Associations of PFAS-related plasma metabolites with cholesterol and triglyceride concentrations.

The wide-spread environmental pollutants per- and polyfluoroalkyl substances (PFAS) have repeatedly been associated with elevated serum cholesterol in humans. However, underlying mechanisms are still unclear. Furthermore, we have previously observed inverse associations with plasma triglycerides. To better understand PFAS-induced effects on lipid pathways we investigated associations of PFAS-related metabolite features with plasma cholesterol and triglyceride concentrations. We used 290 PFAS-related metabolite features that we previously discovered from untargeted liquid chromatography-mass spectometry metabolomics in a case-control study within the Swedish Västerbotten Intervention Programme cohort. Herein, we studied associations of these PFAS-related metabolite features with plasma cholesterol and triglyceride concentrations in plasma samples from 187 healthy control subjects collected on two occasions between 1991 and 2013. The PFAS-related features did not associate with cholesterol, but 50 features were associated with triglycerides. Principal component analysis on these features indicated that one metabolite pattern, dominated by glycerophospholipids, correlated with longer chain PFAS and associated inversely with triglycerides (both cross-sectionally and prospectively), after adjustment for confounders. The observed time-trend of the metabolite pattern resembled that of the longer chain PFAS, with higher levels during the years 2004-2010. Mechanisms linking PFAS exposures to triglycerides may thus occur via longer chain PFAS affecting glycerophospholipid metabolism. If the results reflect a cause-effect association, as implied by the time-trend and prospective analyses, this may affect the general adult population.

Plasma metabolite biomarkers of boiled and filtered coffee intake and their association with type 2 diabetes risk.

BACKGROUND: Habitual coffee intake has been associated with a lower risk of developing type 2 diabetes (T2D), but few studies used biomarkers to reflect intake and investigated different coffee brews, that is boiled and filtered, separately. OBJECTIVES: To identify plasma metabolites associated with boiled or filtered coffee intake and to examine their association with T2D risk in Swedish adults. METHODS: In a case-control study nested within the Västerbotten Intervention Programme, baseline plasma samples from 421 case-control pairs and samples from a subset of 149 pairs at a 10-year follow-up were analysed using untargeted LC-MS metabolomics. We identified metabolites associated with food frequency questionnaires (FFQ)-estimated coffee intake and assessed odds ratios of T2D. RESULTS: In total, 24 and 32 metabolites were associated with boiled or filtered coffee intake. We determined robust metabolite panels for highly specific prediction of boiled or filtered coffee. We observed an inverse association between the metabolite panel of filtered coffee and T2D risk. No association with T2D was observed for the panel of boiled coffee intake. Similar results were observed for FFQ-estimated coffee intake. CONCLUSIONS: We identified plasma metabolites specifically associated with boiled or filtered coffee intake, which might be used as selective biomarkers. Our study supports a protective role of habitual intake of filtered coffee on T2D development. The lack of association for boiled coffee intake might be due to the lack of a protective effect of boiled coffee or due to the limited number of boiled coffee consumers in this population, but it warrants further investigation.

Choosing the number of images and image position when analyzing the UNC Passive Aerosol Sampler for occupational exposure assessment.

The University of North Carolina passive aerosol sampler (UNC sampler) could be an alternative when measuring occupational dust exposure, but the time required for microscopic imaging of the sampler needs to be reduced to make it more attractive. The aims of this study were to (1) characterize the effect on precision when reducing imaging, in order to shorten analysis time and (2) assess if the position of the images makes a difference. Eighty-eight samplers were deployed in different locations of an open pit mine. Sixty images were captured for each UNC sampler, covering 51% of its collection surface, using scanning electron microscopy. Bootstrapped samples were generated with different image combinations, to assess the within-sampler coefficient of variation (CVws) for different numbers of images. In addition, the particle concentration relative to the distance from the center of the sampler was studied. Reducing the number of images collected from the UNC sampler led to up to 8.3% CVws for 10 images when calculating respirable fraction. As the overall CV has previously been assessed to 36%, the additional contribution becomes minimal, increasing the overall CV to 37%. The mean concentrations of the images were modestly related to distance from the center of the sampler. The CVws changed from 8.26% to 8.13% for 10 images when applying rules for the image collection based on distance. Thus, the benefit of these rules on the precision is small and the images can therefore be chosen at random. In conclusion, reducing the number of images analyzed from 60 to 10, corresponding to a reduction of the imaged sampling area from 51% to 8.5%, results in a negligible loss in precision for respirable fraction dust measurements in occupational environments.

Future directions for monitoring and human health research for the Arctic Monitoring and Assessment Programme.

For the last two and a half decades, a network of human health experts under the Arctic Monitoring and Assessment Program (AMAP) has produced several human health assessment reports. These reports have provided a base of scientific knowledge regarding environmental contaminants and their impact on human health in the Arctic. These reports provide scientific information and policy-relevant recommendations to Arctic governments. They also support international agreements such as the Stockholm Convention on Persistent Organic Pollutants (POPs) and the Minamata Convention on Mercury. Key topics discussed in this paper regarding future human health research in the circumpolar Arctic are continued contaminant biomonitoring, health effects research and risk communication. The objective of this paper is to describe knowledge gaps and future priorities for these fields.

Prediagnostic transcriptomic markers of Chronic lymphocytic leukemia reveal perturbations 10 years before diagnosis.

BACKGROUND: B-cell lymphomas are a diverse group of hematological neoplasms with differential etiology and clinical trajectories. Increased insights in the etiology and the discovery of prediagnostic markers have the potential to improve the clinical course of these neoplasms. METHODS: We investigated in a prospective study global gene expression in peripheral blood mononuclear cells of 263 incident B-cell lymphoma cases, diagnosed between 1 and 17 years after blood sample collection, and 439 controls, nested within two European cohorts. RESULTS: Our analyses identified only transcriptomic markers for specific lymphoma subtypes; few markers of multiple myeloma (N = 3), and 745 differentially expressed genes in relation to future risk of chronic lymphocytic leukemia (CLL). The strongest of these associations were consistently found in both cohorts and were related to (B-) cell signaling networks and immune system regulation pathways. CLL markers exhibited very high predictive abilities of disease onset even in cases diagnosed more than 10 years after blood collection. CONCLUSIONS: This is the first investigation on blood cell global gene expression and future risk of B-cell lymphomas. We mainly identified genes in relation to future risk of CLL that are involved in biological pathways, which appear to be mechanistically involved in CLL pathogenesis. Many but not all of the top hits we identified have been reported previously in studies based on tumor tissues, therefore suggesting that a mixture of preclinical and early disease markers can be detected several years before CLL clinical diagnosis.

Iron status influences trace element levels in human blood and serum.

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.

Increased mortality in COPD among construction workers exposed to inorganic dust.

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.

Exposure assessment of monoterpenes and styrene: a comparison of air sampling and biomonitoring.

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.

[No connection between the number of amalgam fillings and health. Epidemiological observations from a population study of women in Gothenburg]. / Inget samband mellan antal amalgamfyllningar och hälsa. Epidemiologiska erfarenheter från populationsstudie av kvinnor i Göteborg.

Number of dental amalgam fillings and baseline serum mercury concentration were assessed with respect to a number of health related variables as part of a population study of women. There was no increased incidence of symptoms, no derangement of laboratory variables of clinical significance, nor any increased mortality or increased risk of myocardial infarction, stroke, diabetes or cancer in women with many amalgam fillings compared with those with few fillings, nor in women with higher serum mercury concentration compared with those with lower serum mercury concentration.

Zinc, magnesium and calcium in human seminal fluid: relations to other semen parameters and fertility.

The effects of zinc, magnesium and calcium in seminal plasma on time-to-pregnancy (TTP) in healthy couples, on conventional semen parameters and computer-assisted semen analysis (CASA) parameters were evaluated. The localization of chelatable zinc ions in seminal plasma and spermatozoa were assessed by autometallography (AMG). Differences in chelatable zinc localization in samples with high and low total zinc were evaluated. Semen samples from 25 couples with short TTP and 25 couples with long TTP were subjected to conventional semen analysis, CASA, zinc and magnesium measurements by inductively coupled plasma mass spectrometry, and calcium by flame atomic absorption spectrometry. The cations were strongly inter-correlated, but no correlation with TTP or conventional semen parameters was found. Semen samples with high zinc concentrations exhibited statistically significant poorer motility assessed by the CASA parameters straight line velocity and linearity than samples with low zinc content. Calcium concentration also showed statistically significant differences for the same parameters, but the effect was removed by entering zinc concentration into a multiple regression model. Semen samples with high total zinc exhibited stronger staining of the seminal plasma at AMG. It is suggested that high seminal zinc concentrations have a suppressing effect on progressive motility of the spermatozoa ('quality of movement'), but not on percentage of motile spermatozoa ('quantity of movement').

Lead in plasma and whole blood from lead-exposed children.

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.

Fractionation of soluble selenium compounds from fish using size-exclusion chromatography with on-line detection by inductively coupled plasma mass spectrometry.

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 and inorganic mercury in serum--correlation to fish consumption and dental amalgam in a cohort of women born in 1922.

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.

Lead concentrations in tibial and calcaneal bone in relation to the history of occupational lead exposure.

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, R2 = 0.78) and calcaneus (R2 = 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 with cumB-Pb, did not significantly change the variance in the relation to bone-Pb.

Plasma and blood lead in humans: capacity-limited binding to delta-aminolevulinic acid dehydratase and other lead-binding components.

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.

Lead concentrations in human plasma, urine and whole blood.

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 microg/l, and the imprecision was 5%. RESULTS: The lead concentration ranges were 0.20-37 microg/l for P-Pb, 0.9-176 microg/l (density adjusted) for U-Pb, and 9-930 microg/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 x 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. CONCLUSIONS: 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.

Lead binding to delta-aminolevulinic acid dehydratase (ALAD) in human erythrocytes.

Over 99% of the lead present in blood is usually found in erythrocytes. To investigate the nature of this selective accumulation of lead in erythrocytes, the specific binding of lead to proteins in human erythrocytes was studied using liquid chromatography coupled to inductively coupled plasma mass spectrometry (LC-ICP-MS). The principal lead-binding protein had a mass of approximately 240 kDa, and adsorption to specific antibodies showed that protein was delta-aminolevulinic acid dehydratase (ALAD). Thus, the previous notion that lead in erythrocytes was bound primarily to haemoglobin has to be revised. Furthermore, in lead-exposed workers, the percentage of lead bound to ALAD was influenced by a common polymorphism in the ALAD gene. Specifically, in seven carriers of the ALAD2 allele, 84% of the protein-bound lead recovered was bound to ALAD compared to 81% in seven homozygotes for the ALAD1 allele whose erythrocytes were matched for blood-lead concentration. The small difference was statistically significant in Wilcoxon matched-pairs signed-rank test (P = 0.03). No ALAD allele-specific difference in ALAD-bound lead was found among 20 unexposed controls. Perhaps the difference in ALAD-bound lead can provide an explanation for the previously reported finding of higher blood-lead levels among carriers of the ALAD2 allele than among ALAD1 homozygotes in lead-exposed populations.

Delta-aminolevulinic acid dehydratase polymorphism: influence on lead levels and kidney function in humans.

Delta-aminolevulinic acid dehydratase (ALAD) polymorphism has been reported to modify lead pharmacokinetics (i.e., individuals who express the ALAD2 allele [ALAD2 subjects] have higher blood lead levels than homozygotes for the ALAD1 allele [ALAD1 subjects]). In our study of 89 lead-exposed workers (7 ALAD2 homozygotes or heterozygotes) and 34 unexposed workers (10 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 ALAD2 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.

Supported liquid membrane enrichment combined with atomic absorption spectrometry for the determination of lead in urine.

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).