Epidemiologic Notes and Reports Cadmium and Lead Exposure Associated with Pharmaceuticals Imported from Asia -- Texas

In August 1988, the Texas Department of Health (TDH) investigated illegal sales in rural west Texas of pharmaceutical drugs manufactured in Asia. These drugs, identified by TDH and Food and Drug Administration (FDA) agents as "chuifong tokuwan" (a pharmaceutical compound manufactured by the Nan Ling Pharmaceutical Company of Hong Kong), are sold in pill form. Chuifong tokuwan contains a drug combination (diazepam, indomethacin, hydrochlorothiazide, mefenamic acid, dexamethasone, lead, and cadmium) that is not approved by FDA and not legal for sale in or importation into the United States. The drugs usually were repackaged and relabeled as "The Miracle Herb--Mother Nature's Finest."

TDH tested 93 self-referred persons who had ingested the pills for exposure to lead and cadmium. Of these, 57 (61%) were female; greater than 90% were white non-Hispanics; the mean age was 55 years. Sixty-six (71%) reported taking the pills to relieve symptoms of medical conditions such as arthralgias (51%) and other pain (headache, stiff neck, back pain (26%)). Twenty-two (24%) persons had elevated urine levels of cadmium; none had elevated levels of lead (blood lead greater than or equal to 25 ug/mL). However, 39 (42%) persons had elevated urine values for retinol-binding protein (RBP), a low-molecular-weight protein indicative of renal tubular dysfunction (1-3). The mean urine cadmium level for exposed persons was 1.8 ug/mL, compared with 0.5 ug/mL for a nonrandom sampling of 14 unexposed persons. In exposed persons, 22 (24%) urine samples tested for cadmium were greater than 2.5 ug/mL, the upper limit of normal. None of the samples from unexposed persons had elevated values.

The chuifong tokuwan seized in this investigation was destroyed. The investigation is continuing. Reported by: D Baker, MS, Food and Drug Div, J Brender, PhD, Environmental Epidemiology, KC Davis, Texas Dept of Health. Surveillance and Programs Br, Div of Environmental Hazards and Health Effects, Center for Environmental Health and Injury Control, CDC.

Editorial Note

Editorial Note: Chuifong tokuwan first appeared in the United States in 1974. Although it was banned by FDA in 1978, the drug is distributed illegally in certain parts of the United States and is sometimes sold by mail. The primary users of chuifong tokuwan in this study were long-time residents of Texas; however, use of unapproved imported drug combinations is common among recent immigrants to the United States, particularly those from Asia and Latin America (4-7). Although these products are frequently perceived as relatively harmless herbal "folk remedies," they often contain cortico- or anabolic steroids; nonsteroidal anti-inflammatory drugs (NSAIDs); prescription antibiotics, such as tetracycline and chloramphenicol; and controlled substances, such as diazepam or narcotics, and have potentially serious or fatal health effects.

Use of chuifong tokuwan may increase the body burden of cadmium and may have contributed to renal tubular dysfunction in persons using this compound. Through chronic exposure, cadmium can accumulate in certain organs, particularly the kidneys. Both cadmium and several of the prescription analgesics in chuifong tokuwan can cause renal tubular cell damage (8-11). Cadmium can adversely affect function of the proximal renal tubules (3,8-10); increased urinary protein excretion of low-molecular-weight proteins (e.g., RBP) is an early consequence of proximal renal tubular damage by cadmium (2,3,9,10).

In persons who were also taking other medications, the analgesic nephropathy associated with chronic use of many NSAIDs may have contributed to renal tubular dysfunction (9,11). Alternatively, increased urinary RBP values could reflect renal dysfunction related to the underlying illness (e.g., arthritis) for which many of the patients took this medication. However, adverse effects on renal function have not been reported with use of either indomethacin or mefenamic acid (the NSAIDs present in the pills analyzed), even with prolonged use (11).

Cadmium is a cumulative toxicant, with a biological half-life of greater than 10 years in humans (12). Medical evaluation, including urine cadmium and urinary RBP values, is recommended for persons who have used chuifong tokuwan. Additional renal-function evaluation should be included in the medical follow-up of persons whose urinary RBP or urine cadmium values are abnormal.

Complex cultural and linguistic barriers necessitate cooperation with traditional healers (e.g., acupuncturists, herbalists) and local leaders of immigrant communities to inform these groups about the hazards associated with use of specific products.

References

1. Kowal NE, Zirkes M. Urinary cadmium and beta 2-microglobulin: normal values and con centration adjustment. J Toxicol Environ Health 1983;11:607-24.

2. Ormos G, Cseh J, Groszmann M, Timar M. Urinary beta 2-microglobulin and retinol binding protein: individual fluctuations in cadmium-exposed workers. Toxicol Lett 1985;27:59-64.

3. Kowal NE, Johnson DE, Kraemer DF, Pahren HR. Normal levels of cadmium in diet, urine, blood, and tissues of inhabitants of the United States. J Toxicol Environ Health 1979;5:995-1014.

4. Chan H, Billmeier GJ Jr, Evans WE, Chan H. Lead poisoning from ingestion of Chinese herbal medicine. Clin Toxicol 1977;10:273-81.

5. Brearley RL, Forsythe AM. Lead poisoning from aphrodisiacs: potential hazard in immigrants. Br Med J 1978;2:1748-9.

6. CDC. Folk remedy-associated lead poisoning in Hmong children--Minnesota. MMWR 1983;32:555-6.

7. Lightfoote J, Blair HJ, Cohen JR. Lead intoxication in an adult caused by Chinese herbal medication. JAMA 1977;238:1539.

8. Adams RG. Environmental cadmium and renal disease (Letter). Lancet 1981;1:845.

9. Boelaert J, Daneels R, Schurgers M. Cadmium, kidneys, and Belgian industry (Letter). Lancet 1981;1:672.

10. Baker EL Jr, Peterson WA, Holtz JL, Coleman C, Landrigan PJ. Subacute cadmium intoxication in jewelry workers: an evaluation of diagnostic procedures. Arch Environ Health 1979;34:173-7.

11. Flower RJ, Moncada S, Vane JR. Analgesic-antipyretics and anti-inflammatory agents; drugs employed in the treatment of gout. In: Gilman AG, Goodman LS, Gilman A, eds. Goodman and Gilman's the pharmacological basis of therapeutics. 6th ed. New York: MacMillan Publishing, 1980:682-728.

12. Lauwerys RR. Industrial chemical exposure: guidelines for biological monitoring. Davis, California: Biomedical Publications, 1983:17.

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