The decrease in population bone lead levels in Canada between 1993 and 2010 as assessed by in vivo XRF.

Objective and Approach: A study, conducted in Toronto, Canada, between 2009 and 2011, measured the bone lead concentrations of volunteers aged 1-82 years using in vivo x-ray fluorescence (XRF) technology. MAIN RESULTS: Bone lead levels were lower compared to Ontario in vivo XRF studies from the early 1990s. In adults, the slope of tibia lead content versus age was reduced by 36-56%, i.e. bone lead levels for a given age group were approximately half compared to the same age group 17 years prior. Further, bone lead levels of individuals fell over that time period. In 2010, an average person aged 57 years had a bone lead level approximately 1/3 less than their bone lead level age 40 years in 1993. Using this data, the half-lives of lead in the tibia were estimated as 7-26 years. Tibia lead levels were found to be low in children. The reduction in bone tibia content in children was not significant (p = 0.07), but using data from additional north eastern US studies, there is evidence that childhood tibia stores are lower than in the 1990s. SIGNIFICANCE: In vivo XRF analysis shows that there has been a reduction in the level of lead in bone in Canada over the last two decades. Public health measures have been very successful in reducing ongoing exposure to lead and in reducing bone lead stores.

Age and sex influence on bone and blood lead concentrations in a cohort of the general population living in Toronto.

OBJECTIVE: To study the age and sex influence on bone and blood lead concentrations in a cohort of the general population living in Toronto. APPROACH: A 109Cd K x-ray fluorescence (KXRF) measurement system was used from 2009 to 2011 in a study that measured the bone lead (Pb) concentration of 263 environmentally exposed individuals residing in Toronto, Ontario, Canada. Tibia (cortical bone) and calcaneus (trabecular bone) lead contents were measured in 134 males and 129 females between 1 and 82 years of age. Whole blood Pb concentration was measured by TIMS (thermal ionization mass spectrometer). Tibia (Ti) and calcaneus (Cal) Pb were examined versus the age of participants, taking into account uncertainties in bone Pb measurement values. MAIN RESULTS: No significant sex differences were observed in any of the age categories. Participants older than 50 years of age demonstrated the highest concentrations of Pb in their blood, tibia, and calcaneus bones. SIGNIFICANCE: In most of the previous publications, uncertainty was not considered in the regression model of bone Pb and age. However, in this paper, we adjusted the bone Pb values for the uncertainty level. This had a significant influence in regression models of bone Pb and thus we recommend that uncertainty be considered in future studies.

Release of lead from bone in pregnancy and lactation.

Concentrations and isotope ratios of lead in blood, urine, 24-h duplicate diets, and hand wipes were measured for 12 women from the second trimester of pregnancy until at least 8 months after delivery. Six bottle fed and six breast fed their infants. One bottle feeder fell pregnant for a second time, as did a breast feeder, and each was followed semicontinuously for totals of 44 and 54 months, respectively. Bone resorption rather than dietary absorption controls changes in blood lead, but in pregnancy the resorption of trabecular and cortical bone are decoupled. In early pregnancy, only trabecular bone (presumably of low lead content) is resorbed, causing blood leads to fall more than expected from hemodilution alone. In late pregnancy, the sites of resorption move to cortical bone of higher lead content and blood leads rise. In bottle feeders, the cortical bone contribution ceases immediately after delivery, but any tendency for blood leads to fall may be compensated by the effect of hemoconcentration produced by the postpartum loss of plasma volume. In lactation, the whole skeleton undergoes resorption and the blood leads of nursing mothers continue to rise, reaching a maximum 6-8 months after delivery. Blood leads fall from pregnancy to pregnancy, implying that the greatest risk of lead toxicity lies with first pregnancies.

The lead content of blood serum.

Serum lead concentrations measured by stable isotope dilution with a thermal ionization mass spectrometer and blood lead concentrations measured by graphite furnace atomic absorption spectrophotometry are reported for 73 women of child bearing age resident in Los Angeles, California. The two quantities are related by the line y=0.00030+0.00241x (r=0.83), where y is serum lead concentration and x is blood lead concentration, both being expressed in units of microg/L. The linearity of the relationship appears to hold to a blood lead concentration of at least 60 microg Pb/L. The slope of the line indicates that lead in serum is 0.24% of that in whole blood in contrast to recent reports of between 0.32 and 0.35% determined by inductively coupled plasma (ICP) mass spectrometry with bismuth used as an internal standard. The discrepancy stems from the ICP mass spectrometer-generated curves not passing through the origin.

Seasonal variation in bone lead contribution to blood lead during pregnancy.

Population blood lead level (PbB) often shows seasonal variation, frequently being higher in summer and lower in winter. As vitamin D metabolites also show seasonal variability, and the metabolites are associated with bone metabolism, some authors have posited a role for bone lead release in seasonal PbB changes. We made third trimester and postdelivery PbB measurements on 414 immigrant women (98% Latina) in Los Angeles. We measured in vivo tibia and calcaneus (heel) lead concentration postdelivery via K-shell X-ray fluorescence. We saw evidence of seasonal variation in prenatal PbB, but not postnatal PbB. PbB was highest in spring and lowest in autumn. Tibia lead concentration was associated with prenatal PbB, as reported before. The contribution of tibia lead to prenatal PbB varied seasonally, with the greatest contribution occurring in the winter quarter and the least in the summer quarter. The temporal pattern of bone lead contribution to PbB follows the seasonal alteration of insolation. There was no seasonal component in prenatal PbB associated with calcaneus lead, nor were there seasonal variations in either calcaneus or tibia lead contributions to postnatal PbB. Bone turnover in the third trimester of pregnancy may be higher in winter months than in summer months, resulting in greater fetal lead exposure in spring than at other times of the year.

Severe lead-induced peripheral neuropathy in a dialysis patient.

Toxic neuropathy caused by lead (manifested as wrist drop) was a frequent phenomenon before 1925. In modern times, it is a distinct rarity. We report herein a Hispanic woman who developed end-stage renal failure, followed by wrist drop, in whom the maximal total blood lead was 69 microg/dL. Measurements of lead in her tibia and calcaneus by K-x-ray fluorescence, however, showed markedly elevated values. The wrist drop cleared after four treatments with intravenous calcium sodium edetate (Ca EDTA). In vitro studies of (210)Pb uptake by red blood cells (RBC) after incubation with normal or uremic plasma indicated that (210)Pb uptake was inhibited by uremic plasma. These studies suggest the presence of a transport inhibitor in uremia that modifies the distribution of lead between plasma and RBC, leading to lower overall blood values.

Acquisition and retention of lead by young children.

The concentrations and isotope ratios of lead in blood and urine, on the hands, and in duplicate diet samples were measured for children living in Omaha, Nebraska. One group consisted of 22 children followed from birth to between 1 and 2 years of age and another group was 20 2- to 4-year-old children followed for 1 year, although some in each group were followed for periods between 3 and 4 years. At no time in life was a component of dietary lead identified in blood by isotope ratios, and blood lead appears dominated by lead derived from the hands, which in turn appears derived from the floors. For some homes floor lead appeared to be a mixture of lead from window sills and from the exterior. Only 2 of the children appear to have ingested lead directly from window sills. Several who lived in homes being remodeled were exposed to lead before the age of 2 years. For those who had been briefly exposed during professional remodeling the blood lead fell with a half-life of 10 months but for those who had suffered prolonged exposure during remodeling by parents the apparent half-life was longer, between 20 and 38 months.

Isotopic ratio analysis in residential lead-based paint and associated surficial dust.

OBJECTIVES: This investigation assessed the contribution of lead in lead-based paint (7 samples) to lead-laden dust (8 samples) in a single suburban vacant residence using isotopic ratio analysis. METHODS: Interior/exterior lead-based paint surface concentration was measured by X-ray fluorescence while dust and scrapings were analyzed chemically for total lead content and by mass spectrometry for the associated isotopic ratios. RESULTS: Four out of 5 comparisons of paint (7 samples) and dust (8 samples) for a given location did not match isotopically. In the one location where the isotopic ratio of the paint and dust samples matched closely, some portions of the paint were not intact. One explanation for the isotopic ratio match is that the dust sample may have actually been contaminated with paint flecks. This explanation appears likely since the isotopic ratio for the lead in the dust and paint sample were not in the modern average range of US environmental lead, strongly indicating a local point source of the lead in this dust sample, namely the paint at this location. Lead dust samples whose isotopic ratio lies in the modern average range for US environmental lead cannot be correlated to the paint which is beneath them, since the isotopic ratio of lead in the dust may actually be a composite of many sources of lead over time, as suggested by an isotopic ratio in the modern average range. CONCLUSIONS: From the samples from this one house, the data dispute the contention that intact lead-based paint chalks and creates lead-contaminated dust on its surface. While leaded household dust may contribute to children's lead exposure, intact paint need not contribute to surficial lead-laden dust. Isotopic ratio measurements can be useful for point-source determination by virtue of sample match and by placement of the ratio on the spectrum of isotopic ratio values for lead. Point-source assessment based on isotopic ratio was either strengthened or weakened by placement outside or within the average range for US environmental lead, respectively.

Evaluation and modification of a physiologically based model of lead kinetics using data from a sequential isotope study in cynomolgus monkeys.

Endogenous (predominantly bone) and exogenous lead were differentially labeled in two 11-year-old female cynomolgus monkeys (Macaca fascicularis) to establish the contributions of the two sources to blood lead. The monkeys had been administered a common lead isotope "mix" at the rate of about 1300 micrograms Pb/kg body wt/day from age 10 months until the start of the study. On day 0, common lead was replaced in sequence by mixes artificially enriched in 204Pb, 206Pb, and 207Pb, given for periods of from 50 to 281 days. Total lead ingestion rate was held constant except during administration of the 207Pb-enriched mix to one of the monkeys, when it was reduced to 650 micrograms/kg/day. Blood and bone were sampled at intervals and analyzed for their content of each of the isotope mixes. A physiologically based model of human lead kinetics was scaled to the cynomolgus monkey and fit to the data to test the correctness of the model structure and to assist with interpretation of study results. Fractional absorption was varied to achieve the best visual fits of the scaled model to blood and bone concentration data for each monkey. The model failed to reproduce the sharp drop in isotope concentrations in blood observed after each exchange of isotope mix. Consequently, it was revised to include a rapid-turnover trabecular bone compartment and a slow-turnover cortical bone compartment, using estimates of trabecular and cortical bone turnover rates from histomorphometric studies in adult cynomolgus monkeys. The revised model fit most of the sets of bone and blood concentrations well. About 17% of the blood lead originated from bone after 11 years of exposure, at blood lead concentrations in excess of 50 micrograms/dl. The rate of return of common lead from bone, as estimated from the model, was 28 micrograms/day just before termination of controlled common lead exposure on day 0. Based on the success of the scaled human model in fitting these data and on the absolute and relative values of bone and blood lead concentrations, the metabolism of lead in the cynomolgus monkey appears to be similar to human lead metabolism.

Use of sequentially administered stable lead isotopes to investigate changes in blood lead during pregnancy in a nonhuman primate (Macaca fascicularis).

The effects of pregnancy on the flux of lead from maternal bone were investigated in five females from a unique colony of cynomolgus monkeys (Macaca fascicularis) which had been dosed orally with lead (approximately 1100-1300 microg Pb/kg body wt) throughout their lives (about 14 years). Through the use of stable lead isotopes 204Pb, 206Pb, and 207Pb, it was possible to differentiate between the lead contributed to blood lead from the skeleton and the lead contributed from the current oral dose. Blood samples and bone biopsy samples taken before, during, and after pregnancy were analyzed for lead (total and stable isotope ratios) by thermal ionization mass spectrometry. Through the use of end-member unmixing equations, the contribution to blood of lead from maternal bone during pregnancy was estimated and compared to the contribution of lead from maternal bone before pregnancy. A 29 to 56% decrease in bone lead mobilization in the first trimester was followed by an increase in the second and third trimesters, up to 44% over baseline levels. In one monkey, the third-trimester increase did not reach baseline levels. In a single low-lead monkey, a similar decrease in the first trimester was followed by a 60% increase in the third trimester, indicating that a similar pattern of flux is seen over a wide range of lead concentrations. Analysis of maternal bone and fetal bone, brain, liver, and kidneys confirmed a substantial transplacental transfer of endogenous lead. Lead concentrations in fetal bone often exceeded maternal bone lead concentrations. From 7 to 39% of the lead in the fetal skeleton originated from the maternal skeleton.

Measurement of the flux of lead from bone to blood in a nonhuman primate (Macaca fascicularis) by sequential administration of stable lead isotopes.

To better understand the kinetics of the transfer of lead from bone to blood, we have developed and tested a method in which sequential doses of lead, each enriched with a different stable isotope, were administered in a nonhuman primate Macaca fascicularis whose skeleton had been previously labeled with lead of known isotopic composition. Lead isotopic ratios of blood and bone samples, analyzed by thermal ionization mass spectrometry (TIMS), were unmixed by isotope dilution techniques. The first label administered allows the contribution from historical bone stores to be measured. Subsequent labels allow measurement of both the historical bone stores and the previous labels that have become recently incorporated into bone. The method may be extended to studies of bone lead mobilization in pregnancy, lactation, menopause, or in disease states such as postmenopausal osteoporosis.

A human in vivo model for the determination of lead bioavailability using stable isotope dilution.

Beverages stored in lead-crystal glass accumulate extraordinary concentrations of lead. We obtained a lead-crystal decanter manufactured with lead from Australia, where the ratio of 206Pb/207Pb is distinctly different from that in the United States. We sought to determine the bioavailability of crystal-derived lead, using the technique of stable isotope dilution in blood. We conducted a single-dose, nonrandomized cross-over study in which participants were admitted to the Clinical Research Center twice, 1 week apart. During the first admission, subjects ingested sherry obtained from the original bottle. During the second admission, they ingested sherry that had been stored in the crystal decanter and that had achieved a lead concentration of 14.2 mu mol/l. After ingesting decanter-stored sherry, mean blood lead rose significantly (p = 0.0003) from 0.10 to 0.18 mu mol/l, while mean 206Pb/207Pb fell from 1.202 to 1.137 (p = 0.0001). On average, 70% of the ingested dose of lead was absorbed. We conclude that lead derived from crystal glass is highly bioavailable; repeated ingestions could cause elevated blood lead concentration. The technique of stable isotope dilution lends itself to the study of the bioavailability of lead in other matrices, including soil.

Stable isotope identification of lead sources in preschool children--the Omaha Study.

The objective was to determine, from analysis of the naturally occurring stable isotopes of lead, the relative contribution of food, handdust, housedust, soil and air lead to the absorbed (urinary) lead and the blood lead of children living in a former smelter city. A longitudinal 12 month study was conducted of 21 children, 2 - 3 years of age, living in central Omaha, balanced for race, gender and socioeconomic status. Field clean samples were collected monthly of 24 hour duplicate diet, handwipe and urine, with quarterly blood lead, annual environmental lead, weekly air for total lead and 206Pb, 207Pb and 208Pb by thermal ionization/mass spectrometry with a 205Pb spike in a Class II laboratory. Despite residence in a smelter city each child had a unique isotopic ratio of handwipe, blood and urine lead, the latter being identical. There was no correlation of handwipe isotopic ratio with proximity to a lead emission source or to the decade of the housing stock. The isotopic ratio of the annual mean handwipe lead predicted 43% of the variance of the annual mean blood and urine lead ratio (r2 = .43; p = .001). Handwipe lead ratios correlated (p < or = .05) with those of the windowsills and air ducts. The mean isotopic ratios of blood and urine lead were lower than those of handwipe and food, consistent with a contribution by endogenous bone lead. Clean catch urine provides a noninvasive index of blood lead isotopic ratio in children, as in adults.

Lead poisoning from retained missiles. An experimental study.

The problem of lead poisoning from bullets has been investigated by surgically implanting discs of lead, each enriched in a different natural isotope, into the tissue of two mongrel dogs and monitoring by mass spectrometry the release of the lead into each animal's blood over the course of 3 years. Lead placed in the knee underwent vigorous attack by the synovial fluid, far in excess of what would be expected from corrosion theory, and reached a maximum concentration in blood 4-6 months after operation. Thereafter, lead concentration exponentially declined as the remaining fragments became encapsulated. The disc placed in muscle was sparingly soluble immediately following implantation. It is concluded that the greatest danger of lead poisoning from an injury involving many fragments having collectively a large surface area will occur within a month, and that the cases of lead poisoning resulting from bullets in joints that occur 5 or more years after injury are caused by continual wear of metal on a joint surface, storage of lead so released in the skeleton, and its subsequent resorption during a change in osteocyte activity.

Effects of alcohol ingestion on zinc content of human and rat central nervous systems.

The abundance of zinc in hippocampal mossy fibers has stimulated investigation of zinc status in various pathologic states in which behavioral or anatomic deficits involving the hippocampus are known to occur. Limited autopsy studies of chronic alcoholic humans have suggested that the content of zinc might be reduced in several brain regions whereas reported attempts to replicate these findings in ethanol-exposed experimental animals have produced inconsistent results. In this comparative study, the zinc concentration in 10 brain regions, all spinal cord segments, and microdissected hippocampal subfields was measured by isotope ratio mass spectrometry. A widespread 15 to 20% reduction in zinc content was observed in all regions of chronic alcoholics compared with controls but a selective involvement of hippocampus was not detected. In the experimental studies, groups of rats were exposed to ethanol by one of three routes: inhalation for 2 weeks, as an ethanol/liquid diet for 3 months, or a single intoxicating i.p. dose. Determinations of tissue uptake of radiozinc and of total zinc content were made. In contrast to human pathologic material, zinc pool size and tissue uptakes were not affected by experimental ethanol administration by any route. This study confirmed that a reduction in zinc concentration occurs in the central nervous system of chronic alcoholics. The animal studies indicated, however, that simple ethanol exposure, even for prolonged periods, does not perturb zinc metabolism in brain. Together, these observations argue that the abnormalities of zinc metabolism in chronic alcoholics are possibly secondary to homeostatic alterations associated with hepatic failure.

Total contribution of airborne lead to blood lead.

A nine year study of blood lead concentrations and isotope ratios carried out on a married couple shows that pulmonary deposition cannot account for all the airborne lead in blood; that lead from bone may comprise 70% of blood lead; and that during pregnancy blood lead may double due to mobilisation of lead from bone.

High accuracy (stable isotope dilution) measurements of lead in serum and cerebrospinal fluid.

The concentration of lead in blood, serum, cerebrospinal fluid, and urine was measured in patients with neurological disease and in control subjects including cases of plumbism. A plot of blood lead versus serum lead resembles the familiar curves of blood lead versus either free erythrocyte porphyrin or urinary delta-aminolaevulinic acid in that serum lead is constant up to a blood lead concentration of 40 micrograms/dl (2 mumol/l) and rises steeply thereafter. The serum lead concentrations yield renal clearances in the range 5-22 ml/min in agreement with values obtained with radiolead on man and predicted from animal studies. The lead content of cerebrospinal fluid is consistently less than that of serum, averaging 50% of the serum concentration for blood leads of less than 20 micrograms/dl (1 mumol/l) but rising to 80-90% in cases of plumbism. Patients with motor neurone disease could not be distinguished from those with other neurological diseases on the basis of the lead content of their serum or cerebrospinal fluid.