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A C Todd

Publications and source records attributed to A C Todd.

At least 37 records · Page 2Linked to original sources
PubMed2001

Associations of lead biomarkers and delta-aminolevulinic acid dehydratase and vitamin D receptor genotypes with hematopoietic outcomes in Korean lead workers.

OBJECTIVES: This study compares and contrasts associations of dimercaptosuccinic acid (DMSA)-chelatable lead, tibia lead, and blood lead with five hematopoietic outcomes and evaluates the effect modification of these relations by polymorphisms in the delta-aminolevulinic acid dehydratase (ALAD) and vitamin D receptor (VDR) genes. METHODS: A cross-sectional study of 798 lead workers and 135 unexposed referents was performed. RESULTS: The DMSA-chelatable lead, tibia lead, and blood lead levels ranged in the lead (Pb) workers from 4.8 to 2103 g, -7 to 338 g Pb/g bone mineral, and 4 to 86 g/dl, respectively. The mean of the hemoglobin, hematocrit, zinc protoporphyrin (ZPP), and urinary (ALAU) and plasma (ALAP) delta-aminolevulinic acid levels of the lead workers were 14.2 (SD 1.4) g/dl, 42.4 (SD 4.4)%, 80.2 (SD 63.5) g/dl, 2.1 (SD 3.7) mg/l, and 17.7 (20.6) g/ml, respectively. After adjustment for the covariates, tibia lead was associated with all five hematopoietic outcomes, while blood lead and DMSA-chelatable lead were associated only with ZPP, ALAP, and ALAU. A comparison of the regression coefficients, total model adjusted R2 values, and delta R2 values revealed that blood lead was the best predictor of ZPP, ALAP, and ALAU. Only tibia lead was significantly associated with hemoglobin and hematocrit levels, but the additional variance explained by tibia lead was (<1%). No clear effect modification of the relations between the lead biomarkers and hematopoietic outcomes studied was caused by ALAD or VDR genotype. CONCLUSIONS: Lead must have a chronic, cumulative effect on hemoglobin and hematocrit levels, and any speculated mechanism cannot merely involve short-term plasma or target organ lead levels.

Adolescent↗
PubMed2000

Past adult lead exposure is associated with longitudinal decline in cognitive function.

OBJECTIVE: To determine whether adults with past exposure to neurotoxicants have progressive declines in cognitive function years after exposure has ceased, and whether tibia lead is a predictor of the magnitude of change. METHODS: A total of 535 former organolead manufacturing workers with a mean age of 55.6 years, a mean duration of 16 years since last occupational lead exposure, and low blood lead levels at the first study visit and 118 controls were evaluated with neurobehavioral tests two to four times over 4 years. "Peak" tibia lead levels, estimated from current levels measured by X-ray fluorescence, were used to predict changes in cognitive function over time. RESULTS: In former lead workers, peak tibia lead ranged from -2.2 to 98.7 microg Pb/g bone mineral. Compared to controls, former lead workers performed worse over time for three tests of visuo-constructive ability and verbal memory and learning (p < 0.05). In former lead workers, peak tibia lead predicted declines for six tests of verbal memory and learning, visual memory, executive ability, and manual dexterity (p < 0.05 for four tests and < 0.10 for two additional tests). On average, for these six tests, an increase of 15.7 microg/g of peak tibia lead was equivalent in its effects on annual test decline to 5 more years of age at baseline. CONCLUSIONS: These are the first data to suggest that cognitive function can progressively decline due to past occupational exposures to a neurotoxicant.

Adult↗
PubMed2000

Maternal bone lead contribution to blood lead during and after pregnancy.

We examined bone lead contribution to blood lead in a group of 311 immigrant women, 99% from Latin America, during the third trimester of pregnancy and 1 to 2 months after delivery. We measured in vivo tibia and calcaneus (heel) bone lead concentration in the postdelivery period with K shell X-ray fluorescence. Prenatal and postnatal geometric mean (range) blood lead level was 2.2 microg/dL (0.4 to 38.7) and 2.8 microg/dL (0.4 to 25.4), reflecting low current exposure. Postnatal blood lead level was significantly higher than prenatal (P<0.0001). Mean (range) tibia and calcaneus lead concentration was 6.7 microg/g (-33.7 to 62.2) and 8.4 microg/g (- 30.1 to 66.4), reflecting varying but elevated past lead exposure. Mean calcaneus lead concentration was significantly higher than mean tibia lead concentration (P = 0.055). Variance-weighted multiple regression and structural equation models showed that both calcaneus and tibia lead were directly associated with prenatal blood lead but only calcaneus lead was associated with postnatal blood lead. Increasing natural log years in the United States independently predicted decreasing calcaneus and third-trimester blood lead. The data suggest that while some exogenous lead sources and modulators of blood lead level, such as use of lead-glazed pottery and calcium in the diet, control lead exposure during and after pregnancy, endogenous lead sources from past exposure before immigration continue to influence blood lead levels in this sample.

Adolescent↗
PubMed2000

Repeatability of tibia lead measurement by X-Ray fluorescence in a battery-making workforce.

The purpose of this study was to remeasure in vivo tibia lead levels in a lead-acid battery manufacturing workforce measured in a previous survey and believed to be unrealistically high. Tibia lead levels were measured by K-shell X-ray fluorescence (XRF) spectroscopy in a stratified random sample (n=40) of the original study group (n=381). The repeat survey showed much lower tibia lead levels (median=54.3 microg lead/g bone mineral, compared to 217.9 microg lead/g bone mineral, n=40). Tibia lead levels were significantly correlated with duration of occupational exposure, zinc protoporphyrin levels, and cumulative blood lead index, but not with current blood lead levels. Thirty-eight of the 40 subjects underwent two consecutive tibia lead measurements to assess the test-retest repeatability of the XRF tibia lead measurement technique. The intraclass correlation coefficient between repeated measurements was 0.926 (P=0.0001). Three measurement pairs differed by more than 20 microg/g. There was no fixed or proportional bias between the two sets of measurements. We conclude that the technique offers a highly repeatable measurement of tibia bone lead. However, care needs to be taken to avoid contamination when performing measurements on active lead workers.

Adult↗
PubMed2000

Contamination of in vivo bone-lead measurements.

This paper addresses one aspect of the calibration of a 109Cd based K-shell x-ray fluorescence measurement system, namely the treatment of the calibration line intercept. Under circumstances of contamination, the intercept may warrant statistical treatment different from that currently performed. This paper proposes refinements to the existing method of subtracting the phantom calibration line intercept from in vivo responses in the calculation of in vivo concentrations. These refinements are recommended because the existing method can underestimate in vivo concentrations by a small amount under normal operating conditions. Contamination of the calibration standard matrix of plaster of Paris by both lead and non-lead contaminants is addressed.

Bone and Bones↗
PubMed2000

Variability in XRF-measured tibia lead levels.

A few studies have examined the variability in 109Cd-based K-shell x-ray fluorescence (KXRF) bone lead measurements from replicate measurements made either at the same time or over a period of time, and one of these studies has shown that the uncertainty in an individual measurement is an underestimate of the standard deviation of replicate measurements. Variability in KXRF tibia lead measurements was assessed from ten cadaver intact legs, from the bare tibiae dissected from nine of these legs, and from four in vivo volunteers. Cadaver legs underwent replicate measurements on multiple occasions. In vivo volunteers underwent single measurements of the left tibia monthly for one year. Average tibia lead levels in the cadaver legs and in vivo volunteers ranged from 6 to 50 and from 6 to 13 microg Pb per g of bone mineral respectively. The factors influencing the standard deviation of replicate measurements were investigated. Both cadaver and in vivo measurements confirmed that the uncertainty in an individual measurement is an underestimate of the standard deviation of replicate measurements, suggesting a methodological deficiency probably shared by most current 109Cd-based K-shell XRF lead measurement systems.

Adult↗
PubMed2000

Coherent scattering and matrix correction in bone-lead measurements.

The technique of K shell x-ray fluorescence of lead in bone has been used in many studies of the health effects of lead. This paper addresses one aspect of the technique, namely the coherent conversion factor (CCF) which converts between the matrix of the calibration standards and those of human bone. The CCF is conventionally considered a constant but is a function of scattering angle. energy and the elemental composition of the matrices. The aims of this study were to quantify the effect on the CCF of several assumptions which may not have been tested adequately and to compare the CCFs for plaster of Paris (the present matrix of calibration standards) and a synthetic apatite matrix. The CCF was calculated, using relativistic form factors, for published compositions of bone, both assumed and assessed compositions of plaster, and the synthetic apatite. The main findings of the study were, first, that impurities in plaster, lead in the plaster or bone matrices, coherent scatter from non-bone tissues and the individual subject's measurement geometry are all minor or negligible effects; and, second, that the synthetic apatite matrix is more representative of bone mineral than is plaster of Paris.

Adult↗
PubMed2000

Associations of tibial lead levels with BsmI polymorphisms in the vitamin D receptor in former organolead manufacturing workers.

We evaluated associations of tibial lead levels with polymorphisms in the vitamin D receptor (VDR) in 504 former organolead manufacturing workers with past exposure to lead. In this cross-sectional study, we measured tibial lead by (109)Cd K-shell X-ray fluorescence. Tibial lead was evaluated in subjects with different VDR genotypes defined using the BsmI restriction enzyme, adjusting for confounding variables. Study participants had a mean age +/- SD of 57.4 +/- 7.6 years. A total of 169 (33.5%) subjects were homozygous for the BsmI restriction site (designated bb), 251 (49.8%) were heterozygous (Bb), and 84 (16.7%) were homozygous for the absence of the restriction site (BB). Among all of the study subjects, tibial lead concentrations were low, with a mean +/- SD of 14.4 +/- 9.3 microg Pb/g bone mineral. There were only small differences in tibial lead concentrations by VDR genotype, with mean +/- SD tibial lead concentrations of 13.9 +/- 7.9, 14.3 +/- 9.5, and 15.5 +/- 11.1 in subjects with bb, Bb, and BB, respectively. In a multiple linear regression model of tibial lead concentrations, the VDR genotype modified the relation between age and tibial lead concentrations; subjects with the B allele had larger increases in tibial lead concentrations with increasing age (0.37, 0.48, and 0.67 microg/g per year of age in subjects with bb, Bb, and BB, respectively; the adjusted p-value for trend in slopes = 0.04). The VDR genotype also modified the relation between years since last exposure to lead and tibial lead concentrations. Subjects with bb evidenced an average decline in tibial lead concentrations of 0.10 microg/g per year since their last exposure to lead, whereas subjects with Bb and BB evidenced average increases of 0.03 and 0.11 microg/g per year, respectively (the adjusted p-value for trend in slopes = 0.01). Polymorphisms in the vitamin D receptor modified the relations of age and years since the last exposure to lead with tibial lead concentrations. Although controversy remains on the influence of the VDR genotype on bone mineral density, the data suggest that variant VDR alleles modify lead concentrations in bone, either by influencing lead content or calcium content or both.

Adult↗
PubMed2000

Calculating bone-lead measurement variance.

The technique of (109)Cd-based X-ray fluorescence (XRF) measurements of lead in bone is well established. A paper by some XRF researchers [Gordon CL, et al. The Reproducibility of (109)Cd-based X-ray Fluorescence Measurements of Bone Lead. Environ Health Perspect 102:690-694 (1994)] presented the currently practiced method for calculating the variance of an in vivo measurement once a calibration line has been established. This paper corrects typographical errors in the method published by those authors; presents a crude estimate of the measurement error that can be acquired without computational peak fitting programs; and draws attention to the measurement error attributable to covariance, an important feature in the construct of the currently accepted method that is flawed under certain circumstances.

Analysis of Variance↗
PubMed2000

Associations of blood lead, dimercaptosuccinic acid-chelatable lead, and tibia lead with polymorphisms in the vitamin D receptor and [delta]-aminolevulinic acid dehydratase genes.

A cross-sectional study was performed to evaluate the influence of polymorphisms in the [delta]-aminolevulinic acid dehydratase (ALAD) and vitamin D receptor (VDR) genes on blood lead, tibia lead, and dimercaptosuccinic acid (DMSA)-chelatable lead levels in 798 lead workers and 135 controls without occupational lead exposure in the Republic of Korea. Tibia lead was assessed with a 30-min measurement by (109)Cd-induced K-shell X-ray fluorescence, and DMSA-chelatable lead was estimated as 4-hr urinary lead excretion after oral administration of 10 mg/kg DMSA. The primary goals of the analysis were to examine blood lead, tibia lead, and DMSA-chelatable lead levels by ALAD and VDR genotypes, controlling for covariates; and to evaluate whether ALAD and VDR genotype modified relations among the different lead biomarkers. There was a wide range of blood lead (4-86 microg/dL), tibia lead (-7-338 microg Pb/g bone mineral), and DMSA-chelatable lead (4.8-2,103 microg) levels among lead workers. Among lead workers, 9.9% (n = 79) were heterozygous for the ALAD(2) allele and there were no homozygotes. For VDR, 10.7% (n = 85) had the Bb genotype, and 0.5% (n = 4) had the BB genotype. Although the ALAD and VDR genes are located on different chromosomes, lead workers homozygous for the ALAD(1) allele were much less likely to have the VDR bb genotype (crude odds ratio = 0.29, 95% exact confidence interval = 0.06-0.91). In adjusted analyses, subjects with the ALAD(2) allele had higher blood lead levels (on average, 2.9 microg/dL, p = 0.07) but no difference in tibia lead levels compared with subjects without the allele. In adjusted analyses, lead workers with the VDR B allele had significantly (p < 0.05) higher blood lead levels (on average, 4.2 microg/dL), chelatable lead levels (on average, 37.3 microg), and tibia lead levels (on average, 6.4 microg/g) than did workers with the VDR bb genotype. The current data confirm past observations that the ALAD gene modifies the toxicokinetics of lead and also provides new evidence that the VDR gene does so as well.

Adolescent↗
PubMed1999

Neurobehavioral function and tibial and chelatable lead levels in 543 former organolead workers.

OBJECTIVE: To evaluate the associations between tibial lead, dimercaptosuccinic acid (DMSA)-chelatable lead, and neurobehavioral function in former organolead manufacturing workers with past exposure to organic and inorganic lead. METHODS: Data were collected from 543 subjects with a mean age of 58 years and an average of 17.8 years since last lead exposure. Years since last exposure to lead was used to estimate tibial lead levels in the year of last occupational lead exposure, termed "peak tibial lead." Current tibial lead levels, measured by x-ray fluorescence, were extrapolated back using a clearance half-time of lead in tibia of 27 years, assuming first-order clearance from tibia. RESULTS: Peak tibial lead levels ranged from -2.2 to 105.9 microg Pb/g bone mineral, and DMSA-chelatable lead levels were between 1.2 and 136 microg. After adjustment for confounding variables, peak tibial lead was a significant negative predictor of performance on the Wechsler Adult Intelligence Scale-Revised vocabulary subtest (p = 0.02), serial digit learning test (p = 0.04), Rey Auditory-Verbal Learning Test (immediate recall and recognition, p = 0.03 for each), Trail Making Test B (p = 0.03), finger tapping (dominant hand [p = 0.02] and nondominant hand [p < 0.01]), Purdue pegboard (dominant hand, nondominant hand, both hands, and assembly, p < 0.01 for each), and Stroop Test (p < 0.01). Moreover, with one exception, average neurobehavioral test scores were poorer at higher peak tibial lead levels. DMSA-chelatable lead was only significantly associated with choice reaction time (p = 0.01). CONCLUSION: Peak tibial lead was consistently associated with poorer neurobehavioral test scores, particularly in the domains of manual dexterity, executive ability, verbal intelligence, and verbal memory.

Adult↗
PubMed1999

Predictors of dimercaptosuccinic acid chelatable lead and tibial lead in former organolead manufacturing workers.

OBJECTIVES: To identify predictors of tibial and dimercaptosuccinic acid (DMSA) chelatable lead in 543 organolead manufacturing workers with past exposure to organic and inorganic lead. METHODS: In this cross sectional study, tibial lead (by 109Cd K-shell x ray fluorescence), DMSA chelatable lead (4 hour urinary lead excretion after oral administration of 10 mg/kg), and several exposure measures were obtained on study participants, mean (SD) age 57.6 (7.6) years. RESULTS: Tibial lead concentrations ranged from -1.6 to 52.0 micrograms lead/g bone mineral, with a mean (SD) of 14.4 (9.3) micrograms/g. DMSA chelatable lead ranged from 1.2 to 136 micrograms, with a mean (SD) of 19.3 (17.2) micrograms. In a multiple linear regression model of tibial lead, age (p < 0.01), duration of exposure (p < 0.01), current (p < 0.01) and past (p = 0.05) cigarette smoking, and diabetes (p = 0.01) were all independent positive predictors, whereas height (p = 0.03), and exercise inducing sweating (p = 0.04) were both negative predictors. The final regression model accounted for 31% of the variance in tibial lead concentrations; 27% was explained by age and duration of exposure alone. DMSA chelatable lead was directly associated with tibial lead (p = 0.01), cumulative exposure to inorganic lead (y.microgram/m3, p = 0.01), current smoking (p < 0.01), and weight (p < 0.01), and negatively associated with diabetes (p = 0.02). The final model accounted for 11% of the variance in chelatable lead. When blood lead was added to this model of DMSA chelatable lead, tibial lead, cumulative exposure to inorganic lead, and diabetes were no longer significant; blood lead accounted for the largest proportion of variance (p < 0.001); and the total model r2 increased to 19%. CONCLUSIONS: The low proportions of variance explained in models of both tibial and chelatable lead suggest that other factors are involved in the deposition of lead in bone and soft tissue. In epidemiological studies of the health effects of lead, evaluation of associations with both these measures may allow inferences to be made about whether health effects are likely to be recent, and thus potentially reversible, or chronic, and thus possibly irreversible. The data also provide direct evidence that in men the total amount of lead in the body that is bioavailable declines with age.

Adult↗
PubMed1999

Lead exposure among young urban women.

OBJECTIVE: Blood lead levels have declined among every age group in the United States, but urban minority residents remain at disproportionate risk for elevated lead levels. Our objective was to measure lead burden in young women of childbearing age in New York City. We also describe successful means of recruiting this population into a cohort study. MATERIAL AND METHODS: Healthy women aged 18-25 attending a New York City health care center in 1995-1998 were eligible for participation. Participants were recruited by health care providers, the study coordinator and the participants themselves. Venous blood samples were obtained for whole blood lead, ferritin and hematocrit measurements, and detailed questionnaires were administered. RESULTS: 239 women have been recruited to date. The population is predominately minority: 62% African-American, 33% Hispanic and 5% Caucasian/Asian. The average age of participants is 19.3 years. Recruitment of participants into the study is predominantly (55%) through "word of mouth" from previously enrolled participants. Few participants learned of the study through their health care providers. The mean blood lead level among study participants is 2.1 +/- 1.7 micrograms/dl, which is consistent with the most recent United States national survey. CONCLUSIONS: Blood lead levels are low in young, urban minority women of childbearing age in New York City. In this population, recruitment efforts were substantially enhanced with the help of enrolled participants and the health care community.

Adolescent↗
PubMed1999

Methodological issues related to studies of lead mobilization during menopause.

While there has been a substantial decline in lead exposure in the United States during the past two decades, mobilization of existing lead stored in bone potentially represents an important endogenous source of exposure for menopausal women. It has been hypothesized that lead may be mobilized from skeletal stores during conditions of high bone turnover, such as during menopause. However, such mobilization has not been documented in prospective studies. This discussion is focussed on some of the methodological difficulties to be anticipated in longitudinal studies of lead mobilization specific to menopause and the issues that need to be taken into account when evaluating the results of such studies. To evaluate whether lead mobilization occurs during menopause, a prospective repeated measures design is needed using X-ray fluorescence analysis of lead in bone and serial measurements of blood lead. Potential confounders and effect modifiers also need to be taken into account in the statistical analysis.

Environmental Exposure↗
PubMed1997

Geriatric bone lead metabolism in a female nonhuman primate population.

A geriatric rhesus monkey (Macaca mulatta) population, previously exposed to lead, was investigated using 109Cd K X-ray fluorescence (K XRF) to determine whether metabolism of lead in bone was similar to that in human populations. The accumulation rate of lead into the tibia in this group of monkeys was determined to be 0.10-0.13 micrograms Pb (g bone mineral)-1 (microgram dl-1 year)-1, which compares well with human data, where the rate has been found to be 0.05-0.10 microgram Pb (g bone mineral)-1 (microgram dl-1 year)-1. In addition, bone lead changes over a 10-month time period were investigated, but no statistically significant difference was found. A halflife for lead in "bone" was calculated by fitting a single exponential model to serial blood lead data; the mean half-life of lead in bone was found to be 3.0 +/- 1.0 years. Both endogenous and exogenous lead exposure were found to be low at the present time, 10 years after cessation of lead intake. It is concluded that rhesus monkeys are an extremely good animal model of human bone lead metabolism and, in addition, that further research is needed to provide a more complete understanding of lead metabolism in geriatric populations.

Animals↗
PubMed1996

Unraveling the chronic toxicity of lead: an essential priority for environmental health.

Although population exposure to lead has declined, chronic lead toxicity remains a major public health problem in the United States affecting millions of children and adults. Important gaps exist in knowledge of the pathophysiology of chronic lead intoxication. These gaps have impeded development of control strategies. To close current gaps in knowledge of chronic lead toxicity, we propose an integrated, multidisciplinary, marker-based research program. This program combines a) direct measurement of individual lead burden by 109Cd X-ray fluorescence analysis of lead in bone, b) determination of ALA-D phenotype, an index of individual susceptibility to lead, and c) assessments of subclinical injury produced by lead in the kidneys, nervous system and, reproductive organs. Data from this research will provide answers to questions of great public health importance: a) Are current environmental and occupational standards adequate to prevent chronic lead intoxication? b) is lead mobilized from the skeleton during pregnancy or lactation to cause fetal toxicity? c) Is lead mobilized from bone during menopause to cause neurotoxicity? d) What is the significance of genetic variation in determining susceptibility to lead? e) What is the contribution of lead to hypertension, renal disease, chronic neurodegenerative disease or declining sperm counts? f) Is chelation therapy effective in reducing body lead burden in persons with chronic overexposure to lead?

Acetylglucosaminidase↗
PubMed1995

Lead poisoning.

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Adult↗