HMs have been prescribed based on thousands of years of experience and the original pharmacological theories in TM. The decoction type of PHM, which is a type of extract prepared through the mixing and dispensing processes of herbs, has been most widely used throughout history and is still the most preferred formulations in China, South Korea, and Japan today . While decoctions have been used for many years with a proven record of safety, the demand for the criteria for the efficacy and safety of decoctions and their regulations is increasing within the society [25, 26].
The TKM clinics of South Korea are required to use the medicinal herbs that conform to the hazardous material test criteria set by Korea MFDS in preparing decoctions. However, it is possible to use herbs that are not tested if these herbs are not included in the list of 601 registered herbs in Korean pharmacopoeia and the Korean herbal pharmacopoeia [1, 18]. Also, of these 601 medicinal herbs, there are only two items that have the criteria on benzopyrene, while 20 are regulated by the criteria for mycotoxin [1, 18]. As the test items for these medicinal herbs vary widely, the safety of the final decoction products has been questioned for years. For this purpose, the researchers conducted this study to secure the safety of the decoction type of PHMs, through the literature review and a process of consensus among experts.
As for the criteria for hazardous materials for the medicinal herbs used in South Korea, Korean pharmacopoeia and the Korean herbal pharmacopoeia requires tests on heavy metal, pesticide residues, sulfur dioxide, mycotoxin, and benzopyrene, depending on the characteristics of each item [1, 18]. And, as for extracts, the ‘quality control guideline for herbal or botanical medicine extracts’ has been used as the basis of regulating the quality of extracts that are used as the raw material for herbal or botanical medicines . As for the extract of raw materials, the required test items are, respectively, heavy metal, pesticide residues, sulfur dioxide, mycotoxin, and other remaining contaminants, while the extracts are to be tested for heavy metal, pesticide residues, solvent residue, and other remaining contaminants . According to the Pharmaceutical Act of South Korea, different purity test requirements apply as outlined in the Korean pharmacopeia and the Korean herbal pharmacopeia [1, 18]. The micro-organism limit tests, in the meantime, cover the total aerobic bacteria, total fungal count, and specific micro-organisms (E. coli, salmonella, Pseudomonas aeroginosa, and Staphylococcus aureus), for the herbal or botanical medicine extracts .
As for heavy metals, Korean pharmacopoeia requires that the total heavy metal is tested or that lead, mercury, arsenic, and cadmium are tested individually . International pharmacopeia or guidelines were also regulating chromium and copper. The heavy metals that were being regulated varied depending on the country. However, all countries were regulating arsenic and lead, while only China had the standard for the total heavy metal . The heavy metal standards were in place in all countries for finished herbal products. And, only China and South Korea had heavy metal standards for herbal materials. Only South Korea had the standard for heavy metal in herbal or botanical medicine extracts.
The literature review on domestic and overseas documents showed that the standards for pesticide residues covered dichloro diphenyl trichloroethane (DDT), benzene hexachloride (BHC), aldrin, dieldrin, and endrin. Europe and the US were regulating aldrin, dieldrin, and endrin, while Japan was regulating two pesticide residues. South Korea was regulating all five pesticide residues.
As for sulfur dioxide, only South Korea had the standard to regulate chemicals as hazardous materials. HM materials are highly subject to the influence of the weather during the drying process. For this reason, it is a common practice to dry such materials indoors using coal as the fuel, instead of drying them outdoors under the sun. While this indoor drying process may be cheaper, it has been known to compromise health . Therefore, it is necessary to set the testing criteria for monitoring sulfur dioxide.
According to Korea pharmacopeia , only Rehmanniae Radix Preparata (熟地黃) and Rehmanniae Radi (地黃) had the standards for testing benzopyrene. A decoction type of PHMs is a type of extraction prepared by mixing and processing herbal materials. However, in TM, the herbal materials go through additional processes, such as frying or burning, to maximize the efficacy in treatment . During this additional processing, benzopyrene may be generated. Therefore, it is necessary to regulate this substance by setting a standard for it.
The standards on mycotoxin are based on aflatoxin, which is known to be of the highest toxicity. When compared based on the requirements on total aflatoxin, South Korea, Europe, and Japan had a stricter standard compared to the US. However, the detailed items of these standards varied among countries. As for South Korea, the requirement for all botanical medicines was total aflatoxin 15 ppb or less and aflatoxin B1 10 ppb or less. For other countries, the standards varied depending on the types of products. The range of total aflatoxin was between 10 and 20 ppb.
In South Korea, the herbal or botanical medicine extracts were being regulated for the contamination by micro-organisms that were not regulated for herbal materials using micro-organism limit tests. The standards covered the total aerobic bacteria, total fungi, and specific micro-organisms (E. coli, salmonella, pseudomonas aeroginosa, and staphylococcus aureus). China had the standards for herbal extracts covering total aerobic bacteria and total fungi. The specific bacteria were not being regulated. The WHO guideline contains somewhat relaxed criteria for the hot water extracts of botanical drugs covering total aerobic bacteria and total fungi compared to the requirements in effect in South Korea. However, the WHO was recommending the regulation of clostridium and shigella, which were not being regulated in South Korea. The United States and Europe had the standard for total aerobic bacteria and total fungi in raw materials and finished products that were plant-based. Europe also had an additional set of criteria for specific micro-organisms (E. coli and salmonella).
A total of seven documents were identified through the search of international search. The result of the literature review showed that only South Korea had quality management standards for herbal or botanical medicine extracts as a medicine product. The expert meeting brought that a total of six items, which were, respectively, heavy metal, pesticide residues, sulfur dioxide, benzopyrene, mycotoxin, and micro-organism limits, were identified as the hazardous materials in a decoction type of PHMs. However, while the said guideline also contained the management criteria for the solvent for extracting, these were dismissed as deemed irrelevant to decoction medicines, which are extracted using hot water. Finally, the six items below are finalized as the hazardous material management standard for decoctions; (1) individual heavy metals (lead, arsenic, mercury, and cadmium), (2) pesticide residues (five pesticides of organic chlorine types), (3) sulfur dioxide, (4) mycotoxin (total aflatoxin and aflatoxin B1), (5) benzopyrene, (6) micro-organisms (total aerobic bacteria, total fungi, E. coli, salmonella, pseudomonas aeroginosa, and staphylococcus aureus).
The strength of this review is that it is the first study that provided the hazardous material test items and criteria for the decoction types of PHMs and can be used as the basis for introducing a safety management system for the decoction types of PHMs by the government in the future.
The limitations of this review are as follows; First, this study is found wanting in terms of the credibility of the experts who selected the test items and criteria (there was no sampling) or their representativeness (only a handful of experts). Second, the literature review was limited to the data that were in English or Korean language. Therefore, the databases from the countries which have been using traditional decoction medicines were not included in the study. Finally, no pilot tests to apply the criteria set in this study were conducted.
In the future, it would be necessary to conduct a pilot test to ensure the validity and credibility of the test items, criteria, and methods, as well as their field relevance. Especially, a sufficient number of decoction monitoring, public hearings and gathering of the opinions from the field would have to be conducted. Finally, it would be necessary for the government to introduce the decoction safety management program so that the people of the country may use proven decoction medicines.