Metabolism of lead-210 in juvenile and adult rhesus monkeys (Macaca mulatta)

Pounds, Joel G.; Marlar, R. J.; Allen, James

doi:10.1007/bf01685858

Cited by 24 publications

(19 citation statements)

References 10 publications

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“…The relative absorption (~ 65%, fasting conditions), and subsequent excretion (3.9%) and retention (61%) of orally dosed 206 Pb tracer in the vehicle group are in general agreement with the ranges observed in previous studies in monkeys (31,32). Further, we observed that the excretion of absorbed Pb via urinary and endogenous fecal routes were comparable in magnitude.…”

Section: Discussionsupporting

confidence: 91%

“…The juvenile monkey model used here closely approximates human metabolism for both Pb (17,38) and succimer (12,39,40), and thus is the most appropriate model available for studies on the effects of succimer on the disposition of GI Pb in children. Adult primates, including humans, are not well suited for estimating GI Pb absorption in juveniles because of the confounding effects of age (32,41,42). Moreover, existing data suggest that there may be species differences (rodents vs. primates) in the pharmacokinetics of succimer (12,39), suggesting that rodent studies on some effects of succimer may not directly extrapolate to humans.…”

Section: Discussionmentioning

confidence: 99%

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Oral succimer decreases the gastrointestinal absorption of lead in juvenile monkeys.

Cremin

Luck

Laughlin

et al. 2001

Environ Health Perspect

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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 microg/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 (204)Pb tracer (5 microg, 24.5 nmol) followed by a single oral dose of stable (206)Pb tracer (72.6 microg, 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.

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Section: Discussionsupporting

confidence: 91%

Section: Discussionmentioning

confidence: 99%

Oral succimer decreases the gastrointestinal absorption of lead in juvenile monkeys.

Cremin

Luck

Laughlin

et al. 2001

Environ Health Perspect

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“…At weaning, however, lead uptake and retention rates abruptly and steeply decline to those of the adult. The infant monkey (73) absorbs much more lead, about 50%, than does the juvenile or adult monkey (74). Kierski (75) showed that the weanling rabbit, 5 weeks old, absorbs twice as much lead from ingested soil as does the older rabbit.…”

Section: Measurable Biomarkers Of Human Lead Exposurementioning

confidence: 99%

Uses and limits of empirical data in measuring and modeling human lead exposure.

Mushak¹

1998

Environ Health Perspect

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“…To date, absorption studies in experimental animals have all utilized ionic Pb (9,(14)(15)(16)(54)(55)(56). However, for the suckling offspring, the principal source of Pb would be mother's milk.…”

Section: Discussionmentioning

confidence: 99%

The Distribution of Lead in Milk and the Fate of Milk Lead in the Gastrointestinal Tract of Suckling Rats

Beach

Henning

1988

Pediatr Res

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ABSTRACT. Milk can be a significant source of lead (Pb) for young mammals, including humans. Certain essential trace elements have previously been shown to be specifically associated with particular milk components and such associations often increase bioavailability. Thus, the first goal of this study was to determine the distribution of P b in cream, casein, and whey fractions of various milks under various conditions using '03Pb a s a tracer. In rat milk almost 90% of the P b was found to be associated with the casein micelles, regardless of: 1) whether the milk was labeled in vivo or in vitro; b) whether the milk was fresh or frozen; and c) the added concentration of P b (over the range 0.01-75 pg/ml). The remainder of the P b was approximately equally distributed between cream and whey. A virtually identical pattern of P b distribution was observed with bovine milk. P b added to infant formula also associated predominantly with casein micelles, although the P b content of this fraction was significantly less than with rat and bovine milks. The second goal of the study was to determine if P b remained associated with casein a s it traversed the gastrointestinal tract of infant rats. For this purpose, rat pups aged 15-16 days were gavaged with 2""b-labeled rat milk, and lumenal contents from the stomach and small intestine were collected 2 h later. Differential centrifugation of the homogenized lumenal contents showed that in the stomach the P b was associated primarily with the casein curd. By the time chyme reached the distal small intestine, P b was found predominantly in a fraction that was not precipitable by high-speed centrifugation (thus, not intact casein micelles), but was nondialyzable. We conclude that P b in milk is protein bound and remains this way a s it traverses the stomach and proximal small intestine of the infant rat. (Pediatr Res 23: 58-62,1988).The deleterious effects of both symptomatic and asymptomatic Pb poisoning are well documented for infants of humans and experimental animals (1-7). This high risk group demonstrates a greater intestinal absorption of Pb than do adults (8-1 1) and as a result may be more susceptible to even modest levels of environmental pollution. There is evidence in rodents that en-

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Metabolism of lead-210 in juvenile and adult rhesus monkeys (Macaca mulatta)

Cited by 24 publications

References 10 publications

Oral succimer decreases the gastrointestinal absorption of lead in juvenile monkeys.

Oral succimer decreases the gastrointestinal absorption of lead in juvenile monkeys.

Uses and limits of empirical data in measuring and modeling human lead exposure.

The Distribution of Lead in Milk and the Fate of Milk Lead in the Gastrointestinal Tract of Suckling Rats

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