Malcolm C. Scott

In vivo measurement of lead in bone using X-ray fluorescence

The factors affecting the accuracy and minimum detectable concentration of in vivo tibia lead measurement are discussed, and it is demonstrated that the use of a 109Cd source in a backscatter geometry and using the 88 keV coherently scattered photon for normalisation optimizes both criteria. The measurement is shown to be independent of variations in source-sample distance, thickness of overlying tissue and tibia size and shape. Applying the same technique in vitro to samples of human tibia and metatarsals, it is shown that the results are not significantly different (p approximately equal to 0.9) from atomic absorption spectrometry results from another laboratory. The results of Monte Carlo dose distribution calculations are presented and compared with measurements using thermoluminescent dosemeters: the mean absorbed dose to a 20 cm leg section is less than 0.1 mGy (10 mrad) and the maximum absorbed skin dose is 0.45 mGy (45 mrad). For this dose the minimum detectable lead concentration is 10 micrograms g-1. Finally, the technique has been applied to groups of normals and occupationally exposed workers, and the means have been shown to be significantly different, namely 10 and 31 micrograms g-1 respectively. In the normal subjects tibia lead correlated strongly with age (r = 0.63, p less than 0.001).

In vivo tibia lead measurements as an index of cumulative exposure in occupationally exposed subjects.

In vivo tibia lead measurements of 20 non-occupationally exposed and 190 occupationally exposed people drawn from three factories were made using a non-invasive x ray fluorescence technique in which characteristic x rays from lead are excited by gamma rays from a cadmium-109 source. The maximum skin dose to a small region of the shin was 0.45 mSv. The relation between tibia lead and blood lead was weak in workers from one factory (r = 0.11, p greater than 0.6) and among the non-occupationally exposed subjects (r = 0.07, p greater than 0.7); however, a stronger relation was observed in the other two factories (r = 0.45, p less than 0.0001 and r = 0.53, p less than 0.0001). Correlation coefficients between tibia lead and duration of employment were consistently higher at all three factories respectively (r = 0.86, p less than 0.0001; r = 0.61, p less than 0.0001; r = 0.80, p less than 0.0001). A strong relation was observed between tibia lead and a simple, time integrated, blood lead index among workers from the two factories from which blood lead histories were available. The regression equation from two groups of workers (n = 88, 79) did not significantly differ despite different exposure conditions. The correlation coefficient for the combined data set (n = 167) was 0.84 (p less than 0.0001). This shows clearly that tibia lead, measured in vivo by x-ray fluorescence, provides a good indicator of long term exposure to lead as assessed by a cumulative blood lead index.

In vivo measurements of lead in bone in long-term exposed lead smelter workers.

In-vivo measurements of lead concentrations in calcaneus (mainly trabecular bone) and tibia (mainly cortical bone) were performed by x-ray fluorescence (XRF) in 70 active and 30 retired lead smelter workers who had long-term exposure to lead. Comparison was made with 31 active and 10 retired truck assembly workers who had no known occupational exposure to lead. After physical examination, all participants provided blood and urine samples and answered a computerized questionnaire. Since 1950, blood lead has been determined repeatedly in lead workers at the smelter, which made it possible to calculate a time-integrated blood lead index for each worker. Lead concentrations in blood, urine, calcaneus, and tibia in active and retired lead workers were significantly higher than in the corresponding control groups (p < .001). The highest bone lead concentrations were found among retired lead workers (p < .001), which was the result of considerably higher lead exposure during 1940 to 1960. Lead concentrations in calcaneus in active lead workers were significantly higher than in tibia when expressed in ug of lead per gram of bone mineral, which suggests a quicker absorption over time in this mainly trabecular bone. The estimated biological half-times were 16 y in calcaneus (95% confidence interval [95% CI] = 11-29 y) and 27 y in tibia (95% CI = 16-98 y). A strong positive correlation was found between lead concentrations in calcaneus and tibia for all lead workers (r = 0.54; p < .001). A strong positive correlation was also found between the bone lead concentrations and the cumulative blood lead index. Blood lead, at the time of study, correlated well with bone lead concentrations in retired--but not in active--workers, reflecting the importance of the endogenous (skeletal) lead exposure. The findings in this study indicate that bone lead measurements by XRF can give a good index of long-term lead exposure. Tibia measurements offer a higher precision than calcaneus measurements. The method is of particular interest in epidemiologic studies of adverse health effects caused by long-term lead exposure.

Kidney effects in long term exposed lead smelter workers.

Occupational exposure to lead may cause kidney damage. This study was carried out on a cohort of 70 active and 30 retired long term exposed lead smelter workers. Their kidney function was compared with 31 active and 10 retired truck assembly workers who had no occupational exposure to lead. The lead workers had been regularly followed up with measurements of lead concentration in blood since 1950. Previous exposure to lead was calculated as a time integrated blood lead index for each worker. Blood and urine samples were obtained from all subjects. The concentration of lead in blood (B-Pb) and urine (U-Pb) was analysed. The urinary concentrations of several sensitive indicators of early tubular (U-beta 2-microglobulin (U-beta 2-m); U-N-acetyl-beta-glucosaminidase (U-NAG)) and glomerular kidney damage (U-albumin) were determined. The B-Pb and U-Pb values were significantly higher among active and retired lead workers compared with their corresponding control groups. The highest concentrations were found among the active lead workers. The concentrations of the parameters of kidney function investigated were of the same magnitude for exposed workers and controls. No clinical signs of renal impairment were found among the workers. No correlations of clinical importance existed between concentrations of U-albumin, U-beta 2-m, and U-NAG activity on the one hand and the concentrations of B-Pb, cumulative blood lead index, U-Pb, and lead concentrations in the calcaneus and tibia on the other, among lead workers and controls. Despite many years of moderate to heavy exposure to lead, particularly for the retired lead workers, no signs of adverse effects on the kidney such as early tubular or glomerular malfunction were found. Reversible changes in kidney function during the 1950s and 1960s could not be excluded, however, due to a greater exposure to lead during that time.

In vivo measurements of bone lead-a comparison of two X-ray fluorescence techniques used at three different bone sites

In vivo bone lead measurements have been made on a group of about 120 people, most of whom were lead exposed workers. Two different x-ray fluorescence (XRF) techniques were used to make measurements at three bone sites. Finger lead was measured using 57Co sources, and lead measurements were made in both tibia and calcaneus with a technique based on 109Cd sources. The results of the bone lead measurements correlated strongly with each other and with the index of cumulative exposure, thus confirming the value and reliability of these in vivo measurements as a tool in the study of chronic lead exposure. Measurement precision, +/- 1 standard deviation, was highest for tibia +/- 7.4 micrograms (g bone mineral)-1, +/- 16.6 micrograms (g bone mineral)-1 for the calcaneus and lowest for phalangeal lead +/- 25.0 micrograms (g bone mineral)-1. Maximum absorbed doses to the skin were comparable for all three measurements (1-3 mGy). The mean whole body dose equivalents were all low, but that for the finger measurement, 0.1 microSv, was significantly less than for the calcaneus and tibia measurements 3-5 microSv.

Relations between liver cadmium, cumulative exposure, and renal function in cadmium alloy workers

Detailed biochemical investigations of renal function were made on 75 male workers exposed to cadmium and an equal number of referents matched for age, sex, and employment status. The exposed group consisted of current and retired workers who had been employed in the manufacture of copper-cadmium alloy at a single factory in the United Kingdom for periods of up to 39 years and for whom cumulative cadmium exposure indices could be calculated. In vivo measurements of liver and kidney cadmium burden were made on exposed and referent workers using a transportable neutron activation analysis facility. Significant increases in the urinary excretion of albumin, retinol binding protein, beta 2 microglobulin, N-acetylglucosaminidase (NAG), alkaline phosphatase, gamma-glutamyl transferase and significant decreases in the renal reabsorption of calcium, urate, and phosphate were found in the exposed group compared with the referent group. Measures of glomerular filtration rate (GFR) (creatinine clearance, serum creatinine, and beta 2 microglobulin) indicated a reduction in GFR in the exposed population. Many of these tubular and glomerular function indicators were significantly correlated with both cumulative exposure index and liver cadmium burden. Using cumulative exposure index and liver cadmium as estimates of dose, a two phase linear regression model was applied to identify an inflection point signifying a threshold level above which changes in renal function occur. Many biochemical variables fitted this model; urinary total protein, retinol binding protein, albumin, and beta 2 microglobulin gave similar inflection points at cumulative exposure levels of about 1100 y.micrograms/m3 whereas changes in the tubular reabsorption of urate and phosphate occurred at higher cumulative exposure indices. Measures of GFR, although fitting the threshold model did not give well defined inflection points. Fewer variables fitted the two phase model using liver cadmium; those that did gave threshold levels in the range 20.3-55.1 ppm. When cadmium workers with cumulative exposure indices of less than 1100 y.micrograms/m3 were compared with their respective referents only serum beta 2 microglobulin and urinary NAG were significantly increased in the exposed group and these differences were not related to the degree of cadmium exposure.(ABSTRACT TRUNCATED AT 400 WORDS)

Comparison of two in vitro methods of bone lead analysis and the implications for in vivo measurements

Atomic absorption spectrometry and x-ray fluorescence have been used to determine the lead content of metatarsal and tibia bone samples. For a range of bone lead levels from 6.5 to 83 micrograms g-1 of ashed bone there is no evidence of a systematic difference between the two techniques of more than 1 microgram g-1. There is, however, some evidence that random differences between the two in vitro analyses applied to the same bone sample are larger than can be accounted for by known measurement uncertainties. Variations in bone composition could account for these differences. Because the x-ray fluorescence technique is applied in an identical way to in vivo analysis, it is concluded that the uncertainties in in vivo measurements are small.

Repeated measurements of tibia lead concentrations by in vivo x ray fluorescence in occupational exposure.

A group of workers occupationally exposed to lead have had measurements of their tibia lead concentrations made on two occasions separated by five years; on the second occasion calcaneus lead concentrations were also measured. The results serve to confirm the reliability of the measurement technique and to illustrate the improved precision achieved through technical improvements. More importantly, the relation between tibia lead concentration and cumulative blood lead found in this longitudinal study was entirely consistent with that previously reported, which had been based on cross sectional studies. Furthermore, the relation between lead concentrations in the tibia and in calcaneus found here was similar to that previously found in a larger cross sectional survey. It is concluded that this technique of measuring bone lead concentrations non-invasively is likely to be used increasingly as a biological monitor of cumulative exposure to lead.

The factors affecting in vivo x-ray fluorescence measurements of lead in bone

Abstract The factors affecting the sensitivity of X-ray fluorescence determination of lead in bone phantoms using 57 Co are investigated with the object of applying the technique to in vivo measurements in tibia. An analysis of the components of the measured pulse height spectrum in a hyperpure Ge detector is presented and the implications for the optimisation of the source-detector configuration discussed. Finally, some preliminary investigations using a 109 Cd source are outlined.

The application of pulse shape discrimination in NE 213 to neutron spectrometry

Abstract The use of a zero-crossing pulse shape discrimination technique to distinguish protons from alpha particles in NE 213 is described, and a theoretical analysis is performed to predict the zero crossing characteristics. It is shown that, irrespective of the particular method of pulse shape discrimination employed, the pulse shape at low energies no longer uniquely determines the particle type for electrons, protons, alpha particles or 12C nuclei, and the general limitations of pulse shape discrimination in NE 213 are deduced. The use of an alpha discrimination technique is then described, enabling neutron spectra to be unfolded from the measured detector response using a differentiak code.