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Article

Herbal Decoctions for the Levels of Sulfur Dioxide, Benzopyrene, and Mycotoxin from Traditional Korean Medicine Clinics: A Preliminary Study

1
Department of Preventive Medicine, College of Korean Medicine, Kyung Hee University, Seoul 02447, Korea
2
Department of Policy Development, National Institute of Korean Medicine Development, Seoul 04554, Korea
3
Division of Clinical Medicine, School of Korean Medicine, Pusan National University, Yangsan 50612, Korea
4
Department of Preventive Medicine, College of Korean Medicine, Daegu Haany University, Gyeongsan 38609, Korea
5
Department of Public Infrastructure Operation, National Institute of Korean Medicine Development, Seoul 04554, Korea
6
Department of Preventive Medicine, College of Korean Medicine, Woosuk University, Jeonju 54986, Korea
*
Authors to whom correspondence should be addressed.
Int. J. Environ. Res. Public Health 2022, 19(20), 13595; https://doi.org/10.3390/ijerph192013595
Submission received: 13 September 2022 / Revised: 16 October 2022 / Accepted: 18 October 2022 / Published: 20 October 2022
(This article belongs to the Special Issue Neurotoxicity Risk Assessment for Human Health)

Abstract

:
In this study, we investigated whether the levels of sulfur dioxide (SO2), benzopyrene, and mycotoxins in herbal decoctions in Korea in 2019 were within normal limits. In total, 30 decoctions composed of multi-ingredient traditional herbs were sampled from traditional Korean medicine (TKM) clinics, TKM hospitals, and external herbal dispensaries in 2019. The decoctions were analyzed for SO2, benzopyrene, and mycotoxins using 10 samples. SO2 and benzopyrene were not detected in any of the herbal decoctions. With regard to mycotoxins, aflatoxin B1 was not detected, but B2 was detected in 7 cases (0.00~0.04 ppb), G1 in 13 cases (0.03~0.29 ppb), and G2 in 9 cases (0.02~0.93 ppb). None of these values exceeded the restrictions in prior studies. Thus, we confirm that the amounts of SO2, benzopyrene, and mycotoxins in herbal decoctions are at safe levels and provides the basis of establishing safety management criteria for herbal decoctions.

1. Introduction

Herbal medicine is a widely utilized treatment that is growing with the global complementary and alternative medicine market [1]. Herbal medicines are used to prevent diseases and promote personal health. Complaints about existing treatments, positive aspects related to herbal medicine, and traditions of family are reasons why people prefer herbal medicine [2].
However, there have been reports about heavy metals, aflatoxins, benzopyrene, and microorganisms in herbal medicines including decoctions around the world [3,4,5,6]. A systematic review by Posadzki et al. [7] found that herbal medicinal products were contaminated or adulterated with insects, rodents, parasites, dust, pollen, microbes, fungi, pesticides, toxins, heavy metals, and so on. Severe side effects such as hepatic encephalopathy, meningitis, multi-organ failure, and death were caused by these contaminants. Although inhalation is the major way of exposing humans to sulfur dioxide (SO2), humans can be exposed through ingestion. SO2 is a severe irritant to the eyes, mucous membranes, epidermis, and other organs [8]. Benzopyrene may cause an acute burning or rash feeling in body parts. Prolonged exposure to benzopyrene can cause skin or lung cancer in humans and damage the developing fetus [9]. Mycotoxins can affect humans in various ways, including neurologic impairment and failure of the liver, kidney, or heart failure. Aflatoxins, known as carcinogens, are potent toxins and also lead to liver impairment in animals [10].
Although herbal medicine has an effect of treating several illnesses, many countries use it continuously at uncontrolled levels [11]. Herbal medicine is a constantly increasing industry and its popularity is international, so more effort should be put into policy to minimize the safety risks and provide scientific evidence [12].
According to the World Health Organization (WHO), in 2018, about 90% of member states and countries had regulations about herbal medicines [13]. Many countries have suggested guidelines on good manufacturing practices (GMP) and methods to standardize the quality of herbal medicines and to make them safe and efficient [14]. However, most guidelines of herbal medicine often follow rules for pharmaceutical products, foods, or food supplements without special consideration [12]. In addition, most countries have no quality control system for herbal decoctions.
Herbal decoctions require strict control of contamination and manufacturing processes [11]. Safety concerns from contamination, heavy metals, and adulteration arise mainly from restricted quality control regulations and deficiency of internationally accepted standards [12]. Reproducible results demand the development, evaluation, and standardization of the latest methods of chemistry, biology, and pharmacology [14].
In the case of Korea, a pilot project to apply herbal decoctions to health insurance has been implemented. However, there is no safety management standard to verify the quality of herbal decoctions. Therefore, the government has attempted to provide guidelines for herbal decoctions. We monitored the quality control of the herbal decoctions as part of this study. We examined and reported on heavy metal and pesticide residue contents in our previous study [15]. In this study, we aimed to investigate herbal decoctions in Korea for SO2, benzopyrene, and mycotoxin to suggest evidence for establishing safety criteria at the government level.

2. Materials and Methods

2.1. Sample Collection

The ten types of decoctions, including Galgeuntang which is commonly used in TKM institutions [16], based on the traditional Korean medicine (TKM) Consumption Statistics Survey 2017, were tested to examine them for SO2, benzopyrene, and mycotoxin content. The formulae and compositions of them have been provided in a previous study [15]. For this study, thirty herbal decoction pouches prescribed by TKM clinics, TKM hospitals, and external herbal dispensaries were obtained from October to December 2019 and were stored in a refrigerator. A total of 10 decoction pouches for each institute were collected when the volume was 80 mL and were not collected when the volume was less than 80 mL.

2.2. Standards and Reagents

The reagents used for the SO2 test were methyl red, 30% hydrogen peroxide solution, hydrochloric acid, 0.01 N sodium hydroxide solution (Factor 1.00, Wako, Tokyo, Japan), ethanol (High-performance liquid chromatography (HPLC) grade, J. T. Baker, Phillipsburg, NJ, USA), and nitrogen gas (purity 99.995%). SO2 was extracted as the test apparatus using a Monier-Williams transformation apparatus and an automatic potentiometer (T50M, Mettler-Toledo, Zurich, Switzerland) was used.
Aflatoxin B1, B2, G1, and G2 mixed solutions (Aflatoxin Mix, Sigma, Burlington, MA, USA) were used as standards for the mycotoxin test. Pididium hydrobromic acid perbromate (PBPB, Sigma, USA) was used as the derivatization reagent; methanol (HPLC grade, J. T. Baker, USA), acetonitrile (HPLC grade, J. T. Baker, USA), acetic acid (HPLC grade, J. T. Baker, USA), and Tween 20 were used as solvents. (Bio-Rad, Hercules, CA, USA); and an immunoaffinity column (AflaTest, Vicam, Manchester, TN, USA) was used.
The standard used for the benzopyrene test was benzopyrene (Sigma, USA). Furthermore, 3-methylcholanthrene (Sigma, USA) was used as an internal standard, and n-hexane (HPLC grade, J. T. Baker, USA), acetonitrile (HPLC grade, J. T. Baker, USA), anhydrous sodium sulfate (HPLC grade, J. T. Baker, USA), dichloromethane (J. T. Baker, USA), and a Florisil cartridge (1 g, Sep-Pak® Waters, Bedford, MA, USA) were used.

2.3. Experimenting Methods

2.3.1. Pre-Treatment of Samples

For the testing SO2, benzopyrene, and mycotoxins, all testing solutions were prepared in accordance with the Korea Pharmacopoeia (KP) General Testing Process [17].

2.3.2. Analysis Instrument and Analysis Conditions

The SO2 test adhered to the Korean Pharmacopoeia [17]. Purity Test of Herbal Medicine Test Method SO2 test method [17]. The amount of SO2 was calculated using an automatic potentiometer for the collected solution using an SO2 extraction device (Figure 1) according to the Monier-Williams method [18,19]. In the Monier-Williams method [18,19], SO2 is released from sulphites and some bound compounds when a sample is mixed with an acid normally hydrochloric acid, but sometimes phosphoric acid and heated. The SO2 is distilled using a stream of nitrogen gas which carries the gaseous SO2 into an absorbing solution of hydrogen peroxide (H2O2) where it is oxidised to sulphuric acid. The amount of SO2 distilled into the H2O2 is determined by titration with 0.1 M sodium hydroxide. Moreover, 1 mL of 0.1 M NaOH is equivalent to 3.203 mg SO2.
HPLC was used to analyse mycotoxins and benzopyrene [17,20,21]. The instrument analysis conditions are listed in Table 1 and Table 2.

2.4. Validation of the Test Method

The recovery rate was calculated by following method: A sample with no detectable analytical material was selected and then the standard solution was added. This process was repeated three times. The difference between the concentrations of the samples including the standard and the control was calculated. The limit of detection (LOD) and the limit of quantitation (LOQ) were calculated using the following formulas, consisting of the standard deviation of the reaction (σ) and the gradients of the measurement graph (S). The average of three repetitions of the measured standard solutions were applied in a stepwise manner.
LOD = 3.3 × σ/S, LOQ = 10 × σ/S
σ: the mean standard deviation; S: the individual slop.

2.4.1. Recovery Rate

The recovery rates of the SO2 tests were measured for each concentration using potassium metabisulfite (Table 3). The recovery rate test of the mycotoxin was performed such that the final detection concentrations were 5, 10, and 20 ppb (Table 4). The recovery rate of the benzopyrene test was measured such that the final detection concentration was 20 ppb of benzopyrene (Table 5).

2.4.2. Detection Limit (LOD), and Quantitation Limit (LOQ) of the Analytical Equipment

The LOD and LOQ of analysis equipment are listed in Table 6 and Table 7.

2.5. Test Criteria

The test items and safety management criteria for SO2, mycotoxin, and benzopyrene were developed in accordance with the findings of literature reviews and consensus among experts. More details on the development process can be found in a previous paper [22]. SO2 should be ≤30 ppm, the mycotoxin standard should be ≤15 ppb of total aflatoxin, and ≤10 ppb of aflatoxin B1. The concentration of benzopyrene should be ≤5 ppb.

3. Results

3.1. Sulfur Dioxide (SO2)

SO2 content was analyzed in 10 samples of decoctions frequently prescribed in Korea collected from TKM clinics, TKM hospitals, and external herbal dispensaries, respectively, making a total of 30 samples. No SO2 content was detected in any of the samples (Table 8).

3.2. Mycotoxin

Mycotoxin detection was analyzed in 10 samples of decoctions frequently prescribed in Korea collected from TKM clinics, TKM hospitals, and external herbal dispensaries, respectively, making a total of 30 samples. Aflatoxin B1 was not detected in any samples, B2 was detected in 7 cases (0.00~0.04 ppb), G1 in 13 cases (0.03~0.29 ppb), and G2 in 9 cases (0.02~0.93 ppb). The total aflatoxin content of all herbal decoctions was ≤0.96 ppb (Table 9).

3.3. Benzopyrene

Benzopyrene was analyzed in 10 samples of decoctions frequently prescribed in Korea collected from TKM clinics, TKM hospitals, and external herbal dispensaries, respectively, making a total of 30 samples. Benzopyrene was not detected in any of the herbal decoctions (Table 10).

4. Discussion

According to the previous study [22], a set of safety management standards on SO2, benzopyrene, and mycotoxins was identified through the literature reviews (e.g., the WHO guidelines for regulation of herbal medicines, Japanese pharmacopeia, Japanese standards for nonpharmacopeial crude drugs, pharmacopeia of People’s Republic of China, the US botanical drugs guidance, European pharmacopeia, and a quality control guideline for herbal or botanical medicine extracts of Korea) and the expert consensus.
The amount of SO2 was found to be less than the quantitative or detection limit in all herbal decoctions. It appears that SO2 would have been washed away during washing processes, even if it was previously present in the decoctions [23]. In Yu’s study, SO2 was detected in only 1 (0.7%) out of 155 samples of herbal decoctions, and the level of sulfites was high (17.6 mg/kg) in the same sample for unknown reasons [24].
With regard to mycotoxins, aflatoxin was detected in 18 samples. The concentrations of aflatoxin in 17 samples were below 0.3 ppb, which is low. However, in SSanghwatang from a certain Korean medicine hospital, 0.96 ppb of aflatoxin was detected. Aflatoxins are secondary metabolites produced by different fungal strains such as Aspergillus flavus and Aspergillus parasiticus. Aflatoxin B1 is the most recurrent and harmful toxin. Aflatoxin B1 manifests a wide range of cytotoxicity in neuronal cells [25] and is considered to be carcinogenic (Group 1) and potentially carcinogenic for humans (Group 2B) [26].
According to a study from Pakistan on aflatoxin content in herbal formulations, total Aflatoxins were detected in 52.5% of analysed samples, with Aflatoxin B1 being the most frequently occurring (46.3%), followed by Aflatoxin G1 (35.6%), Aflatoxin B2 (34.5%), and Aflatoxin G2 (27%) [6]. In a study conducted in Nigeria, aflatoxin contamination was discovered in 48 (84.21%) out of 57 herbal medicine samples [27]. B1 was not detected in this study, and the results for G1, B2, and G2 were similar. Aflatoxin was managed by applying criteria only to 20 kinds of raw herbs as of 2022. Even though Aflatoxin B1 was not detected in these analyses, additional standards for the management of herbal decoctions would be necessary to eliminate the risk of neurotoxicity.
Benzopyrene was not detected in any sample. Polycyclic aromatic hydrocarbons can be generated from the incomplete combustion of organic matter or produced when organic sediments are chemically transformed into fossil fuels such as oil and coal [28]. Benzo[a]pyrene is considered to be a Group 1 compound (carcinogenic to humans). In December 2009, the Korea Food and Drug Administration established a benzopyrene standard of less than 5 μg/kg for all herbal medicines (except for mineral herbal medicines), and they also announced a test method [29].
Because of the potential health risks, the WHO and some countries such as the United States and Europe developed a program to manage the quality of herbal medicine [30,31,32]. Although there are many regulations on herbal medicines in Korea, such as GMP, the herbal decoction lacks a safety management standard. The herbal decoction generally undergoes a packing process after extraction, which may cause contamination. Hence, it is necessary to check the hygiene management of manufacturing environments and develop guidelines for post-extraction processes. As a member of the Pharmaceutical Inspection Cooperation Scheme (PIC/S), South Korea is required to follow the GMP, good laboratory practice (GLP), and good clinical practice (GCP) guidelines [33,34]. In the manufacture of herbal medicinal products, the PIC/S guide was more detailed than hGMP. Only the PIC/S guide had an exact clause about proper solvent and herbal preparation. According to the PIC/S, regulation should be determined for the relevant guidance on quality, so the regulation in Korea should follow the international guidance quickly.

Limitation of This Study

This study has several limitations. First, the sample size was small. Since herbal decoctions had to be collected and manufactured on the same day, only 30 samples were analysed in this study. In addition, the regional distribution of samples was relatively uneven. Second, the types of herbal decoctions constituting the 10 prescriptions used in the analysis were all different. Therefore, it was difficult to identify some of the detected factors for SO2 and mycotoxin (e.g., preparation environment, composition of herbal medicines, or storage conditions). Third, in some cases, the labels for a single dose were not clear. In the case of herbal medicinal products considered to be pharmaceuticals, there are standardized bottles or packages. It is also necessary to consider applying similar standards to herbal medicinal products and to calculate the total amount of decoctions compared to the amounts of raw herbs. There are still potential risk factors, such as Staphylococcus aureus which can cause shock, so hygiene management is required when preparing decoctions.

5. Conclusions

In conclusion, this study examined the content of SO2, benzopyrene, and mycotoxins in herbal decoctions from Korean medical institutions. Because these decoctions were made from pharmaceutical-grade herbs, there were no hazardous safety issues. However, systematic complements are needed to meet consumers’ high demand for the safety of herbal decoctions.

Author Contributions

Conceptualization, H.I.J., K.H.K. and S.-H.S.; methodology, H.I.J., B.-C.S., K.H.K. and S.-H.S.; software, J.-H.W.; validation, J.-H.W.; formal analysis, J.-H.W.; investigation, J.-H.W.; resources, J.-H.W.; data curation, J.-H.W.; writing—original draft preparation, H.I.J., J.-E.H. and S.-H.S.; writing—review and editing, S.J., B.-C.S. and K.H.K.; visualization, H.I.J.; supervision, J.-H.W.; project administration, J.-H.W. and S.-H.S.; funding acquisition, S.-H.S. All authors have read and agreed to the published version of the manuscript.

Funding

This research was supported by a grant from the Project of National Development Institute of Korean Medicine, Accreditation of External Herbal Dispensaries of Traditional Korean Medicine Clinics, funded by the Korean Ministry of Health and Welfare.

Institutional Review Board Statement

Not applicable.

Informed Consent Statement

Not applicable.

Data Availability Statement

The data will be made available upon reasonable request.

Acknowledgments

Authors thank the Association of Korean Medicine (https://www.akom.org/Home/Main, accessed on 9 October 2022) and chungyeon external herbal dispensary (https://the-han.co.kr/, accessed on 9 October 2022) for providing the decoction samples.

Conflicts of Interest

The authors declare that there are no conflicts of interest regarding the publication of this paper.

Abbreviations

GCP; good clinical practice, GMP; good manufacturing practices, GLP; good laboratory practice, HPLC; high-performance liquid chromatography, KP; Korea Pharmacopoeia, LOD; limit of detection, LOQ; limit of quantitation, PIC/S; Pharmaceutical Inspection Cooperation Scheme, SO2; sulfur dioxide, TKM; traditional Korean medicine, WHO; World Health Organization.

References

  1. Herbal Medicine Market Share, Analysis (2029) | COVID-19 Impact. Available online: https://www.fortunebusinessinsights.com/herbal-medicine-market-106320 (accessed on 5 September 2022).
  2. Welz, A.N.; Emberger-Klein, A.; Menrad, K. Why People Use Herbal Medicine: Insights from a Focus-Group Study in Germany. BMC Complement. Altern. Med. 2018, 18, 92. [Google Scholar] [CrossRef]
  3. Luo, L.; Wang, B.; Jiang, J.; Fitzgerald, M.; Huang, Q.; Yu, Z.; Li, H.; Zhang, J.; Wei, J.; Yang, C.; et al. Heavy Metal Contaminations in Herbal Medicines: Determination, Comprehensive Risk Assessments, and Solutions. Front. Pharmacol. 2021, 11, 595335. [Google Scholar] [CrossRef] [PubMed]
  4. Chien, M.-Y.; Yang, C.-M.; Chen, C.-H. Organochlorine Pesticide Residue in Chinese Herbal Medicine. J. Pestic. Sci. 2022, 47, 30–34. [Google Scholar] [CrossRef] [PubMed]
  5. De Lima, C.M.S.; Fujishima, M.A.T.; de Lima, B.P.; Mastroianni, P.C.; de Sousa, F.F.O.; da Silva, J.O. Microbial Contamination in Herbal Medicines: A Serious Health Hazard to Elderly Consumers. BMC Complement. Med. Ther. 2020, 20, 17. [Google Scholar] [CrossRef] [PubMed]
  6. Javed, A.; Naeem, I.; Benkerroum, N.; Riaz, M.; Akhtar, S.; Ismail, A.; Sajid, M.; Khan, M.T.; Ismail, Z. Occurrence and Health Risk Assessment of Aflatoxins through Intake of Eastern Herbal Medicines Collected from Four Districts of Southern Punjab—Pakistan. Int. J. Environ. Res. Public Health 2021, 18, 9531. [Google Scholar] [CrossRef]
  7. Posadzki, P.; Watson, L.; Ernst, E. Contamination and Adulteration of Herbal Medicinal Products (HMPs): An Overview of Systematic Reviews. Eur. J. Clin. Pharmacol. 2013, 69, 295–307. [Google Scholar] [CrossRef]
  8. Agency for Toxic Substances and Disease Registry Sulfur Dioxide | Medical Management Guidelines | Toxic Substance Portal | ATSDR. Available online: https://wwwn.cdc.gov/TSP/MMG/MMGDetails.aspx?mmgid=249&toxid=46 (accessed on 9 October 2022).
  9. New Jersey Department of Health. Right to Know Hazardous Substance Fact Sheet; New Jersey Department of Health: Trenton, NJ, USA, 2017.
  10. Food and Drug Administration Chemical Hazards | FDA. Available online: https://www.fda.gov/animal-veterinary/biological-chemical-and-physical-contaminants-animal-food/chemical-hazards (accessed on 9 October 2022).
  11. Tschinkel, P.F.S.; Melo, E.S.P.; Pereira, H.S.; Silva, K.R.N.; Arakaki, D.G.; Lima, N.V.; Fernandes, M.R.; Leite, L.C.S.; Melo, E.S.P.; Melnikov, P.; et al. The Hazardous Level of Heavy Metals in Different Medicinal Plants and Their Decoctions in Water: A Public Health Problem in Brazil. Biomed Res. Int. 2020, 2020, 1465051. [Google Scholar] [CrossRef] [Green Version]
  12. Zhou, X.; Li, C.-G.; Chang, D.; Bensoussan, A. Current Status and Major Challenges to the Safety and Efficacy Presented by Chinese Herbal Medicine. Medicines 2019, 6, 14. [Google Scholar] [CrossRef] [Green Version]
  13. WHO. WHO Global Report on Traditional and Complementary Medicine 2019; WHO: Luxembourg, 2019.
  14. Noviana, E.; Indrayanto, G.; Rohman, A. Advances in Fingerprint Analysis for Standardization and Quality Control of Herbal Medicines. Front. Pharmacol. 2022, 13, 853023. [Google Scholar] [CrossRef]
  15. Jeong, H.I.; Han, J.-E.; Shin, B.-C.; Jang, S.B.; Won, J.-H.; Han Kim, K.; Sung, S.-H. Monitoring of Heavy Metals and Pesticide Residues of Herbal Decoctions in Traditional Korean Medicine Clinics in Korea. Int. J. Environ. Res. Public Health 2022, 19, 8523. [Google Scholar] [CrossRef]
  16. Ministry of Health and Welfare. The 2017 Korean Medicine Utilization and Herbal Medicine Consumption Survey. Available online: https://www.koms.or.kr/board/researchReport/view.do?post_no=46&menu_no=21 (accessed on 1 April 2022).
  17. Ministry of Food and Drug Safety. The Korean Pharmacopoeia; Ministry of Food and Drug Safety: North Chungcheong, Korea, 2022.
  18. Lafeuille, J.-L.; Lefevre, S.; Achouri, D. Determination of Added Sulfites in Dried Garlic with a Modified Version of the Optimized Monier-Williams Method. J. AOAC Int. 2007, 90, 1090–1097. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  19. Warner, C.R.; Daniels, D.H.; Joe, F.L.; Fazio, T. Reevaluation of Monier-Williams Method for Determining Sulfite in Food. J. Assoc. Off. Anal. Chem. 1986, 69, 3–5. [Google Scholar] [CrossRef]
  20. Turner, N.W.; Bramhmbhatt, H.; Szabo-Vezse, M.; Poma, A.; Coker, R.; Piletsky, S.A. Analytical Methods for Determination of Mycotoxins: An Update (2009–2014). Anal. Chim. Acta 2015, 901, 12–33. [Google Scholar] [CrossRef] [PubMed]
  21. Gazioglu, I.; Tekkeli, S.E.K. Development and Validation of a HPLC Method for the Determination of Benzo(a)Pyrene in Human Breast Milk. Food Sci. Biotechnol. 2017, 26, 319–322. [Google Scholar] [CrossRef] [PubMed]
  22. Jeong, H.I.; Kim, K.H.; Won, J.H.; Sung, G.U.; Kim, J.W.; Han, J.; Sung, A.D.M.; Park, E.J.; Sung, S.H. Development of Hazardous Materials Management Standard for Decoction Type of Personalized Herbal Medicine. J. Pharmacopunct. 2020, 23, 71–78. [Google Scholar] [CrossRef] [PubMed]
  23. Chang-Seob, S.; Dae-Sun, H.; Jun-Kyoung, L.; Hye-Kyung, H.; Jin-Mi, C.; Young-Ran, U.; Seol, J.; Hyeun-Kyoo, S. Concentration of Heavy Metals, Residual Pesticides and Sulfur Dioxide before/after a Decoction—In Prescription Consist of Sipjeondaebo-Tang. J. Korean Oriental. Med. 2009, 30, 108–117. [Google Scholar]
  24. Yu, I.S.; Lee, J.S.; Kim, S.D.; Kim, Y.H.; Park, H.W.; Ryu, H.J.; Lee, J.H.; Lee, J.M.; Jung, K.; Na, C.; et al. Monitoring Heavy Metals, Residual Agricultural Chemicals and Sulfites in Traditional Herbal Decoctions. BMC Complement. Altern. Med. 2017, 17, 154. [Google Scholar] [CrossRef] [Green Version]
  25. Huang, B.; Chen, Q.; Wang, L.; Gao, X.; Zhu, W.; Mu, P.; Deng, Y. Aflatoxin B1 Induces Neurotoxicity through Reactive Oxygen Species Generation, DNA Damage, Apoptosis, and S-Phase Cell Cycle Arrest. Int. J. Mol. Sci. 2020, 21, 6517. [Google Scholar] [CrossRef]
  26. World Health Organization. Aflatoxins: Some Naturally Occurring Substances: Food Items and Constituents, Heterocyclic Aromatic Amines and Mycotoxins. IARC Monogr. Eval. Carcinog. Risks Hum. 1993, 56, 245–395. [Google Scholar]
  27. Ikeagwulonu, R.C.; Onyenekwe, C.C.; Oshim, I.O.; Olise, N.A.; Odeyemi, O.; Ojidei, C.K. Investigation of the Levels of Total Aflatoxin in Herbal Traditional Medicines from Selected Vendors Dealers in South-Eastern Nigeria. J. Adv. Med. Pharm. Sci. 2020, 22, 26–31. [Google Scholar] [CrossRef] [Green Version]
  28. Ravindra, K.; Sokhi, R.; van Grieken, R. Atmospheric Polycyclic Aromatic Hydrocarbons: Source Attribution, Emission Factors and Regulation. Atmos. Environ. 2008, 42, 2895–2921. [Google Scholar] [CrossRef]
  29. Korea Food & Drug Administration. Criteria and Method of Benzopyrene for Herbal; Korea Food & Drug Administration: Osong, Korea, 2009.
  30. Human Health Risk Assessment | US EPA. Available online: https://www.epa.gov/risk/human-health-risk-assessment (accessed on 1 April 2022).
  31. Herbal Medicinal Products | European Medicines Agency. Available online: https://www.ema.europa.eu/en/human-regulatory/herbal-medicinal-products (accessed on 1 April 2022).
  32. World Health Organization. WHO Guidelines for Assessing Quality of Herbal Medicines with Reference to Contaminants and Residues; World Health Organization: Geneva, Switzerland, 2007.
  33. Segalstad, S.H. International IT Regulations and Compliance: Quality Standards in the Pharmaceutical and Regulated Industries; John Wiley & Sons Inc.: Hoboken, NJ, USA, 2008; p. 324. [Google Scholar]
  34. Pharmaceutical Inspection Cooperation Scheme. Annual Report 2019; Pharmaceutical Inspection Cooperation Scheme: Geneva, Switzerland, 2020. [Google Scholar]
Figure 1. Sulfur dioxide (SO2) extraction device. A: Inlet Adapter, B: Addition Funnel, C: 3-N Flask, D: Gas Inlet Adapter, E: Allihn Condenser, F: Bubbler Tube, G: Cylinder.
Figure 1. Sulfur dioxide (SO2) extraction device. A: Inlet Adapter, B: Addition Funnel, C: 3-N Flask, D: Gas Inlet Adapter, E: Allihn Condenser, F: Bubbler Tube, G: Cylinder.
Ijerph 19 13595 g001
Table 1. HPLC analysis conditions for mycotoxin.
Table 1. HPLC analysis conditions for mycotoxin.
InstrumentAnalysis Condition
(Waters, USA 2475 FLD, Alliance 2695)
ColumnXbridge C18 (4.6 × 250 mm, 5 μm)
Mobile phaseWater·Methanol·Acetonitrile (60:25:15)
Flow rate1.0 mL/min
Injection volume10 μL
Post-column derivatization systemPost Column Reaction Module (PBPB)
DetectorFluorescence (Ex: 365 nm Em: 435 nm)
HPLC: high performance liquid chromatography.
Table 2. HPLC analysis conditions for benzopyrene.
Table 2. HPLC analysis conditions for benzopyrene.
InstrumentAnalysis Condition
(Waters, USA 2475 FLD, Alliance 2695)
ColumnPAH C18 (4.6 × 250 mm, 5 μm)
Mobile phaseAcetonitrile·Water (8:2)
Flow rate1.0 mL/min
Injection volume10 μL
DetectorFluorescence (Ex: 294 nm Em: 404 nm)
HPLC: high performance liquid chromatography.
Table 3. Recovery rate of analysis equipment for SO2.
Table 3. Recovery rate of analysis equipment for SO2.
7.5 ppm15 ppm30 ppm60 ppm
Recovery rate (%)84.3 ± 5.088.3 ± 5.088.7 ± 3.190.3 ± 5.5
Table 4. Recovery rate of analysis equipment for mycotoxin.
Table 4. Recovery rate of analysis equipment for mycotoxin.
5 ppb10 ppb20 ppb
Recovery rate (%)Aflatoxin B188.3 ± 6.291.7 ± 6.996.8 ± 5.5
Aflatoxin B284.6 ± 1.289.3 ± 5.296.2 ± 6.8
Aflatoxin G179.7 ± 3.789.6 ± 9.489.8 ± 5.0
Aflatoxin G278.6 ± 3.282.7 ± 3.082.8 ± 2.3
Table 5. Recovery rate of analysis equipment for benzopyrene.
Table 5. Recovery rate of analysis equipment for benzopyrene.
Benzopyrene3-Methylcholanthrene
Recovery rate (%)105.3 ± 7.484.2 ± 6.3
Table 6. Detection limit and quantitation limit of analysis equipment for mycotoxin.
Table 6. Detection limit and quantitation limit of analysis equipment for mycotoxin.
Limit of Detection (ppm)Limit of Quantitation (ppm)
Aflatoxin B10.070.24
Aflatoxin B20.050.18
Aflatoxin G10.070.22
Aflatoxin G20.050.15
Table 7. Detection limit and quantitation limit of analysis equipment for benzopyrene.
Table 7. Detection limit and quantitation limit of analysis equipment for benzopyrene.
Limit of Detection (ppm)Limit of Quantitation (ppm)
Benzopyrene0.0250.077
Table 8. SO2 detection result of herbal decoctions.
Table 8. SO2 detection result of herbal decoctions.
Herbal DecoctionsTKM Clinics
(ppm)
TKM Hospitals
(ppm)
External Herbal Dispensaries (ppm)
Galgeun-tang0.0000.0000.000
Kangwhalyupung-tang0.0000.0000.000
Dangguisu-san0.0000.0000.000
Dokhwalgisaeng-tangNDNDND
Banhasasim-tangNDND0.000
Bangpungtongseong-sanNDNDND
Bojungikgi-tangNDNDND
Sipjeondaebo-tangNDNDND
Ssanghwa-tangNDNDND
Ojeok-sanNDNDND
Test criteria≤30 ppm≤30 ppm≤30 ppm
0.000: less than the quantitative limit, ND: less than the detection limit, TKM: traditional Korean medicine, External herbal dispensaries: type of pharmacy that provides various types of herbal medicines to other TKM clinics or hospitals.
Table 9. Mycotoxin detection result of herbal decoctions.
Table 9. Mycotoxin detection result of herbal decoctions.
Herbal DecoctionsAflatoxin B1
(ppb)
Aflatoxin B2
(ppb)
Aflatoxin G1
(ppb)
Aflatoxin G2
(ppb)
Total Aflatoxin
(ppb)
TKM ClinicsGalgeun-tangNDNDND0.050.05
Kangwhalyupung-tangNDND0.040.020.05
Dangguisu-sanND0.010.120.020.15
Dokhwalgisaeng-tangND0.000.050.030.08
Banhasasim-tangNDNDNDNDND
Bangpungtongseong-sanNDNDND0.030.03
Bojungikgi-tangNDND0.29ND0.29
Sipjeondaebo-tangND0.010.05ND0.06
Ssanghwa-tangNDND0.030.930.96
Ojeok-sanNDNDNDNDND
TKM HospitalsGalgeun-tangNDNDNDNDND
Kangwhalyupung-tangNDNDNDNDND
Dangguisu-sanNDNDNDNDND
Dokhwalgisaeng-tangND0.040.05ND0.09
Banhasasim-tangNDNDNDNDND
Bangpungtongseong-sanNDNDNDNDND
Bojungikgi-tangNDNDNDNDND
Sipjeondaebo-tangND0.020.11ND0.12
Ssanghwa-tangNDND0.05ND0.05
Ojeok-sanNDND0.06ND0.07
External Herbal DispensariesGalgeun-tangNDNDNDNDND
Kangwhalyupung-tangNDNDNDNDND
Dangguisu-sanNDNDNDNDND
Dokhwalgisaeng-tangNDNDNDNDND
Banhasasim-tangNDNDNDNDND
Bangpungtongseong-sanNDNDNDNDND
Bojungikgi-tangNDNDNDNDND
Sipjeondaebo-tangNDNDNDNDND
Ssanghwa-tangNDNDNDNDND
Ojeok-sanNDNDNDNDND
Test criteria≤15 ppb of total aflatoxin and ≤10 ppb of aflatoxin B1
ND: less than the detection limit, TKM: traditional Korean medicine, External herbal dispensaries: type of pharmacy that provides various types of herbal medicines to other TKM clinics or hospitals.
Table 10. Benzopyrene detection result of herbal decoctions.
Table 10. Benzopyrene detection result of herbal decoctions.
Herbal DecoctionsTKM Clinics
(ppb)
TKM Hospitals
(ppb)
External Herbal Dispensaries (ppb)
Galgeun-tangNDNDND
Kangwhalyupung-tangNDNDND
Dangguisu-sanNDNDND
Dokhwalgisaeng-tangNDNDND
Banhasasim-tangNDNDND
Bangpungtongseong-sanNDNDND
Bojungikgi-tangNDNDND
Sipjeondaebo-tangNDNDND
Ssanghwa-tangNDNDND
Ojeok-sanNDNDND
Test criteria≤5 ppb≤5 ppb≤5 ppb
ND: less than the detection limit, TKM: traditional Korean medicine, External herbal dispensaries: type of pharmacy that provides various types of herbal medicines to other TKM clinics or hospitals.
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Jeong, H.I.; Han, J.-E.; Shin, B.-C.; Jang, S.; Won, J.-H.; Kim, K.H.; Sung, S.-H. Herbal Decoctions for the Levels of Sulfur Dioxide, Benzopyrene, and Mycotoxin from Traditional Korean Medicine Clinics: A Preliminary Study. Int. J. Environ. Res. Public Health 2022, 19, 13595. https://doi.org/10.3390/ijerph192013595

AMA Style

Jeong HI, Han J-E, Shin B-C, Jang S, Won J-H, Kim KH, Sung S-H. Herbal Decoctions for the Levels of Sulfur Dioxide, Benzopyrene, and Mycotoxin from Traditional Korean Medicine Clinics: A Preliminary Study. International Journal of Environmental Research and Public Health. 2022; 19(20):13595. https://doi.org/10.3390/ijerph192013595

Chicago/Turabian Style

Jeong, Hye In, Ji-Eun Han, Byung-Cheul Shin, Soobin Jang, Jae-Hee Won, Kyeong Han Kim, and Soo-Hyun Sung. 2022. "Herbal Decoctions for the Levels of Sulfur Dioxide, Benzopyrene, and Mycotoxin from Traditional Korean Medicine Clinics: A Preliminary Study" International Journal of Environmental Research and Public Health 19, no. 20: 13595. https://doi.org/10.3390/ijerph192013595

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