Kinetics of lead retention and distribution in suckling and adult rats

The kinetics of lead distribution was studied in suckling and adult rats 8 days after a single intraperitoneal injection of ²⁰³Pb. Marked differences were observed in the kinetics of lead retention and distribution in suckling as compared to adult rats. The rate of ²⁰³Pb disappearance was lower in the whole body, blood and kidneys, but higher in the liver, while the deposition processes predominated in the brain, femur and teeth of sucklings as compared to adult animals.     

Influence of age on whole-body retention and distribution of 115mCd in the rat

The influence of age on whole-body retention and organ distribution of intraperitoneally applied ^115mCdCl₂ was studied in 1-, 3-, 6-, and 52-week-old rats. The mean percent values of ^115mCd retention in the whole body decreased with increasing age. The distribution of ^115mCd in the body on the 14th day after application shows that in all age groups most of the cadmium is accumulated in the liver (45–56%) and kidneys (4–6%). In younger rats the percentage of cadmium in the kidney and blood was always higher than in older animals in contrast to the liver where it was lower. The percentage of the dose in the liver, kidneys, and blood represents however, a considerably lower fraction of the total whole-body retention in younger animals than in older rats. It is therefore concluded that age bears a significant influence on cadmium metabolism. This might be important for estimating cadmium body burden and critical organ exposure in the youngest age group.     

Lead and cadmium in hair as an indicator of body burden in rats of different age

Summary The purpose of this work was to evaluate whether hair values of lead and cadmium can be used as an indicator of the body burden of these metals in different age groups.The experiments were performed on rats aged 2 and 18 weeks, which received²⁰³pb and^115mcd by intraperitoneal injection. The whole body retention and the retention of these radioisotopes in the hair (including the skin) was determined 7 days later. Younger animals showed a higher retention in the whole body and hair of radioactive lead and cadmium. The hair values when expressed as the percentage of the whole body retention were for²⁰³pb the same in young and adult rats but for^115mcd they were 2 to 3 times higher in young animals than in adults. It is concluded that lead hair values are a good indicator of the total body burden in both age groups. However, the cadmium body burden of young animals would be greatly overestimated if based on hair values only. This findings might be relevant for interpreting results of hair concentrations of lead and cadmium in children.     

Predictors of DMSA chelatable lead, tibial lead, and blood lead in 802 Korean lead workers

OBJECTIVES—To examine the interrelations among chelatable lead (by dimercaptosuccinic acid, DMSA), tibial lead, and blood lead concentrations in 802 Korean workers with occupational exposure to lead and 135 employed controls with only environmental exposure to lead.
METHODS—This was a cross sectional study wherein tibial lead, DMSA chelatable lead, and blood lead were measured. Linear regression was used to identify predictors of the three lead biomarkers, evaluating the influence of age, job duration, sex, education level, alcohol and tobacco use, creatinine clearance rate, and body mass index.
RESULTS—DMSA chelatable lead concentrations ranged from 4.8 to 2102.9 µg and were positively associated with age, current smoking, and creatinine clearance rate. On average, women had 64 µg less DMSA chelatable lead than men. When blood lead and its square were added to a model with age, sex, current smoking, body mass index, and creatinine clearance rate, blood lead accounted for the largest proportion of the variance and sex became of borderline significance. Tibial lead concentrations ranged from −7 to 338 µg/g bone mineral and were positively associated with age, job duration, and body mass index. Women had, on average, 9.7 µg/g less tibial lead than men. Blood lead concentrations ranged from 4.3 to 85.7 µg/dl and were positively associated with age and tibial lead, whereas current smokers had higher blood lead concentrations and women had lower blood lead concentrations.
CONCLUSIONS—The data suggest that age and sex are both predictors of DMSA chelatable lead, blood lead, and tibial lead concentrations and that tibial lead stores in older subjects are less bioavailable and may contribute less to blood lead concentrations than tibial lead stores in younger subjects. Although blood lead concentrations accounted for a large proportion of the variance in DMSA chelatable lead concentrations, suggesting that measurement of both in epidemiological studies may not be necessary, the efficacy of each measure in predicting health outcomes in epidemiological studies awaits further investigation.


Keywords: dimercaptosuccinic acid; bone lead; x ray fluorescence     

Distribution of lead-203 in human peripheral blood in vitro.

In-vitro experiments using 203Pb were performed to identify the lead binding components in human peripheral blood. The distribution of lead in plasma, in the red cell membrane, and within the red cell was also investigated. Studies of the distribution of 203Pb in whole blood showed that at a lead concentration of 2.45 mumol/l (50 micrograms/100 ml) about 94% of lead had been incorporated by the erythrocytes and 6% remained in the plasma. After extraction of lipid by a methanol/chloroform mixture, about 75% of the lead was found to be associated with the protein fraction. The lipid contained about 21% of the 203Pb, the remainder being in the aqueous plasma. SDS polyacrylamide gel electrophoresis of blood plasma showed that almost 90% of the 203Pb was present in the albumin fraction; the remainder was likely to be associated with high molecular weight globulins. Several binding sites were identified on the erythrocyte membrane. The high molecular weight component, about 130 000-230 000, was the most important 203Pb binding site. Chemical modification of membrane proteins suggested that the carboxyl groups are the major ligand responsible for most of the lead binding. SH groups of the membrane may have a minor role, but amino groups did not appear to affect the lead binding. The binding of lead to erythrocytes was not confined to membranes, over 80% of lead in blood penetrates into erythrocytes and binds to intracellular components. Gel chromatography of the haemolysate showed that over 90% of the 203Pb was attached to the haemoglobin molecule.     

Postprandial leucine deficiency failed to alter muscle protein synthesis in growing and adult rats

ObjectiveThis study examined the effect of a specific acute postprandial leucine deficiency on skeletal muscle protein synthesis in growing and adult rats. Because the anabolic action of dietary leucine supplementation is controversial, except during aging, we hypothesized that the maximum leucine effect might be already achieved for a normal postprandial rise of leucine. Preventing this rise during the 1- to 3-h period after feeding may reveal the leucine regulation.MethodsOn the day of the experiment, rats were fasted (postabsorptive, PA group) or fed for 1 h a control meal (postprandial, control, PP group) or a leucine-poor meal (postprandial, PP-Leu group). Muscle protein synthesis was assessed in vivo, over the 1- to 3-h period after meal distribution, using the flooding dose method (L-1-¹³C phenylalanine).ResultsAs expected, the postprandial increase in plasma free leucine was specifically abolished after feeding the leucine-poor meal, whereas all the other plasma free amino acids were roughly at normal postprandial levels. Plasma insulin increased after feeding in young rats but was constant in adult rats. Plasma insulin was similar whatever dietary leucine levels. Rates of muscle protein synthesis were stimulated by feeding in gastrocnemius and soleus muscles from young rats but only in gastrocnemius muscles from adult rats. The PP-Leu group did not differ from the control PP group regarding muscle protein synthesis.ConclusionThe rise in plasma free leucine is not required for the stimulation of muscle protein synthesis during the 1- to 3-h period after feeding young and adult rats, as previously observed in old rats.     

Kinetics of the Distribution and Excretion of Lead in the Rat

The kinetics of the distribution and excretion of lead (²¹⁰Pb) were studied in rats for 14 days after single intravenous injections of 100 μg. of lead per rat.

The results show that in the blood the lead is bound mainly to the cells, and that the ratio of lead in the cells and plasma is constant throughout the whole period. ²¹⁰Pb is rapidly distributed in the tissues, the highest concentrations being in the kidneys, liver, and bones.

The kinetics of the disappearance of ²¹⁰Pb from the organs and tissues follow the pattern of first order reactions. The disappearance curves in the blood, plasma, haematic cells, and some other tissues can be expressed as sums of exponential functions. In contrast, the removal of metal from the bone tissue occurs at a constant and extremely slow rate.

The metal is excreted by the faeces and urine. The rates reach their maxima within 24 hours and decrease asymptotically afterwards. More ²¹⁰Pb was excreted in the faeces (35·7%) than in the urine (15·9%) during the 14 days of observation.

     

Distribution and excretion of lead in young and adult female mice

The kinetics of whole body lead elimination and organ distribution were studied in 10-day-old and adult female mice following a single dose of lead. Necropsies were performed periodically during the 50-day experiment to assess organ lead distributions and lead elimination. Between Days 15 and 50 excretion of lead was found to occur nearly equally through urinary and fecal routes. Whole body lead retention during the terminal elimination phase was observed to have a half-time similar to that of lead retained in femur. Rates of lead elimination from femur and from whole body of young mice were apparently less rapid than comparable elimination rates in adult mice. Lead fluxes from the brains of young and adult mice were closely approximated by single component exponential equations. The results suggest that a three-compartment model does not adequately account for the kinetics of lead distribution and retention in mouse brain after a single dose.     

In vivo and in vitro dermal penetration of 2,4,5,2',4',5'-hexachlorobiphenyl in young and adult rats

Penetration of 2,4,5,2',4',5'-[14C]hexachlorobiphenyl (HCB) through skin of young (33 days) and adult (82 days) female Fischer 344 rats was determined in vivo and by two in vitro methods. In vivo dermal penetration at 120 hr was 45% in young and 43% in adults. At 72 hr in vivo dermal penetration was 35% in young and 26% in adults compared to 1.5% for young and 1.0% for adult as measured with a continuous flow in vitro system and 2.9% for young and 1.9% for adults as measured with a static in vitro system. Most of the dermally absorbed HCB remained in the body as only 4.9 and 2.6% of that absorbed was excreted by young and adult rats, respectively, at the end of 120 hr. Significant differences in dermal penetration and kinetics of HCB between young and adult female rats were observed. The elimination of HCB-derived material was approximately six times higher in feces than in urine. A physiological pharmacokinetic model was fitted to the organ and tissue radioactivity distribution data. Parameters in the model determined from dermal dosing of female Fischer 344 rats were in reasonable agreement with those reported in the literature for adult male Sprague-Dawley rats (iv dose). The rat constant for dermal penetration was 0.83 x 10(-4) min-1 for adults and 0.96 x 10(-4)min-1 for young. The delay or lag time parameter for dermal penetration was 4.4 hr in adults and 1.1 hr in young.     

Plasma-lead concentration: investigations into its usefulness for biological monitoring of occupational lead exposure

BACKGROUND: The lead concentration in plasma is correlated to that in whole blood with a two to fourfold variation. It has never been investigated if this variation is inter-individual. METHODS: Lead and hemoglobin were determined in blood and plasma from 13 lead workers with a history of relatively high blood-lead concentrations, sampled three times during 1 day. The variation in the distribution of lead between cells and plasma was studied, but not the variation in the lead concentrations as such. RESULTS: Blood hemoglobin decreased with rising plasma lead (0.9-3.0 microg/L). Regarding the distribution of lead, no effect of current exposure during the day or of recent meals appeared. As much as 84% of the overall variance of the distribution of lead between cells and plasma could be attributed to individual factors. After adjustment for erythrocyte volume fraction this decreased to 67%. Plasma samples with elevated hemoglobin concentrations (due to in vitro hemolysis) had somewhat elevated lead concentrations. CONCLUSIONS: Plasma lead is not significantly altered by variation in a single day's exposure and, therefore, the choice of time of the day is not critical for sampling. However, plasma lead is negatively correlated to blood hemoglobin and mild hemolysis (not visible by the eye) in a sample may increase plasma lead with up to 30%. Finally, plasma provides lead exposure information that differs from whole blood, but it is not clear which one of these is the biomarker with the closest relation to exposure and/or effects.     

Assessment of simulated high-dose partial-body irradiation by PCC-R assay

The estimation of the dose and the irradiated fraction of the body is important information in the primary medical response in case of a radiological accident. The PCC-R assay has been developed for high-dose estimations, but little attention has been given to its applicability for partial-body irradiations. In the present work we estimated the doses and the percentage of the irradiated fraction in simulated partial-body radiation exposures at high doses using the PCC-R assay. Peripheral whole blood of three healthy donors was exposed to doses from 0–20 Gy, with ⁶⁰Co gamma radiation. To simulate partial body irradiations, irradiated and non-irradiated blood was mixed to obtain proportions of irradiated blood from 10–90%. Lymphocyte cultures were treated with Colcemid and Calyculin-A before harvest. Conventional and triage scores were performed for each dose, proportion of irradiated blood and donor. The Papworth''s u test was used to evaluate the PCC-R distribution per cell. A dose-response relationship was fitted according to the maximum likelihood method using the frequencies of PCC-R obtained from 100% irradiated blood. The dose to the partially irradiated blood was estimated using the Contaminated Poisson method. A new D₀ value of 10.9 Gy was calculated and used to estimate the initial fraction of irradiated cells. The results presented here indicate that by PCC-R it is possible to distinguish between simulated partial- and whole-body irradiations by the u-test, and to accurately estimate the dose from 10–20 Gy, and the initial fraction of irradiated cells in the interval from 10–90%.     

Behavior of Lead and Zinc in Plasma,Erythrocytes, and Urine and ALAD in Erythrocytes following Intravenous Infusion of CaEDTA in Lead Workers

To evaluate the effect of calcium disodium ethylenediamine tetraacetate (CaEDTA) on concentrations of lead and zinc in plasma, erythrocytes, whole blood, and urine, we administered CaEDTA by intravenous infusion for 1 hr to seven lead workers with blood lead concentrations of 46-67μg/100 g (mean 54 μg/100 g). The plasma lead concentration (PPb) and the mobilization yield of lead in urine by CaEDTA were highest during the period between 1 and 2 hr after the infusion was started. In contrast, the lead concentration in erythrocytes (EPb) and in whole blood (BPb) remained unchanged during the 24 hr following infusion. Plasma zinc concentration (PZn) also fell rapidly following CaEDTA infusion; the decline was followed by a gradual rise in the zinc concentration in erythrocytes (EZn) without alteration in the zinc in whole blood. The mobilization yield of zinc in urine by CaEDTA (MZn) reached its highest level within 1 hr after the start of the infusion. Delta-aminolevulinic acid dehydratase (ALAD) activity in erythrocytes gradually increased for 5 hr following CaEDTA infusion. These observations suggest that (1) PPb concentration is a more sensitive indicator of the body burden of chelatable lead than is either BPb or EPb; (2) MZn is mobilized mostly from plasma during the first several hours following the start of CaEDTA infusion, and the fall in PZn concentration following infusion is compensated first by a rise in EZn concentration and then by an immediate redistribution of zinc in other organs to the blood; and (3) Pb-inhibited ALAD activity is reactivated by the increased EZn during and shortly after CaEDTA infusion.     

delta-Aminolevulinic acid dehydratase genotype modifies four hour urinary lead excretion after oral administration of dimercaptosuccinic acid.

OBJECTIVES: Previous research suggests that binding of lead by delta-aminolevulinic acid dehydratase (ALAD) may vary by ALAD genotype. This hypothesis was tested by examining whether ALAD genotype modifies urinary lead excretion (DMSA chelatable lead) after oral administration of dimercaptosuccinic acid (DMSA). METHODS: 57 South Korean lead battery manufacturing workers were given 5 mg/kg oral DMSA and urine was collected for four hours. Male workers were randomly selected from two ALAD genotype strata (ALAD1-1, ALAD1-2) from among all current workers in the two plants (n = 290). Subjects with ALAD1-1 (n = 38) were frequency matched with subjects with ALAD1-2 (n = 19) on duration of employment in the lead industry. Blood lead, zinc protoporphyrin, and plasma aminolevulinic acid concentrations, as well as ALAD genotype, duration of exposure, current tobacco use, and weight were examined as predictors or effect modifiers of levels of DMSA chelatable lead. RESULTS: Blood lead concentrations ranged from 11 to 53 micrograms/dl, with a mean (SD) of 25.4 (10.2) micrograms/dl. After 5 mg/kg DMSA orally, the workers excreted a mean (SD) 85.4 (45.0) micrograms lead during a four hour urine collection (range 16.5-184.1 micrograms). After controlling for blood lead concentrations, duration of exposure, current tobacco use, and body weight, subjects with ALAD1-2 excreted, on average, 24 micrograms less lead during the four hour urine collection than did subjects with ALAD1-1 (P = 0.05). ALAD genotype seemed to modify the relation between plasma delta-aminolevulinic acid (ALA) and DMSA chelatable lead. Workers with ALAD1-2 excreted more lead, after being given DMSA, with increasing plasma ALA than did workers with ALAD1-1 (P value for interaction = 0.01). CONCLUSIONS: DMSA chelatable lead may partly reflect the stores of bioavailable lead, and the current data indicate that subjects with ALAD1-2 have lower stores than those with ALAD1-1. These data provide further evidence that the ALAD genotype modifies the toxicokinetics of lead-for example, by differential binding of current lead stores or by differences in long-term retention and deposition of lead.     

Pharmacokinetics of intravascularly administered (65)Zinc in channel catfish (Ictalurus punctatus)

Comparison was made of the pharmacokinetics of the radioisotope (65)Zinc ((65)Zn) in blood, plasma, and whole body of adult channel catfish (Ictalurus punctatus) following intravascular (iv) administration. A two-compartment model described the pharmacokinetics of (65)Zn in plasma and blood during the first 40 days following iv administration, but was unable to describe the long-term disposition of (65)Zn. Whole-body counting revealed that approximately half of the (65)Zn dose was sequestered in a slowly exchangeable pool with a half-life of 1.5 years. Greater than 99% of the circulating (65)Zn was bound to plasma proteins, whereas there was less than 1% binding to red blood cells. Synthesis of the results for channel catfish and existing data in other species indicates three phases in the pharmacokinetics of zinc. The first phase consists of initial distribution outside the vascular system to kidney, liver, and other organs (alpha phase in blood and plasma; t(1/2) of 4 to 5 h). The second phase involves distribution from organs to a slowly exchangeable zinc pool, likely consisting of bone (beta phase in blood and plasma; alpha phase in whole body; t(1/2) of 4 to 20 days). The third phase appears to involve a slow turnover of sequestered zinc (t(1/2) greater than 1 year). Blood sampling or short-term whole-body measurements will underestimate the persistence of zinc in fish, thus prolonged sampling and measurement of whole-body concentrations are necessary to characterize the pharmacokinetics of zinc.     

Age Differences in Metals in the Blood of Herring (Larus argentatus) and Franklin's (Larus pipixcan) Gulls

Concentrations of heavy metals and selenium were measured in the blood of adult and young herring (Larus argentatus) and Franklin's (Larus pipixcan) gulls collected during the same breeding season in colonies in the New York Bight and in northwestern Minnesota, respectively. Concentrations were expected to be higher in young herring gulls collected in an urban, industrialized area, compared to young Franklin's gulls collected in a relatively pristine prairie marsh. Exposure is similar for the fledgling and adult gulls because by the time the blood of young gulls is drawn both adults and young have been eating foods from the surrounding region for two months; leading to the prediction that metal levels should be similar in adults and young. However, young Franklin's gulls had significantly higher levels of arsenic, cadmium, and manganese than adults; adults had significantly higher levels of mercury and selenium. Young herring gulls had significantly higher concentrations of arsenic and selenium, but lower levels of lead than adult herring gulls. Interspecific comparisons indicated that young Franklin's gulls had significantly higher levels of cadmium than young herring gulls, and adult Franklin's gulls had higher levels of selenium and chromium than adult herring gulls, but for all other comparisons herring gulls had higher levels of metals in their blood. Young herring gulls chicks had higher arsenic, manganese, and selenium levels and lower cadmium and lead levels in 1993 than in 1994. Overall, the levels in the two species were usually within an order of magnitude. Received: 11 November 1996/Accepted: 16 April 1997     

Oxidative Effects of Lead in Young and Adult Fisher 344 Rats

Lead poisoning has been extensively studied over the years. Many adverse physiological and behavioral impacts on the human body have been reported due to the entry of this heavy metal. It especially affects the neural development of children. The current study investigates the effect of lead exposure in young (1.5 months) and adult (10 months) male Fisher 344 rats. Five weeks of lead administration resulted in a profound change in the lead levels in the red blood cells (RBCs) of the young lead-exposed group (37.0 ± 4.47 μg/dl) compared to the control (<1 μg/dl) and adult (27.4 ± 8.38 μg/dl) lead-exposed groups. Therefore, this study confirms the fact that gastrointestinal absorption of lead in young is greater than that of adults. Furthermore, glutathione and glutathione disulfide (GSSG) levels in RBCs, liver, and brain tissues were measured to determine thiol status; malondialdehyde (MDA) levels of lipid peroxidation and catalase activity were measured to assess changes in oxidative stress parameters. Liver GSSG and MDA levels were significantly higher in the young lead-exposed group than those in the adult lead-exposed group. In RBCs and brains, however, adult lead-exposed animals have shown more elevated MDA levels than young animals exposed to the same lead treatment. Received: 14 February 2002/Accepted: 6 August 2002     

Determination of plasma lead levels in normal subjects and in lead-exposed workers

ABSTRACT Lead levels in whole blood and in plasma were measured in 64 non-exposed and in 29 exposed subjects with signs and symptoms of varying severity. Lead was determined by atomic absorption spectrophotometry after chelation with ammonium pyrrolidine dithiocarbamate and extraction with methyl isobutyl ketone. The method has a sensitivity of 0·4 μg/100 ml (0·02 μmol/l) for whole blood and of 0·2 μg/100 ml (0·01 μmol/l) for plasma and is reliably accurate and precise. Plasma lead increases progressively and significantly with the increase of whole blood lead, while its relative percentage in the plasma remains practically constant at all concentrations in whole blood. In exposed subjects a highly significant correlation was found between lead in plasma and lead in urine (r = 0·549) but the correlation coefficient was higher for whole blood lead versus urinary lead (r = 0·938). Aminolevulinic acid excretion in urine appeared to be significantly related to plasma lead concentration (r = 0·563) but to a greater extent to whole blood levels (r = 0·801). There was no significant correlation between lead in plasma and the logarithm of aminolevulinic acid dehydratase. The hypothesis is advanced that plasma lead, the more biologically active fraction of the metal, could be related to different individual sensitivities which would condition the development of toxic effects in various organs at different levels of lead.     

Lead level of whole blood and plasma in workers exposed to lead stearate

In a group of 23 male workers exposed to lead stearate the levels of lead in whole blood and plasma were determined and compared to those obtained from a group of 23 subjects exposed to inorganic lead compounds. The mean values for lead in whole blood were similar in both groups, while the mean lead concentration in plasma was 0.1729 (SD 0.0677) mumol/l for those exposed to lead stearate and 0.0936 (SD 0.0577) mumol/l for those exposed to other lead compounds. The difference was highly significant. The percentage ratio for lead in plasma to lead in whole blood, which can be considered a "bioavailability index" for lead, proved to be two times higher for stearate workers than for subjects exposed to inorganic lead compounds. The data suggest that the different chemical properties of absorbed lead stearate may cause a different distribution of the metal in different blood compartments, the plasma compartment having a higher affinity for lead stearate than for other lead compounds. Because the plasma fraction has a greater bioavailability, lead stearate could induce toxic effects that differ (possibly being severer) from those caused by other lead compounds at similar absorbed doses.     

Fetal lead exposure at each stage of pregnancy as a predictor of infant mental development

BACKGROUND: The impact of prenatal lead exposure on neurodevelopment remains unclear in terms of consistency, the trimester of greatest vulnerability, and the best method for estimating fetal lead exposure. OBJECTIVE: We studied prenatal lead exposure's impact on neurodevelopment using repeated measures of fetal dose as reflected by maternal whole blood and plasma lead levels. METHODS: We measured lead in maternal plasma and whole blood during each trimester in 146 pregnant women in Mexico City. We then measured umbilical cord blood lead at delivery and, when offspring were 12 and 24 months of age, measured blood lead and administered the Bayley Scales of Infant Development. We used multivariate regression, adjusting for covariates and 24-month blood lead, to compare the impacts of our pregnancy measures of fetal lead dose. RESULTS: Maternal lead levels were moderately high with a first-trimester blood lead mean (+/- SD) value of 7.1 +/- 5.1 microg/dL and 14% of values >or=10 microg/dL. Both maternal plasma and whole blood lead during the first trimester (but not in the second or third trimester) were significant predictors (p < 0.05) of poorer Mental Development Index (MDI) scores. In models combining all three trimester measures and using standardized coefficients, the effect of first-trimester maternal plasma lead was somewhat greater than the effect of first-trimester maternal whole blood lead and substantially greater than the effects of second- or third-trimester plasma lead, and values averaged over all three trimesters. A 1-SD change in first-trimester plasma lead was associated with a reduction in MDI score of 3.5 points. Postnatal blood lead levels in the offspring were less strongly correlated with MDI scores. CONCLUSIONS: Fetal lead exposure has an adverse effect on neurodevelopment, with an effect that may be most pronounced during the first trimester and best captured by measuring lead in either maternal plasma or whole blood.     

The effect of chelating agents on lead excretion in rats in relation to age.

The purpose of the present work was to determine the influence of age on the effectiveness of chelating agents in enhancing lead elimination from the body.Using the method of ²⁰³Pb-labeling, three doses of lead in the form of acetate (1.0 μg/kg, 0.5 mg/kg, 5.0 mg/kg) were applied intraperitoneally or intravenously to female albino rats aged 15 days and 18 weeks. Solutions of EDTA and of BAL (0.2 mmole/kg) were administered by a single or repeated intraperitoneal injection immediately after lead had been given. The whole body retention of ²⁰³Pb was measured at various time intervals in a twin crystal assembly.Both chelating agents caused a lower excretion of lead in 15-day-old rats than in adult animals. The poorer efficiency of chelating compounds in immature organisms was found to be independent of the lead dose, route of lead administration, chelating agent:metal molar ratio, and frequency of chelating treatment. The authors introduce the concept of a lower “free lead” level, due to a higher stability and/or inertness of lead linkages with body ligands in the growing organism as an explanation of the results obtained.