope of traditional Chinese medicine safety research and the establishment of traditional Chinese medicine safety evaluation map, so that traditional Chinese medicine can better serve all mankind.