Jimmy Börjesson

Effects of Lead on the Endocrine System in Lead Smelter Workers

Abstract In this study of the effects of lead on the endocrine system, 77 secondary lead-smelter workers (i.e., 62 active and 15 retired) were compared with 26 referents. Lead concentrations were determined in plasma with inductively coupled plasma mass spectrometry (i.e., index of recent exposure), in blood with atomic absorption spectrophotometry and in fingerbone with K x-ray fluorescence technique (i.e., index of long-term exposure). In addition, pituitary hormones were determined in serum by fluoroimmunoassay and thyroid hormones and testosterone in serum were determined with radioimmunoassay. Nine lead workers and 11 referents were challenged with gonadotrophin-releasing hormone and thyrotrophin-releasing hormone, followed by measurements of stimulated pituitary hormone levels in serum. Median levels of lead in plasma were 0.14 μg/dl (range = 0.04–3.7 μg/dl) in active lead workers, 0.08 μg/dl (range = 0.05–0.4 μg/dl) in retired lead workers and 0.03 μg/dl (range = 0.02–0.04 μg/dl) in referents (1 μg/dl = 48.3 nmol/l). Corresponding blood lead concentrations were 33.2 μg/dl (range = 8.3–93.2 μg/dl), 18.6 μg/dl (range = 10.4–49.7 μg/dl) and 4.1 μg/dl (range 0.8–6.2 μg/dl), respectively. Respective bone lead levels were 21 μg/gm (range = -13 to 99 μg/gm), 55 μg/gm (range = 3–88 μg/gm) and 2 μg/gm (range = -21 to 14 μg/gm). Concentrations of basal serum hormone (i.e., free thyroid hormones, thyrotrophin, sex hormone binding globulin and testosterone) were similar in the 3 groups. There were no significant associations between the hormones mentioned herein and blood plasma, blood lead and bone lead levels. In the challenge test, stimulated follicle-stimulating hormone levels were significantly lower in lead workers (p = .014) than in referents, indicating an effect of lead at the pituitary level. Also, there was a tendency toward lower basal stimulated follicle-stimulating hormone concentrations in lead workers (p = .08). This effect, however, was not associated with blood plasma level, blood lead level, or bone lead level. In conclusion, a moderate exposure to lead was associated with only minor changes in the male endocrine function, particularly affecting the hypothalamic-pituitary axis. Given that sperm parameters were not studied, the authors could not draw conclusions about fertility consequences.

In vivo analysis of cadmium in battery workers versus measurements of blood, urine, and workplace air.

OBJECTIVES: To measure in vivo the cadmium concentrations in kidney cortex (kidney-Cd) and in superficial liver tissue (liver-Cd) of nickel cadmium battery workers, and to compare the results with other commonly used estimates of cadmium exposure (current concentrations of cadmium in blood (B-Cd) and urine (U-Cd)) or repeated measurements of cadmium in workplace air (CumAir-Cd). METHODS: The study comprised 30 workers with a range of duration of exposure of 11-51 years. 13 subjects were currently employed, whereas the other 17 had a median period without occupational exposure of eight years before the measurements. The in vivo measurements were made with an x ray fluorescence technique permitting average detection limits of 30 and 3 micrograms cadmium per g tissue in kidney and liver, respectively. RESULTS: 19 of 30 (63%) people had kidney-Cd and 13 of 27 (48%) had liver-Cd above the detection limits. Kidney-Cd ranged from non-detectable to 350 micrograms/g and liver-Cd from non-detectable to 80 micrograms/g. The median kidney-Cd and liver-Cd were 55 micrograms/g and 3 micrograms/g, respectively. Kidney-Cd correlated significantly with B-Cd (r, 0.49) and U-Cd (r, 0.70), whereas liver-Cd correlated significantly with U-Cd (r, 0.58). Neither kidney-Cd nor liver-Cd correlated with the CumAir-Cd. The prevalence of beta 2-microglobulinurea increased with increased liver-Cd. CONCLUSIONS: Current U-Cd can be used to predict the kidney-Cd and liver-Cd measured in vivo. In vivo measurements of kidney-Cd and liver-Cd were not shown to correlate with the individual cadmium exposure estimates, obtained by integration of the cadmium concentration in workplace air. There may be several reasons for this, including uncertainties in the estimate of the individual cumulative exposures as well as in the in vivo measurements. There was a suggestion of a relation between liver-Cd and tubular proteinuria.

A neurobehavioural study of long-term occupational inorganic lead exposure

A group of 38 male workers at a secondary smelter (period of employment 2-35 years; median 10 years) was divided into two subgroups depending on bone-lead concentration, arranged as 19 matched pairs according to age, education and job level. The median concentrations for finger-bone lead (Bone-Pb) were 16 vs. 32 micrograms/g; for current blood-lead (B-Pb), 1.6 vs. 1.8 mumol/1; for retrospective peak blood-lead (Peak-Pb), 2.7 vs. 3.0 mumol/1; and for a retrospective cumulative blood lead index (CBLI), 143 vs. 233 mumol/l x months. Nineteen unexposed male workers from a nearby mechanical plant served as controls, using the same matching algorithm. The triplets were examined with a standardised neuropsychological test battery, and four questionnaires for self-rating of symptoms and activity/stress level related to work environment. No sign of behavioural deterioration was observed in the exposed groups, either in objective cognitive tests or in subjective symptom/mood self-rating scales. Despite the limited sample size, the statistical power was sufficient to conclude that a concealed lead-associated effect was unlikely. Covariations between behavioural measures and lead exposure indices were generally low and non-significant, as a whole not exceeding a random level. No confounding or effect-modifying factor was detected that could explain the results as a type II error. To conclude, a current B-Pb of 1.8 mumol/l was not associated with adverse behavioural effects, and a long-term lead exposure around 2.0 mumol/l for 13 years (mean values) was not associated with permanent brain dysfunction.

Lead in fingerbone : A tool for retrospective exposure assessment

Exposure to inorganic lead may cause many adverse health effects. When absorbed, lead is accumulated in large part in bone. In this study, we investigated the relationship between lead concentration in fingerbone, exposure time, and lead in blood. We also sought to design a model that made it possible to use fingerbone lead as an indicator of earlier exposure. The study comprised 137 active workers from a secondary lead smeltery. Workers had undergone regular determinations of blood lead (i.e., up to 6 times/y) for up to 24 y. In addition, during the period 1979-1992, workers underwent up to four fingerbone lead assessments via noninvasive x-ray fluorescence. We calculated cumulative blood lead, adjusted for time-related reduction of bone lead according to a transfer of lead from bone to blood, for each worker. We obtained the best fit of bone lead to cumulative adjusted blood lead when we assumed a 14-y half-time for the transfer coefficient. This half-time was similar to the terminal half-time for lead in bone in retired smelters, whom we studied earlier by longitudinal in vivo measurements. We described models for the accumulation of bone lead on blood lead and exposure time. The combined data on bone lead and exposure time may be used to estimate a mean blood lead during previous exposure. Such estimates will be valuable in epidemiological studies aimed at evaluating the toxic effects of long-term lead exposure in lead workers for whom data on previous blood lead levels are lacking.

In vivo XRF as a means to evaluate the risk of kidney effects in lead and cadmium exposed smelter workers.

The effect on kidney function was studied in 22 smelter workers with concomitant exposure to lead and cadmium. One active and five retired workers showed early signs of kidney dysfunction. They all had a long-term and high lead exposure, while their kidney cadmium concentrations measured in vivo by XRF techniques were low to moderate. Thus, the exposure to lead has been a greater risk, although an interaction between lead and cadmium could not be excluded.

Medical applications of X-ray fluorescence for trace element research

Techniques for estimation of element levels directly in humans (noninvasive in vivo) or in samples (in vitro) from humans are reviewed. Toxic, nonessential, trace elements may cause temporary or permanent damage to various organs and tissues in humans. There is thus a need to control the concentrations. Knowledge of the relations between toxic effects and element concentration may be extracted from measurements in humans as well as in samples from humans and her environment. Applications traditionally include occupationally exposed subjects, but an increasing research area is studies of members of the general population and of patients undergoing therapy for malignant and other diseases. Most in vivo XRF studies deal with lead in bone and cadmium in kidneys. For retired lead workers, a clear association has been demonstrated between bone lead and blood lead, due to endogenous lead excretion from the skeleton. A study of mercury in vivo showed that the technique is capable of detecting mercury in heavily exposed workers kidneys. In vivo XRF in cancer and rheumatology patients has helped to understand how platinum and gold are retained in the human body. The newest in vivo applications include zinc in prostate gland and arsenic in skin. (c) 2007 International Centre for Diffraction Data. (Less)

Kidney cadmium as compared to other markers of cadmium exposure in workers at a secondary metal smelter

BACKGROUND The aim of the study was to evaluate whether cadmium concentrations in kidney (K-Cd), blood (B-Cd) or urine (U-Cd) could reveal previous occupational cadmium exposure at a metal smelter. METHODS The study included 90 smelters and 35 controls (B-Cd and U-Cd determination). In a subgroup (N = 33), K-Cd was also determined. RESULTS B-Cd (median 4.6; range 0.5-53 nmol/L), U-Cd (0. 29; 0.04-1.9 micromol/mol creatinine) and K-Cd (14; 3-61 microg/g wet weight) were similar to reported concentrations in the general Swedish population. In the subgroup, significant associations (P<0. 001) were obtained between B-Cd and K-Cd (r = 0.70), U-Cd and K-Cd (r = 0.60) and between U-Cd and B-Cd (r = 0.62). Multiple regression analyses revealed smoking as the major predictor of K-Cd, B-Cd, and U-Cd. B-Cd and U-Cd were both associated with the duration of employment at the smelter. CONCLUSIONS There was no statistically significant evidence of previous occupational exposure at the smelter from measurement of K-Cd.

Lead accumulation in highly exposed smelter workers.

The skeleton is the main depot for lead following years of occupational exposure and may contain >90% of the body burden. Skeletal lead acts as an internal source of blood lead (B-Pb). The slow turnover rate of bone lead implies that its concentration in bone is a measure of long-term exposure. Discussions within the European Community (EC) presumably will lead to a new directive with a maximum permissible B-Pb limit of 50 μg/dL (2.4 μmol/L) or 60 μg/dL (2.9 μmol/L) instead of today’s limit of 70 μg/dL (3.4 μmol/L). For lead workers with a long duration of exposure, the endogenous exposure may significantly add to the B-Pb due to recent external exposure. Thus, to understand the consequences of a lower B-Pb limit, it is important to study the relationship between lead in bone and in blood and to relate these to occupational exposure. Information from a German smeltery showed high B-Pb levels and, in view of the proposed new B-Pb limit, the issue of a collaborative study to map the boneand blood-lead levels was raised.

Feasibility of a Fluorescent X‐ray Source for in Vivo X‐ray Fluorescence Measurements of Kidney and Liver Cadmium

A novel X-ray tube (“Fluorex”) mainly producing characteristic X-rays from a changeable internal secondary anode was developed at Philips Research Laboratory in Hamburg, Germany.1 The most significant feature of this tube compared to a conventional one is the emission of a few characteristic K X-ray lines in a narrow energy band (at present from a secondary tantalum [Ta] target emitting Kα,β energies of 56–67 keV) and a low fluence rate of bremsstrahlung. If the energy of the characteristic X-rays could be matched so as to lie just above the absorption edge of cadmium (Cd; 26.7 keV), or somewhat higher for deeper organs, then optimal conditions for detecting Cd in vivo could be reached. It is well known that Cd accumulates in the kidneys and liver, that its retention there is efficient, that the Cd concentration in our environment and food, as well as in the human body, has increased over the years, and that a significant fraction of the population already has kidney-Cd values at or above a critical level (50 μg/g). Smokers have significantly elevated Cd levels. Women of reproductive age may be another risk group, as they have an increased risk for iron deficiency and, therefore, might instead take up more Cd. Until now we used stationary hospital-based equipment, which was built around an X-ray tube that was previously used for radiotherapy.2 The equipment was shown to have the potential to detect and quantify Cd levels down to 3–4 μg/g for superficial organs (at 30–40 mm depth), and down to 30–40 μg/g for more deep-seated organs (70 mm). The aim of the present study was to investigate the feasibility of the Fluorex Xray tube for in vivo measurement of kidney and liver Cd, and to find out whether the presence of a spectrum with photons, most of which have energies above the K-absorption edge of Cd, implies any advantage compared to our current technique.