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John D. Cremin, Jr.,¹ Melissa L. Luck,² Nellie K. Laughlin,² and Donald R. Smith¹

¹Environmental Toxicology, University of California, Santa Cruz, California, USA
²Harlow Center for Biological Psychology, University of Wisconsin, Madison, Wisconsin, USA

Abstract

Although succimer (Chemet, meso-2,3-dimercaptosuccinic acid, DMSA) is considered to be a safe and effective chelating agent for the treatment of lead poisoning in humans, there is concern that it may increase the gastrointestinal (GI) absorption and retention of Pb from exposures suffered concurrent with treatment. This concern is justified because the availability of Pb-safe housing during outpatient treatment with oral succimer is limited. We used a juvenile nonhuman primate model of moderate childhood Pb intoxication and a sensitive double stable Pb isotope tracer methodology to determine whether oral succimer chelation affects the GI absorption and whole-body retention of Pb. Infant rhesus monkeys (n = 17) were exposed to Pb daily for 1 year postpartum to reach and maintain a target blood lead (BPb) level of 35-40 µg/dL. Animals were administered succimer (n = 9) or vehicle (n = 8) over two successive 19 day succimer treatment regimens beginning at 53 and 65 weeks of age. The present study was conducted over the second chelation regimen only. Animals received a single intravenous (iv) dose of stable ²⁰⁴Pb tracer (5 µg, 24.5 nmol) followed by a single oral dose of stable ²⁰⁶Pb tracer (72.6 µg, 352 nmol) immediately before chelation, in order to specifically evaluate GI Pb absorption and whole-body Pb retention with treatment. We collected complete urine and fecal samples over the first 5 days and whole blood over the first 8 days of treatment for analyses of stable Pb isotopes using magnetic sector inductively-coupled plasma mass spectrometry. Results indicate that succimer significantly reduced the GI absorption of Pb (vehicle, 64.9% ± 5.5 ; succimer, 37.0% ± 5.8 ; mean ± SEM) . Succimer also significantly increased the urinary excretion of endogenous Pb by approximately 4-fold over the vehicle treatment, while endogenous fecal Pb excretion was decreased by approximately 33%. Finally, although succimer reduced the whole-body retention of endogenous Pb by approximately 10% compared to vehicle, the majority (77%) of the administered internal dose of Pb tracer was retained in the body when assessed after 5 days of treatment. These data do not support the concern that succimer treatment increases GI Pb absorption. Key words: 2, 3-dimercaptosuccinic acid, absorption, chelation, Chemet‚ lead, lead exposure, nonhuman primate, succimer. Environ Health Perspect 109:613-619 (2001) . [Online 11 June 2001]

http://ehpnet1.niehs.nih.gov/docs/2001/109p613-619cremin/ abstract.html

Address correspondence to D.R. Smith, Environmental Toxicology, Applied Sciences Building, University of California, 1156 High Street, Santa Cruz, CA 95064 USA. Telephone: (831) 459-5041. Fax: (831) 459-3524. E-mail: dsmith@biology.ucsc.edu

We thank N. Giles, L. Handschke, K. Meyer, D. Makuch, R. McCann, and H. Gottfried for assistance with the study ; R.E. Lasky for statistical assistance ; and D. Woolard for analytical assistance. We also thank W. Rogan for providing succimer placebo and Bock Pharmacol and Sanofi Pharmaceuticals, Inc. for providing succimer (as Chemet) .

This research was supported in part by NIEHS grants R01 #ES06918 and F32 #ES05870.

Received 16 November 2000 ; accepted 21 December 2000.