Adulteration and Contaminants in Chinese Patent Medicines

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References

[No authors listed] Chinese herbal creams may contain steroids. BMJ. 1999 Feb 27;318(7183):C.

[No authors listed] From the Centers for Disease Control and Prevention. Jin bu huan toxicity in children--Colorado, 1993. JAMA. 1993 Sep 15;270(11):1298, 1302.

[No authors listed] From the Centers for Disease Control and Prevention. Jin bu huan toxicity in adults--Los Angeles, 1993.JAMA. 1994 Feb 9;271(6):423-424.

Anderson LA. Concern regarding herbal toxicities: case reports and counseling tips. Ann Pharmacother. 1996 Jan;30(1):79-80.

Atherton DJ, Rustin MH, Brostoff J. Need for correct identification of herbs in herbal poisoning. Lancet. 1993 Mar 6;341(8845):637-638. (Letter)

Azuno Y, Yaga K, Sasayama T, Kimoto K. Thrombocytopenia induced by Jui, a traditional Chinese herbal medicine. Lancet. 1999 Jul 24;354(9175):304-305. (Letter)

Bateman J, Chapman RD, Simpson D. Possible toxicity of herbal remedies. Scott Med J. 1998 Feb;43(1):7-15. (Review)

Blackwell R. Adverse Events Involving Certain Chinese Herbal Medicines and the Response of the Profession. J Chinese Medicine. Jan 1996, 50. (See http://www.acupuncture.com/Herbology/Toxic.htm.)

Bullock K. Herbal remedies. Am Fam Physician. 1999 Oct 15;60(6):1661-1662, discussion 1665-1666.

But PP, Tomlinson B, Cheung KO, Yong SP, Szeto ML, Lee CK. Adulterants of herbal products can cause poisoning. BMJ. 1996 Jul 13;313(7049):117. (Letter)

But PP. Herbal poisoning caused by adulterants or erroneous substitutes. J Trop Med Hyg 1994 Dec;97(6):371-374.
Abstract:  Six cases of herbal poisoning involving six patients in Hong Kong, Taipei and Kuala Lumpur are reported. The sources of poisoning were identified as adulterants (Podophyllum emodi) or erroneous substitutes (Datura metel). In cases of suspected herbal poisoning, it is recommended that the prescriptions, herbal residues and herb samples should be collected for pharmacognostical and chemical analysis to substantiate the cause of poisoning. Insofar as it is possible, an estimate of the amount of herbs consumed should also be obtained, to establish whether the amount of toxin present is sufficient to account for the symptoms.
 
But PP. Need for correct identification of herbs in herbal poisoning. Lancet. 1993 Mar 6;341(8845):637. (Letter)

Chan TY, Tomlinson B, Critchley JA.  Aconitine poisoning following the ingestion of Chinese herbal medicines: a report of eight cases. Aust N Z J Med 1993 Jun;23(3):268-271.
Abstract:  BACKGROUND: Traditional Chinese medicines often contain 'chuanwu' and 'caowu', the roots of certain Aconitum species which are thought to have an anti-inflammatory effect in many conditions. Excessive amounts of these materials, which contain diterpene alkaloids particularly aconitine, can produce toxic effects and occasional fatalities. AIMS: This study was conducted to document the adverse effects related to these herbal medicines which resulted in hospital admission and to determine the outcome in these patients. METHODS: A retrospective survey was conducted of patients admitted to the Prince of Wales Hospital, Hong Kong with suspected adverse effects from Chinese herbal medicines containing chuanwu or caowu over a two year period from 1989 to 1991. RESULTS: Eight patients were identified with features of mild to moderate intoxication including nausea and vomiting, paraesthesiae or numbness in the mouth and extremities, hypotension and ventricular extrasystoles. The management of aconitine poisoning is essentially supportive and in-hospital observation with ECG monitoring should be continued for at least 24 hours because of the risk of cardiovascular collapse and ventricular arrhythmias. The medical profession and general public should be alerted to the potential toxicity of these herbs and their usage should be controlled by legislation in Hong Kong as it is in some other countries.

Chan TY, Tomlinson B, Tse LK, Chan JC, Chan WW, Critchley JA.  Aconitine poisoning due to Chinese herbal medicines: a review. Vet Hum Toxicol 1994 Oct;36(5):452-455.
Abstract:  Both "chuanwu", the main root of Aconitum carmichaeli, and "caowu", the root of A kusnezoffii, are believed to possess anti-inflammatory, analgesic and cardiotonic effects and have been used in Chinese materia medica mainly for the treatment of musculoskeletal disorders. They contain the highly toxic C19 diterpenoid alkaloids of aconitine, mesaconitine and hypaconitine. After ingestion, patients may present with signs and symptoms that are typical of aconitine poisoning. Death may occur from ventricular arrhythmias, which are most likely to occur within the first 24 h. Management of aconitine poisoning is essentially supportive. There are no adequate studies in humans to indicate the most effective treatment of the ventricular arrhythmias. All clinicians should be alerted to the potential toxicity of "chuanwu" and "caowu".

Chan TY, Chan JC, Tomlinson B, Critchley JA.  Chinese herbal medicines revisited: a Hong Kong perspective Lancet 1993 Dec 18-25;342(8886-8887):1532-1534.
Abstract:  Chinese herbal medicines (CHM) and Chinese proprietary medicines (CPM) are widely used by people of Chinese origin throughout the world. Although the use of these medicinal materials rarely causes significant toxic effects, cases of severe and even fatal poisoning have occurred after medication with herbs containing aconitine, podophyllin, and anticholinergic substances. Furthermore, CHM and CPM are often adulterated with substituted herbs, heavy metals, and western medicines; such contamination can have important clinical consequences. In Hong Kong, surveillance and legislation are required to control the use of some of these herbal preparations. In other countries, medical practitioners should also be aware of the possibility that these herbal-medicine-related remedies may cause significant clinical problems in their Chinese patients.

Chan TY, Chan AY, Critchley JA. Hospital admissions due to adverse reactions to Chinese herbal medicines. J Trop Med Hyg. 1992 Aug;95(4):296-298.
Abstract: Chinese herbal medicines (CHM) are commonly used in Hong Kong. To determine the importance of adverse reactions to CHM as a cause of medical admissions in Hong Kong, all 1701 patients admitted to two general medical wards at the Prince of Wales Hospital over an eight-month period were prospectively studied. In only three patients (0.2%) was the admission attributed to the adverse effects of CHM. These were life-threatening in two cases ('dazao'-induced angio-neurotic oedema and liquorice-induced hypokalaemic periodic paralysis). Despite this low incidence of adverse reactions, in communities where CHM are commonly used, it is important that there is a continuing effort to collect new information on the safety of these compounds.

Chan TY. Monitoring the safety of Chinese herbal medicines in Hong Kong. Ann Pharmacother. 1996 Sep;30(9):1039-1040

Chan TY, Lee KK, Chan AY, Critchley JA. Poisoning due to Chinese proprietary medicines. Hum Exp Toxicol 1995 May;14(5):434-436.
Abstract:  1. To determine the toxic potentials of those Chinese proprietary medicines (CPM) which are commonly used for self-poisoning by adults in Hong Kong, all patients admitted to four of the eight general medical wards at the Prince of Wales Hospital between January 1988 and December 1993 were retrospectively studied. 2. There were 54 women and 17 men with their age ranging from 15 to 86 years. Twenty-three subjects (32%) also took alcohol, chemicals or drugs. Of the 51 subjects (72%) who had taken topical medicaments, 22 had no symptoms while 28 had minor features of gastrointestinal irritation (n = 26), mild (n = 2) or severe (n = 1) salicylate poisoning. Of the 17 subjects (24%) who had taken CPM tablets/capsules, nine had mild symptoms including nausea/vomiting and drowsiness. The three remaining patients (4%) who had ingested liquid CPM preparations were asymptomatic. Elevated plasma salicylate or paracetamol concentrations (> 0.1 mmol l-1) were found in some patients who had taken topical medicaments and CPM tablets/capsules, respectively. All the 71 patients completely recovered. 3. Most of the CPM used for self-poisoning in Hong Kong were of low to moderate toxicity except for those containing wintergreen oil (methyl salicylate).
 
Chan TY, Critchley JA.  Usage and adverse effects of Chinese herbal medicines. Hum Exp Toxicol 1996 Jan;15(1):5-12.
Abstract:  The great majority of Chinese herbal preparations are safe, and in the past, some useful Western drugs have been derived from these herbs. Nearly all serious poisonings are due to the few preparations containing aconitine, podophyllin or anticholinergics or else proprietary preparations containing dangerous Western drugs or heavy metals. Both medical professionals and the general public should be alerted to the potential toxicity of herbal remedies. There should be frequent monitoring of Chinese herbal medicines or their derivatives, such as some Chinese proprietary medicines, for undeclared Western drugs and heavy metals. Mothers should be discouraged from treating their children with herbal or proprietary medicines. There should be continuing efforts to collect safety information on these widely used products.

Chan TY. The prevalence use and harmful potential of some Chinese herbal medicines in babies and children. Vet Hum Toxicol 1994 Jun;36(3):238-240.
Abstract:  This article reviews the prevalence use of Chinese herbal medicines (CHM) in Chinese pregnant women, babies and children living in Hong Kong and the harmful potential of some CHM and Chinese proprietary medicines (CPM) in babies and children. The use of CHM appears to be common amongst Chinese pregnant women. The possible effects of these herbs on the fetus and baby and their overall safety are not known. This practice should be discouraged since there is suggestion that maternal consumption of CHM might increase the risk of neonatal jaundice. Both "chuen-lin" and "yin-chen" can displace bilirubin from their serum protein binding and increase the risk of hyperbilirubinaemia. These herbs should not be given to the neonates. The use of CPM-containing undeclared drugs of high toxicity or lead, arsenic and mercurial compounds should be banned. The medical profession and the general public should be alerted to the harmful potential of some of the CHM and CPM. There should be continuing efforts to collect information on the safety of these compounds.
 
Cheng TJ, Wong RH, Lin YP, Hwang YH, Horng JJ, Wang JD. Chinese herbal medicine, sibship, and blood lead in children. Occup Environ Med 1998 Aug;55(8):573-576.
Abstract: OBJECTIVES: Risk factors for increased blood lead concentration (BPb) has been investigated. However, the effect of sibship and Chinese herbal medicine on BPb has not been systematically studied. In this study BPb data from voluntary testing was used to determine if Chinese herbal medicine and sibship were associated with BPb. METHODS: 319 children aged 1-7 were tested for BPb. Meanwhile, parents were interviewed to obtain information including consumption of Chinese herbal medicine, living environment, lifestyle, and sibship of the children tested. RESULTS: The mean (SD) BPb of 319 preschool children was 4.4 (2.4) micrograms/dl. The consumption of Ba-baw-san (a Chinese herbal medicine) was significantly associated with increased BPb in children (p = 0.038). Further multivariate regression analysis of BPb in 50 pairs of siblings showed the factors of being brothers explained 75% of variation for BPb, and being sisters and brother-sister explained 51% and 41% of variation respectively. CONCLUSION: Chinese herbal medicine and children's play patterns within the family expressed in different types of sibship are the main determinants of low concentrations of BPb in preschool children of Taiwan.

Cheng TO. Herbal remedies. Am Fam Physician. 1999 Oct 15;60(6):1661; discussion 1665-6.

D'Arcy PF. Traditional Chinese medicines: safety hazards. Adverse Drug React Toxicol Rev 1999 Jun;18(2):53-57.

de Smet PA, Elferink F. [Chinese pills still contaminated]. Ned Tijdschr Geneeskd. 1988 Feb 21;132(9):407-408. [Article in Dutch]

De Soriano G, Chase D. Safety of herbal remedies. J R Soc Med. 1998 Oct;91(10):561. (Letter)

Dharmananda S. ITM START : The Story of Jin Bu Huan. Portland, OR.: Institute for Traditional Medicine, Nov 1993.
 
Dharmananda S. ITM START: Drugs in Imported Chinese Herb Products. Portland, OR.: Institute for Traditional Medicine, Nov. 1996.

Du S, Cao F, Lei S. [A survey of adverse effects of Chinese herbal drugs in China, 1915-1990]. Chung Kuo Chung Yao Tsa Chih. 1992 Jul;17(7):435-8. Review) [Article in Chinese]

Ernst E. Harmless Herbs? A Review of the Recent Literature. Am J Med 1998 Feb104(2):170-178.
 
Ferguson JE, Chalmers RJ, Rowlands DJ.  Reversible dilated cardiomyopathy following treatment of atopic eczema with Chinese herbal medicine. Br J Dermatol 1997 Apr;136(4):592-593.
Abstract:  Chinese herbal medicines are increasingly being used as an alternative treatment for chronic skin disease. Most patients and many doctors remain insufficiently aware of their potential toxicity. We report a patient with eczema who developed a severe cardiomyopathy following a 2-week course of Chinese herbal medicine. The connection between the two conditions was not made until 2 weeks after presentation when the patient was specifically asked if she had ingested any unusual substances. The belief that herbs, as natural products available without prescription, are harmless, is commonplace and patients may not consider them worthy of mention during a standard medical history.

Fratkin JP. Chinese Herbal Patent Formulas. Portland, OR.: Institute for Traditional Medicine, 1986.

Fratkin JP. Toxic Contaminants in Chinese Patent Medicines. Oriental Medicine Journal. Vol. 6, No. 3-4, Fall/Winter 1997.
 
Graham-Brown RA, Bourke JF, Bumphrey G. Chinese herbal remedies may contain steroids. BMJ. 1994 Feb 12;308(6926):473. (Letter)

Graham-Brown R. Toxicity of Chinese herbal remedies. Lancet. 1992 Sep 12;340(8820):673-674.

Gu Y, Yuan H. [A review of the adverse effects of Chinese herbal drugs as published in Chinese journals in 1993 and 1994]. Chung Kuo Chung Yao Tsa Chih. 1995 Aug;20(8):502-507. (Review) [Article in Chinese]

Horowitz RS, Dart RC, et al. Jin bu huan toxicity in children--Colorado. Morb Mortal Wkly Rep 1993 Aug 27;42(33):633-636.
Abstract:  The consumption of traditional ethnic remedies can have adverse health effects, especially among children. Life-threatening bradycardia with rapid onset and central nervous system (CNS) and respiratory depression developed in three unrelated children in Colorado during 1993 following ingestion of Jin Bu Huan tablets, a Chinese herbal medicine used for relieving pain. This report summarizes the investigations of these cases.

Horowitz RS, Feldhaus K, Dart RC, Stermitz FR, Beck JJ.  The clinical spectrum of Jin Bu Huan toxicity. Arch Intern Med 1996 Apr 22;156(8):899-903.
Abstract:  Herbal medications and other nontraditional medical therapies are becoming increasingly popular in the United States. We describe three children and three adults in whom severe toxic effects developed after ingestion of a Chinese herbal medication, jin bu huan, which is sold as Jin Bu Huan Anodyne Tablets. Jin bu huan produced distinct clinical syndromes after acute ingestion in children and long-term use in adults. A single, acute ingestion in children rapidly produced life-threatening neurologic and cardiovascular manifestations, while long-term jin bu huan use in adults was associated with hepatitis. Jin bu huan contains levo-tetrahydropalmatine, a potent neuroactive substance. The constituents of jin bu huan are misidentified on the package, resulting in significant delay in identifying the plant alkaloid responsible for its toxicity. Although perceived as innocuous, jin bu huan may produce major health effects. The highly concentrated formulation, the lack of childproof packaging, and the product insert listing indications for the treatment of serious medical conditions may all contribute to the development of toxic reactions.
 
Huang WF, Wen KC, Hsiao ML. Adulteration by synthetic therapeutic substances of traditional Chinese medicines in Taiwan. J Clin Pharmacol 1997 Apr;37(4):344-350.
Abstract: The adulteration by synthetic therapeutic substances of traditional Chinese medicines has been reported on various occasions and has been a public health concern in Taiwan over the past several years. A large-scale effort was initiated in 1992 to screen traditional Chinese medicines that were suspected of adulteration with synthetic therapeutic substances. The term "adulteration" refers to traditional Chinese medicines that are tested and found to contain chemical substances not prescribed or labeled as part of the intended use. A total of 2,609 samples were collected by eight major general hospitals in Taiwan. Samples were collected through physicians' referrals during patients visits. The samples were analyzed by hospital pharmacists following the established standard procedures in comparison to references by thin-layer chromatography. An average of 23.7% (n = 618) of the samples collected from the eight hospitals were adulterated. Four samples with either a rheumatoid or an antiinflammatory indication contained six different kinds of adulterants. More than half (52.8%) of the adulterated traditional Chinese medicines contained two or more adulterants. The sources of adulterated samples and their claimed indications, as well as the most frequently detected synthetic therapeutic substances, are presented in this report. The controversies regarding the combination of synthetic therapeutic substances and traditional Chinese medicines without adequate labeling should be resolved through regulatory actions for better safety of drug use.
 
Hughes JR, et al. Oral dexamethasone masquerading as a Chinese herbal remedy. Br J Dermatol. 1994 Feb;130(2):261.

Huxtable RJ. The myth of beneficient nature: the risks of herbal preparations. Ann Intern Med 1992;17 (2), 165-166.

Jadoul M, de Plaen JF, Cosyns JP, Van Ypersele de Strihou C. Adverse effects from traditional Chinese medicine. Lancet. 1993 Apr 3;341(8849):892-893. (Letter)

Kane JA, Kane SP, Jain S. Hepatitis induced by traditional Chinese herbs; possible toxic components. Gut. 1995 Jan;36(1):146-147.
Abstract: Traditional Chinese herbal remedies are widely available in the United Kingdom for the treatment of chronic skin disorders. Their benefits are considerable, but their use is completely unregulated. Two patients are described here who suffered an acute hepatitic illness related to taking traditional Chinese herbs. Both recovered fully. The mixtures that they took included two plant components also contained within the mixture taken by a previously reported patient who suffered fatal hepatic necrosis. These cases high-light the need for greater awareness of both the therapeutic and toxic potential of herbal remedies, as well as greater control of their use.

Kang-Yum E, Oransky SH.  Chinese patent medicine as a potential source of mercury poisoning. Vet Hum Toxicol 1992 Jun;34(3):235-238.
Abstract:  This research is an effort to create an awareness. of the potential hazards of some Chinese patent medicines which contain mercurial ingredients. This should be of consideration when screening symptomatic patients who are of Asian ethnic background or other users of these medicines. This research discusses reported cases of mercury poisoning related to the use of Chinese patent medicines and the potential toxicity of cinnabar (red mercuric sulfide) and calomel (mercurous chloride), 2 mercurials commonly used in these medicines. A list of mercurial-containing Chinese patent medicines available on the open market in North America has been compiled, together with their traditional uses and mercurial contents and is presented as a quick reference for Specialists in Poison Information. This class of medicine may not pose a problem when used appropriately; however, its misuse, abuse, overdosage and improper storage can lead to serious mercury poisoning.
  
Kaptchuk TJ. Acute hepatitis associated with jin bu huan. Ann Intern Med. 1995 Apr 15;122(8):636.

Kiefer DS, Barrett B. Herbal remedies. Am Fam Physician. 1999 Oct 15;60(6):1662, 1665; discussion 1665-6.

Ko R, Au A. The Compendium of Asian Patent Medicines. California Department of Health Services, Food and Drug Branch. 1997.

Kolev ST, Leman P, Kite GC, Stevenson PC, Shaw D, Murray VS. Toxicity following accidental ingestion of Aconitum containing Chinese remedy. Hum Exp Toxicol. 1996 Oct;15(10):839-842.
Abstract: Various species of Aconitum are commonly used in traditional Chinese medicine. These plants are known to contain highly potent cardiotoxins. A 22 year old Chinese male accidentally ingested a herbal liniment prepared from Aconitum with near fatal results. His ventricular tachyarrhythmias responded to standard treatment including the use of i.v. magnesium.

Larrey D. Hepatotoxicity of herbal remedies. J Hepatol. 1997;26 Suppl 1:47-51. (Review)

Liu HN, Jaw SK, Wong CK. Chinese herbs and atopic dermatitis. Lancet. 1993 Nov 6;342(8880):1175-1176. (Letter)

Lu W, Jiang H. [Consideration and reflection on the study of the processing of Chinese herbal medicine]. Chung Kuo Chung Yao Tsa Chih. 1990 Feb;15(2):89-92, 126. [Article in Chinese]

Markowitz SB, Nunez CM, Klitzman S, Munshi AA, Kim WS, Eisinger J, Landrigan PJ. Lead poisoning due to Hai Ge Fen, the porphyrin content of individual erythrocytes. JAMA. 1994;271(12), 932-934.
Abstract: A 45-year-old Korean man developed abdominal colic, muscle pain, and fatigue. Following a 3-week hospitalization, acute intermittent porphyria was diagnosed based on the symptoms and a high level of urinary delta-aminolevulinic acid (378 mumol/L [4.95 mg/dL]). However, discovery of an elevated blood lead level (3.7 mumol/L [76 micrograms/dL]) subsequently led to the correct diagnosis. No occupational source of lead exposure was identified. The patient reported ingesting a Chinese herbal preparation for 4 weeks prior to becoming ill. A public health investigation revealed that the source of lead exposure was hai ge fen (clamshell powder), one of the 36 ingredients of the Chinese herbal medicine. We used fluorescence image-based cytometry to determine the frequency distribution of the zinc protoporphyrin content in circulating red blood cells and found that 70% of the patient's cells contained elevated levels of zinc protoporphyrin, consistent with the duration of lead exposure and effect of lead on heme synthesis. Analysis of zinc protoporphyrin content in circulating red blood cell distributions may be useful in the diagnosis, therapy, and kinetic modeling of lead poisoning. Environmental lead poisoning is best addressed through the close collaboration of clinicians, public health specialists, and laboratory scientists.

McIntyre M. Chinese herbs: risk, side effects, and poisoning: the case for objective reporting and analysis reveals serious misrepresentation. J Altern Complement Med. 1998 Spring;4(1):15-16.

Ng TH, Chan YW, Yu YL, Chang CM, Ho HC, Leung SY, But PP. Encephalopathy and neuropathy following ingestion of a Chinese herbal broth containing podophyllin. J Neurol Sci. 1991 Jan;101(1):107-113.
Abstract: Two patients developed podophyllin intoxication following ingestion of a broth of the Chinese herb guijiu. The neurological manifestations are described and the pathology of the peripheral neuropathy is fully documented with ultrastructural and quantitative studies.

Perharic-Walton L, Murray V. Toxicity of Chinese herbal remedies. Lancet. 1992 Sep 12;340(8820):674.

Picciotto A, Campo N, Brizzolara R, Giusto R, Guido G, Sinelli N, Lapertosa G, Celle G. Chronic hepatitis induced by Jin Bu Huan. J Hepatol 1998 Jan;28(1):165-167.
Abstract:  BACKGROUND/AIMS: Jin Bu Huan and other Chinese herbal products are widely taken remedies. They have been developed as a natural alternative to traditional drugs in the treatment of various ailments. Their ability to induce several side effects such as acute hepatitis has already been described. We report a case of chronic hepatic damage following administration of Jin Bu Huan Anodyne tablets. METHODS: The patient, a 49-year-old man, developed biochemical signs of liver damage 2 months after beginning Jin Bu Huan intake (3 tablets/daily) including biopsy-proven chronic hepatitis with moderate fibrosis. Virological, autoimmune, metabolic or other hepatotoxic causes were excluded. Liver function impairment was resolved by discontinuing Jin Bu Huan intake. CONCLUSIONS: This case reinforces the already known hepatotoxicity of this product and should make us think more about the uncontrolled use of alternative products.
 
Pillans PI. Toxicity of herbal products. N Z Med J. 1995 Nov 24;108(1012):469-471.

Register of Chinese Herbal Medicine (1992). Patent medicines warning. RCHM Newsletter, October 1992.

Register of Chinese Herbal Medicine (1993). Steroids in skin creams. RCHM Newsletter, May 1993.

Ries CA, Sahud MA.Agranulocytosis caused by Chinese herbal medicines. Dangers of medications containing aminopyrine and phenylbutazone. JAMA 1975 Jan 27;231(4):352-355.
Abstract:  Four non-Chinese patients, middle-aged or older, developed agranuloctyosis while taking Chinese herbal medicines for relief of arthritis and back pain. All four developed life-threatening infections with bacterial sepsis; one died. The herbal medicines were shown to contain substantial amounts of undeclared aminopyrine and phenylbutazone, drugs that are well-known causes of agranulocytosis. These Chinese herbal medicines are widely available over the counter throughout the United States.
 
Rustin MH, Atherton DJ. Chinese herbs and atopic dermatitis. Lancet. 1994 Feb 19;343(8895):489. (Letter)

Sanders D, Kennedy N, McKendrick MW. Monitoring the safety of herbal remedies. Herbal remedies have a heterogeneous nature. BMJ. 1995 Dec 9;311(7019):1569.

Segasothy M, Samad S. Illicit herbal preparation containing phenylbutazone causing analgesic nephropathy. Nephron. 1991;59, 166-167.

Siegel RK. Kola, ginseng and mislabelled herbs. JAMA 1977;237, 25.

Tai YT, But PP, Young K, Lau CP. Cardiotoxicity after accidental herb-induced aconite poisoning. Lancet. 1992 Nov 21;340(8830):1254-1256.
Abstract: Aconitine and its related alkaloids are known cardiotoxins with no therapeutic role in modern western medicine. The rootstocks of Aconitum plants, which contain aconite alkaloids, have been common components of Chinese herbal recipes. We have documented life-threatening intoxication in 17 Chinese subjects after accidental herb-induced aconite poisoning. All patients developed symptoms of aconite toxicity within 2 h of herb ingestion. Most developed tachyarrhythmias, including ventricular tachycardia and fibrillation from which 2 patients died. Toxicological evaluation revealed that aconites from the Aconitum rootstocks were the only plausible casual factor for intoxication. These cases point to the need for strict surveillance of herbal substances with low safety margins.

Tang Y. [Compatibility of toxic Chinese medicines]. Chung Kuo Chung Yao Tsa Chih. 1996 Jul;21(7):438-41 inside backcover. [Artcile in Chinese]

Tie B, Qi W, Chen G. Determination of soluble mercury contents in Chinese traditional patent medicines for children. Chung Kuo Chung Yao Tsa Chih 1990 Oct;15(10):602-604, 639.
Abstract:  Soluble mercury contents in Baochi San, Xiaoer Zhibon Ding and Xiaoer Baishou Dan have been determined using dithizone method. This method has the advantages of short digestion time, clear digestion end point, simple operation and reproducible results. The recovery rate ranges from 98.4 to 103%. The data obtained can be used as a reference for controlling soluble mercury contents in Chinese traditional patent medicines containing cinnabar.
 
Vautier G, Spiller RC. Safety of complementary medicines should be monitored. BMJ. 1995;311, 633.

Wood B, Wishart J. Potent topical steroid in a Chinese herbal cream. N Z Med J. 1997 Nov 14;110(1055):420-421.
Abstract: Steroids have been discovered previously in oral "herbal" preparations. Using liquid chromatography, we have now confirmed the presence of the potent topical steroid, clobetasol proprionate, in a Chinese herbal cream.

Woolf GM, Petrovic LM, Rojter SE, Wainwright S, Villamil FG, Katkov WN, Michieletti P, Wanless IR, Stermitz FR, Beck JJ, et al.  Acute hepatitis associated with the Chinese herbal product jin bu huan. Ann Intern Med 1994 Nov 15;121(10):729-735.
Abstract:  OBJECTIVE: To describe the hepatotoxicity associated with ingestion of the Chinese herbal product Jin Bu Huan Anodyne Tablets (Lycopodium, serratum) and to propose possible mechanisms of injury. DESIGN: Retrospective analysis. SETTING: Academic hepatology units and private practice facilities. PATIENTS: Seven previously healthy patients. MEASUREMENTS: Clinical, laboratory, radiologic, and histologic studies. RESULTS: Acute hepatitis occurred after a mean of 20 weeks (range, 7 to 52 weeks) of Jin Bu Huan ingestion and resolved in six patients within a mean of 8 weeks (range, 2 to 30 weeks); another patient is currently improving. Hepatitis was associated with symptoms of fever, fatigue, nausea, pruritus, and abdominal pain and with signs of jaundice and hepatomegaly. Biopsy specimens showed that one patient had hepatitis with eosinophils (consistent with a drug reaction) and the other had mild hepatitis, moderate fibrosis, and microvesicular steatosis. Decreasing the Jin Bu Huan dose in one patient improved liver test results. Reusing Jin Bu Huan in two other patients caused abrupt recrudescence of hepatitis. CONCLUSION: Jin Bu Huan can cause liver injury. Although the hepatotoxic mechanisms are not defined, they may include hypersensitive or idiosyncratic reactions or direct toxicity to active metabolites. Hepatotoxicity caused by herbal products underscores the toxicity caused by herbal products underscores the importance of national surveillance programs and quality control of the manufacture of these products.

Woolf GM, Rojter SE, et al . Jin Bu Huan toxicity in adults - Los Angeles 1993. MMWR Morb Mortal Wkly Rep. 1993 Dec 3;42(47):920-922.
Abstract:  Jin Bu Huan (JBH) is a traditional Chinese herbal product used as a sedative and analgesic. During 1993, public health and health-care providers in Colorado reported three children with unintentional overdoses of JBH that caused central nervous system and respiratory depression with rapid onset of life-threatening bradycardia. Subsequently, the first cases of acute hepatitis attributed to use of JBH were diagnosed in three women in Los Angeles during July and August 1993. Patients 1 and 2 were referred to a Los Angeles hepatology clinic by their physicians; patient 3 was identified by patient 2. All three patients had purchased JBH at the same health-food store. This report summarizes the investigation of these cases.

Woolf GM, Petrovic LM, Rojter SE, Wainwright S, Villamil FG, Katkov WN, Michieletti P, Wanless IR, Stermitz FR, Beck JJ, et al. Acute hepatitis associated with the Chinese herbal product Jin Bu Huan. Annals of Internal Medicine. 1994 Nov 15;121(10):729-735.
Abstract: OBJECTIVE: To describe the hepatotoxicity associated with ingestion of the Chinese herbal product Jin Bu Huan Anodyne Tablets (Lycopodium, serratum) and to propose possible mechanisms of injury. DESIGN: Retrospective analysis. SETTING: Academic hepatology units and private practice facilities. PATIENTS: Seven previously healthy patients. MEASUREMENTS: Clinical, laboratory, radiologic, and histologic studies. RESULTS: Acute hepatitis occurred after a mean of 20 weeks (range, 7 to 52 weeks) of Jin Bu Huan ingestion and resolved in six patients within a mean of 8 weeks (range, 2 to 30 weeks); another patient is currently improving. Hepatitis was associated with symptoms of fever, fatigue, nausea, pruritus, and abdominal pain and with signs of jaundice and hepatomegaly. Biopsy specimens showed that one patient had hepatitis with eosinophils (consistent with a drug reaction) and the other had mild hepatitis, moderate fibrosis, and microvesicular steatosis. Decreasing the Jin Bu Huan dose in one patient improved liver test results. Reusing Jin Bu Huan in two other patients caused abrupt recrudescence of hepatitis. CONCLUSION: Jin Bu Huan can cause liver injury. Although the hepatotoxic mechanisms are not defined, they may include hypersensitive or idiosyncratic reactions or direct toxicity to active metabolites. Hepatotoxicity caused by herbal products underscores the toxicity caused by herbal products underscores the importance of national surveillance programs and quality control of the manufacture of these products.

Wrinkle A. Herbal Quality Issues: What Every Practitioner Should Know. Oriental Medicine. Winter 1999; 4.

Wu MS, Hong JJ, Lin JL, Yang CW, Chien HC. Multiple tubular dysfunction induced by mixed Chinese herbal medicines containing cadmium. Nephrol Dial Transplant. 1996 May;11(5):867-870.

Yang HY, Chen CF. Pharmacology and toxicology of herbal medicine: subacute toxicity of commonly used Chinese drugs. J Toxicol Sci. 1998 Jul;23 Suppl 2:229-233.

Yuan HN, Wang CJ. [Principal factors causing adverse effects of Chinese herbal drugs]. Chung Kuo Chung Yao Tsa Chih. 1994 Jan;19(1):52-55. (Review) [Article in Chinese]

Yuan ST, Zhang JX. [Advances in the study on the processing of Chinese herbal drugs in 1993]. Chung Kuo Chung Yao Tsa Chih. 1994 Oct;19(10):632-634. (Review) [Article in Chinese]

Zhang ZW, Watanabe T, Shimbo S, Higashikawa K, Ikeda M.  Lead and cadmium contents in cereals and pulses in north-eastern China Sci Total Environ 1998 Sep 18;220(2-3):137-145.
Abstract:  It is known that, unlike Japanese, Koreans or southern Chinese who depend on rice as a major source of energy for daily life, people in north-eastern China rely not only on rice, but on wheat and other cereals and to a lesser extent also on pulses. Cereal and pulse samples were collected from open markets in north-eastern China, and analyzed by inductively-coupled plasma spectrometry (ICP-MS) for two potentially hazardous heavy metals--lead (Pb) and cadmium (Cd). The average Pb level in cereals (31.3 ng Pb/g as a geometric mean) and that of pulses (25.7 ng Pb/g) were similar to each other with no significant difference. Among the cereals, Pb contents were higher in foxtail millet (54.3 ng/g) and lower in maize (35.4 ng Pb/g; grain and flour in combination), wheat flour (28.8 ng Pb/g) and rice flour (22.7 ng Pb/g). Lead levels in two important types of pulses, kidney bean and soybean (24.6 and 30.8 ng Pb/g, respectively), were comparable to the levels in rice and wheat. In contrast, Cd levels were substantially higher in pulses (55.7 ng Cd/g) than in cereals (9.2 ng Cd/g), and among the pulses, Cd in soybean (55.7 ng Cd/g) was significantly higher than that in kidney bean (23.8 ng Cd/g). The possible public health implication of the Pb and Cd levels, especially the high Pb level in foxtail millet (54.3 ng Pb/g) and the high Cd level in soybean (73.5 ng Cd/g), is discussed.

Zhong SM Yu HW (1995). General classification of traditional Chinese herbal materials based on a survey of the products available from ten suppliers in the European countries. Report published by the Research Development Division, East-West Herbs Ltd., Langston Priory Mews, Kingham, Oxfordshire OX7 6UP.

Zhu T, Lu C. [A preliminary exploration of the toxicity of certain Chinese herbal drugs containing alkaloids and the prevention of their poisoning]. Chung Kuo Chung Yao Tsa Chih. 1992 Apr;17(4):248-250. (Review) [Article in Chinese]