An overview of the treatment of childhood SLE

OBJECTIVES: Previous research suggests that binding of lead by delta-aminolevulinic acid dehydratase (ALAD) may vary by ALAD genotype. This hypothesis was tested by examining whether ALAD genotype modifies urinary lead excretion (DMSA chelatable lead) after oral administration of dimercaptosuccinic acid (DMSA). METHODS: 57 South Korean lead battery manufacturing workers were given 5 mg/kg oral DMSA and urine was collected for four hours. Male workers were randomly selected from two ALAD genotype strata (ALAD1-1, ALAD1-2) from among all current workers in the two plants (n = 290). Subjects with ALAD1-1 (n = 38) were frequency matched with subjects with ALAD1-2 (n = 19) on duration of employment in the lead industry. Blood lead, zinc protoporphyrin, and plasma aminolevulinic acid concentrations, as well as ALAD genotype, duration of exposure, current tobacco use, and weight were examined as predictors or effect modifiers of levels of DMSA chelatable lead. RESULTS: Blood lead concentrations ranged from 11 to 53 micrograms/dl, with a mean (SD) of 25.4 (10.2) micrograms/dl. After 5 mg/kg DMSA orally, the workers excreted a mean (SD) 85.4 (45.0) micrograms lead during a four hour urine collection (range 16.5-184.1 micrograms). After controlling for blood lead concentrations, duration of exposure, current tobacco use, and body weight, subjects with ALAD1-2 excreted, on average, 24 micrograms less lead during the four hour urine collection than did subjects with ALAD1-1 (P = 0.05). ALAD genotype seemed to modify the relation between plasma delta-aminolevulinic acid (ALA) and DMSA chelatable lead. Workers with ALAD1-2 excreted more lead, after being given DMSA, with increasing plasma ALA than did workers with ALAD1-1 (P value for interaction = 0.01). CONCLUSIONS: DMSA chelatable lead may partly reflect the stores of bioavailable lead, and the current data indicate that subjects with ALAD1-2 have lower stores than those with ALAD1-1. These data provide further evidence that the ALAD genotype modifies the toxicokinetics of lead-for example, by differential binding of current lead stores or by differences in long-term retention and deposition of lead.     

Impact of air pollution by lead on the heme biosynthetic pathway in school-age children

Blood-lead level (Pb-B), erythrocyte delta-aminolevulinic acid dehydratase (ALAD) activity, free erythrocyte porphyrin (FEP) concentration, delta-aminolevulinic acid concentration in urine (ALAU), hematocrit value, and hemoglobin concentration were compared for groups of children 10-13 years old from areas differently polluted by lead (rural area and lead smelter area). The biological responses of the children were also compared with those observed in adults similarly exposed to lead (Pb-B: 10-40 mug/100 ml). Compared with the rural children, children living less than 1 km from the smelter exhibited a significant increase of Pb-B and FEP, a significant inhibition of ALAD, and a slight positive correlation of ALAU with Pb-B; however, they showed no biological signs of anemia. In children living approximately 1.5 km from the smelter, there was still a significant increase of Pb-B and a concomitant inhibition of ALAD, but no change in FEP concentration. Comparison of the dose-response curves between Pb-B and FEP in adult males, adult females, and children indicates that the sensitivity to lead is in the order of children larger than or equal to women greater than men. Based on the FEP response, it is proposed that 25 mug Pb/100 ml blood be regarded as the maximum biologically allowable concentration of lead in blood of school-age children.     

Hypomethylation in cervical tissue: is there a correlation with folate status?

5-Aminolevulinic acid (ALA) is the first intermediate substrate in the heme synthetic pathway and is the substrate of aminolevulinic acid dehydratase (ALAD, porphobilinogen synthase). Because lead effectively inhibits ALAD activity, resulting in accumulation of ALA in urine and blood, urinary ALA (ALAU) has been used as a biomarker for lead exposure or early biologic effect of lead. Intraindividual variation in urinary excretion of ALA requires the use of 24-hour urine samples or adjustment of single urine samples by other normalizing variables, such as urinary creatinine concentration. Previous studies of ALAU concentration have used various adjustment methods; however, few have compared creatinine-adjusted ALAU concentration with ALA concentration in plasma (ALAP) from subjects with low (< 30 micrograms/dL) to moderate (< 60 micrograms/dL) levels of blood lead. To determine if creatinine-adjusted ALAU is associated with ALAP, we measured ALAU, ALAP, and urinary creatinine in 65 Korean lead workers with blood lead concentrations in the range of 14-60 micrograms/dL. ALAU, ALAU/creatinine, or ALAU/log creatinine all correlated with ALAP. However, ALAU/creatinine correlated more closely with ALAP based on Spearman's r (rs = 0.40, P, = 0.0009), supporting the use of ALA/creatinine in single urine samples as a surrogate for ALAP.     

The CarboMedics valve: experience with 1,049 implants

There is a high density of industries for the production of ceramic tiles in the District of Scandiano (province of Reggio Emilia, Emilia Romagna region). In this area, since the beginning of 1970s, the time trend of Pb exposure in ceramic tile plants has been evaluated by means of biological monitoring (BM) data collected at the Service of Prevention and Safety in the Work Environment and its associated Toxicology Laboratory. From these data, a clear decreasing time trend of exposure levels is documented, the reduction being more evident during the seventies and in 1985-88. During the seventies BM was introduced systematically in all ceramic tile plants with the determination of delta-aminolevulinic acid in urine (ALA-U). As a consequence of the BM programme, hygienic measures for the abatement of pollution inside the plants were implemented, and a reduction, from 20.6% to 2%, of ALA-U values exceeding 10 mg/l, was observed. In 1985, the determination of lead in blood (PbB) replaced that of ALA-U in the BM programmes and highlighted the persistence of high level of exposure to Pb, which could not be outlined by means of ALA-U because of its lower sensitivity. PbB levels were 36.1 micrograms/100 ml and 25.7 micrograms/100 ml in male and female workers, respectively. These results required the implementation, within the plants, of additional hygienic measures and a significant reduction of PbB was obtained in the following three years. In 1988 PbB levels were 26.0 +/- 10.7 and 21.6 +/- 10.3 micrograms/100 ml in male and female workers, respectively. In 1993-95 Pb levels were obtained from 1328 male and 771 female workers of 56 plants, accounting for about 40% of the total number of workers in the ceramic industry, in the zones of Sassuolo and Scandiano. Exposure levels are not different from those observed in the preceding years, with PbB levels of 25.3 +/- 11.1 and 19.1 +/- 9.2 micrograms/100 ml in male and female workers, respectively.     

Lead exposure of workers in the ceramics industry and relevant factors

To clarify lead exposure and factors relevant to it, an occupational health survey and air lead-concentration survey were conducted among 425 workers in the ceramics industry in the Seto region in Aichi Prefecture. As for biological monitoring, blood lead level was measured according to sex, job, product, factory size and duration of lead exposure. The following major findings were obtained in the present analysis. Workers making dolomite novelties showed higher blood lead levels than those making porcelain novelties, semi-porcelain novelties and tableware. The difference in blood lead level by job was statistically significant, but not that by factory size. In males, the highest blood lead level was found for spray painting work (28.7 micrograms/dl), followed by glazing work (28.0 micrograms/dl), kiln work (23.3 micrograms/dl) and painting work (22.3 micrograms/dl). In females, the blood lead level for painting work (13.5 micrograms/dl) was lower than those for glazing work (26.1 micrograms/dl) and kiln work (31.4 micrograms/dl). The blood lead level was significantly increased with the number of years of lead exposure in females (painting work). It was coincidentally clarified that the environmental lead concentration varied according to the job in which workers were engaged. As protective measures against lead exposure for workers in the ceramics industry, the development of nonlead paint and glaze and the introduction of more effective dust collectors at the workplace should be established.     

HLA antigens in three Siberian populations

The biological responses of the heme biosynthesis pathway in male workers moderately exposed to lead are discussed in relation to the concentration of lead in the blood. The level of erythrocyte delta-aminolevulinic acid dehydratase (ALA-D) activity in the group of lead-exposed workers was remarkably reduced while the level of erythrocyte protoporphyrin (Proto) in them was strikingly increased, compared to normal levels. On the other hand, the amounts of hemoglobin (Hb) and urinary delta-aminolevulinic acid (ALA) in the group of lead-exposed workers kept the normal levels. In the workers moderately exposed to lead, the log of erythrocyte Proto level was closely correlated to the blood lead level and the sensitivity of the Proto test was almost equal to that of erythrocyte ALA-D test. It was observed that the erythrocyte Proto was remarkably increased even in lead-exposed workers whose ALA excretion into the urine was in the range of normal level.     

Lead absorption and renal dysfunction in a South African battery factory

OBJECTIVES: To test the association between inorganic lead (Pb) exposure, blood pressure, and renal function in South African battery factory workers, with both conventional and newer measures of renal function and integrity. METHODS: Renal function measures included serum creatinine, urea, and urate (n = 382). Urinary markers (n = 199) included urinary N-acetyl-beta-D-glucosaminidase (NAG), retinol binding protein, intestinal alkaline phosphatase, tissue non-specific alkaline phosphatase, Tamm-Horsfall glycoprotein, epidermal growth factor, and microalbuminuria. RESULTS: Mean current blood Pb was 53.5 micrograms/dl (range 23 to 110), median zinc protoporphyrin 10.9 micrograms/g haemoglobin (range 1.9 to 104), and mean exposure duration 11.6 years (range 0.5 to 44.5). Mean historical blood Pb, available on 246 workers, was 57.3 micrograms/dl (range 14 to 96.3). After adjustment for age, weight and height, positive exposure response relations were found between current blood Pb, historical blood Pb, zinc protoporphyrin (ZPP), and serum creatinine and urate. Blood pressure was not associated with Pb exposure. Among the urinary markers, only NAG showed a positive association with current and historical blood Pb. CONCLUSION: An exposure-response relation between Pb and renal dysfunction across the range from < 40 to > 70 micrograms/dl blood Pb was found in this workforce, with conventional measures of short and long term Pb exposure and of renal function. This could not be explained by an effect on blood pressure, which was not associated with Pb exposure. The findings probably reflect a higher cumulative renal burden of Pb absorption in this workforce in comparison with those in recent negative studies. The results also confirm the need for strategies to reduce Pb exposure among industrial workers in South Africa.     

Linkage analysis of infantile pyloric stenosis and markers from chromosome 9q11-q33: no evidence for a major gene in this candidate region

In order to investigate useful indicators of lead contamination, 108 Japanese Black calves from a lead-contaminated farm were used. The lead concentrations in blood (Ph-B), delta-aminolevulinic acid dehydratase (ALA-D) activities, and free erythrocyte protoporphyrin (FEP) concentrations were examined. A significant negative correlation was obtained between Pb-B concentrations and ALA-D activities (r = -0.621, p < 0.01). A significant positive correlation was obtained between Ph-B concentrations and FEP concentrations (r = 0.850, p < 0.01). The calves were divided by Pb-B concentrations (micrograms/100 ml) into 5 groups (A = < or = 30, B = 31 approximately 90, C = 91 approximately 150, D = 151 approximately 210, E = > or = 211) to observe the relation of ALA-D activities, FEP concentrations and ALA-D activities in group B (r = -0.706, p < 0.05). A significant positive correlation was obtained between Pb-B concentrations and FEP concentrations in groups A, B and D (A = r = 0.496, p < 0.01; B = r = 0.686, p < 0.01; D = r = 0.529, p < 0.05). These results indicate that FEP concentrations were good indicators of lead contamination.     

Childhood lead poisoning in Asturias

We have determined the blood lead levels of 1,242 children, from newborn to 14 years old, and 79 young mothers in a period of 10 months in Asturias (Spain). All of them were selected at random among those who consulted one of the three main hospitals in Asturias, but none were diagnosed as lead poisoning. We have found a mean blood lead level of 22.11 micrograms/dl; 23.55% had high levels (= 25 micrograms/dl). Sex was not significantly associated with blood lead levels either in the whole sample or in different age groups. Blood lead level increases rapidly from birth (19.3 micrograms/dl) to the age of one year (23.3 gamma/dl), fluctuating around this level until the age of 7. Then it declines with age until adolescence (19.6 micrograms/dl). From October (25.5 micrograms/dl) to July (20.9 micrograms/dl) the decrease in lead blood level was statistically significant. No difference has been found between urban and rural population. The decree of urbanization has not been found significant. The mean blood lead level in the mothers was 20.5 micrograms/dl.     

Non-occupational lead exposure and hypertension in northern Italy

BACKGROUND: Previous research has addressed the issue that low-level blood lead concentration could be associated with an increased risk of hypertension. METHODS: This paper examines the cross-sectional association between blood lead and hypertension in 630 adult males not employed in activities characterized by specific exposure to lead and living in two Northern Italian cities (Verona and Brescia). The participants, aged 26-69 years, constituted a random sample of the patients in the practice of a general practitioner (Verona) and of regular blood donors (Brescia). Logistic regression analysis was used to evaluate the effects of selected variables (blood lead, blood cadmium, zinc erythroprotoporphyrin, haemoglobin, whole blood viscosity, age, body mass index, smoking habits and alcohol consumption) on the probability of being hypertensive. RESULTS: The blood lead concentration (range: 4.3-46.9 micrograms/dl; median: 14.8 micrograms/dl) was very similar in the two samples, whereas the prevalence of hypertension was significantly higher in the Verona sample than in the Brescia sample (20.4% versus 8.3%). Hypertensive subjects showed significantly higher blood lead levels than normotensive ones. In a preliminary (univariate) analysis blood lead levels, body mass index (BMI) and age were each significantly related to the prevalence of hypertension. After adjusting for age and/or BMI, statistical significance of the relationship between blood lead and hypertension was lost.CONCLUSIONS. The present study showed that blood lead is weakly related to hypertension in non-occupationally exposed men. The statistical significance of this association disappeared when age and BMI were used to make adjustments.     

Environmental urban lead exposure and blood lead levels in children of Mexico City

Lead contamination is now a leading public health problem in Mexico. However, there are few data on the lead content of various environmental sources, and little is known about the contribution of these sources to the total lead exposure in the population of children residing in Mexico City. We conducted a cross-sectional study in a random sample of 200 children younger than 5 years of age who lived in one of two areas of Mexico City. Environmental samples of floor, window, and street dust, paint, soil, water, and glazed ceramics were obtained from the participants' households, as well as blood samples and dirt from the hands of the children. Blood lead levels ranged from 1 to 31 micrograms/dl with a mean of 9.9 micrograms/dl (SD 5.8 micrograms/dl). Forty-four percent of the children 18 months of age or older had blood lead levels exceeding 10 micrograms/dl. The lead content of environmental samples was low, except in glazed ceramic. The major predictors of blood lead levels were the lead content of the glazed ceramics used to prepare children's food, exposure to airborne lead due to vehicular emission, and the lead content of the dirt from the children's hands. We conclude that the major sources of lead exposure in Mexico City could be controlled by adequate public health programs to reinforce the use of unleaded gasoline and to encourage production and use of unleaded cookware instead of lead-glazed ceramics.     

Exposure to lead among the population of Barcelona: chronologic trends from 1984 to 1995

BACKGROUND: This study was designed to determine current lead exposure in the Barcelona population and to evaluate the changes occurred during the last 10 years. Blood lead concentration was investigated in a random sample of 694 healthy subjects (age range: 0-65 years). PATIENTS AND METHODS: Adults were random selected from a group of blood donors. Samples of children analysed were selected from subjects with a preoperatory analyses without any disease that could modify blood lead levels. Lead levels were determined by atomic absorption spectrometry. RESULTS: Blood lead concentration was 4.06 +/- 1.4 micrograms/dl in umbilical cord, 8.9 +/- 2.9 micrograms/dl in the paediatric population and 7.8 +/- 4.2 micrograms/dl in the total of adults analyzed. There was statistical differences between the younger subjects and the older population. In 1984 the results found were 18.6 +/- 6.6 micrograms/dl. CONCLUSIONS: The results obtained show that in the last 10 years a reduction on the blood lead levels was occurred. This reduction is parallel with a diminish in the lead petrol concentration in the ambient air.     

Short summary of the VIII International Symposium on Hypoxia (Lake Lewis, Canada, February 9-13, 1993)

Paresthesias are a frequently reported symptom of methylmercury exposure in adults, while peripheral neuropathy has long been known to result from high-level lead exposure. Despite this, no objective determination of somatosensory function has been performed in either humans or animals for either toxicant. Somatosensory function was assessed following developmental methylmercury exposure or lifetime lead exposure in monkeys (Macaca fascicularis) by determination of sensitivity to vibration applied to the fingertip. Vibration thresholds were determined over a number of frequencies, from 25 to 250 Hz, by means of a behavioral procedure. The underside of the tip of the monkey's middle finger was precisely positioned over a blunt probe attached to a vibrator. The monkey signaled detection of the vibration by breaking contact with a stainless steel bar with the free hand. At each of the five frequencies tested, the amplitude of the vibration was manipulated systematically to determine the monkey's threshold of detection. Four of five monkeys dosed with methylmercury from birth to 7 years of age, with blood mercury levels during dosing of 0.8-1.1 micrograms/g, exhibited elevated thresholds when tested at 18 years of age. Two monkeys dosed in utero through 4 years of age, with blood mercury levels of 0.35 micrograms/g during dosing, were impaired when tested at 15 years of age, while two monkeys with histories of blood mercury levels of 0.70 were relatively unimpaired. Lifetime exposure to lead resulting in stable blood lead levels of 20-25 micrograms/dl resulted in elevated vibration sensitivity only at the highest frequency in all four individuals tested. However, only two of six individuals with high lead levels (60-130 micrograms/dl) exhibited impairment. These results represent severe impairment in methylmercury-exposed monkeys 11 years after cessation of dosing and extend previous research documenting visual and auditory impairment in these monkeys. While effects of lifetime lead exposure on vibration sensitivity observed in the present study are suggestive, there is clearly a need for further research.     

Lead suppresses chimeric human transferrin gene expression in transgenic mouse liver

The major iron-transport protein in serum is transferrin (TF) which also has the capacity to transport other metals. This report presents evidence that synthesis of human TF can be regulated by the metal lead. Transgenic mice carrying chimeric human TF-chloramphenicol acetyl transferase (CAT) genes received lead or sodium salts by intraperitoneal injections or in drinking water. Transgene expression in liver was suppressed 31 to 50% by the lead treatment. Lead regulates human TF transgenes at the mRNA level since liver CAT enzyme activity, CAT protein, and TF-CAT mRNA levels were all suppressed. The dosages of lead did not alter synthesis of the other liver proteins, mouse TF and albumin, as measured by Northern blot analysis of total liver RNA and rocket immunoelectrophoresis of mouse sera. Moderate levels of lead exposure were sufficient to evoke the human TF transgene response; blood lead levels in mice that received lead acetate in drinking water ranged from 30 micrograms/dl to 56 micrograms/dl. In addition to suppressing expression of TF-CAT genes in transgenic mice, lead also suppressed synthesis of TF protein in cultured human hepatoma HepG2 cells. The regulation of human TF apparently differs from the regulation of mouse TF which is unresponsive to lead exposure.     

A unique pulmonary venous abnormality: with associated pulmonary arterial anomaly and arteriovenous malformation

Lead and cadmium were administered intraperitoneally, singly and jointly, to the mice. The levels of cadmium, copper, manganese, lead and zinc were determined in liver, kidney and brain by atomic absorption spectrophotometric technique and delta-aminolevulinic acid dehydratase (ALA-D) activity was determined in erythrocytes. The tissue levels of some of these metals were found significantly altered by cadmium and lead both, but cadmium was found to have no effect on blood on ALA-D activity.     

Low-level lead exposure and children's intelligence from recent epidemiological studies in the U.S.A. and other countries to progress in reducing lead exposure and screening in the U.S.A

From the 1980s many well-designed epidemiological studies have confirmed that low-level, subclinical lead exposure in early life is associated with decrements in children's intelligence. Neurodevelopmental deficits from exposure to a low level of lead have been held to be not only an American problem, but also a worldwide issue in the past decade. Good epidemiological studies were reported from England, Scotland, Germany, Greece, Australia and New Zealand. Well-designed cross-sectional and prospective studies were carried out to quantify the magnitude of the relation between full scale IQ in children aged five years or more and the burden of lead (PbB or PbT) in early life of children. Of five cross-sectional studies of blood lead, two demonstrated a significant inverse association between lead and IQ even after adjustment for confounders. Two other studies, however, showed no firm evidence of inverse association after adjustment for confounders, and the remaining study demonstrated no significant inverse association of five cross-sectional studies of tooth lead, two indicated an inverse association between tooth lead and IQ, two others showed no significant inverse association after adjustment for confounders, and the remaining one manifested no association. Of four prospective studies, two revealed strong evidence of an inverse association between blood lead at the age of around two years and IQ. Another one, however, revealed an inverse association between mean postnatal blood level and IQ, while the remaining one demonstrated no significant inverse association between IQ and postnatal blood lead level after adjustment for confounders. In a comprehensive review of 26 epidemiological studies since 1979, including a meta-analysis, Pococok et al. indicated that doubling of the body lead burden (from 10 to 20 micrograms/dl) blood lead or (from 5 to 10 micrograms/g) tooth lead is typically associated with a mean deficit in full-scale IQ of around 1-2 IQ points. Lead in interior household dust, exterior surface soil, and old residential lead paint, which is deteriorated or removed, constitute the major sources of lead poisoning in children in the United States. Infants and children, who typically engage in hand to mouth activities, frequently come into contact with lead dust in soil and on the floor. Marked declines both in air lead and blood lead concentrations are evident parallel to the phase-down of lead in gasoline and soldered cans by U.S. food processors. The major source of lead in drinking water is from lead pipes used in household plumbing. The CDC revised its guidelines concerning childhood lead poisoning, stating that community prevention activities should be triggered when a large percentage of children in a community have blood lead levels of 10 micrograms/dl, the lowest level at which neurodevelopmental effects were believed to occur. For children with blood lead level concentrations between 10 and 14 micrograms/dl, more frequent rescreening may be needed. For concentrations between 15 and 19 micrograms/dl, in addition to more frequent screening, nutritional and educational advice should be given. In cases where these levels persist, there should be environmental investigation and intervention. All children with blood levels of 20 micrograms/dl or greater should receive environmental evaluation and medical examination. Such children may need pharmacological treatment.     

Blood lead levels in preschool children in Rawalpindi

Blood lead levels were determined in preschool children residing in Urban areas of Rawalpindi city. Of 92 (50 males and 42 females) children aged one to 5 years were included in the study. Blood lead levels ranged from 7 micrograms/dl to 34 micrograms/dl (mean 18.8 micrograms/dl). The mean lead levels were slightly higher in males (20.3 micrograms/dl) than in females (17.2 micrograms/dl) and over 90% children had lead levels above the acceptable limit of 10 micrograms/dl. Use of leaded petrol, contaminated surma, leaded paints and pica in children are common in our country and may lead to increased lead levels and appropriate measures should be taken to control this trend.     

Effects of administration of some monoamine-synthesis blockers and precursors on ovariectomy-induced rise in plasma gonadotropin II in the catfish Heteropneustes fossilis

This study was performed to evaluate the bioavailability and effects of lead in wildlife at a trap and skeet range. The total lead concentration in a composite soil sample (pellets removed) was 75,000 micrograms/g dry weight. Elevated tissue lead concentrations and depressed ALAD activities in small mammals and frogs indicate that some of the lead deposited at the site is bioavailable. Mean tissue lead concentrations (micrograms/g dry wt.) in white-footed mice (Peromyscus leucopus) at the range liver = 4.98, kidney = 34.9, femur = 245) were elevated (P < 0.01) 5- to 64-fold relative to concentrations in mice from a control area. Tissue lead concentrations in the only shorttail shrew (Blarina brevicauda) captured at the range (liver = 34.1, kidney = 1506, femur = 437) were elevated 35- to 1038-fold. Femur lead concentrations in green frogs (Rana clamitans) at the range (1,728 micrograms/g) were elevated nearly 1000-fold, and the lead concentration in a pooled kidney sample (96.2 micrograms/g) was elevated 67-fold. There was significant depression of blood ALAD activity in mice (P = 0.0384) and depression of blood and liver ALAD activity in frogs (P < 0.001). Hematological and histopathological lesions associated with lead toxicosis were observed in some animals. Hemoglobin concentrations were reduced 6.7% in mice (P = 0.0249), but hematocrit was not significantly affected in mice or frogs. Intranuclear inclusions were present in the renal proximal tubular epithelium of two of the mice and the shrew that were captured at the range, and necrosis of the tubular epithelium was also evident in one of the mice. Kidney:body weight ratios were similar in range and control mice. Soil ingestion may be a significant route of lead uptake in small mammals at the range. However, the tendency of lead to concentrate in the bones rather than in more digestible soft tissues may minimize food chain uptake of lead by predators, especially raptors that regurgitate undigestible material.     

A study of the effects of exposure misclassification due to the time-window design in pharmacoepidemiologic studies

This paper presents a model for predicting blood lead levels in adults who are exposed to elevated environmental levels of lead. The model assumes a baseline blood lead level based on average blood lead levels for adults described in two recent U.S. studies. The baseline blood level in adults arises primarily from exposure to lead in diet. Media-specific ingestion and absorption parameters are assessed for the adult population, and a biokinetic slope factor that relates uptake of lead into the body to blood lead levels is estimated. These parameters are applied to predict blood lead levels for adults exposed to a hypothetical site with elevated lead levels in soil, dust and air. Blood lead levels ranging from approximately 3-57 micrograms/dl are predicted, depending on the exposure scenarios and assumptions.     

Blood lead concentration and biological effects in workers exposed to very low lead levels

A longitudinal study was carried out on two groups of workers engaged in tin/lead alloy welding in the telecommunication sector. The risk of exposure was evaluated by measuring levels of airborne lead (PbA) and the amount of lead absorbed (PbB). The-correlated effects were assessed by determining zinc protoporphyrin (ZPP) and hemoglobin levels (Hb) and red blood cell (RBC) count. We also recorded subjective symptoms reported by workers. One group of welders composed of 365 subjects underwent two monitoring sessions performed in 1991 and 1995, respectively (Group A). A second group of welders (whose number fluctuated between 148 and 247 subjects) underwent yearly testing for 7 consecutive years (1988-1994; Group B). Results indicated a very low risk of lead exposure during microwelding operations (PbA range, 1.5-24 micrograms/m3). In fact, blood concentrations of Pb (range, 5-55, micrograms/dL) among both groups of welders were significantly higher than those in the general population in Rome (PbB range, 5-16 micrograms/dL); nevertheless, they were significantly lower than the Occupational Safety and Health Administration's permissible exposure limits ZPP determined only in Group B of welders ranged from 5 to 16 micrograms/dL (median, 22 micrograms/dL). No variation was found in the other biological parameters investigated, and no health effects were observed. During the study period, the introduction of some technological innovations led to a further reduction in Pb exposure and, subsequently, to its total elimination. PbB concentrations gradually declined to lower values (6-36 micrograms/dL), and it was interesting to note that ZPP concentrations also decreased to normal levels (range, 2-47 micrograms/dL; median, 11 micrograms/dL), demonstrating that the effect of lead on heme synthesis may occur even at very low levels of Pb exposure.