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Background: We studied changes in blood concentrations of the soluble B-cell activation markers sCD27 and sCD30 in relation to future lymphoma risk, by investigating repeated pre-diagnostic plasma samples from the same individuals. High levels of sCD27 and sCD30 have been associated with lymphoma risk in previous prospective studies based on a single pre-diagnostic blood sample per participant. These studies, however do not inform about the dynamics of the marker-disease association on an individual level hampering its interpretation and potential use in lymphoma diagnostics and disease monitoring. Methods: In the Northern Sweden Health and Disease Study cohort we identified 170 individuals who had donated two pre-diagnostic blood samples and subsequently developed B-cell lymphoma. Blood samples were donated 13.2±4.4 and 5.5±4.0 years (mean±SD) prior to diagnosis, respectively. Cancer-free controls from the same cohort were individually matched to cases on a 1:1 ratio on sex, age and blood draw dates. We investigated associations between lymphoma risk by subtypes and marker concentrations; as measured separately at baseline, at time of the repeated sample, as well as the association with rate of change (slope) while adjusting for the baseline marker concentration. Findings: We observed strong associations between B-cell lymphoma risk and sCD27 and sCD30 concentrations, both at baseline and at time of the repeated blood sample. Associations were evident in samples collected up to 25 years before diagnosis. Blood concentrations of sCD27 and sCD30 increased significantly closer to diagnosis among future B-cell lymphoma cases, while they remained temporally stable among controls. Modeling measures of baseline and slope simultaneously with multivariable conditional logistic regression to estimate odds ratios (ORs), revealed significant associations between both slope and baseline measures and lymphoma risk; sCD27 (ORBaseline=7.2, Ptrend=2.8 x 10-4; ORSlope=2.8, Ptrend=2.2 x 10-4), and sCD30 (ORBaseline=2.9, Ptrend=3.7 x 10-4; ORSlope=2.9, Ptrend=0.001) (ORs 4th vs. 1st quartile; P for linear trend based on median values of analyte quartiles used as a continuous variable). Subtype specific analyses showed that the association between lymphoma risk and slope was restricted to indolent subtypes and mainly driven by chronic lymphocytic leukemia; sCD27 (ORSlope=6.7, Ptrend=1.3 x 10-5), and sCD30 (ORSlope=5.9, Ptrend=4.8 x 10-5), while associations with baseline marker concentration were evident among different subtypes, including diffuse large B-cell lymphoma. Interpretation: B-cell lymphoma risk seems to be influenced by increased sCD27 and sCD30 blood concentrations more than two decades before diagnosis. Increased concentrations of these B-cell activation markers among different future lymphoma subtypes early in life may reflect a constitutional predisposition, suggesting a role of B-cell activation in lymphoma development at early stages across subtypes. The observed increase of sCD27 and sCD30 concentrations closer to diagnosis however, seems to be subtype-specific and restricted to indolent lymphoma cases. Therefore, these markers may reflect early progression of undiagnosed disease and could potentially be utilized to improve lymphoma diagnostics and disease monitoring in indolent lymphoma. Disclosures No relevant conflicts of interest to declare.

In 31 children exposed to lead and 13 considerably less exposed children ("unexposed"), the plasma (Pb-P) concentrations ranged from 0.46 to 18.4 (median, 2.4) and from 0.14 to 0.38 (median, 0.21) microg/L, respectively. Corresponding whole-blood concentrations (Pb-B) were 99-920 (median, 370) and 39-120 (median, 66) microg/L, respectively. The relation between Pb-B and Pb-P was nonlinear; when Pb-P rose, the Pb-B increased relatively less. There was a close association between Pb-B and log Pb-P (r=0.95; P=0.0001). When these data were compared to previous data on adults, there was no major difference between children and adults in the Pb-B/Pb-P relation. Free erythrocyte protoporphyrins in blood were associated with Pb-P (r=0.75; P=0.0001) and Pb-B (r=0.90; P=0.0001). Also, there was an association between blood-hemoglobin concentration and Pb-P in both exposed (r=-0.67; P=0.0001) and unexposed (r=-0.67; P=0.01) children; the corresponding figures for Pb-B were r=-0.42; P=0.02, and r=-0.80; P=0.001, respectively. Thus, at least with regard to toxicity on hematopoiesis at high lead levels, Pb-P may be a more relevant indicator of exposure and risk than Pb-B. Because the curved Pb-B/Pb-P relation indicates a saturation of binding sites for lead in red cells, exposure and risk at high lead levels may easily be underestimated from Pb-B data.

Fish accumulate significant amounts of selenium and are an important dietary source of this element. Some studies have however indicated a low bioavailability of the selenium from fish. Since little is known of the selenium forms in fish, we have studied soluble selenium compounds in fish species, and compared different techniques for fractionation of selenocompounds (size-exclusion chromatography, ultrafiltration, and precipitation with trichloroacetic acid). The size-exclusion column (Superdex 200 HR 10/30) was coupled on-line to inductively coupled plasma mass spectrometry (ICP-MS). The limit of detection was 0.20 microgram l-1 and the selenium response was linear in the investigated concentration range of 0-20 micrograms l-1 (r2 = 0.98). For plaice 47% of the selenium was extractable while the extraction efficiency for cod was 23%. The fish extracts were injected onto the column four times each and the variation in the quantitative data for different selenium-containing fractions between the runs was small (RSD < 10%). The recovery of selenium in the chromatographic step was about 70%, indicating some interaction between the fish extracts and the column material. Ultrafiltration using a membrane with a cut-off at M(r) 10,000 gave results similar to the size-exclusion fractionation, for cod about 20% of the soluble selenium had a M(r) < 10,000 and the corresponding value for plaice was 69%. Removal of high-molecular-weight compounds from the sample by trichloroacetic acid precipitation showed a similar proportion of low-molecular-weight compounds for plaice (77%), while the obtained value for cod was higher (38%) compared with the other techniques.

Methylmercury in serum (S-MeHg) was assessed from serum concentrations of total (S-TotHg) and inorganic mercury (S-InoHg), determined by cold vapor-atomic absorption spectrometry. The samples were collected from 135 women on two occasions, in 1968-1969 and 1980-1981. In a subgroup of 29 women, an association was found between S-MeHg and the amount of fish consumed in 1968-1969 (r = 0.38, P = 0.04). The association was stronger (r = 0.50; P = 0.006) when the individuals' mean S-MeHg from 1968-1969 and 1980-1981 were plotted vs fish consumption 1968-1969. In the group, as a whole, there was an association between S-InoHg and number of dental amalgam surfaces, in both 1968-1969 (r = 0.48, P = 0.0001) and 1980-1981 (r = 0.57, P < 0.0001). The S-InoHg increased by approximately 0.1 nmol/L per amalgam tooth surface, corresponding to an uptake of approximately 0.2 microgram/day per amalgam surface, but with considerable interindividual differences. The levels were lower in 1980-1981 than in 1968-1969 for both MeHg and InoHg. The medians and ranges (nmol/L) were for MeHg 1968-1969: 3.6 (0.3-11.9); MeHg 1980-1981, 2.0 (-0.4-8.7); InoHg 1968-1969, 3.3 (0.7-11.8); InoHg 1980-1981, 1.7 (0.1-11.8); TotHg 1968-1969, 7.2 (1.9-18.8); and TotHg 1980-1981, 3.9 (1.0-14.2). The decrease in S-MeHg is probably due to a decreased consumption of MeHg via contaminated fish. The decrease in S-InoHg may reflect a decrease in environmental exposure, but the possibility of contamination of the 1968-1969 samples at sampling and/or storage cannot be excluded.

Objectives This study tested a simple model of the relationship between the lead concentration in bone (bone-Pb), exposure time, and lead in plasma (P-Pb) and whole blood (B-Pb) to make it possible to use bone-Pb as a retrospective exposure index. Methods Seventy-seven active lead workers and 24 referents were studied. The bone-Pb in tibia (T-Pb) and calcaneus (C-Pb) was measured by in vivo X-ray fluorescence. P-Pb was calculated from B-Pb by use of the nonlinear relationship between these variables. Cumulative B-Pb (cumB-Pb) and P-Pb (cumP-Pb) were calculated to the time of the bone-Pb measurements. In addition, cumP-Pb was adjusted by applying varying rate constants for the transfer of lead from bone to plasma. Results There were close linear associations between the lead concentrations in tibia (proportion of variance explained, R 2 =0.78) and calcaneus (R 2 =0.80), on one hand and the cumB-Pb on the other. The best fit of bone-Pb to the adjusted cumP-Pb (0.79 for T-Pb; 0.82 for C-Pb) was obtained for the terminal phase half-times of 13 and 12 years, respectively. Conclusions The combined data on bone-Pb and exposure time make it possible to estimate previous mean P-Pb and B-Pb. Such estimates will be valuable in studies of toxic effects on long-term exposed lead workers when data on the intensity of previous exposure are lacking. The use of P-Pb in modeling bone-Pb kinetics is physiologically relevant, but the use of adjusted cumP-Pb, as compared cumB-Pb, did not significantly change the variance in the relation to bone-Pb.

In 42 lead-exposed workers (22 male and 20 female), we found a close nonlinear relation between blood and plasma lead concentrations, determined by inductively coupled plasma mass spectrometry (ICP-MS). The concentration medians and ranges were lead in whole blood, 270 (97 to 950) micrograms/L and lead in plasma, 1.1 (0.2 to 13) micrograms/L. Proteins from lysed erythrocytes were studied by gel chromatography with ICP-MS detection. We then found capacity-limited binding for lead to delta-aminolevulinic acid dehydratase (ALAD), as well as to two other components (with apparent molecular masses of 45 and < 10 kDa, respectively). The strongest affinity for lead was indicated for ALAD (35-81% of the lead in blood) and could be described by a capacity of 850 micrograms/L and a dissociation constant of 1.5 micrograms/L. The 45-kDa protein carried 12-26% of the blood lead, and the < 10-kDa component less than 1%. A model based on these three components, plus a fourth one for unrecovered lead (2-45%), is proposed. No binding of lead to hemoglobin was found. There was an association between zinc and lead in whole blood; however, zinc did not significantly affect the lead distribution in erythrocytes.

Objectives Blood-lead levels (B-Pb), and to some extent urinary lead (U-Pb), are the most employed measures of lead exposure and risk. However, the small fraction of lead present in plasma (usually below 1% of that in blood) is probably more relevant to lead exposure and toxicity. Nevertheless, the lead content of plasma lead (P-Pb) has only seldom been used, mainly due to analytical limitations, which have now been overcome. We examined P-Pb in occupationally exposed subjects, as well as its relationship with B-Pb and U-Pb. Methods Blood samples were obtained from 145 male workers, 110 of whom were employed in lead work. After a simple dilution of plasma, P-Pb was determined by inductively coupled plasma mass spectrometry. The detection limit was 0.04 µg/l, and the imprecision was 5%. Results The lead concentration ranges were 0.20–37 µg/l for P-Pb, 0.9–176 µg/l (density adjusted) for U-Pb, and 9–930 µg/l for B-Pb. A close exponential relation was obtained between B-Pb and P-Pb. When B-Pb was plotted versus log P-Pb, a straight line (log P-Pb=0.00225 · B-Pb – 0.58; r=0.97) was obtained. Both the relation between U-Pb and P-Pb and that between U-Pb and B-Pb showed a large scattering (r=0.78 in both cases). The relation to B-Pb appeared to be exponential, while that to P-Pb appeared to be linear. Conclusion The low detection limit and good precision of P-Pb determinations make it possible to use P-Pb in assessments of lead exposure and risk. Furthermore, in relative terms, P-Pb is a more sensitive measure than B-Pb, especially at high lead levels. This development is of importance for studies of exposure, possibly also for studies of risks.

A method for the inductively coupled plasma mass spectrometry (ICP-MS) multi-element analysis of diluted human blood and serum was used for the following elements: Co, Ni, Cu, Zn, Ga, Se, Rb, Mo, Rh, Pd, Cd, Sn, Sb, W, Pt, Hg, Tl and Pb. Sample pretreatment was a simple dilution (ten times for blood and five times for serum) with a solution containing 5 g l -1 of 25% ammonia, 0.5 g l -1 Triton X-100, and 0.5 g l -1 EDTA in Millipore water. In and Sc were used as internal standards. For sample introduction a flow-injection-type technique (based on time instead of volume) was used. The determinations were carried out first in a peak-jumping mode for selected masses, and then in a scanning mode. Each determination of a preparation took 75 s. The results for reference samples agreed with recommended or certified values for Co, Cu, Zn, Rb, Cd, Tl and Pb in blood, and for Rb, Mo and Cd in serum. For Ni and Hg in blood, and Cu and Zn in serum, the results agreed with one of two reference samples. The detection limits for all these elements (except for Tl) were sufficient for analysis of samples from the general population. On the other hand, the results for Se in blood, and for Co, Ni, Se, Sn and Hg in serum did not agree with recommended or certified values. No reference samples are available for Ga, Mo, Rh, Pd, Sn, Sb, W, or Pt in blood, or for Ga, Rh, Pd, W, Pt, or Pb in serum. Generally, the limits of detection for the elements in the latter group (below 0.15 µg l -1 ) are close to or above the levels present in the general population.

In the Corrientes river basin, Peruvian Amazon, lead exposure among indigenous communities was first reported in 2006. To address controversy regarding the main source of exposure, this study aimed to identify the sources and risk factors for lead exposure among children from the communities in question, and to clarify the potential relationship with oil activity.This cross-sectional study was conducted in six communities. Participants were children aged 0-17 years and their mothers. Data collection included blood lead levels (BLLs) and hemoglobin determination, a questionnaire on risk factors and environmental sampling. We used age-stratified multivariate regression models, with generalized estimating equation to account for correlation within households.Twenty-seven percent of the children had BLLs ≥10 μg/dl. Mother's BLLs ≥10 μg/dl, playing and chewing lead scraps, fishing ≥three times/week, and living in highly oil-exposed communities increased the risk of having BLLs ≥10 μg/dl. Lead concentrations in sediment, soil, dust, and fish samples were below reference values.Mother's BLLs ≥10 μg/dl, playing and chewing lead scraps to manufacture fishing sinkers were the most important risk factors for children's BLLs ≥10 μg/dl. The connection with oil activity appears to be through access to metal lead from the industry's wastes.

Background: Cadmium (Cd) and lead (Pb) are hypothesised to be risk factors for non-Hodgkin's lymphoma (NHL), a group of haematological malignancies with a suspected environmental aetiology. Within the EnviroGenoMarkers study we utilised pre-diagnostic erythrocyte concentrations of Cd and Pb to determine whether exposure was associated with risk of B-cell NHL and multiple myeloma. Methods: 194 incident cases of B-cell NHL and 76 cases of multiple myeloma diagnosed between 1990 and 2006 were identified from two existing cohorts; EPIC-Italy and the Northern Sweden Health and Disease Study. Cases were matched to healthy controls by centre, age, gender and date of blood collection. Cd and Pb were measured in blood samples provided at recruitment using inductively coupled plasma-mass spectrometry. Logistic regression was applied to assess the association with risk. Analyses were stratified by cohort and gender and by subtype where possible. Results: There was little evidence of an increased risk of B-cell NHL or multiple myeloma with exposure to Cd (B-cell NHL: OR 1.09 95%CI 0.61, 1.93, MM: OR 1.16 95% CI: 0.40, 3.40) or Pb (B-cell NHL: 0.93 95% CI 0.43, 2.02, multiple myeloma: OR 1.63 95% CI 0.45, 5.94) in the total population when comparing the highest to the lowest quartile of exposure. However, gender and cohort specific differences in results were observed. In females the risk of B-cell NHL was more than doubled in those with a body burden of Cd >1 mu g/L (OR 2.20 95% CI; 1.04, 4.65). Conclusions: This nested case-control study does not support a consistent positive association between Cd or Pb and NHL, but there is some indication of a gender specific effect suggesting further research is warranted.

OBJECTIVES: To test a simple procedure for preparing samples for measurement of lead in blood plasma (P-Pb) and whole blood (B-Pb) by inductively coupled plasma mass spectrometry (ICP-MS), to measure P-Pb and B-Pb in lead workers and controls, and to evaluate any differences in the relation between B-Pb and P-Pb between people. METHODS: P-Pb and B-Pb were measured by ICP-MS in 43 male lead smelter workers and seven controls without occupational exposure to lead. For analysis, plasma and whole blood were diluted 1 in 4 and 1 in 9, respectively, with a diluted ammonia solution containing Triton-X 100 and EDTA. The samples were handled under routine laboratory conditions, without clean room facilities. RESULTS: P-Pb was measured with good precision (CV = 5%) even at concentrations present in the controls. Freeze storage of the samples had no effect on the results. The detection limit was 0.015 microgram/l. The P-Pb was 0.15 (range 0.1-0.3) microgram/l in controls and 1.2 (0.3-3.6) micrograms/l in lead workers, although the corresponding B-Pbs were 40 (24-59) micrograms/l and 281 (60-530) micrograms/l (1 microgram Pb/I = 4.8 nmol/l). B-Pb was closely associated with P-Pb (r = 0.90). The association was evidently non-linear; the ratio B-Pb/P-Pb decreased with increasing P-Pb. CONCLUSIONS: By means of ICP-MS and a simple dilution procedure, P-Pb may be measured accurately and with good precision down to concentrations present in controls. Contamination of blood at sampling and analysis is no major problem. With increasing P-Pb, the percentage of lead in plasma increases. In studies of lead toxicity, P-Pb should be considered as a complement to current indicators of lead exposure and risk.

The coupling of gel chromatography to ICP-MS was evaluated as a tool for the study of lead bound in vivo to proteins in erythrocytes. The chromatogram obtained showed three peaks for lead at apparent molecular masses of 240, 45 and

Exposure to methylmercury from fish has been associated with increased risk of myocardial infarction (MI) in some studies. At the same time, marine n-3 (omega-3) PUFAs are an inherent constituent of fish and are regarded as beneficial. To our knowledge, no risk-benefit model on the basis of data on methylmercury, PUFA, and MI risk has yet been presented.The objective of this study was to describe how exposure to both marine n-3 PUFAs and methylmercury relates to MI risk by using data from Finland and Sweden.We used matched case-control sets from Sweden and Finland that were nested in population-based, prospective cohort studies. We included 361 men with MI from Sweden and 211 men with MI from Finland. MI risk was estimated in a logistic regression model with the amount of mercury in hair (hair-Hg) and concentrations of n-3 PUFAs (EPA and DHA) in serum (S-PUFA) as independent variables.The median hair-Hg was 0.57 μg/g in Swedish and 1.32 μg/g in Finnish control subjects, whereas the percentage of S-PUFA was 4.21% and 3.83%, respectively. In combined analysis, hair-Hg was associated with higher (P = 0.005) and S-PUFA with lower (P = 0.011) MI risk. Our model indicated that even a small change in fish consumption (ie, by increasing S-PUFA by 1%) would prevent 7% of MIs, despite a small increase in mercury exposure. However, at a high hair-Hg, the modeled beneficial effect of PUFA on MI risk was counteracted by methylmercury.Exposure to methylmercury was associated with increased risk of MI, and higher S-PUFA concentrations were associated with decreased risk of MI. Thus, MI risk may be reduced by the consumption of fish high in PUFAs and low in methylmercury.

Objectives: The aim of the study was to make an international comparison of blood levels of cadmium (B-Cd), lead (BPb) and mercury (B-Hg) of women in seven European, and three non-European cities, and to identify determinants. Materials and Methods: About 50 women (age: 46–62) from each city were recruited (totally 480) in 2006–2009. Interview and questionnaire data were obtained. Blood samples were analysed in one laboratory to avoid interlaboratory variation. Results: Between the European cities, the B-Pb and B-Cd results vary little (range of geometric means: 13.5–27.0 μg/l and 0.25–0.65 μg/l, respectively); the variation of B-Hg was larger (0.40–1.38 μg/l). Between the non-European cities the results for B-Pb, B-Cd and B-Hg were 19.2–68.0, 0.39–0.99 and 1.01–2.73 μg/l, respectively. Smoking was a statistically signifi cant determinant for B-Cd, while fi sh and shellfi sh intakes contributed to B-Hg and B-Pb, amalgam fi llings also contributed to B-Hg. Conclusions: The present results confi rm the previous results from children; the exposure to lead and cadmium varies only little between different European cities suggesting that other factors than the living area are more important. The study also confi rms the previous fi ndings of higher cadmium and lead levels in some non-European cities. The geographical variation for mercury is signifi cant.

PURPOSE: Methodological differences in assessing dietary acrylamide (AA) often hamper comparisons of intake across populations. Our aim was to describe the mean dietary AA intake in 27 centers of 10 European countries according to selected lifestyle characteristics and its contributing food sources in the European Prospective Investigation into Cancer and Nutrition (EPIC) study. METHODS: In this cross-sectional analysis, 36 994 men and women, aged 35-74 years completed a single, standardized 24-hour dietary recall using EPIC-Soft. Food consumption data were matched to a harmonized AA database. Intake was computed by gender and center, and across categories of habitual alcohol consumption, smoking status, physical activity, education, and body mass index (BMI). Adjustment was made for participants' age, height, weight, and energy intake using linear regression models. RESULTS: Adjusted mean AA intake across centers ranged from 13 to 47 μg/day in men and from 12 to 39 μg/day in women; intakes were higher in northern European centers. In most centers, intake in women was significantly higher among alcohol drinkers compared with abstainers. There were no associations between AA intake and physical activity, BMI, or education. At least 50 % of AA intake across centers came from two food groups "bread, crisp bread, rusks" and "coffee." The third main contributing food group was "potatoes". CONCLUSIONS: Dietary AA intake differs greatly among European adults residing in different geographical regions. This observed heterogeneity in AA intake deserves consideration in the design and interpretation of population-based studies of dietary AA intake and health outcomes.

Background Fish consumption and intake of omega-3 fatty acids from fish are associated with a lower risk of cardiovascular disease. However, a prospective study from northern Sweden showed that high consumption of fish is associated with an increased risk of stroke in men, but not in women. The current study aimed to determine if fish consumption is differently related to lifestyle in men compared with women in northern Sweden. Methods Lifestyle information on 32,782 men and 34,866 women (aged 30–60 years) was collected between 1992 and 2006 within the Västerbotten Intervention Programme (a health intervention in northern Sweden). Spearman correlations coefficients (Rs) were calculated between self-reported consumption of fish and other food items. Lifestyle variables were compared between fish consumption categories. Results Fish consumption was positively associated with other foods considered healthy (e.g., root vegetables, lettuce/cabbage/spinach/broccoli, chicken, and berries; Rs = 0.21-0.30), as well as with other healthy lifestyle factors (e.g., exercise and not smoking) and a higher educational level, in both men and women. The only gender difference found, concerned the association between fish consumption and alcohol consumption. Men who were high consumers of fish had a higher intake of all types of alcohol compared with low to moderate fish consumers. For women, this was true only for wine. Conclusions Except for alcohol, the association between fish consumption and healthy lifestyle did not differ between men and women in northern Sweden. It is important to adjust for other lifestyle variables and socioeconomic variables in studies concerning the effect of fish consumption on disease outcome.

Lead in blood is a major concept in biomonitoring of exposure but investigations of its alternatives are scarce. The aim of the study was to describe different lead biomarkers' variances, day-to-day and between individuals, estimating their fraction of the total variance. Repeated sampling of whole blood, plasma and urine were conducted for 48 lead-exposed men and 20 individuals under normal environmental lead exposure, in total 603 measurements. For lead workers, the fraction of the total variance attributed to differences between individuals was 91% for whole-blood lead (geometric mean 227 μg/l; geometric standard deviation (GSD): 1.55 μg/l); plasma 78% (0.57 μg/l; GSD: 1.84 μg/l); density-adjusted urine 82%; and unadjusted urine 75% (23.7 μg/l; GSD: 2.48 μg/l). For the individuals under normal lead exposure, the corresponding fractions were 95% of the total variance for whole blood (20.7 μg/l; GSD: 8.6 μg/l), 15% for plasma (0.09 μg/l; GSD: 0.04 μg/l), 87% for creatinine-adjusted urine and 34% for unadjusted (10.8 μg/l; GSD: 6.7 μg/l). Lead concentration in whole blood is the biomarker with the best ability to discriminate between individuals with different mean concentration. Urinary and plasma lead also performed acceptably in lead workers, but at low exposures plasma lead was too imprecise. Urinary adjustments appear not to increase the between-individual fraction of the total variance among lead workers but among those with normal lead exposure.

Background and Aims: EnviroGenomarkers is a project aiming at the development of a new generation of biomarkers to study the role of environmental agents in human disease through the large-scale ap...

To assess potential risk factors associated with elevated blood lead levels (BLLs) among children in two communities from the Corrientes River basin in the Peruvian Amazon.Children aged 0-17 years were screened for BLLs, hemoglobin levels, and anthropometric measures. Dwelling, family, and child data were collected through a parental questionnaire. Statistical analysis included descriptive and bivariate analysis. Multiple linear and logistic regressions using generalized estimating equations were also conducted to determine associated risk factors. A map of each community was drawn to examine the spatial distribution of BLLs.Of 208 children (88 from 23 households of the Peruanito community and 120 from 28 households of Santa Isabel), 27.4% had BLLs10 µg/dL. The geometric mean (± standard deviation) BLL was 8.7 ± 4.0 µg/dL (range 3.0-26.8 µg/dL). In the total population, linear regression analysis indicated that age was positively associated with BLLs (P0.05). Logistic regression analysis showed that boys had 2.12 times greater odds of having BLLs10 µg/dL than girls (P0.05). Among the children 0-3 years, those whose mothers had BLLs10 µg/dL had 45.0% higher odds of presenting BLLs10 µg/dL than children whose mothers had BLLs10 µg/dL (P0.05).Older age, male gender, and mothers' BLL10 µg/dL were the main risk factors for elevated BLLs. The higher risk in boys 7-17 years suggests that exposure could be related to specific activities in this group, such as fishing and hunting. Continuous monitoring of BLLs in the Corrientes River population is recommended.

Background The n-3 polyunsaturated fatty acids eicosapentaenoic acid and docosahexaenoic acid, which are present in fish, are protective against myocardial infarction. However, fish also contains methylmercury, which influences the risk of myocardial infarction, possibly by generating oxidative stress. Methylmercury is metabolized by conjugation to glutathione, which facilitates elimination. Glutathione is also an antioxidant. Individuals with certain polymorphisms in glutathione-related genes may tolerate higher exposures to methylmercury, due to faster metabolism and elimination and/or better glutathione-associated antioxidative capacity. They would thus benefit more from the protective agents in fish, such as eicosapentaenoic+docosahexaenoic acid and selenium. The objective for this study was to elucidate whether genetic polymorphisms in glutathione-related genes modify the association between eicosapentaenoic+docosahexaenoic acid or methylmercury and risk of first ever myocardial infarction. Methods Polymorphisms in glutathione-synthesizing (glutamyl-cysteine ligase catalytic subunit, GCLC and glutamyl-cysteine ligase modifier subunit, GCLM) or glutathione-conjugating (glutathione S-transferase P, GSTP1) genes were genotyped in 1027 individuals from northern Sweden (458 cases of first-ever myocardial infarction and 569 matched controls). The impact of these polymorphisms on the association between erythrocyte-mercury (proxy for methylmercury) and risk of myocardial infarction, as well as between plasma eicosapentaenoic+docosahexaenoic acid and risk of myocardial infarction, was evaluated by conditional logistic regression. The effect of erythrocyte-selenium on risk of myocardial infarction was also taken into consideration. Results There were no strong genetic modifying effects on the association between plasma eicosapentaenoic+docosahexaenoic acid or erythrocyte-mercury and risk of myocardial infarction risk. When eicosapentaenoic+docosahexaenoic acid or erythrocyte-mercury were divided into tertiles, individuals with GCLM-588 TT genotype displayed a lower risk relative to the CC genotype in all but one tertile; in most tertiles the odds ratio was around 0.5 for TT. However, there were few TT carriers and the results were not statistically significant. The results were similar when taking plasma eicosapentaenoic+docosahexaenoic acid, erythrocyte-selenium and erythrocyte-mercury into account simultaneously. Conclusions No statistically significant genetic modifying effects were seen for the association between plasma eicosapentaenoic+docosahexaenoic acid or erythrocyte-mercury and risk of myocardial infarction. Still, our results indicate that the relatively rare GCLM-588 TT genotype may have an impact, but a larger study is necessary for confirmation.

Studies of underground miners have documented an increased risk of lung cancer mainly linked to radon exposure but possibly influenced by other concurrent exposures.A cohort study was carried out in 8321 iron ore miners with low exposure to radon, employed in 1923-1998 and followed up for lung cancer in 1958-2000. Historical exposures to radon, crystalline silica and diesel exhaust were assessed. Data including exposure to radon, quartz and diesel exhaust from another mine with higher exposure to radon were reanalysed.Miners had increased risk for lung cancer (SIR 1.48 (95% CI 1.22 to 1.78), based on 112 cases during 227,000 person-years). The increased risk could not be explained by exposure to radon or diesel exhaust but was associated with exposure to crystalline silica: SIR 0.96 (0.53 to 1.62), 1.45 (1.10 to 1.87), 1.99 (1.31 to 2.90) and 1.77 (0.92 to 3.10) in groups with exposure to 0, 0-2, 2-5 and5 mg years/m3, respectively. Reanalysis of data from the other mine indicated that quartz was a possible confounder in the analysis of relationship between radon and lung cancer. In the highest radon exposed group, the point estimate for the RR decreased from 5.65 to 3.90 when adjusting for concurrent exposure to quartz.Crystalline silica, a known carcinogen, probably affects lung cancer risk in iron ore miners. The main implication of the results is for interpretation of the dose-response curve for radon and lung cancer in underground iron ore miners. Since exposure to radon and quartz is often correlated, quartz exposure can be an important confounder.

Lead ( Pb) is one of the most important models for biomonitoring of exposure, with the blood Pb concentration as a predominant choice in practice and in epidemiology. In this article the alternatives for biomarkers to blood are reviewed. This overview focuses on a number of different qualities that are of importance in the evaluation of a biomarker's usefulness and performance. The qualities scrutinized included: (1) analytical accuracy and precision; (2) cost; (3) practical issues; (4) what is reflected by the biomarker; (5) relationship to exposure; and (6) relationship to effects. Data indicate that the best biomarker in some circumstances may be blood, but bone or teeth (for past exposures), feces (for current gastrointestinal exposure), or urine (for organic Pb) are sometimes more useful. A striking feature is that no generally accepted biomarker of bioavailable Pb exists, though plasma, bone, teeth, urine, and hair have all been discussed. For one of the most used applications of blood Pb, monitoring of lead workers' exposure, blood has important shortcomings in that it shows a poor response to changes in exposure at high levels. The alternative of plasma has not been sufficiently evaluated to be considered an alternative in occupational health services, although previous analytical problems are basically overcome. Possibly, urine deserves also more attention. Almost all biomarkers lack systematic data on variation within and between individuals.

Results of previous studies on fish intake and stroke risk have been inconclusive. Different stroke types have often not been separated. Our aim was to elucidate whether intake of fish, Hg or the sum of proportions of fatty acids EPA (20 : 5n-3) and DHA (22 : 6n-3) influence the risk of haemorrhagic or ischaemic stroke. Within a population-based cohort from a community intervention programme, 369 stroke cases and 738 matched controls were identified and included in the present nested case–control study. Information on fish intake had been recorded at recruitment, i.e. before diagnosis. Hg levels were determined in erythrocyte membranes, also collected at recruitment, and the relative content of fatty acids was measured in erythrocyte membranes or plasma phospholipids. The results showed that in women there was a non-significant decrease in stroke risk with increasing fish intake (OR 0·90 (95 % CI 0·73, 1·11) per meal per week). The risk in women differed significantly (P = 0·03) from that in men, in whom the OR for stroke rose with increasing fish intake (OR 1·24 (95 % CI 1·01, 1·51) per meal per week). The corresponding risk in men for Hg was 0·99 (95 % CI 0·93, 1·06), and for the sum of proportions of EPA and DHA 1·08 (95 % CI 0·92, 1·28). We conclude that the relationship between stroke risk and fish intake seems to be different in men and women. Increased levels of EPA and DHA do not decrease the risk for stroke and there is no association between stroke risk and Hg at these low levels.

OBJECTIVES: A growing number of epidemiological studies are showing that ambient exposure to particulate matter air pollution is a risk factor for cardiovascular disease; however, whether occupational exposure increases this risk is not clear. The aim of the present study was to examine whether occupational exposure to particulate air pollution increases the risk for ischaemic heart disease and cerebrovascular disease. METHODS: The study population was a cohort of 176,309 occupationally exposed Swedish male construction workers and 71,778 unexposed male construction workers. The definition of exposure to inorganic dust (asbestos, man-made mineral fibres, dust from cement, concrete and quartz), wood dust, fumes (metal fumes, asphalt fumes and diesel exhaust) and gases and irritants (organic solvents and reactive chemicals) was based on a job-exposure matrix with focus on exposure in the mid-1970s. The cohort was followed from 1971 to 2002 with regard to mortality to ischaemic heart disease and cerebrovascular disease. Relative risks (RR) were obtained by the person-years method and from Poisson regression models adjusting for baseline values of blood pressure, body mass index, age and smoking habits. RESULTS: Any occupational particulate air pollution was associated with an increased risk for ischemic heart disease (RR 1.13, 95% CI 1.07 to 1.19), but there was no increased risk for cerebrovascular disease (RR 0.97, 95% CI 0.88 to 1.07). There was an increased risk for ischaemic heart disease and exposure to inorganic dust (RR 1.07, 95% CI 1.03 to 1.12) and exposure to fumes (RR 1.05, 95% CI 1.00 to 1.10), especially diesel exhaust (RR 1.18, 95% CI 1.13 to 1.24). There was no significantly increased risk for cerebrovascular disease and exposure to inorganic dust, fumes or wood dust. CONCLUSIONS: Occupational exposure to particulate air pollution, especially diesel exhaust, among construction workers increases the risk for ischaemic heart disease.

There is an unexplained male predominance among patients with gastric cancer, and many carcinogens are found in male-dominated dusty occupations. However, the relation between occupational exposures and risk of gastric cancer remains unclear. To investigate whether airborne occupational exposures might influence the risk of noncardia gastric cancer, we used a large, prospective cohort study of male Swedish construction workers. These workers were, during the period 1971-1993, regularly invited to health examinations by a nationwide occupational health service organization. Data on job titles and other variables were collected through self-administered questionnaires and forms completed by the health organization's staff. Industrial hygienists assessed 12 specific airborne occupational exposures for 200 job titles. Gastric cancer, death or emigration occurring during follow-up in 1971-2002 were identified by linkage to the Swedish registers of Cancer, Causes of Death and Total Population, respectively. Incidence rate ratios (IRR) and 95% confidence intervals (CI), adjusted for attained age, tobacco smoking, calendar period and body mass, were derived from Cox regression. Among 256,357 cohort members, contributing 5,378,012 person-years at risk, 948 noncardia gastric cancers were identified. Increased risk of this tumor was found among workers exposed to cement dust (IRR 1.5 [95% CI 1.1-2.1]), quartz dust (IRR 1.3 [95% CI 1.0-1.7]) and diesel exhaust (IRR 1.4 [95% CI 1.1-1.9]). Dose-response relations were observed for these exposures. No consistent positive associations were found regarding exposure to asbestos, asphalt fumes, concrete dust, epoxy resins, isocyanates, metal fumes, mineral fibers, organic solvents or wood dust. In conclusion, this study provides some support to the hypothesis that specific airborne exposures increase the risk of noncardia gastric cancer. © 2007 Wiley-Liss, Inc.

When assessing occupational exposures, repeated measurements are in most cases required. Repeated measurements are more resource intensive than a single measurement, so careful planning of the measurement strategy is necessary to assure that resources are spent wisely. The optimal strategy depends on the objectives of the measurements. Here, two different models of random effects analysis of variance (ANOVA) are proposed for the optimization of measurement strategies by the minimization of the variance of the estimated log-transformed arithmetic mean value of a worker group, i.e. the strategies are optimized for precise estimation of that value. The first model is a one-way random effects ANOVA model. For that model it is shown that the best precision in the estimated mean value is always obtained by including as many workers as possible in the sample while restricting the number of replicates to two or at most three regardless of the size of the variance components. The second model introduces the 'shared temporal variation' which accounts for those random temporal fluctuations of the exposure that the workers have in common. It is shown for that model that the optimal sample allocation depends on the relative sizes of the between-worker component and the shared temporal component, so that if the between-worker component is larger than the shared temporal component more workers should be included in the sample and vice versa. The results are illustrated graphically with an example from the reinforced plastics industry. If there exists a shared temporal variation at a workplace, that variability needs to be accounted for in the sampling design and the more complex model is recommended.

The lead concentration in plasma is correlated to that in whole blood with a two to fourfold variation. It has never been investigated if this variation is inter-individual.Lead and hemoglobin were determined in blood and plasma from 13 lead workers with a history of relatively high blood-lead concentrations, sampled three times during 1 day. The variation in the distribution of lead between cells and plasma was studied, but not the variation in the lead concentrations as such.Blood hemoglobin decreased with rising plasma lead (0.9-3.0 microg/L). Regarding the distribution of lead, no effect of current exposure during the day or of recent meals appeared. As much as 84% of the overall variance of the distribution of lead between cells and plasma could be attributed to individual factors. After adjustment for erythrocyte volume fraction this decreased to 67%. Plasma samples with elevated hemoglobin concentrations (due to in vitro hemolysis) had somewhat elevated lead concentrations.Plasma lead is not significantly altered by variation in a single day's exposure and, therefore, the choice of time of the day is not critical for sampling. However, plasma lead is negatively correlated to blood hemoglobin and mild hemolysis (not visible by the eye) in a sample may increase plasma lead with up to 30%. Finally, plasma provides lead exposure information that differs from whole blood, but it is not clear which one of these is the biomarker with the closest relation to exposure and/or effects.

The time trends of exposure to heavy metals are not adequately known. This is a worldwide problem with regard to the basis for preventive actions and evaluation of their effects. This study addresses time trends for the three toxic elements cadmium (Cd), mercury (Hg), and lead (Pb). Concentrations in erythrocytes (Ery) were determined in a subsample of the population-based MONICA surveys from 1990, 1994, and 1999 in a total of 600 men and women aged 25-74 years. The study took place in the two northernmost counties in Sweden. To assess the effect of changes in the environment, adjustments were made for life-style factors that are determinants of exposure. Annual decreases of 5-6% were seen for Ery-Pb levels (adjusted for age and changes in alcohol intake) and Ery-Hg levels (adjusted for age and changes in fish intake). Ery-Cd levels (adjusted for age) showed a similar significant decrease in smoking men. It is concluded that for Pb and maybe also Hg the actions against pollution during recent decades have caused a rapid decrease of exposure; for Hg the decreased use of dental amalgam may also have had an influence. For Cd, the decline in Ery-Cd was seen only in smokers, indicating that Cd exposure from tobacco has decreased, while other environmental sources of Cd have not changed significantly. To further improve the health status in Sweden, it is important to decrease the pollution of Cd, and actions against smoking in the community are important.

Objective: The rising incidence and the strong male predominance among patients with esophageal and gastric cardia adenocarcinoma remain unexplained. We hypothesized that occupational airborne exposures in a traditional male dominated industry might contribute to these observations. Methods: A prospective, large cohort study of Swedish construction workers was linked to the Swedish population-based registers of Cancer, Causes of Death and Total Population. 260,052 men were followed from 1971 through 2000. Industrial hygienists assessed specific exposures for 200 job titles, and occupational airborne exposures were analyzed separately and combined. Incidence rate ratios (IRR), with 95% confidence intervals (CI), were estimated in multivariable Cox regression models adjusted for attained age, calendar period, smoking status and body mass. Results: We found positive associations between high exposure to asbestos (IRR 4.5 [95% CI 1.4-14.3]) and cement dust (IRR 3.8 [95% CI 1.5-9.6]) and risk of esophageal adenocarcinoma. Associations were seen between high exposure to asphalt fumes (IRR 2.3 [95% CI 1.0-5.3]) and wood dust (IRR 4.8 [95% CI 1.2-19.4]) and risk of cardia adenocarcinoma. No consistent associations regarding esophageal squamous-cell carcinoma were found. Conclusions: Exposure to asbestos and cement dust may be risk factors for esophageal adenocarcinoma, and exposure to asphalt fumes and wood dust may increase the risk of cardia adenocarcinoma. However, these associations cannot explain the major sex differences or the increasing incidence trends of these tumors. © Springer 2005.

The aim of this study was to find out if occupational exposure to dust, fumes or gases, especially among never-smokers, increased the mortality from chronic obstructive pulmonary disease (COPD). A cohort of 317,629 Swedish male construction workers was followed from 1971 to 1999. Exposure to inorganic dust (asbestos, man-made mineral fibres, dust from cement, concrete and quartz), gases and irritants (epoxy resins, isocyanates and organic solvents), fumes (asphalt fumes, diesel exhaust and metal fumes), and wood dust was based on a job-exposure matrix. An internal control group with "unexposed" construction workers was used, and the analyses were adjusted for age and smoking. When all subjects were analysed, there was an increased mortality from COPD among those with any airborne exposure (relative risk 1.12 (95% confidence interval (CI) 1.03-1.22)). In a Poisson regression model, including smoking, age and the major exposure groups, exposure to inorganic dust was associated with an increased risk (hazard ratio (HR) 1.10 (95% CI 1.06-1.14)), especially among never-smokers (HR 2.30 (95% CI 1.07-4.96)). The fraction of COPD among the exposed attributable to any airborne exposure was estimated as 10.7% overall and 52.6% among never-smokers. In conclusion, occupational exposure among construction workers increases mortality due to chronic obstructive pulmonary disease, even among never-smokers.

Food is the main source of trace elements for the general population. The gastrointestinal absorption of certain trace elements, e.g., cadmium, is strongly influenced by iron (Fe) status. This factor may also be relevant for the bioavailability of other trace elements. Therefore, we investigated relationships between Fe status indicators and trace element concentrations in blood and serum of 234 boys and girls at ages 15 and 17 years. Fe status was measured using serum ferritin (S-Ft), soluble transferrin receptor in serum (sTfR), and the ratio sTfR/S-Ft. The trace elements we investigated were, in blood, cadmium, cobalt, copper, zinc, selenium, rubidium, mercury, and lead, and, in serum, cobalt, copper, zinc, selenium, rubidium, tungsten, mercury, and lead. We found inverse correlations between Fe status and blood cadmium, blood or serum cobalt, or blood copper. There were positive correlations between Fe status and mercury concentrations. Selenium was positively correlated with sTfR. The relationships between Fe status and lead were equivocal. There were fewer correlations for serum than for blood, but the inverse relationships between Fe status and cobalt were equally strong in serum and blood. We found only occasional, and perhaps spurious, correlations with zinc, rubidium, and tungsten. In conclusion, previous indications that cadmium, cobalt, and copper are absorbed by transport mechanisms similar to that of Fe are supported by this study. Strong positive correlations between Fe status and mercury concentrations remain to be explained.

We examined the relationships between occupational exposures and the risk of multiple myeloma among male construction workers in Sweden. A total of 446 myeloma subjects were identified among 365,424 male workers followed from 1971 to 1999. Occupational exposure was assessed using a semiquantitative job-exposure matrix, based on a survey carried out by the Construction Industry's Organization for Working Environment, Occupational Safety and Health in Sweden. Rate ratios (RRs) in the exposed groups relative to the unexposed groups were estimated by Poisson regression. We found an increased risk (RR = 1.3, 95% CI 1.04-1.71) among construction workers exposed to diesel exhaust. Adjustment for other occupational exposures did not change this estimate (RR = 1.3, 95% CI 1.00-1.77). However, there was no monotonic increase in risk with estimated level of exposure (RR for low = 1.4, moderate = 1.1, high = 1.4). There was no evidence of increased risk associated with the other occupational exposures among these construction workers, including asbestos, asphalt, cement dust, metal dust, mineral wool, organic solvents, stone dust and wood dust. Occupational exposure to diesel exhaust in the Swedish construction industry may present a small risk of multiple myeloma, but lack of an exposure-response trend tempers our ability to draw clear conclusions.

Background: Within- and between-worker variance components have seldom been reported for both environmental and biological data collected from the same persons. Aims: To estimate these variance components and their ratio for air contaminants and urinary metabolites in two different work environments and to predict the attenuation of exposure-response relationships based on these measures. Methods: Parallel measurements of air and urine were performed among workers exposed to monoterpenes in sawmills (urinary metabolite: verbenol) and styrene in reinforced plastics factories (urinary metabolite: mandelic acid). Results: Among the sawmill workers, variance components of the air and urinary verbenol results were similar; for the reinforced plastics workers the estimated between-worker variance component was greater for styrene in air than mandelic acid in urine. This suggests that attenuation bias would be about equal if air or biological monitoring were employed for monoterpene exposures, but would be greater if urinary mandelic acid were used instead of airborne styrene in an investigation of styrene exposure. Conclusions: Personal air samplers provide data with similar or superior quality to urinary metabolites as measures of exposure to these monoterpenes in sawmills and styrene in reinforced plastics factories.

Some studies have indicated an increased risk of lung cancer among asphalt workers. This study investigates the risk of lung cancer in Swedish asphalt workers.A cohort of 6,150 asphalt workers, mainly employed in road construction, was compared to the general population, and to a reference group of construction workers not exposed to asphalt fumes. The exposure to polyaromatic hydrocarbons (PAH) at paving in Sweden during the 1980s and 1990s were estimated to be in the order of one or a few micrograms per cubic meter, but must have been higher in earlier years.Thirty-two lung cancer cases were observed among asphalt workers. The relative risk (SIR) and 95% confidence intervals were 0.98 (0.67-1.39). The corresponding relative risk, as compared to a group of construction workers and adjusted for smoking habits, was 1.03 (0.70-1.45). We found no increased risk for other cancers investigated or death in other lung diseases.Asphalt workers do not have any increased lung cancer risk from exposure to fumes and gases from asphalt at the exposure levels that occurred in Sweden during the 1960s and 1970s.

The influence of gender, age, residential area, and socioeconomic status on the blood and serum levels of 13 trace elements was studied in boys and girls living in two Swedish cities with different socioeconomic and environmental characters. The same groups of adolescents were sampled twice, at ages 15 (n=372) and 17 (n=294) years. All the investigated factors were shown to be of importance. Age was important for most elements; e.g., copper levels in both blood and serum increased in girls, and selenium increased in serum from both genders. Lead decreased approximately 10% in blood from the first to the second sampling, and cadmium increased in blood, however not in nonsmokers. The age factor may also reflect temporal changes in environmental exposure, especially for nonessential elements. Girls had higher levels of cobalt and copper, while lead in blood was higher in boys. Smoking girls had higher copper levels than nonsmoking girls. Residential area influenced all elements. The teenagers with university-educated mothers had higher levels of cadmium in blood than those with only primary school-educated mothers.

If there is an effect of lead exposure on malaria, then the activity of delta-aminolevulinate dehydratase (ALAD) may play a role, as ALAD is imported by the parasite from the host

Another fundamental error in "What is the meaning of non-linear dose-response relationships between blood lead concentrations and IQ?" became obvious in the authors' response to comments.

Supported liquid membrane (SLM) methodology was used for sample clean-up and enrichment of lead in urine prior to determination by AAS. Lead ions at pH 3 were extracted across a membrane solution containing 40% m/m di-2-ethylhexylphosphoric acid dissolved in kerosene and back-extracted into an acceptor solution of 1 mol l-1 nitric acid. The mechanism of mass transfer is a proton gradient across the membrane. The concentration range investigated was between 5 and 80 ng ml-1 and the extraction time was varied between 0.5 and 4 h, leading to enrichment factors of up to 200. The extraction efficiency was about 95%. The detection limit, expressed as 3 sigma of five replicate determinations, using a 45 min enrichment of a urine sample low in lead, was 0.1 and 6.0 micrograms l-1 for ETAAS, and FAAS respectively. The results obtained by the developed method agreed with those obtained by direct ICP-MS determinations for reference urine samples and samples from occupationally lead-exposed workers. The linear correlation coefficient was 0.97, the slope of the regression line was 1.06 and the intercept was -0.37 microgram l-1. The 95% confidence intervals for the slope and the intercept were 0.95 to 1.18 and -3.9 to 3.1, respectively. The results at the 95% confidence level for reference urine material were of 91 +/- 1.5 and 92 +/- 2.0 micrograms l-1 for ICP-MS and SLM-AAS, respectively, which agreed well with the recommended value of 90 micrograms l-1 (range 83-97 micrograms l-1).

Delta-aminolevulinic acid dehydratase (ALAD) polymorphism has been reported to modify lead pharmacokinetics (i.e., individuals who express the ALAD 2 allele [ALAD2 subjects] have higher blood lead levels than homozygotes for the ALAD 1 allele [ALAD1 subjects]). In our study of 89 lead-exposed workers (7 ALAD2 homozygotes or heterozygotes) and 34 unexposed workers (100 ALAD2 heterozygotes), concentrations of urinary calcium and creatinine were lower in ALAD2 subjects than in ALAD1 subjects (respective medians: calcium-78 mg/l versus 185 mg/l, p =.003; creatinine-11.2 mmol/l versus 14.9 mmol/l, p =.008). No association was found between ALAD genotype and blood lead levels or bone lead levels. However, expression of the ALAD 2 allele occurred less frequently among lead-exposed workers than in unexposed controls. The results indicated the presence of ALAD allele-specific differences in kidney function, as well as a possible genetic healthy-worker selection.

Inorganic mercury (InoHg) in whole blood and erythrocytes was determined by cold vapour atomic absorption spectrometry (CVAAS) after overnight treatment with sulfuric acid at 45 degrees C and reduction with SnII in the acidic mixture. Total mercury (TotHg) was determined after digestion with a mixture of nitric and perchloric acids. Mercury vapour was preconcentrated on an amalgamation trap made of gold wire. The mercury was rapidly released by inductive heating of the trap. InoHg could be determined specifically in the presence of methylmercury (MeHg). The concentration of MeHg could be calculated by subtracting the concentration of InoHg from that of TotHg. Calculated concentrations of MeHg in erythrocytes showed a strong correlation with the results of a gas chromatographic method, though a discrepancy in calibration was indicated. The detection limits (3 s) in blood (0.5 g) were 0.06 ng g-1 for TotHg and 0.04 ng g-1 for InoHg and S(r) for a 5 ng g-1 whole blood sample was 2% (n = 10) for both TotHg and InoHg.

What is the meaning of non-linear dose-response relationships between blood lead concentrations and IQ?

We are grateful for the valuable comments by D.M. Bernstein. We fully agree with him that the papers we cited do not corroborate our findings. The cited papers do …