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5 METHODS FOR ASSESSING EXPOSURE TO LEAD
Pages 191-252

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From page 191...
... by the age of 6-12 months, shows up in prenatal or postnatal blood as lead concentrations that are common in the general population and that until recently were not consiclered detrimental to human health (Bellinger et al., 1987,1991a; Dietrich et al., 1987a; McMichae!
From page 192...
... Decreases in blood lead concentrations reportedly are associated with the decrease in atmospheric emissions of gasoline lead aerosols. The Correlation between the decreases in blood lead and gasoline lead emissions is consistent with other recent observations of decreases in environmental lead concentrations associated with decreases in atmospheric emissions of industrial lead (Trefry et al., 1985; Boyle et al., 1986; Shen and Boyle, 19881.
From page 193...
... dL) blood lead concentrations when amounts of contaminant lead introduced during sampling, storage, and analysis were kept constant (!
From page 194...
... 194 o ._ 0 o o o m 3 o ._ 0 o 0 up o o I I: o ns I: C)
From page 195...
... Measurements of bone lead and blood lead in pregnant women throughout the course of pregnancy and assessments of amniotic-fluid lead concentrations and placental lead concentrations at term collectively hold promise for further characterizing the dynamics of maternal-fetal lead transfer. Clinical research studies are examining epidemiologic issues related to the best measures of exposure and of the duration of exposure.
From page 196...
... The recent development of the ability to measure lead averaged over short periods (blood lead) , intermediate periods (trabecular bone)
From page 197...
... Isolation of the secondary dentin requires use of lead-free surfaces of cutting tools, lead-free work surfaces, and so forth. MI^SUQRM[MIT OF L"D 1~ SPI CIF'C T'SSUI S Whole Glooll The most commonly used technique to measure blood lead concentrations involves analysis of venous blood after chemical degradation (for example, wet ashing with nitric acid)
From page 198...
... After monochromatic separation and photomultiplier enhancement of the signal, lead concentration is measured electronically (Slavin, 1988~. Because it is much more sensitive than flame methods, the electrothermal or graphite-furnace technique permits use of small sample volumes, 5-20 ,uL.
From page 199...
... in whole blood is not a sensitive screening method for identifying lead-poisoned people at blood lead concentrations below 50 vigil, according to analyses of results of the NHANES II general population survey (Mahaftey and Annest, 19861. Data from Chicago's screening program for high-risk children recently analyzed by CDC and the Chicago Department of Health indicated further the current limitations of EP for screening.
From page 200...
... 200 on 1 00 00 on e.
From page 201...
... 20 o A Go 8 ~ _ o A J\1 ° ~ To C ID o ~ ~ ° 2 ~- ~ a ~ ~ E == ~ E by: - - _ C I; ~ o o~ ~ a.> it.
From page 202...
... population survey, in large part because of concurrent iron deficiency, the data confirm that unacceptably high numbers of children with increased blooci lead concentrations will be missed by EP screening, particularly at blood lead concentrations below 25 lug/. Unfortunately, there is no feasible substitute for this heretofore convenient, practical, and effective too]
From page 203...
... concentrations have been reported even with IDMS (Rabinowitz et al., 1976~; these results can be ascribed to problems in laboratory contamination. Collectively, therefore, it appears unlikely that measurement of lead in plasma can be applied widely to delineating lead exposure In sensitive populations.
From page 204...
... With AAS, both flame and nameless variations are often used. Lead concentrations are often high enough to permit dilution or chelation-extraction, thereby also minimizing calcium-phosphorus effects.
From page 205...
... Mass spectrometers can also be used to measure stable lead isotopic compositions; to identity different sources of contaminant lead, from cellular to global; and to investigate lead metabolism without exposing people to radioactivity or artificially increased lead concentrations. Mass spectrometers have a special niche in lead analyses, even though the measurements are relatively expensive, sophisticated, and time-consuming.
From page 206...
... This section adciresses both existing ant] projected applications of mass spectrometry in analysis of lead concentrations and isotopic compositions in biologic ant} environmental matrices.
From page 207...
... Blank measurements are especially appropriate for IDMS, because high concentrations of sensitivity and precision are required to measure the lead concentrations of "trace-metal-clean" reagents and containers accurately. That is illustrat ed in Table 5-4, a tabulation of lead blank measurements for blood lead analyses in a trace-metal-clean laboratory.
From page 208...
... The former, which is relatively unusual among the heavier elen~ents, requires separate isotopic analyses of unspiked samples. That necessitates additional analyses for lead concentration measurements, but it also provides unique applications of lead isotopic composition measurements that are addressed in the following section.
From page 210...
... Stable lead isotopic compositions differ among geologic formations with different ages, parent-daughter isotope ratios, and weathering processes. There is no measurable biologic, chemical, or physical fractionation of lead isotopes in the environment, and natural differences in lead isotopic compositions in geologic formations persist after the lead has been extracted and processed (Russell and Farquhar, 1960; Barnes et al., 19781.
From page 211...
... 1981 1.207 Rabinowitz, 1987 West Coast 1963 1.143 Shirahataetal., 1980 West Coast 1965 1.153 Chow and Johnstone, 1965 West Coast 1974 1.190 Patterson and Settle, 1987 West Coast 1978 1.922 Shirahata et al., 1980 Midwest 1989- 1.913 Slur, and Barge, 1987 1984 Mi~lwest 1986 1.221 Sturges and Barrie, 1987 895~0 confidence limit of 206Pb::07Pb measurements <0.005. capabilities of mass spectrometry, have given new impetus to the use of stable lead isotopes in this type of analysis.
From page 212...
... isotopic tracer studies. Conversely' gas-chromatography mass spectrometry (GC-MS)
From page 213...
... METHODS FOR ~S"Sl~G ~POSUQE TO Low TABLE 5-7 Lead-Metabolism Studies Using Radioisotopes An Radio isotope Study SubJect Reference Pao3 ~ A Bone cell lead-calcium interactions Rosen and Pounds, 1989 203Pb Gastrointestinal lead absorption Watson et al., 1986 2o3pb Lead retention Campbell et al., 1984 2o3pb Gastrointestinal lead absorption Blake and Mann, 1983 203Pb Gastrointestinal lead absorption Blake et al., 1983 203Pb Lead absorption Flanagan-et al., 1982 203Pb Gastrointestinal lead absorption Heard and Chamberlain, 1982 :03Pb Oral lead absorption Watson etal., 1980 203Pb Gastrointestinal lead absorption Blake, 1976 2'0Pb Osteoblastic lead toxicity Long et al., 1990 'Pub Gastrointestinal lead absorption Hursh and Suomela, 1968 en'luctivel, C':unl~! Plasma Mafia Sl,~`ctrome One of the major advances in analyses of both lead concentrations and isotopic compositions has been the recent development of inductively coupled plasma mass spectrometry (ICPMS)
From page 214...
... Additionally, numerous investigators are now addressing the need to compare ICPMS with other analytic techniques (Hieftje and Vickers, 1989) , including the first intercalibrated measurements of lead isotopic compositions in blood (Delves and Campbell, 1988; Campbell and Delves, 19891.
From page 215...
... , and Delves and Campbell (1988) measured lead isotopic compositions in other environmental matrices.
From page 216...
... The potential for SIMS analysis of lead in biologic and environmental samples remains in question. [~low-DiscI~arec MASS S',ectromet Advances in gIow-discharge mass spectrometry have indicated its potential for elemental analyses in solid matrices.
From page 217...
... . Laser techniques have several advantages for microprobe analyses of lead concentrations in biologic matrices, including its high detection efficiency (about lo-20 g)
From page 218...
... Their analyses indicate that the relative detection limit of lead in biologic material with a lateral resolution of ~ ,um with LAMMA (5 ,ug/g) is about 100 times better than that obtained with a Ca~neca IMS-3F ion microscope and that the useful yield of lead ions was about 100 times better with LAMMA (10-3)
From page 219...
... Originally, liquid samples containing the lead analyte were aspirated into the flame of an AA spectrometer. That approach was generally unsatisfactory for trace analysis because a large sample was required and the detection limit was too high.
From page 221...
... £2~ o ~o o ~ a ~z z ~ - ~ it hi~ ~ ~ a)
From page 222...
... Across various sample types, detection is readily achievable below the parts-per-billion level; in simple matrices, th detection limit is around 0.05~.5 ppb. High sensitivity permits matrix modification with diluents.
From page 223...
... In practice, both laboratory time and available sample sizes are limited, and this results in finite sensitivity. The ASV process collects all the metal of interest at the deposition step, which is the principal factor in ASV's high operational sensitivity flow detection limit)
From page 224...
... Second, the sensitivity is such Mat it is appropriate for the low average lead concentrations in media now being encountered. As in the case of AAS, detection limits are mediumspecific; in simple media, such as water, 10-100 pg can be measured.
From page 225...
... . Treatment of the cells with lead produced marked increases in intracellular free calcium; and concurrent measurements of intracellular free lead yielded a concentration of about 25 pM (Schanne et al., 1989~.
From page 226...
... ml CALClUM-D'SODBUM DOT Pl ovoc~no~ BEST The calcium-disodium EDTA (CaNa2EDTA) provocation test is a diagnostic and therapeutic test to ascertain which children with blood lead concentrations between 25 and 55 ~g/~L will respond to the chelating agent CaNa2EDTA with a brisk lead diuresis (Piomelli et al., 1984; CDC, 1985~.
From page 227...
... The residence time of lead in bone is long, and these methods could broaden the range of information available in biologic monitoring of lead exposure to reflect long-term body stores associated with chronic exposure and thereby complement plasma and whole-blood lead measurements, which respond principally to acute exposure. Bone lead measurements might or might not be related directly to adverse biologic effects of lead exposure.
From page 228...
... There are two strategies for minimizing the extent to which Compton-scattered photons limit the precision of XRF. One uses the angular dependence of Compton scattering and a choice of energy of incoming photons to minimize He interference of this scattering in the measurement of lead x rays (AhIgren et al., 1976; Somewaille et al., 1985~.
From page 229...
... This feature of elastic scattering can be used to standardize lead concentration to bone in practical measurements (Somervaille et al., 1985~. angles, and for high atomic numbers Dosimet~ Bone lead XRF measurements require irradiation with ionizing radiation, so the radiation dose and associated risk are important.
From page 230...
... 230 "EASU~G LEAD Exposure B~ SENSITIVE POPU[AIIO~S TABLE 5-9 Characteristics of L-Line and K-Line XRF Instrumentsa Characteristic L-Line K-Line Fluorescing source Energy of imparted x 20 keVb rays Low-energy generator: '09CdC incident photons are polarizedb 88 keVC Dosimetry, pSv Infants 2.5&C 1.16 f Children 1.Ob'8 0.46'f Teenagers 0.56c 0.26'f Adults 0.36c 0.04&'f Dosimetry during -0.003 % of natural -0.002 ~ of natural pregnancy background radiation background radiation during 9-mo preg- during 9-mo preg nancyg nancyf Minimal detection limit 4 ppmh with 3 mm of overlying skin Validation with whole Yes limbs 6 ppm' Yes Type of bone sampled Cortexh Cortex and trabecular Counting time 16.5 mint Counts corrected for No bone mineral content Replicate reproducibility +2 ppmi (95% confiin viva after reposi- dence limits) tioning of instrument 30 mince Yes Not yet published
From page 231...
... , ~ mln and increase sensitivity Express data as Pb:Sr ratios Use larger-volume hyperpure germaIiium detectors and faster electronics to increase count rate Modify geometry to narrow Comptom peak, reducing background ~AIthough dosimetnc assessments of KXRF and LXRF instruments followed ICRP 60 guidelines (ICRP, 1991) , these estimates were obtained through different protocols, conditions and assumptions.
From page 232...
... If one uses a factor of 2 and compares the attenuation of only the La X rays and He combined effect of attenuation of incoming 88-keV photons and Kin x rays, He half-value Sickness for ~ x rays is I.6 mm in soft tissue (muscle) and 0.35 mrn in bone, and He half-value thickness for K x rays is 19.0 mm in muscle and 9.0 mm in bone.
From page 233...
... investigated bone lead concentrations in a nonoccupationally exposed population of adults and children living near Munich, Germany. In infants, the geometric mean lead concentration was less than ~ Gig wet weight in temporal bone, femur, and pelvic bone.
From page 235...
... Some consideration might be given to the fact that soft tissue overlying tibia is more sensitively sampled than the bone itself; data on this subject are currently lacking. Some data show that bone lead concentration is relatively uniform along a tibia (Wittmers et al., 1988)
From page 236...
... , but He same researchers later developed an improved version in which a better detection limit was achieved with polarized x rays to reduce the extent of Compton scattering observed in the region of the lent1 x rave (VVielo _4, ~ ~ ~ , _, _ ~ polski et al., 1989)
From page 237...
... · Photon spectra from XRF instruments should be carefully measured, including entrance dose, imparted energy, and effective dose (ICRP, 1991~. · Minimal detection limits (MDEs)
From page 238...
... · The effective dose of x rays in sieverts should be calculated by combining absorbed~ose data with geometric measurements on subjects of various age groups while they are being measured for bone lead under standard instrument operating conditions. The calculations must be expressed according to the most current National Council on Radiation Protection and Measurements (NCRP)
From page 239...
... A blood lead concentration might be more useful when lead exposure can be reliably assumed to have been at a given concentration, as in occupationally exposed adults, than when intermittent exposure is occurring or has occurred, as in children exposed to leaded paint. With the recent development of compiementary K-line and L-line XRF techniques to measure bone lead stores noninvasively (Somervaille et al., 198S, 1986, 1988; Rosen et al., 1989, 1991; Wielopolski et al., 1989; Rosen and Markowitz, 1993)
From page 240...
... , are being coupled to several over outcome measures, including biochemical, electrophysiologic, and neurobehavioral characteristics. Bone lead concentrations were measured with EXRF in children whose homes had undergone lead abatement; some of them had undergone successful chelation therapy, as judged by conventional criteria (including return of blood lead and ery~rocyte protoporphyrin concentrations to acceptable concentrations)
From page 241...
... The in vivo precision of EXRF measurements was determined from duplicate measurements in 37 randomly selected children who had tibial bone lead concentrations of 8~7 Gag (mean, 16 + ~ SEM)
From page 242...
... The usefulness of the EXRF technique can probably be expanded by measuring the ratio of the L-line bone lead concentration to He K-line signal in the 10- to 16-keV interval of the XRF spectrum (Rosen et al., 1989~. Standard reference materials are now needed for external and internal instrument calibrations for both the L-line and K-line techniques.
From page 243...
... For the L-line XRF instrument, studies are in progress to calibrate the instrument with the use of surgically amputated limbs from children. · It is important to incorporate bone lead measurements in sensitive populations coupled to multiple outcome measures, and such outcome measures (biochemical, electrophysiologic, and neurobehavioral)
From page 244...
... Statistical evaluation of laboratory data is essential to detect systematic bias CTaylor, 19871. Whether a laboratory participates in a roundrobin proficiency testing program or uses regression analyses, tests of homogeneity, or other statistical methods, the acceptability of the laboratory results is based on stringently defined methods for assessing potential error.
From page 245...
... . As acceptable concentrations of lead in blood and other biologic media become lower, the availability of standard reference materials and their wider distribution to laboratories become increasingly important.
From page 246...
... Temporal considerations are also important in the measurement of lead and biologic indicators of lead toxicity, because these substances might circulate in biologic fluids with specific and different patterns of ultradian (between an hour and a day) and circadian rhythmicity (Rabinowitz and Needleman, 1982~.
From page 247...
... It should be noted that the erythrocyte protoporphyrin (EP) test is an insensitive assay at blood lead concentrations below 50 ~g/~L (Mahaffey and Annest, 1986~; widespread use of properly obtained fingerstick samples appears to be necessary in screening large populations.
From page 248...
... Both AAS and ASV are theoretically adequate for Me new, more rigid performance and proficiency demands being placed on laboratories in light of lower body lead burdens and exposure and toxicity guidelines, provided that attention to rigid protocols is scrupulous. It appears that blood lead measurements will continue to have an important place in the human toxicology of lead, primarily as an index of recent exposure.
From page 249...
... They include complementary methods: EXRF and KXRF. Developments in in vivo XRF analysis of human bone lead are occurring in parallel with increases in knowledge of two closely related subjects: the quantitative relation of lead exposure to bone lead concentrations and the quantitative relation of bone lead concentration, either total or compartmentspecific, to either the extent of resorption into the circulation or the health risks associated with such resorption.
From page 250...
... Lead concentrations of 2-10 Agog are the lowest that are quantifiable wig XRF me~ods. Those concentrations are higher than bone lead concentrations of many adults and most children, but not higher than those of occupationally exposed people or people with atypically increased environmental lead exposures.
From page 251...
... Major developments in inductively coupled plasma mass spectrometry have indicated that it will soon become common in hospitals and commercial laboratories, where it might be used for bow lead concentration and isotopic-composition analyses of biologic tissues and environmental materials. Comparable advances in other types of mass spectrometry indicate that they could also soon be used to measure lead in solid materials; they include gas~ischarge mass spectrometry, secondary-ion mass spectrometry, and laser-microprobe mass analysis.
From page 252...
... which had much better contamination control and laboratory technique Han most screening programs, showed a significant risk of misclassification of a child's blood lead concentration as being above 30 ~g/~L because of He analytic error (Annest et al., 19821. Reliable detection of blood lead concentrations of lO ~g/~L will require considerably more care and probably different methods from those now used.


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