Evert Nieboer

Human health risk assessment for aluminium, aluminium oxide, and aluminium hydroxide.

Note: This article was originally published with an incorrect version of the Acknowledgments, which appeared on p. 218 of the print version. The correct version of the Acknowledgments appeared on pp. 1–2. The corrected article is available below.

Persistent Organic Pollutants in Norwegian Men from 1979 to 2007: Intraindividual Changes, Age–Period–Cohort Effects, and Model Predictions

Background: Longitudinal monitoring studies of persistent organic pollutants (POPs) in human populations are important to better understand changes with time and age, and for future predictions. Objectives: We sought to describe serum POP time trends on an individual level, investigate age–period–cohort effects, and compare predicted polychlorinated biphenyl (PCB) concentrations to measured values. Methods: Serum was sampled in 1979, 1986, 1994, 2001, and 2007 from a cohort of 53 men in Northern Norway and analyzed for 41 POPs. Time period, age, and birth cohort effects were assessed by graphical analyses and mixed-effect models. We derived the predicted concentrations of four PCBs for each sampling year using the CoZMoMAN model. Results: The median decreases in summed serum POP concentrations (lipid-adjusted) in 1986, 1994, 2001, and 2007 relative to 1979 were –22%, –52%, –54%, and –68%, respectively. We observed substantial declines in all POP groups with the exception of chlordanes. Time period (reflected by sampling year) was the strongest descriptor of changes in PCB-153 concentrations. Predicted PCB-153 concentrations were consistent with measured concentrations in the study population. Conclusions: Our results suggest substantial intraindividual declines in serum concentrations of legacy POPs from 1979 to 2007 in men from Northern Norway. These changes are consistent with reduced environmental exposure during these 30 years and highlight the relation between historic emissions and POP concentrations measured in humans. Observed data and interpretations are supported by estimates from the CoZMoMAN emission-based model. A longitudinal decrease in concentrations with age was evident for all birth cohorts. Overall, our findings support the relevance of age–period–cohort effects to human biomonitoring of environmental contaminants. Citation: Nøst TH, Breivik K, Fuskevåg OM, Nieboer E, Odland JØ, Sandanger TM. 2013. Persistent organic pollutants in Norwegian men from 1979 to 2007: intraindividual changes, age–period–cohort effects, and model predictions. Environ Health Perspect 121:1292–1298; http://dx.doi.org/10.1289/ehp.1206317

Blood lead and cadmium and birth weight among sub-arctic and arctic populations of Norway and Russia

BACKGROUND Delivering women and their newborns in the Kola Peninsula of Russia and the neighboring arctic area of Norway were studied to explore relationships between maternal cadmium and lead status and birth weight as a pregnancy outcome. METHODS Life-style information, maternal blood and cord blood specimens were collected from 50 consecutive mother-infant pairs from hospital delivery departments in three Russian and three Norwegian communities. Pregnancy outcomes were verified by consulting medical records. Lead and cadmium were determined in the blood samples by electrothermal atomic absorption spectrometry. RESULTS The median blood-cadmium concentration for the Russian mothers was 2.2 nmol/L (n = 148) versus 1.8 nmol/L in the Norwegian group (n = 114, p = 0.55). A weak association was observed between maternal cadmium and amount smoked (r = 0.30, p<0.001); no correlation was found between maternal blood cadmium and birth weight. The corresponding maternal lead values were 0.14 (Russia) and 0.06 micromol/L (Norway), p<0.001. The latter lead concentration constitutes one of the lowest adult population values reported to date. Maternal and cord blood lead levels were strongly correlated (r = 0.88, p<0.001). In a multivariate linear regression model, maternal blood lead was recognized as a negative explanatory variable (p<0.05) for birth weight and childs body mass index (BMIC), with or without adjustment for gestational age. A similar association was suggested by ANOVA-analysis of maternal blood lead by quartiles. CONCLUSION Maternal blood-lead level as an environmental factor is an apparent predictor of low birth weight and BMIC. It reduced substantially the contribution of a country factor in explaining the observed differences in birth weight.

Repeated measurements of per- and polyfluoroalkyl substances (PFASs) from 1979 to 2007 in males from Northern Norway: assessing time trends, compound correlations and relations to age/birth cohort.

BACKGROUND Longitudinal biomonitoring studies can provide unique information on how human concentrations change over time, but have so far not been conducted for per- and polyfluoroalkyl substances (PFASs) in a background exposed population. OBJECTIVES The objectives of this study were to determine: i) serum PFAS time trends on an individual level; ii) relative compositions and correlations between different PFASs; and iii) assess selected PFAS concentrations with respect to periodic (calendar year), age and birth cohort (APC) effects. METHODS Serum was sampled from the same 53 men in 1979, 1986, 1994, 2001 and 2007 in Northern Norway and analysed for 10 PFASs. APC effects were assessed by graphical and mixed effect analyses. RESULTS The median concentrations of perfluorooctane sulphonic acid (PFOS) and perfluorooctanoic acid (PFOA) increased five-fold from 1979 to 2001 and decreased by 26% and 23%, respectively, from 2001 to 2007. The concentrations of PFOS and PFOA peaked during 1994-2001 and 2001, respectively, whereas perfluorohexane sulphonic acid (PFHxS) increased to 2001, but did not demonstrate a decrease between 2001 and 2007. Perfluorononanoic acid (PFNA), perfluorodecanoic acid (PFDA), and perfluoroundecanoic acid (PFUnDA) displayed increasing trends throughout the entire study period (1979-2007). Although PFOS comprised dominating and stable proportions of PFAS burdens during these years, the contributions from PFOA and PFHxS were considerable. The evaluation of APC effects demonstrated that calendar year was the dominating influence on concentrations of PFOA, PFUnDA, and PFOS, although time-variant and weaker associations with age/birth cohort were indicated. CONCLUSIONS The concentration changes of 10 PFASs in the repeated measurements from 1979 to 2007 demonstrated divergent time trends between the different PFASs. The temporal trends of PFASs in human serum during these 30years reflect the overall trends in historic production and use, although global transport mechanisms and bioaccumulation potential of the different PFASs together with a varying extent of consumer exposure influenced the observed trends. Sampling year was the strongest descriptor of PFOA, PFUnDA and PFOS concentrations, and the calendar-year trends were apparent for all birth year quartiles. Discrepancies between the trends in this current longitudinal study and previous cross-sectional studies were observed and presumably reflect the different study designs and population characteristics.

Partition of perfluoroalkyl substances (PFASs) in whole blood and plasma, assessed in maternal and umbilical cord samples from inhabitants of arctic Russia and Uzbekistan.

Perfluoroalkyl substances (PFASs) are ubiquitous in the environment world-wide. Our overall objective was to assess the exposure to PFASs experienced by delivering women and their new-borns in the industrial city of Norilsk (arctic Russia) and the rural Aral Sea region of Uzbekistan, with the secondary objective of evaluating the distribution of PFASs between blood cell and plasma fractions. Six PFASs were detected in every sample from Norilsk city with the plasma concentration sequence of: PFOS≫PFOA>PFNA>FOSA>PFHxS>PFUnDA. In the Uzbekistani samples, only PFOS was reported above the MDL (0.08 ng/mL). The median plasma concentrations of PFOS of 11.0 ng/mL for the Norilsk mothers was comparable to that reported for western countries, while that for Uzbekistan was considerably lower (0.23 ng/mL). Apparent increases in the maternal-cord concentration ratios for both whole blood and plasma were evident with the length of the carbon chain for both the carboxylate and the sulfonate PFASs. The median value of this ratio for FOSA in plasma was the lowest, while that for whole blood was the highest. Other than for FOSA, the observed plasma-whole blood concentration ratios for maternal and umbilical cord blood were consistent with a priori calculations using appropriate packed cell and plasma volumes for neonates and pregnant women at term. Clearly FOSA favored whole blood, and acid-base equilibrium calculations suggested that the resonance-stabilized sulfonamidate ion resides in the blood cell fraction. Thus for PFASs and related compounds with pK values with magnitudes comparable to physiological pH, it is pertinent to measure the cell-associated fraction (separately or as whole blood). Our study illustrates that consideration of both the physico-chemical properties of the contaminants and the physiological attributes of blood matrices were helpful in the interpretation of our findings.

The identification of lead ammunition as a source of lead exposure in First Nations: The use of lead isotope ratios

The use of lead shotshell to hunt water birds has been associated with lead-contamination in game meat. However, evidence illustrating that lead shotshell is a source of lead exposure in subsistence hunting groups cannot be deemed definitive. This study seeks to determine whether lead shotshell constitutes a source of lead exposure using lead isotope ratios. We examined stable lead isotope ratios for lichens, lead shotshell and bullets, and blood from residents of Fort Albany and Kashechewan First Nations, and the City of Hamilton, Ontario, Canada. Data were analyzed using ANOVA and regression analyses. ANOVA of isotope ratios for blood revealed significant differences with respect to location, but not sex. Hamilton differed from both Kashechewan and Fort Albany; however, the First Nations did not differ from each other. ANOVA of the isotope ratios for lead ammunition and lichens revealed no significant differences between lichen groups (north and south) and for the lead ammunition sources (pellets and bullets). A plot of (206)Pb/(204)Pb and (206)Pb/(207)Pb values illustrated that lichens and lead ammunition were distinct groupings and only the 95% confidence ellipse of the First Nations group overlapped that of lead ammunition. In addition, partial correlations between blood-lead levels (adjusted for age) and isotope ratios revealed significant (p<0.05) positive correlations for (206)Pb/(204)Pb and (206)Pb/(207)Pb, and a significant negative correlation for (208)Pb/(206)Pb, as predicted if leaded ammunition were the source of lead exposure. In conclusion, lead ammunition was identified as a source of lead exposure for First Nations people; however, the isotope ratios for lead shotshell pellets and bullets were indistinguishable. Thus, lead-contaminated meat from game harvested with lead bullets may also be contributing to the lead body burden.

The interaction of metal ions with synthetic DNA: Induction of conformational and structural transitions

The propensity of a large number of metal ions to induce cooperative conformational or structural transitions in double-stranded poly d(G-C) was assessed by UV and CD spectrometry. This ability was seen to be an intrinsic property of most metal ions. The observed (metal ion)/(polydeoxynucleotide) mole ratio calculated per G-C base pair and corresponding to the midpoints of the principal transition ranged from 0.3 (Ag(II) to 100 (Al(III)). A strong correlation was seen [y = -1.01(log x) + 3.26, r = 0.95, n = 20] between the (metal ion)/(poly d(G-C)) mole ratio required for the transition midpoint (x) and a covalent index to complex stability (y) of the metal ions. This relationship was independent of the types of transitions observed (monophasic or biphasic) or of specific conformations (e.g., B, Z, psi). The y index measures the ability of metal ions to bind to nitrogen and/or sulphur donor atoms in ligands compared to oxygen centers; equilibrium analysis indicates that the mole-ratio x decreases with increasing affinity of metal ions for poly d(G-C). Thus the observed relationship suggests that base-nitrogen binding facilitates the induced transitions. In general, metal ions designated as Class B or nitrogen/sulphur seeking (Ag(I), Hg(II), and Ru(III)) induced monophasic transitions, whereas Class A or oxygen seeking ions (La(III), Ce(III), Tb(III), Dy(III)) induced biphasic transitions. Transitions generated by ions of more ambivalent ligand preference (Borderline ions) were either monophasic (Mn(II), Fe(III), Cu(II), Cd(II), In(III), and Pb(II)) or biphasic (Cr(III), Co(II), Ni(II) and Zn(II)). Poorly defined transition-curve profiles were observed for Pt(II), Pd(II), and Al(III). Specific conformational assignments were made for some of the observed transitions. For a limited number of metal ions (Ni(II), Cu(II), Cd(II), Ag(I), Hg(II)), interaction with calf thymus DNA was similarly examined. In these instances, the susceptibility to DNase I digestion of both the DNA and polydeoxynucleotide complexes was assessed.

Characterisation of workers' exposure in a Russian nickel refinery

In support of a feasibility study of reproductive and developmental health among females employed in the Monchegorsk (Russia) nickel refinery, personal exposure and biological monitoring assessments were conducted. The inhalable aerosol fraction was measured and characterised by chemical speciation and particle-size distribution measurements. Unexpected findings were that: (i), pyrometallurgical working environments had significant levels of water-soluble nickel; (ii), significant exposure to cobalt occurred for the nickel workers; (iii), particles of size corresponding to the thoracic and respirable fractions appeared to be virtually absent in most of the areas surveyed. The water-soluble fraction is judged to be primarily responsible for the observed urinary nickel and cobalt concentrations. It is concluded relative to current international occupational-exposure limits for nickel in air, and because of the high nickel concentrations observed in urine, that the Monchegorsk nickel workers are heavily exposed. The implication of this finding for follow-up epidemiological work is alluded to.

Intra- and intercompartmental associations between levels of organochlorines in maternal plasma, cord plasma and breast milk, and lead and cadmium in whole blood, for indigenous peoples of Chukotka, Russia.

Long-range transport of pollutants towards circumpolar regions emphasizes the need for up-to-date and reliable biological monitoring data. This paper explores the use, reliability and availability of maternal blood (MB) and plasma (MP), cord blood (CB) and plasma (CP) and mothers milk (MM) in terms of assessing exposure to persistent toxic substances (PTSs). It is concluded that MP has the best combination of availability, sensitivity in terms of number of PTSs, their detection frequency and concentrations, and physiological relevance. The study group consisted of 48 pregnant women of indigenous origin from the Chuchki district in the eastern Russian arctic. Blood, CB and MM specimens were collected from all women and MP, CP and MM were analyzed for the Arctic Monitoring and Assessment Programme (AMAP) suite of organochlorines (OCs) and metals (Pb and Cd in MB and CB). Generally speaking, the levels of PTSs coincided with those indicated in several AMAP publications from Chukotka and other areas of northern Russia. The correlations of PTS concentrations between the three body fluid compartments exceeded the minimum statistical requirements of alpha = 0.05 and beta = 0.20 for most of the compounds, with r > 0.46 except for Cd (r = 0.05); lipid adjustments for the OCs did not affect the r-values to any significant extent. The majority of the inter-OC correlations within compartments also fulfilled the indicated statistical condition. Careful consideration is given to the replacement of concentrations below the detection limit, OC detection frequency, the criteria for log-transformation of the data, analytical uncertainty, and biological variability. Practical implications of the findings are explored.

Relevance of reactivity determinants to exposure assessment and biological monitoring of the elements

2 Determinant factors in the biological chemistry and Solids are the most commonly encountered forms of metals toxicology of the elements and metalloids in human respiratory exposures. Particle size 2.1 Introductory comment determines what can be inhaled and where in the respiratory 2.2 Physical state tract particles penetrate and are deposited, while particle 2.3 Atomic properties surface activity and solubility influence the extent and rate of 2.4 Determinants of reactivity absorption of its constituents by the lung or by the gastrointes2.4.1 Ionic and covalent bonding tendencies and donor-atom tinal (GI ) tract. As shown later, these properties can also preference mediate the type and degree of tissue injury on contact. 2.4.2 Metal-ion complex formation and stability Under standard conditions (25 °C and 101.3 kPa), very few 2.4.3 Kinetic aspects compounds of metals and metalloids are liquids. Exceptions 2.4.4 Solubility are mercury metal, nickel tetracarbonyl, certain alkyl deriva2.4.5 Speciation of the elements tives of, for example, lead, mercury and tin and chlorides of 2.4.6 Radical formation arsenic and germanium. If not contained, such liquids release 2.4.7 Particle size and shape vapours, which in most cases are extremely toxic.2,3 Vapours 2.4.8 Physico-chemical properties of solid surfaces can also arise from solids by sublimation, of which arsenic 2.5 Biological factors trioxide ( 193 °C ) is an example. 2.5.1 Compartmentalization Gases are common forms of compounds that have as 2.5.2 Respiratory tract deposition and clearance components the lighter elements (e.g., N, O, S, halogens) and 2.5.3 Bioavailability and uptake some elements with high atomic masses such as As, Sb and 2.5.4 Biological turnover time and bioaccumulation Se. Obviously the most frequently encountered environmental 2.5.5 Tolerance and susceptibility gaseous pollutants are included in the former group, namely 3 Conclusion sulfur dioxide, ozone, carbon monoxide, carbon dioxide and