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. 2001 Feb;109(2):167–171. doi: 10.1289/ehp.01109167

Diagnostic chelation challenge with DMSA: a biomarker of long-term mercury exposure?

H Frumkin 1, C C Manning 1, P L Williams 1, A Sanders 1, B B Taylor 1, M Pierce 1, L Elon 1, V S Hertzberg 1
PMCID: PMC1240638  PMID: 11266328

Abstract

Chelation challenge testing has been used to assess the body burden of various metals. The best-known example is EDTA challenge in lead-exposed individuals. This study assessed diagnostic chelation challenge with dimercaptosuccinic acid (DMSA) as a measure of mercury body burden among mercury-exposed workers. Former employees at a chloralkali plant, for whom detailed exposure histories were available (n = 119), and unexposed controls (n = 101) completed 24-hr urine collections before and after the administration of two doses of DMSA, 10 mg/kg. The urinary response to DMSA was measured as both the absolute change and the relative change in mercury excretion. The average 24-hr mercury excretion was 4.3 microg/24 hr before chelation, and 7.8 microg/24 hr after chelation. There was no association between past occupational mercury exposure and the urinary excretion of mercury either before or after DMSA administration. There was also no association between urinary mercury excretion and the number of dental amalgam surfaces, in contrast to recent published results. We believe the most likely reason that DMSA chelation challenge failed to reflect past mercury exposure was the elapsed time (several years) since the exposure had ended. These results provide normative values for urinary mercury excretion both before and after DMSA challenge, and suggest that DMSA chelation challenge is not useful as a biomarker of past mercury exposure.

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Selected References

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  1. Aposhian H. V., Aposhian M. M. meso-2,3-Dimercaptosuccinic acid: chemical, pharmacological and toxicological properties of an orally effective metal chelating agent. Annu Rev Pharmacol Toxicol. 1990;30:279–306. doi: 10.1146/annurev.pa.30.040190.001431. [DOI] [PubMed] [Google Scholar]
  2. Aposhian H. V., Bruce D. C., Alter W., Dart R. C., Hurlbut K. M., Aposhian M. M. Urinary mercury after administration of 2,3-dimercaptopropane-1-sulfonic acid: correlation with dental amalgam score. FASEB J. 1992 Apr;6(7):2472–2476. doi: 10.1096/fasebj.6.7.1563599. [DOI] [PubMed] [Google Scholar]
  3. Aposhian H. V., Maiorino R. M., Rivera M., Bruce D. C., Dart R. C., Hurlbut K. M., Levine D. J., Zheng W., Fernando Q., Carter D. Human studies with the chelating agents, DMPS and DMSA. J Toxicol Clin Toxicol. 1992;30(4):505–528. doi: 10.3109/15563659209017938. [DOI] [PubMed] [Google Scholar]
  4. Bergdahl I. A., Schütz A., Ahlqwist M., Bengtsson C., Lapidus L., Lissner L., Hulten B. Methylmercury and inorganic mercury in serum--correlation to fish consumption and dental amalgam in a cohort of women born in 1922. Environ Res. 1998 Apr;77(1):20–24. doi: 10.1006/enrs.1997.3820. [DOI] [PubMed] [Google Scholar]
  5. Bluhm R. E., Bobbitt R. G., Welch L. W., Wood A. J., Bonfiglio J. F., Sarzen C., Heath A. J., Branch R. A. Elemental mercury vapour toxicity, treatment, and prognosis after acute, intensive exposure in chloralkali plant workers. Part I: History, neuropsychological findings and chelator effects. Hum Exp Toxicol. 1992 May;11(3):201–210. doi: 10.1177/096032719201100308. [DOI] [PubMed] [Google Scholar]
  6. Buchet J. P., Lauwerys R. R. Influence of 2,3-dimercaptopropane-1-sulfonate and dimercaptosuccinic acid on the mobilization of mercury from tissues of rats pretreated with mercuric chloride, phenylmercury acetate or mercury vapors. Toxicology. 1989 Mar;54(3):323–333. doi: 10.1016/0300-483x(89)90067-x. [DOI] [PubMed] [Google Scholar]
  7. Bunn W. B., 3rd, McGill C. M., Barber T. E., Cromer J. W., Jr, Goldwater L. J. Mercury exposure in chloralkali plants. Am Ind Hyg Assoc J. 1986 May;47(5):249–254. doi: 10.1080/15298668691389720. [DOI] [PubMed] [Google Scholar]
  8. Börjesson J., Mattsson S. Toxicology; in vivo x-ray fluorescence for the assessment of heavy metal concentrations in man. Appl Radiat Isot. 1995 Jun-Jul;46(6-7):571–576. doi: 10.1016/0969-8043(95)00093-3. [DOI] [PubMed] [Google Scholar]
  9. Chisolm J. J., Jr Mobilization of lead by calcium disodium edetate. A reappraisal. Am J Dis Child. 1987 Dec;141(12):1256–1257. doi: 10.1001/archpedi.1987.04460120018020. [DOI] [PubMed] [Google Scholar]
  10. EMMERSON B. T., THIELE B. R. Calcium versenate in the diagnosis of chronic lead nephropathy. Med J Aust. 1960 Feb 13;47(1):243–248. doi: 10.5694/j.1326-5377.1960.tb105344.x. [DOI] [PubMed] [Google Scholar]
  11. Florentine M. J., Sanfilippo D. J., 2nd Elemental mercury poisoning. Clin Pharm. 1991 Mar;10(3):213–221. [PubMed] [Google Scholar]
  12. Forman J., Moline J., Cernichiari E., Sayegh S., Torres J. C., Landrigan M. M., Hudson J., Adel H. N., Landrigan P. J. A cluster of pediatric metallic mercury exposure cases treated with meso-2,3-dimercaptosuccinic acid (DMSA) Environ Health Perspect. 2000 Jun;108(6):575–577. doi: 10.1289/ehp.00108575. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Frumkin H., Letz R., Williams P. L., Gerr F., Pierce M., Sanders A., Elon L., Manning C. C., Woods J. S., Hertzberg V. S. Health effects of long-term mercury exposure among chloralkali plant workers. Am J Ind Med. 2001 Jan;39(1):1–18. doi: 10.1002/1097-0274(200101)39:1<1::aid-ajim1>3.0.co;2-n. [DOI] [PubMed] [Google Scholar]
  14. Gale G. R., Smith A. B., Jones M. M., Singh P. K. meso-2,3-dimercaptosuccinic acid monoalkyl esters: effects on mercury levels in mice. Toxicology. 1993 Jul 11;81(1):49–56. doi: 10.1016/0300-483x(93)90155-l. [DOI] [PubMed] [Google Scholar]
  15. Gerhardsson L., Börjesson J., Mattsson S., Schütz A., Skerfving S. Chelated lead in relation to lead in bone and ALAD genotype. Environ Res. 1999 May;80(4):389–398. doi: 10.1006/enrs.1998.3936. [DOI] [PubMed] [Google Scholar]
  16. Gonzalez-Ramirez D., Maiorino R. M., Zuniga-Charles M., Xu Z., Hurlbut K. M., Junco-Munoz P., Aposhian M. M., Dart R. C., Diaz Gama J. H., Echeverria D. Sodium 2,3-dimercaptopropane-1-sulfonate challenge test for mercury in humans: II. Urinary mercury, porphyrins and neurobehavioral changes of dental workers in Monterrey, Mexico. J Pharmacol Exp Ther. 1995 Jan;272(1):264–274. [PubMed] [Google Scholar]
  17. Grandjean P., Guldager B., Larsen I. B., Jørgensen P. J., Holmstrup P. Placebo response in environmental disease. Chelation therapy of patients with symptoms attributed to amalgam fillings. J Occup Environ Med. 1997 Aug;39(8):707–714. doi: 10.1097/00043764-199708000-00004. [DOI] [PubMed] [Google Scholar]
  18. Graziano J. H. Conceptual and practical advances in the measurement and clinical management of lead toxicity. Neurotoxicology. 1993 Summer-Fall;14(2-3):219–223. [PubMed] [Google Scholar]
  19. Guha Mazumder D. N., Ghoshal U. C., Saha J., Santra A., De B. K., Chatterjee A., Dutta S., Angle C. R., Centeno J. A. Randomized placebo-controlled trial of 2,3-dimercaptosuccinic acid in therapy of chronic arsenicosis due to drinking arsenic-contaminated subsoil water. J Toxicol Clin Toxicol. 1998;36(7):683–690. doi: 10.3109/15563659809162616. [DOI] [PubMed] [Google Scholar]
  20. Halbach S., Kremers L., Willruth H., Mehl A., Welzl G., Wack F. X., Hickel R., Greim H. Systemic transfer of mercury from amalgam fillings before and after cessation of emission. Environ Res. 1998 May;77(2):115–123. doi: 10.1006/enrs.1998.3829. [DOI] [PubMed] [Google Scholar]
  21. Houeto P., Sandouk P., Baud F. J., Levillain P. Elemental mercury vapour toxicity: treatment and levels in plasma and urine. Hum Exp Toxicol. 1994 Dec;13(12):848–852. doi: 10.1177/096032719401301205. [DOI] [PubMed] [Google Scholar]
  22. Hu H., Aro A., Rotnitzky A. Bone lead measured by X-ray fluorescence: epidemiologic methods. Environ Health Perspect. 1995 Feb;103 (Suppl 1):105–110. doi: 10.1289/ehp.95103s1105. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Hu H., Rabinowitz M., Smith D. Bone lead as a biological marker in epidemiologic studies of chronic toxicity: conceptual paradigms. Environ Health Perspect. 1998 Jan;106(1):1–8. doi: 10.1289/ehp.981061. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Hursh J. B., Cherian M. G., Clarkson T. W., Vostal J. J., Mallie R. V. Clearance of mercury (HG-197, HG-203) vapor inhaled by human subjects. Arch Environ Health. 1976 Nov-Dec;31(6):302–309. doi: 10.1080/00039896.1976.10667240. [DOI] [PubMed] [Google Scholar]
  25. Kostial K., Restek-Samarzija N., Blanusa M., Piasek M., Jones M. M., Singh P. K. Combined oral treatment with racemic and meso-2,3-dimercaptosuccinic acid for removal of mercury in rats. Pharmacol Toxicol. 1997 Nov;81(5):242–244. doi: 10.1111/j.1600-0773.1997.tb00054.x. [DOI] [PubMed] [Google Scholar]
  26. Kostial K., Restek-Samarzija N., Blanusa M., Piasek M., Prester L., Jones M. M., Singh P. K. Racemic-2,3-dimercaptosuccinic acid for inorganic mercury mobilization in rats. J Appl Toxicol. 1997 Jan-Feb;17(1):71–74. doi: 10.1002/(sici)1099-1263(199701)17:1<71::aid-jat395>3.0.co;2-u. [DOI] [PubMed] [Google Scholar]
  27. Lee B. K., Schwartz B. S., Stewart W., Ahn K. D. Provocative chelation with DMSA and EDTA: evidence for differential access to lead storage sites. Occup Environ Med. 1995 Jan;52(1):13–19. doi: 10.1136/oem.52.1.13. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Liang Y. Y., Zhang J. S., Tao Z. Q., Yan X. M., Xu X. H., Chen Z. J. [Effect of dimercaptosuccinic acid per os on distribution and excretion of 210Pb and 203Hg in mice]. Zhongguo Yao Li Xue Bao. 1994 Jul;15(4):379–382. [PubMed] [Google Scholar]
  29. Liebelt E. L., Shannon M., Graef J. W. Efficacy of oral meso-2,3-dimercaptosuccinic acid therapy for low-level childhood plumbism. J Pediatr. 1994 Feb;124(2):313–317. doi: 10.1016/s0022-3476(94)70326-4. [DOI] [PubMed] [Google Scholar]
  30. Littlejohn D., Fell G. S., Ottaway J. M. Modified determination of total and inorganic mercury in urine by cold vapor atomic absorption sectrometry. Clin Chem. 1976 Oct;22(10):1719–1723. [PubMed] [Google Scholar]
  31. Lorscheider F. L., Vimy M. J., Summers A. O. Mercury exposure from "silver" tooth fillings: emerging evidence questions a traditional dental paradigm. FASEB J. 1995 Apr;9(7):504–508. [PubMed] [Google Scholar]
  32. MCGILL C. M., LADD A. C., JACOBS M. B., GOLDWATER L. J. MERCURY EXPOSURE IN A CHLORINE PLANT. J Occup Med. 1964 Aug;6:335–337. doi: 10.1097/00043764-196408000-00003. [DOI] [PubMed] [Google Scholar]
  33. Mottet N. K., Body R. L. Mercury burden of human autopsy organs and tissues. Arch Environ Health. 1974 Jul;29(1):18–24. doi: 10.1080/00039896.1974.10666520. [DOI] [PubMed] [Google Scholar]
  34. Mückter H., Liebl B., Reichl F. X., Hunder G., Walther U., Fichtl B. Are we ready to replace dimercaprol (BAL) as an arsenic antidote? Hum Exp Toxicol. 1997 Aug;16(8):460–465. doi: 10.1177/096032719701600807. [DOI] [PubMed] [Google Scholar]
  35. Nierenberg D. W., Nordgren R. E., Chang M. B., Siegler R. W., Blayney M. B., Hochberg F., Toribara T. Y., Cernichiari E., Clarkson T. Delayed cerebellar disease and death after accidental exposure to dimethylmercury. N Engl J Med. 1998 Jun 4;338(23):1672–1676. doi: 10.1056/NEJM199806043382305. [DOI] [PubMed] [Google Scholar]
  36. Roels H. A., Boeckx M., Ceulemans E., Lauwerys R. R. Urinary excretion of mercury after occupational exposure to mercury vapour and influence of the chelating agent meso-2,3-dimercaptosuccinic acid (DMSA). Br J Ind Med. 1991 Apr;48(4):247–253. doi: 10.1136/oem.48.4.247. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Sandborgh Englund G., Dahlqvist R., Lindelöf B., Söderman E., Jonzon B., Vesterberg O., Larsson K. S. DMSA administration to patients with alleged mercury poisoning from dental amalgams: a placebo-controlled study. J Dent Res. 1994 Mar;73(3):620–628. doi: 10.1177/00220345940730030701. [DOI] [PubMed] [Google Scholar]
  38. Schwartz B. S., Stewart W. F., Todd A. C., Links J. M. Predictors of dimercaptosuccinic acid chelatable lead and tibial lead in former organolead manufacturing workers. Occup Environ Med. 1999 Jan;56(1):22–29. doi: 10.1136/oem.56.1.22. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Slikkerveer A., Noach L. A., Tytgat G. N., Van der Voet G. B., De Wolff F. A. Comparison of enhanced elimination of bismuth in humans after treatment with meso-2,3-dimercaptosuccinic acid and D,L-2,3-dimercaptopropane-1-sulfonic acid. Analyst. 1998 Jan;123(1):91–92. doi: 10.1039/a704945e. [DOI] [PubMed] [Google Scholar]
  40. Smith R. G., Vorwald A. J., Patil L. S., Mooney T. F., Jr Effects of exposure to mercury in the manufacture of chlorine. Am Ind Hyg Assoc J. 1970 Nov-Dec;31(6):687–700. doi: 10.1080/0002889708506315. [DOI] [PubMed] [Google Scholar]
  41. Sällsten G., Barregård L., Schütz A. Clearance half life of mercury in urine after the cessation of long term occupational exposure: influence of a chelating agent (DMPS) on excretion of mercury in urine. Occup Environ Med. 1994 May;51(5):337–342. doi: 10.1136/oem.51.5.337. [DOI] [PMC free article] [PubMed] [Google Scholar]
  42. Sällsten G., Barregård L., Schütz A. Decrease in mercury concentration in blood after long term exposure: a kinetic study of chloralkali workers. Br J Ind Med. 1993 Sep;50(9):814–821. [PMC free article] [PubMed] [Google Scholar]
  43. Takahata N., Hayashi H., Watanabe S., Anso T. Accumulation of mercury in the brains of two autopsy cases with chronic inorganic mercury poisoning. Folia Psychiatr Neurol Jpn. 1970;24(1):59–69. doi: 10.1111/j.1440-1819.1970.tb01457.x. [DOI] [PubMed] [Google Scholar]
  44. Todd A. C., Chettle D. R. In vivo X-ray fluorescence of lead in bone: review and current issues. Environ Health Perspect. 1994 Feb;102(2):172–177. doi: 10.1289/ehp.94102172. [DOI] [PMC free article] [PubMed] [Google Scholar]
  45. Zalups R. K. Influence of 2,3-dimercaptopropane-1-sulfonate (DMPS) and meso-2,3-dimercaptosuccinic acid (DMSA) on the renal disposition of mercury in normal and uninephrectomized rats exposed to inorganic mercury. J Pharmacol Exp Ther. 1993 Nov;267(2):791–800. [PubMed] [Google Scholar]
  46. de la Torre A., Bellés M., Llobet J. M., Mayayo E., Domingo J. L. Comparison of the effectiveness of 2,3-dimercaptopropanol (BAL) and meso-2,3-dimercaptosuccinic acid (DMSA) as protective agents against mercuric chloride-induced nephrotoxicity in rats. Biol Trace Elem Res. 1998 Jul;63(1):1–10. doi: 10.1007/BF02785272. [DOI] [PubMed] [Google Scholar]

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