Bone Lead Concentrations Research Articles

Chronic Occupational Lead Exposure and Testicular Endocrine Function

The effects of moderate lead exposure on testicular endocrine function were evaluated in a group of 90 males who were occupationally exposed to inorganic lead. Lead concentrations in blood and bone were measured as indices of short-term and long-term, cumulative exposure, respectively. The results of this study show that the lead exposure levels encountered in the UK at present may result in a subclinical increase in follicle stimulating hormone (FSH), which is related to blood lead levels. This suggest that lead may be causing some subclinical primary damage to the seminiferous tubules in the testes. However, at blood lead levels of less than 47 micrograms dl-1 this effect on serum FSH is not apparent. There was no significant effect on serum testosterone concentrations or the free testosterone index. The mean luteinizing hormone (LH) level in the exposed group was found to be lower than in the control population. However, there appeared a confoundingly significant positive correlation between serum luteinizing hormone levels and the length of occupational lead exposure within the exposed group.

Investigations on the composition of horse bones

Specific gravity and the content of dry matter, crude protein, ash, major minerals as well as trace elements were determined in the rostral process of the nasal bone, the rib, the caudal vertebrae and the cannon bone in 50 horses of different age. In contrast to the skeleton of other domestic animals, the horse skeleton showed a lower magnesium concentration, a tendency towards higher calcium content and a wider ratio of calcium to phosphorus. Dry matter and ash content increased from birth up to the age of 60 months while the crude protein content decreased. The calcium content increased with age to a considerable degree but the phosphorus content only to a small amount, so the ratio of calcium to phosphorus increased as well. The magnesium, potassium and chlorine content decreased with increasing age while the zinc content did not show any relation to age. The copper content increased until the age of 8 years and thereafter decreased again. The lead content of the skeleton depended on age and exposure (contamination of the living area). The lead content of the caudal vertebrae was highly correlated with the lead content of the other bones of the same horse investigated (r=≥0.96**). For the estimation of age the specific gravity of the cannon bone is best suited (r=0.92**). A post mortum diagnosis of magnesium, potassium or zinc deficiency should be possible by analysis of the caudal vertebrae because the content of this bone is strongly related to that of the other bones and the concentration of these elements is also related to the intake. For the estimation of the sodium supply only the rib or the cannon bone should be used. The calcium content of the cannon bone was closely related to the concentration in the caudal vertebrae (r=0.73**).

Lead concentrations in human bones from the Canadian population

Stable lead was determined in post-mortem samples of human bones from three Canadian cities. All age groups and both sexes were represented. The cities selected for investigation were Winnipeg, Montreal and Charlottetown. No significant difference was found between the locations, although levels tended to be higher for Montreal. Mean lead concentrations (μg Pb/g ash) were 8.98 ± 1.17, 11.11 ± 1.74 and 8.47 ± 1.06 for Winnipeg, Montreal and Chalottetown, respectively. Corresponding geometric means were 6.21, 7.88 and 6.71, respectively. Individual values ranged from 0.45 to 240.07 μg Pb/g ash. Concentrations were highest in the > 20-year age group, indicating increased body burden with age. An increase in lead concentration was observed for the ages 1–11 years with a decrease for the 12–19-year age group. Differences in concentrations between the sexes were not significant. Higher than average concentrations were observed in samples obtained from Winnipeg for the period 1976–1980, particularly in the 1–4-year age group. A similar pattern was observed in the air lead concentrations, suggesting a possible correlation between the concentrations of lead in the air and in bones at Winnipeg.

X-ray fluorescence: Issues surrounding the application of a new tool for measuring burden of lead

Studies of lead toxicity would greatly benefit from a convenient, noninvasive measure of body lead burden. X-ray fluorescence (XRF) promises to provide such a measure by rapidly estimating lead content in bone, the repository of greater than 95% of an adult's lead stores (73% in children). Two separate XRF techniques exist, L-XRF and K-XRF. They differ in terms of calibration method and type of bone sampled. They also involve different radiation energies; however, radiation doses and concomitant risks are similarly low. Since interpretation of an XRF measurement depends to an extent on the distribution of lead in the skeleton, this topic is reviewed. Available data suggest that trabecular and cortical bone comprise two distinct compartments with regard to lead kinetics. Within each compartment, however, there also appears to be a significant degree of variability. Furthermore, there is evidence to suggest that the subperiosteal surface layer of cortical bone has a pattern of lead absorption and release that is different from the rest of cortical bone. This may have implications for (1) the choice of XRF technique, since the L-XRF technique measures lead in surface bone, whereas the K-XRF technique derives an estimate of lead from the full thickness of bone, and (2) the selection of bone sites for taking XRF measurements. More research is necessary to fully optimize the applicability of the XRF instrument.

Reducing bone lead content by chelation treatment in chronic lead poisoning: An in vivo X-ray fluorescence and bone biopsy study

A stained-glass artist with longstanding exposure to lead presented with neuropsychiatric symptoms. He was evaluated before and after chelation treatment by the CaNa2 EDTA lead mobilization test, iliac crest bone lead measurement, and in vivo tibial X-ray fluorescence (XRF). The three methods showed a progressive fall in body lead stores during chelation therapy in association with improvement in symptoms and a fall in blood lead and zinc protoporphyrin levels. In vivo tibial XRF is a safe, rapid, and noninvasive technique for detecting excessive body lead burdens. XRF measurement of bone lead content is a practical method for monitoring the efficacy of therapy as well as for establishing the diagnosis.

L-line x-ray fluorescence of cortical bone lead compared with the CaNa2EDTA test in lead-toxic children: public health implications.

Mild to moderate lead toxicity (blood lead, 25-55 micrograms/dl) is a preventable pediatric illness affecting several million preschool children ("lead-toxic children") in the United States. In-hospital lead-chelation treatment is predicated upon a positive CaNa2EDTA test, which is difficult to perform and impractical in large populations. After the development of an L-line x-ray fluorescence technique (LXRF) that measures cortical bone lead content safely, rapidly, and noninvasively, this study was initiated in lead-toxic children to compare LXRF with the CaNa2EDTA test. Moreover, LXRF provided the opportunity to quantify bone lead content. From blood lead and LXRF alone, 90% of lead-toxic children were correctly classified as being CaNa2EDTA-positive or -negative. In 76% of 59 lead-toxic children, bone lead values measured by LXRF were equal to or greater than those measured in normal and industrially exposed adults. These results indicate that LXRF may be capable of replacing the CaNa2EDTA test. When considered with the known neurotoxic effects on children of "low levels" of exposure to lead, these results also suggest that either an excessively narrow margin of safety or insufficient safety is provided by present U.S. guidelines, which classify an elevated blood lead concentration as 25 micrograms/dl or greater.

Effects in rats of iron on lead deprivation

In two fully crossed, two-factor experiments, F1 generation male rats were fed a basal diet supplemented with lead (lead acetate) at 0 or 2 micrograms/g and iron (ferric sulfate) at 50 or 250 micrograms/g (Experiment 1). Supplements in Experiment 2 were lead at 0 or 1 micrograms/g and iron at 50, 250, or 1000 micrograms/g. After 28 or 50 d in Experiment 1, and 35 d in Experiment 2, a relationship between lead and iron was found. Body weight was lower in low-lead than lead-supplemented 28-d-old rats regardless of dietary iron, whereas hematocrit and hemoglobin were lower in low-lead than lead-supplemented rats fed 50 micrograms iron/g diet. A similar finding was obtained with hematocrit and hemoglobin in 35-d-old rats. Dietary lead did not affect rats fed 250 or 1000 micrograms iron/g diet. Also, feeding low dietary lead did not affect 50-d-old rats regardless of dietary iron. Liver and bone concentrations of lead were markedly affected by dietary lead and iron. The concentration of lead in liver and bone was lower in low-lead than lead-supplemented rats. Compared to rats fed 50 micrograms iron/g diet, rats fed 250 micrograms iron/g diet exhibited a decreased lead concentration in liver and bone. This decrease was accentuated by lead supplementation. The findings suggest that lead acted pharmacologically to affect iron metabolism in rats.

Bone lead in dialysis patients

We measured lead and calcium in multiple bone biopsies from 11 cadavers without known excessive past exposure to lead. Paired iliac crest, transiliac and tibial bone biopsies from these cadavers indicated that in bone biopsy specimens the lead/calcium ratio is more reproducible than the absolute lead concentration. There were no significant differences between the lead/calcium ratios from the iliac crest, transiliac, or tibial specimens. Transiliac bone biopsies from 35 patients (13 patients showing symptoms of slight or moderate degree of renal failure, medical history of gout and/or arterial hypertension and 22 lead workers with chelatable lead in excess of 1000 micrograms) indicated that the lead and the lead/calcium ratio in bone biopsies reflect body lead stores as estimated by the EDT A test (r = 0.87 and 0.83, respectively). Chemical and histological studies of transiliac biopsies previously obtained from 153 dialysis patients (from 8 dialysis centers from Belgium, France and Germany) for studies of aluminum-induced bone disease showed that chronic renal failure and dialysis do not cause accumulation of lead in bone and elevated bone lead does not appear to alter trabecular bone histomorphometry. We found that in 5% of the hemodialysis population studied, bone lead concentrations approximated levels found in active lead workers.

Lead in Vertebral Bone Biopsies from Active and Retired Lead Workers

Samples of vertebral bone were obtained by skeletal biopsy and lead concentrations were determined by atomic absorption spectroscopy. The median level of lead in bone in 27 active lead workers was 29 micrograms/g wet weight (range 2-155), corresponding to 370 micrograms/g calcium (range 30-1,120). In 9 retired workers, the corresponding levels were 19 micrograms/g (5-76) and 250 micrograms/g calcium (60-700); in 14 reference subjects without occupational exposure, 1.3 micrograms/g (1-4) and 13 micrograms/g calcium (8-40). The bone lead content rose with time of exposure. Comparison of levels in vertebra with those in fingerbone, as measured by in vivo x-ray fluorescence in the same subjects, strongly suggested the presence of lead pools with different kinetics. The accumulation pattern, as well as the relation between levels in vertebra and fingerbone, suggests a much shorter half-time of lead in the mainly trabecular vertebral bone as compared to the mainly cortical fingerbone. Further, there was an association between vertebral and blood lead levels in the retired workers, which shows a considerable endogenous lead exposure from the skeletal pool.

Effects of 1.2 μM lead in the laboratory mouse: Developmental and behavioural consequences of chronic treatment

Lead acetate, as a 0.025% (1.2 μM) solution in the drinking fluid, did not adversely affect the reproductive success in breeding mice, weights of pups at birth or cause delays in development. At 21 days, the treated offspring showed reduced weights but these returned to normal values in adulthood. Offspring of treated mice were given 1.2 μM lead acetate as drinking fluid after weaning. The mean daily intake of lead amounted to 2.4 and 2.6 mg/100 g body wt in females and males respectively and caused significant increases in the concentrations of lead in bone and brain. Sequestration of bone was greater in females than males. The behaviour of the offspring was examined by ethological analysis of social encounters between pairs of unfamiliar mice of similar treatment groups in a neutral cage. Evidence of enhanced reactivity to the test situation was seen in treated males at age 3–4 weeks by increased social investigation during the first 3 min of the 20 min encounter, at 7–8 weeks by decreased immobility in the final 5 min of the test and at 18–19 weeks by an increased duration of exploratory behaviour. However, when encountering females at 30–31 weeks, the treated males showed more immobility than did the controls. Treated females at 3–4 weeks, in the first 3 min of the test, showed a decreased frequency of exploratory behaviour and increased immobility, but at 7–8 and 18–19 weeks they showed enhancement of social and sexual investigation. Behaviour was unaltered at 30–31 weeks in encounters with unfamiliar males. The major effect of lead at this small concentration appeared as changed reactivity to the test environment. Behavioural effects were sex-dependent and altered with increase in age.

Effects of lead in the laboratory mouse—2: Development and social behaviour after lifelong administration of a small dose of lead acetate in drinking fluid

Administration of 0.13% lead acetate solution as drinking fluid to breeding mice was without significant effect on the numbers of live or dead births or on weight of pups at 1 day. The appearance of fur was delayed and the body weights at 21 days and 31–38 weeks were smaller than in controls. On weaning, the treated offspring received 0.13% lead acetate as drinking fluid. Concentrations of lead in bone and brain were markedly raised above control levels at 18 and 34 weeks, being greatest at 34 weeks. There were no significant sex differences. The behaviour of the treated offspring in social encounters was shown by ethological procedures to differ from that of controls. The most consistent change after treatment with lead was enhancement of social and sexual investigation. This was seen in females at 26–27 weeks when encountering male partners, in isolated males at 32–33 weeks encountering male partners and in group-housed males and females in single sex encounters at 17–18 weeks. At 17–18 weeks, the duration of this behaviour was increased in treated females in the first 3 min and in treated males in the final 5 min of the 20 min period of observation. Behavioural changes in juvenile mice at 6–7 weeks occurred only during the final 5 of the 20 min observation. At 3–4 weeks only a marginal difference in behaviour was detectable, this being in the treated females. Overall the behavioural effects of lead differed between males and females and were different in juveniles from those seen in adulthood.

Environmental contaminants in surrogates, foods, and feathers of California condors (Gymnogyps californianus)

California condor (Gymnogyps californianus) foods and feathers, and turkey vultures (Cathartes aura), common ravens (Corvus corax), and their eggs were collected within the condor range to determine exposure of condors to environmental contaminants. Samples were analyzed for organochlorines and trace elements. Food items contained low concentrations of organochlorines and generally low concentrations of lead. DDE was detected in all vulture carcasses and nearly all raven carcasses at generally moderate concentrations. Other organochlorines occurred infrequently in carcasses and generally at low concentrations. Turkey vulture eggshells were 16% thinner than the pre-DDT mean; there was no change in shell thickness of raven eggs. Vulture eggs contained an average of 6.9 ppm DDE and two contained excessive concentrations of endrin. DDE concentrations were low in raven eggs. Residues of As, Cd, Cr, Cu, Fe, Hg, Ni, Se, Tl, and Zn in tissues of vultures and ravens appeared normal when compared with reference values for other species. Lead concentrations in bone of turkey vultures and feathers of condors appeared to be elevated above normal background concentrations in some cases. Current exposure of condors to organochlorines appears low; however, we are concerned about the excessive exposure of turkey vultures to organochlorines, possibly in Central America. Lead exposure to vultures and condors has occurred, but its significance to their populations is unknown.

In vivo bone lead measurements: a rapid monitoring method for cumulative lead exposure.

Lead concentrations (microgram/g wet weight) in human bone (tibia) were measured noninvasively in vivo employing an X-ray fluorescence technique. Forty-five workers who had been subjected to chronic industrial exposure were found to have a mean bone lead content of 52.9 micrograms/g wet weight (0 to 198 micrograms/g). In addition to bone lead content, blood lead, body burden of lead as assessed by urinary lead excretion after EDTA chelation, zinc protoporphyrin, and unstimulated urinary lead excretion were evaluated. The results suggest that the in vivo measurement of tibia lead content may serve as an acceptable indicator of body lead burden and provide a practical technique for lead screening purposes. The correlation coefficient between X-ray fluorescence findings and lead excretion following Ca-EDTA administration is 0.69; p less than 0.001.

Lead in bone III. Prediction of social correlates from skeletal lead content in four Colonial American populations (Catoctin Furnace, College Landing, Governor's Land, and Irene Mound).

Lead content was determined in the skeletal tissue of 82 individuals representing two black and two white Colonial American populations: Catoctin Furnace, College Landing, Governor's Land, and Irene Mound. Group and individual differences in bone lead concentrations were used to assess behavioral, social and occupational characteristics. Variations in skeletal lead content suggested that the white owners of the Catoctin iron furnace shared little of their food and beverage with their black, male, industrial slaves, but that some of these workers' women had access to the owners' food sources--probably via domestic duty assignments. A broad range of lead concentrations in bones of the free blacks at College Landing implies a wide range of economic success among these tradesmen. Bone lead content of the white populations at Governor's Land and Irene Mound helped confirm family relationships that had been assigned on an archaeological and osteological basis, and also suggested that the social and functional status of the white tenant farmers' white servants frequently differed little from that of black slaves. These findings suggest that, when applied in appropriate circumstances, lead studies of archaeological skeletal tissue may provide information supplemental to that derived from historical, archaeological, or other conventional sources.

Lead concentrations in bones from a Neolithic long barrow

Lead concentrations were determined in ribs obtained from the Neolithic long barrow at Hazelton and compared with those in a series of modern bones. The mean lead concentration in the neolithic material was about two-and-a-half times less than the contemporary mean indicating that human activity has considerably increased the human body burden of lead.

705—A simple, rapid and sensitive alternating current tast-polarographic method for lead determination in bones

A simple and reliable alternating current tast-polarographic method is described to determine lead concentration in bone. The bone samples are solubilized and oxidized with a HNO 3-HClO 4 mixture and after evaporating the acids the residue is dissolved in 20% citric acid used as a supporting electrolyte. The high inorganic salt concentrations from the bone matrix do not impede the polarographic measurement. Sensitivity: 2 p.p.m. lead in bone. Standard error: 6%. Reliability range: 2–1000 p.p.m.

Failure of Chelation Therapy in Lead Nephropathy

A patient with lead nephropathy and gout was treated with three months of edetic acid chelation. The therapy resulted in normalization of a previously abnormal result of edetic acid lead mobilization test. Nevertheless, progressive renal insufficiency occurred. At autopsy, an increased bone lead content was documented, suggesting that the edetic acid lead mobilization test may underestimate total body lead stores and that chelation therapy may not be effective in reversing advanced lead nephropathy. Alternatively, a longer period of therapy may be necessary to remove lead stores. More studies are needed to determine the relationship between the results of the edetic acid test and bone lead stores. Methods other than the edetic acid lead mobilization test should be considered to monitor the adequacy of treatment in lead nephropathy.

The influence of dietary citrate on the absorption and retention of orally ingested lead.

The influence of dietary citrate on the toxicity of orally ingested lead was investigated in male weanling mice. Twenty-four animals were divided into three equal groups. Group 1 served as controls, groups 2 and 3 were given 20 micrograms lead (as lead acetate) per g/diet, group 3 also received 4% sodium citrate in the diet. After 5 weeks, blood and tissue lead levels were measured. All mice given lead-supplemented diets had higher concentrations of lead in blood, liver, kidney, brain and bone than the control group, but the increase was significantly greater in the group given 4% sodium citrate in the diet. This work demonstrated that dietary citrate at levels which can be present in food significantly increases lead toxicity.

Chronic renal failure with gout: A marker of chronic lead poisoning

EDTA (calcium disodium edetate) lead mobilization and x-ray fluorescence (XRF) finger bone lead tests were done in 42 patients with chronic renal failure and without persisting lead intoxication. Nineteen of 23 patients with gout and 8 of 19 without gout had positive EDTA lead mobilization tests. Those patients with gout excreted significantly more excess lead chelate than those without gout. In the gout group 17 patients denied any childhood or industrial exposure to lead. They had a greater number of positive tests and excreted significantly more excess lead chelate than 14 patients with neither gout nor lead exposure. These results confirm that gout in the presence of chronic renal failure is a useful marker of chronic lead poisoning. Of 27 patients with positive lead mobilization tests, only 13 had elevated XRF finger bone lead concentrations (sensitivity 48%). Three of 15 patients with negative lead mobilization tests had elevated XRF finger bone lead concentrations (specificity 80%). Although the XRF finger bone lead test is a convenient noninvasive addition to the diagnostic evaluation of patients with chronic renal failure and gout, its application is limited due to the lack of sensitivity of the method.

Lead Toxicity and Metabolism from Lead Sulfate Fed to Holstein Calves

Sixteen Holstein intact male calves averaging 85kg and 74 days of age were assigned randomly to four dietary lead treatments according to body weight. They were fed for ad libitum consumption a control diet containing no added lead or the control diet supplemented with 500, 1500, or 4500ppm lead as lead sulfate. One calf fed 1500ppm lead and all four calves fed 4500ppm lead died within 6 to 10 days after initiation of treatments. Death was sudden with few or no clinical signs prior to death. Those clinical signs that did appear included muscular tremors, gnashing of teeth, bellowing, and convulsions. Four control, four 500ppm lead, and two 1500ppm lead-fed calves survived the 7-wk experimental period. Feed consumption, body weight changes, glutamic oxaloacetic transaminase and alkaline phosphatase activity in blood plasma, and hemoglobin were not affected significantly by lead treatments. Packed cell volume in calves fed 500 and 1500ppm added lead was reduced. Lead concentrations in blood, kidney, liver, bone, brain, and muscle were elevated in lead supplemented calves above those of controls. The highest concentrations of lead were in kidney and liver.