Chelatable Lead Research Articles

Conversion rate of non-chelatable to chelatable lead after CaEDTA injection: a kinetic study in two lead workers.

AbstractDiminution rate of body burden of chelatable lead (CPb) after injection of calcium disodium ethylenediamine tetraacetate (CaEDTA) was estimated at between 0.7 and 0.4% per week in two lead workers after termination of lead exposure. Hence, alteration in body burden of CPb during the week after a single injection of CaEDTA was simulated by two different equations. The first equation was (1 + α−1.3β)6 (1–1.03k + α) A = 0.993A or 0.996A, where A = body burden of CPb just before CaEDTA injection; α = proportion of CPb converted from non‐chelatable lead (NPb) to A during the 24 h after CaEDTA injection; k = proportion of 24‐h mobilization yield of lead by CaEDTA to A; and β = proportion of 24‐h spontaneous urinary lead excretion to A. This equation was based on the assumption that the amount of lead converted to CPb during 24 h was proportional to the initial level of CPb. The second equation, i.e. (1–1.03k) (1–1.3β)6 A + {(1–1.3β)6 + (1–1.3β)5 + … + (1–1.3β) + 1} αA = 0.996A or 0.996A, assumed that the amount of lead converted to CPb during 24 h was nearly constant during a week after CaEDTA injection. The conversion rate (α) was obtained as a solution of each equation after determination of k and β according to our model. It was estimated that the amount of lead corresponding to 2% of body burden of CPb, i.e. 0.23 mg and 0.35 mg, was converted from NPb to CPb during the 24 h after CaEDTA injection in the two lead workers with blood lead concentrations of 44 μg per 100 g and 61 μg per 100 g, respectively. A previous model for estimating body burden of CPb from mobilization yield of lead by CaEDTA was amended in the light of this estimation.

Assessment of the Body Charge of Chelatable Lead : A Model and Its Application to Lead Workers

Assessment of the Body Charge of Chelatable Lead : A Model and Its Application to Lead Workers

Biological monitoring of workers with past lead exposure. Biochemical findings.

In 56 subjects with lead exposure that had terminated at least 3 a previously and in a reference group of nonexposed subjects, the behavior of several biochemical indicators of dose and effect were studied. The mean values for blood lead (PbB) (1.4 +/- 0.4 mumol/l), chelatable lead (PbUEDTA) (3.4 +/- 1.5 mumol/24 h) and free erythrocyte protoporphyrin (FEP) (62 +/- 25.2 micrograms/100 ml red blood cells) were found to be significantly higher in the subjects with past lead exposure than in the referents. The cut-off levels (mean + 2 SD calculated for the reference group) of PbB, PbUEDTA and FEP were exceeded in 35.7, 67.9, and 28.6% of the exposed subjects, respectively. A normalization of lead doses and indicators of effect was reached only when the exposure had not exceeded 2 a. The time elapsed after termination of exposure did not significantly reduce the PbB level and PbUEDTA excretion, whereas these parameters correlated significantly with the length of exposure. A close correlation was found between the PbB and the PbUEDTA. Due to poor sensitivity at PbUEDTA values of less than 5.3 mumol/24 h (91% of the cases), PbB and FEP were not useful for subjects whose exposure had terminated more than 3 a earlier. In these cases, only PbUEDTA was capable of revealing elevated active lead deposits.

Assessment of the body burden of chelatable lead: a model and its application to lead workers.

A hypothetical model was introduced to estimate the body burden of chelatable lead from the mobilisation yield of lead by calcium disodium ethylenediamine tetra-acetate (CaEDTA). It was estimated that, on average, 14 and 19% of the body burden was mobilised into the urine during the 24 hours after an injection of 53.4 mumol (20 mg) and 107 mumol (40 mg) CaEDTA per kg bodyweight, respectively. The body burden of chelatable lead ranged from 4 mumol (0.8 mg) to 120 mumol (24.9 mg) (mean 37 mumol (7.7 mg) in lead workers with blood lead concentrations of 0.3-2.9 mumol/kg (6-60 microgram/100 g) (mean 1.4 mumol/kg (29 microgram/100 g)). There were linear relationships between blood lead concentrations and body burden of chelatable lead on a log scale.

6β-hydroxycortisol:a marker for hepatic enzyme inhibition by lead

Lead(Pb) ion is known to inhibit cytochrome P-450 dependent hepatic microsomal activity.To measure inhibitory effects of Pb on hepatic enzyme activity 6βOHF excretion was determined in 11 children(age 2-9 yrs)with mild to moderate Pb intoxication(n1 renal function) prior to chelation therapy.6βOHF is formed by the hepatic cytochrome P-450 dependent mixed function oxidase system. Correlations were examined between 6βOHF and blood Pb, erythrocyte protoporphyrin (EP) and urinary Pb excretion after a CaNa2 EDTA provocative test.The CaNa2EDTA provocative test provides an accurate “chemical biopsy” of chelatable lead stores.6βOHF excretion in normal controls was 0.28±.03 mg/m2/24h.Excretion in Pb burdened children was reduced to 0.17±.02 mg/m2/24h;(p<.01).There was a highly significant correlation between 6βOHF and EP,(r=-0.7, p<.01) and 6βOHF and urinary Pb(r= -0.74,p<.01) but none between blood Pb and 6βOHF.17OH corticosteroid and free cortisol excretion were not different from normal controls and correlations between these cortisol metabolites and EP or urinary Pb were not significant.Conclusions:Children with undue Pb absorption may have decreased 6βOHF excretion.Since adrenal function is not impaired,reduced 6βOHF excretion may be secondary to inhibitory action of Pb ion on microsomal enzyme systems.6βOHF measurements provide a sensitive probe when evaluating inhibitory effects of foreign compounds on hepatic enzyme activity.

Behaviour of indicators of exposure and effect after cessation of occupational exposure to lead.

The behaviour of blood lead (PbB) and of some indicators of effect (erythrocyte protoporphyrin IX (EP), delta-aminolaevulinic acid dehydratase activity of erythrocytes (ALAD), and urinary delta-aminolaevulinic acid (ALAU)) were studied in subjects who had ceased working with inorganic lead for at least one year. Relations between these indices and chelatable lead (PbU-EDTA (lead in urine after injection of CaNa2 EDTA 1 g intravenously)), a test that is used to evaluate the lead deposits in the body, were also analysed. As a comparison, a group of subjects currently exposed was studied. In the workers with past exposure the PbB values were significantly lower, at the same PbU-EDTA levels, than those found in subjects at work. The relation between EP and PbU-EDTA shows that, corresponding levels of chelatable lead, the values of the erythrocyte metabolite are identical in the two groups. Considering the EP-PbB relation, however, at the same PbB levels the protoporphyrin values appear distinctly more altered in the subjects with past exposure. Similar results were obtained from a study of the relations between ALAD and PbU-EDTA and between ALAD and PbB. The relation between ALAU and PbU-EDTA, however, shows that, at the same PbU-EDTA levels the urinary metabolic in past-exposed subjects is distinctly lower than in subjects at work, while the relation between ALAU and PbB shows that, for similar blood lead values, the ALAU levels are identical. On the basis of the results obtained it is concluded that in subjects with past exposure, EP and ALAD can be used in establishing the persistence and extent of an "active deposit" of lead in the organism, while PbB is of very limited use.

Chelatable lead body burden (by calcium-disodium EDTA) and blood lead concentration in man.

The cheletable part of lead body burden was measured in 32 workers and seven office workers after an infusion test with CaNa2EDTA. The workers had been exposed to lead at a lead and zinc processing unit for one to three years (mean one year). There was good correlation (r = 0.87) between blood lead and chelatable urinary lead excretion described by the equation y = 0.07 . 10(0.46.x). From this equation it can be predicted that the generally accepted limit value for chelatable urinary lead excretion, 0.42 mumol/mmol CaNa2EDTA administered per 24 hours (3.1 mumol/24 hours or 650 micrograms/24 hours), corresponds to a blood lead concentration (PbB) of 1.7 mumol/l (or 35 micrograms/100 ml), which is lower than the commonly accepted limit value of 2.9 mumol/l (or 60 micrograms/100 ml) for occupationally lead-exposed persons. There was a better correlation between the cheletable lead excretion and the urinary ALA-excretion (r = 0.45; p less than 0.001) than between PbB and the urinary ALA-excretion (r = 0.26; p greater than 0.05).

Indicators of internal dose in current and past exposure to lead.

Chelatable lead (PbU-EDTA) is the best indicator of lead concentration at the critical organ level (indicator of dose). However, since this test is not easily applicable for the biological monitoring of lead-exposed subjects, the current practice is to determine lead in blood (PbB) and/or in urine (PbU). But these tests are indicators of exposure and not of dose. To analyze the reliability of PbB and PbU in estimating lead dose, the relationships between PbU-EDTA and PbB and between PbU-EDTA and PbU were studied in two groups of male lead workers: 48 currently exposed and 45 with past exposure to lead.

Dose-effect and dose-response relationships for lead in children

Lead absorption and prevention of the serious effects of lead re-examined from the viewpoints of the critical organ and clinical effect concepts and the associated dose-effect and dose-response relationships. If the critical organ is the first affected and the critical effect is the first measurable adverse effect, intervention on this basis should prevent the occurrence of later, more serious effects. In the range of lead absorption of greatest current pediatric concern (blood lead in the range of 50 to 80 mug/dl), blood lead values are not a good predictor of critical effect, whereas chelatable lead is significantly and linearly related to evidence of critical effect on hemoglobin synthesis in the bone marrow. Erythrocyte protoporphyrin and delta-aminolevulinic acid and coproporphyrin in urine are indicators of this effect. The dose-response concept provides a better way of viewing the relationship between blood lead and measures of adverse effect than do the classifications of "sensitivity," "specificity", "false negatives," and "false positives," which are often employed in the evaluation of screening tests. The dose-response concept recognizes the uniqueness of the individual and the presence of susceptible and resistant individuals in heterogeneous population groups. With the dose-response concept, individuals may be identified as reactors or nonreactors, according to whether they exhibit a particular effect. Among the various indicators of lead's critical (or first) effect on hemoglobin synthesis, erythrocyte protoporphyrin potentially is the most practical for monitoring children at high risk for plumbism.

Red blood cell beta-aminolevulinic acid dehydrase activity. An index of body lead burden.

It has been suggested that the measurement of the degree of inhibition of red blood cell (RBC) δ-aminolevulinic acid dehydrase (ALAD) activity is a useful indicator for the detection of children with increased lead absorption. Twenty children had simultaneous measurements of blood lead and RBC-ALAD activity, and then received chelation treatment with edetic acid (EDTA). The inhibition of RBC-ALAD activity was found to be highly correlated with the amount of lead excreted in the urine. In this study, the measurement of RBC-ALAD appeared to be superior to the measurement of blood lead in identifying those children with an increased burden of chelatable lead.