Temporal trends in the lead concentrations of umbilical cord blood.

Umbilical cord blood specimens from 11,837 births between April 1979 and April 1981 have been analyzed for lead by anodic stripping voltammetry. The mean was 6.56 +/- 3.19 (standard deviation) micrograms per deciliter of blood, and the range was 0.0 to 37.0 micrograms per deciliter. The mean decreased annually by 0.77 +/- 0.03 microgram per deciliter, about 11 percent. Lead concentrations were higher in infants born in summer than in infants born in winter (7.17 versus 5.99, probability less than .001). A Fourier model of the data is presented, and possible reasons for the decline are discussed.

Lead metabolism in the normal human: stable isotope studies.

Kinetic and metabolic balance studies in a healthy man fed a diet normal in lead content and labeled with lead-204 indicated that approximately two-thirds of his assimilated lead was dietary in origin; the remainder was inhaled. Kinetic analysis shows that the isotopic data can be interpreted by a three-compartment model.

Kinetic analysis of lead metabolism in healthy humans.

The steady state kinetics of lead metabolism were studied in five healthy men with stable isotope tracers. Subjects lived in a metabolic unit and ate constant low lead diets. Their intake was supplemented each day with 79--204 mug of enriched lead-204 as nitrate which was ingested with meals for 1--124 days. The concentration and isotopic composition of lead was determined serially in blood, urine, feces, and diet and less commonly in hair, nails, sweat, bone, and alimentary tract secretions by isotopic dilution, mass spectrometric analysis. The data suggest a three compartmental model for lead metabolism. The first compartment encompasses blood and is 1.5--2.2 times larger than the blood mass. It contains approximately 1.7--2.0 mg of lead and has a mean life of 35 days. This pool is in direct communication with ingested lead, urinary lead, and pools two and three. The second compartment is largely composed of soft tissue, contains about 0.3--0.9 mg of lead, and has a mean life of approximately 40 days. This pool gives rise to lead in hair, nails, sweat, and salivary, gastric, pancreatic, and biliary secretions. Pool three resides primarily in the skeleton, contains the vast quantity of body lead, and has a very slow mean life. Bones appear to differ in their rates of lead turnover. Within the relatively small changes in blood lead observed in the present study, the transfer coefficients between the pools remained constant.

Effects of chromium and yeast supplements on carbohydrate and lipid metabolism in diabetic men.

Diabetes mellitus has been shown to develop as a consequence of chromium (Cr) deficiency in experimental animals and in humans sustained by prolonged total parenteral nutrition. Prior limited trials in humans had indicated that Cr supplements, in either inorganic or organic form, may improve carbohydrate utilization. We report here a clinical double-blind, random crossover trial of inorganic Cr trichloride, a brewer's yeast that contained Cr as glucose tolerance factor (GTF), a brewer's yeast extract without GTF, and a placebo. Forty-three outpatient diabetic men received three of these supplements for 4 mo each. Subgroups included 21 ketosis-prone men; 7 ketosis-resistant, nonobese men; and 15 ketosis-resistant obese men. Chromium levels were followed pre- and posttreatment in hair, red blood cells, plasma, and urine. Response of carbohydrate metabolism to treatment was assessed in terms of change in insulin requirements, fasting plasma glucose, plasma cholesterol, and triglycerides, as well as change in plasma glucose, glucagon, and insulin or C-peptide levels in response to a standard meal. In some men, these parameters were also measured after i.v. tolbutamide. Both the inorganic and organic oral Cr supplements increased measurable body pools of Cr in hair and red blood cells by about 25%. However, fasting plasma glucose and lipids and the glucose response to either the standard meal or to tolbutamide were not significantly altered by any of the treatments. Despite this lack of effect on carbohydrate levels, the ketosis-resistant subgroups demonstrated a significant increase in postprandial insulin after treatment with the brewer's yeast that contained GTF.

Effect of food intake and fasting on gastrointestinal lead absorption in humans.

The effect of food intake versus brief fasting on gastrointestinal absorption of lead was measured in five healthy men who were living in a metabolic unit and eating constant lead diets. Lead absorpiton was assessed by the difference between dietary intake and output of 1) lead tracers composed of nonradioactive isotopes which were ingested as a single dose either with food or during a 16-hr fast, 2) lead tracers ingested with meals for relatively long periods (2 to 124 days), and 3) total led in ingested foods. Absorption estimated by 1) was confirmed by increments in tracer concentrations in blood. Lead tracers were given as nitrate, cysteine complex, or sulfide. Absorption was 10.3 +/- 2.2% (SD) for food lead; 8.2 +/- 2.8% for tracers ingested with food; and 35 +/- 13% (P < 0.01) percent for tracers ingested without food. The increased absorption of lead when ingested without food should be considered when the hazards of exposure to lead are determined.

Toxicokinetics of bone lead.

This article discusses bone as a source of lead to the rest of the body and as a record of past lead exposure. Bone lead levels generally increase with age at rates dependent on the skeletal site and lead exposure. After occupational exposure, the slow decline in blood lead, a 5- to 19-year half-life, reflects the long skeletal half-life. Repeated measurements of bone lead demonstrate the slow elimination of lead from bone. Stable isotope ratios have revealed many details of skeletal uptake and subsequent release. The bulk turnover rates for compact bone are about 2% per year and 8% for spine. Turnover activity varies with age and health. Even though lead approximates calcium, radium, strontium, barium, fluorine, and other bone seekers, the rates for each are different. A simple, two-pool (bone and blood) kinetic model is presented with proposed numerical values for the changes in blood lead levels that occur with changes in turnover rates. Two approaches are offered to further quantify lead turnover. One involves a study of subjects with known past exposure. Changes in the ratio of blood lead to bone lead with time would reflect the course of bone lead availability. Also, stable isotopes and subjects who move from one geographical area to another offer opportunities. Sequential isotope measurements would indicate how much of the lead in blood is from current exposure or bone stores, distinct from changes in absorption or excretion.

Stable isotope mass spectrometry in childhood lead poisoning.

In order to better understand the relative importance of various sources of lead in childhood lead poisoning, high-precision, isotoperatio, solid-source-mass spectrometry of microgram-sized lead samples was applied to three hospitalized cases in Boston, ranging in age from 1.5 to 14 yr, that had blood-lead levels of 0.7-1.2 µg/g. The lead isotopes in the ambient Boston environment (air, soil, and dust) were also measured.In each case, the isotopic composition (IC) of the child's blood lead was identical with the IC of lead paint taken from the child's residence at a site accessible to the child. Fecal lead samples were also identical to that particular paint. Soil lead IC did not always match the IC of local paints. Paint samples vary widely in their IC's (206/204=17.5-19.4, about 200 times analytical reliability). Dust in homes that never had lead paint contained lead that resembled lead in urban soils. Dust lead IC did not necessarily have the same IC as current automobile lead emissions, but appeared to reflect the long-term accumulation of several sources of urban lead fallout.Limitations and implications of this data are discussed.

Environmental, demographic, and medical factors related to cord blood lead levels.

Blood lead was measured at birth for 11,837 infants in Boston. Extensive maternal demographic, pregnancy, and delivery characteristics were recorded for 4354 of them. For 249 of these, intensive environmental sampling was done. Many medical factors were unrelated to blood lead, including diabetes, venereal diseases, preeclampsia, toxemia, hypertension, age, hematocrit, contraceptive use, presentation, type of delivery, fetal distress, premature rupture of membrane, blood type, gestational age, birthweight, Apgar score, jaundice, and mortality by one month. However, use of tobacco, alcohol, coffee, tea, or marihuana, having had an abortion, receiving welfare and being unmarried, Black, or Hispanic are associated with significantly elevated blood lead. Being college educated, Jewish, younger, and multiparitous are related to lower blood lead levels. Environmental factors covarying with blood lead included dust and soil lead and refinishing activity, but not water, air, or paint lead or traffic density. Many of these predictors are intercorrelated. Simultaneous, step-wise regression models of blood lead ranking these factors are presented. Only 18% of the variance is explainable. Temporal and geographic patterns exist even after taking these maternal and environmental factors into account.

Clinical trial of chromium and yeast supplements on carbohydrate and lipid metabolism in diabetic men.

Chromium (Cr) deficiency in experimental animals and in humans sustained by prolonged total parenteral nutrition has been shown to cause diabetes mellitus. Prior trials in humans indicated that Cr supplements, in either inorganic or organic form, may improve carbohydrate utilization. We report here a clinical double-blind, random cross-over trial of inorganic chromium trichloride, a brewer's yeast that contained Cr as glucose-tolerance-factor (GTF), a brewer's yeast extract without GTF, and a placebo. Forty-three outpatient diabetic men received three of these supplements for 4 months each. Subgroups included 21 ketosis-prone, 7 ketosis-resistant non-obese, and 15 ketosis-resistant obese men. Cr levels were followed pre- and post-treatment in hair, red blood cells, plasma, and urine. Response of carbohydrate metabolism to treatment was assessed in terms of change in insulin requirements, fasting plasma glucose, plasma cholesterol, and triglycerides, as well as the change in plasma glucose, glucagon, and insulin or C-peptide levels in response to a standard meal. In some men, these parameters were also measured after iv tolbutamide. Both the inorganic and organic oral Cr supplements increased measurable body pools of Cr in hair and red blood cells by about 25%. However, fasting plasma glucose and lipids and the glucose response to either the standard meal or to tolbutamide were not significantly altered by any of the treatments.

Dentine lead and child intelligence in Taiwan.

It is well known that lead is a developmental neurotoxin, but, because many factors influence a child's development, a safe level of lead for children is still not clear. In this study, personal lead exposure was assessed. A total of 940 deciduous teeth--mostly incisors--was collected from 764 children in grades 1-3 who attended 7 primary schools. Two of the primary schools were near smelters, 4 were in Taipei City, and 1 was located in a coastal village. Teachers were provided with a questionnaire about classroom performance, and 97% completed and returned the questionnaire to the laboratory. Parents were given a questionnaire about family background, pregnancy, and health history (92% returned). Dentine lead levels of shed incisors for children in Taipei City were higher than levels reported in Boston, i.e., mean (standard deviation) of 4.4 (3.5) versus 3.3 (2.5) micrograms/g, respectively (p less than .001). The lead values were significantly higher in children who attended school near a smelter than in children who attended school in Taipei City: 6.3 (3.3) (p less than .001). The mean lead levels in children who attended school in a coastal village was 5.1 (2.8). The ranges for all schools overlapped, which indicated that there were multiple lead sources. Intelligence scores from Raven's Colored Progressive Matrices Test were negatively correlated with lead levels, especially among girls and among children whose parents had less education. We adjusted for other risk factors--most notably parental education, which correlates inversely with lead levels--and found that the role of the lead term was lowered but not eliminated.

Stable isotopes of lead for source identification.

Lead is unique among all the metals in having variations among mining districts in the relative abundances of its stable (non-radioactive) isotopes. Since first described in 1927, many applications have been reported, mostly for geological uses. More recently archeological, environmental, bio-kinetic and public health uses have been found. The abundances of the four stable isotopes are usually determined with specialized mass spectrometry using rapid mass scanning cycles or multiple collectors. The relative abundances are commonly expressed as 206/204, 206/207, and 206/208 atomic ratios. Precision of 0.5% for 206/204 and even better (0.03%) for the other pairs are obtainable. The three ratios co-vary strongly and depend on when the ore was formed. This provides a tracer for following a particular batch of lead, since the ratio can only change when the lead is mixed with a different lead. A major limitation of this method is that it is useful only to those problems where the potential sources are isotopically distinct and few in number. The covariance of the ratios usually allows for only two sources to be considered. Potential sources can often be ruled out.

Relationships between serial blood lead levels and exfoliated tooth dentin lead levels: models of tooth lead kinetics.

Because bones and permanent teeth accumulate lead, exfoliated deciduous teeth have been utilized as retrospective markers of cumulative exposure in epidemiological surveys. In this paper we describe four models of lead uptake by the coronal dentin of shed primary teeth, each with different assumptions and ramifications. Each model is characterized by different relationships between blood lead at several ages and tooth lead. Values observed in our cohort of normal Boston children are most compatible with models positing the largest lead contribution coming at older ages (i.e., closer to age at exfoliation). Characteristics of models incompatible with our data include (1) lead deposition only during initial calcification and (2) no loss or resorption of lead.

Occurrence of elevated protoporphyrin levels in relation to lead burden in infants.

Simultaneous blood lead (PbB), erythrocyte protoporphyrin (EP), and hematocrit measurements were made semiannually in 232 normal infants from 6 to 24 months of age. The PbB averaged 7 (SD = 5) and ranged from 0 to 64 micrograms/dl. The incidence of elevated EP, a marker for deranged heme synthesis, was unrelated to PbB at levels below 15 micrograms/dl but was fourfold greater among the infants with PbB above 15 micrograms/dl. This relationship persisted even after eliminating the 31 (4%) anemic (hematocrit less than 33%) samples. The confounding effects of iron deficiency are discussed.

Discovering unrecognized lead-smelting sites by historical methods.

OBJECTIVES: Our objective was to enumerate unrecognized former lead smelters in the United States. METHODS: Defunct smelters were identified by historical research. The compiled list was compared with government registries of hazardous sites. Soil samples were taken from 10 sites. RESULTS: Approximately 430 sites were unknown to the federal authorities. Only 5 of 319 sites were known to authorities in the top 8 states. Nine of the 10 sites sampled exceeded residential standards for soil lead level. CONCLUSIONS: Approximately 430 former lead-smelting sites were unrecognized in the United States. Sampling results indicate that the sites may pose a threat to public health.

Magnitude of lead intake from respiration by normal man.

Lead metabolism of five normal men was studied in a hospital metabolic unit in order to measure the daily intake of lead by respiration in urban adults. Subjects ingested a constant diet, and samples of blood, urine, feces, and diet were analyzed periodically for lead isotopic abundances by mass spectrometry. Three men were fed daily a stable isotope tracer of lead for 83 to 124 days in order to distinguish ingested from respired lead. Also, three men lived in rooms with filtered, low-lead air for 25 to 50 days in order to examine the response of blood lead levels to a change in airborne lead exposure. The quantity of respired lead intake was determined from the lead balance data, labeling of blood lead with a dietary lead tracer, and the response of blood lead levels and lead balances to exposure to low-lead air. The results indicate that these men absorbed a mean of 14 +/- 4 (S.D.) microgram/day of lead while exposed to the ambient levels of about 2 microgram/m3 of airborne lead. About twice this amount was absorbed from the diet.

Early sensory-motor development and prenatal exposure to lead.

As part of a longitudinal study of the early developmental effects of exposure to lead, we administered the Bayley Scales of Infant Development at age 6 months to infants classified into three groups based on their umbilical cord blood lead levels ("low": mean = 1.8 micrograms/dl; "mid": mean = 6.5 micrograms/dl; "high": mean = 14.6 micrograms/dl). No infant had a cord blood lead level greater than 30 micrograms/dl, the level currently regarded as the upper limit of "normal" for young children. Multiple regression analyses indicated that high cord blood levels were associated with lower covariance-adjusted scores on the Mental Development Index. Scores on the Psychomotor Development Index were not significantly related to cord blood lead level. The level of lead in blood at 6 months of age was not associated with scores on either the Mental or Psychomotor Development Index. These data are compatible with the hypothesis that low levels of lead delivered transplacentally are toxic to infants.

Elimination kinetics of blood lead in workers with chronic lead intoxication.

Blood lead elimination half-lives were determined for 65 patients with occupational chronic lead intoxication who were removed from exposure, treated with intravenous EDTA, and followed for periods of up to 2,419 days. The median overall blood lead elimination half-life was 619 days in patients with normal renal function and 1,907 days in patients with renal impairment. Slow-phase elimination half-lives in patients followed for longer than 5 years ranged from 1,658 to 7,189 days. Blood lead concentrations declined during periods of chelation with a mean half-life of 7 days and rebounded to near prechelation concentrations following termination of chelation with a mean doubling time of 27 days. The overall blood lead elimination half-life was positively associated with length of follow-up (p less than 0.001), age (p = 0.04), and duration of exposure (p = 0.02), but was not associated with the initial blood lead concentration following cessation of exposure or the total amount of EDTA received.