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Biomedical subjects

E Sabbioni

Publications and source records attributed to E Sabbioni.

At least 19 recordsLinked to original sources

Trace element reference values in tissues from inhabitants of the EU. XII. Development of BioReVa program for statistical treatment.

Statistical data treatment is a key point in the assessment of trace element reference values being the conclusive stage of a comprehensive and organized evaluation process of metal concentration in human body fluids. The EURO TERVIHT project (Trace Elements Reference Values in Human Tissues) was started for evaluating, checking and suggesting harmonized procedures for the establishment of trace element reference intervals in body fluids and tissues. Unfortunately, different statistical approaches are being used in this research field making data comparison difficult and in some cases impossible. Although international organizations such as International Federation of Clinical Chemistry (IFCC) or International Union of Pure and Applied Chemistry (IUPAC) have issued recommended guidelines for reference values assessment, including the statistical data treatment, a unique format and a standardized data layout is still missing. The aim of the present study is to present a software (BioReVa) running under Microsoft Windows platform suitable for calculating the reference intervals of trace elements in body matrices. The main scope for creating an ease-of-use application was to control the data distribution, to establish the reference intervals according to the accepted recommendation, on the base of the simple statistic, to get a standard presentation of experimental data and to have an application to which further need could be integrated in future. BioReVa calculates the IFCC reference intervals as well as the coverage intervals recommended by IUPAC as a supplement to the IFCC intervals. Examples of reference values and reference intervals calculated with BioReVa software concern Pb and Se in blood; Cd, In and Cr in urine, Hg and Mo in hair of different general European populations.

Databases, Factual↗

Promotion of research on in vitro immunotoxicology.

ECVAM was established to play a leading role at the European level in the independent evaluation of the reliability and relevance of test methods and testing strategies for specific purposes through research on advanced methods and new test development and validation, so that chemicals and products of various kinds, including medicines, vaccines, medical devices, cosmetics, household products and agricultural products, can be manufactured, transported and used more economically and more safely, whilst the current relevance on animal test procedures is progressively reduced. Nowhere is this activity more necessary than in the field of immunotoxicology, where we know that chemicals and products of many kinds have the potential to stimulate, modulate or suppress the induction or expression of various types of immune responses. The problem is to effectively evaluate the potency of these effectors, and, since the available information is currently based on rather qualitative animal tests, to evaluate the true relevance of this knowledge and apply it intelligently in risk assessment processes which will protect human beings without unnecessarily limiting the development and use of materials which otherwise have economic, health and social benefits. The way forward must depend on the following: (a) a better understanding of immunotoxicological processes, based on a sounder understanding of the immune system itself (and of its network of control systems and interrelationships with other body systems); (b) The use of in vitro (not in vivo) systems based on human (not animal) cells and tissues; (c) integrated and tiered testing strategies, incorporating QSAR, as well as in vitro approaches; (d) taking advantage of the use of cells or factors from humans who have been exposed to potential immunotoxins, be this voluntarily, occupationally, environmentally or by accident; and (e) the recognition that virtually everything will effect one or more aspects of the immune system at some dose level and, in some circumstances, deciding when such effects are relevant, is the key to immunotoxicity testing. Some current ECVAM-sponsored work and activities at ECVAM are described.

Academies and Institutes↗

The potencial role of rare earths in the pathogenesis of interstitial lung disease: a case report of movie projectionist as investigated by neutron activation analysis.

A 60-year-old male subject who worked as a movie projectionist and who was exposed for 12 years to rare earths (RE) containing dusts from cored arc light carbon electrodes was investigated. Chest X-ray films and pulmonary function tests showed an interstitial lung disease, emphysema and a severe obstructive impairment with marked decrease of carbon monoxide diffusion capacity. The histological examination of a transbronchial biopsy confirmed the diffuse interstitial lung fibrosis. Neutron activation analysis (NAA) of the biopsy showed concentrations of cerium (Ce), lanthanum (La), neodimium (Nd), samarium (Sm), terbium (Tb) and ytterbium (Yb) which were high compared to the corresponding elements in the transbronchial biopsies of 5 unexposed subjects as a control group. Thorium (Th) (which is generally present as an impurity of the RE compounds) was also determined in order to estimate the radiation dose in the lung of the worker. On the basis of the clinical observations, of the analytical results by neutron activation analysis of RE and of the presence of Th in the transbronchial biopsy, as well as of the differential diagnosis, which tended to exclude other occupational or non-occupational lung diseases, a relation between the observed interstitial lung fibrosis and occupational exposure to RE is highly probable.

Biopsy↗

Trace metals in oral mucosa in relation to the lichen ruberplanus pathology. A preliminary study carried out by neutron activation analysis.

Lichen ruberplanus, contact allergy and hypersensitivity can be linked to oral exposure to metals released from metal alloys commonly used in dentistry. In this context neutron activation analysis was developed for the microdetermination of 36 elements in oral mucosa biopsies of two patients affected by lichen ruber planus and of five subjects as control group. In order to minimise metal contamination during sample collection, biopsies were taken by laser bistoury technique and then submitted to radiochemical neutron activation analysis (RNAA). Among the metals analysed, chromium showed obvious high concentration in gingival biopsies of the two pathological subjects compared to the corresponding tissues of control group. Cobalt and nickel were also determined in higher concentrations, but only in one of the oral mucosa of the two patients. The present findings way support the hypothesis concerning a potential link of lichen ruber planus condition with the exposure to Cr, Co and Ni as released into oral cavity from prosthodontic alloys.

Adult↗

Lymphocyte subpopulations, cytokines and trace elements in asymptomatic atopic women exposed to an urban environment.

This study evaluates the immune response to exposure to an urban environment from 30 non-atopic and 30 non-symptomatic women with history of respiratory and/or cutaneous allergies. Blood lymphocyte subsets and serum interleukin (IL) 4 and interferon gamma (INF-gamma) of the two groups were similar, while serum IgE and "in vitro" production of IL-4 and INF-gamma by mononuclear blood cells of the atopic women were higher spontaneously or in the presence of PHA, respectively. Blood lead of the nonatopic women (mean 55 microg/l) was positively correlated with CD4+-CD45RO-, CD3+-CD8+ and CD3--HLA-DR+ lymphocyte subsets, while urinary trans-trans muconic acid (a metabolite of benzene) of both groups of women (mean about 50 microg/l) was significantly correlated with NK CD16+CD56+ lymphocytes. Urine chromium of the non-atopic subjects was significantly correlated with activated T, B and NK HLA-DR+ cells. Urine nickel of both groups of women was correlated with CD4+-CD45RO+ "memory" lymphocytes and their ratio with CD4+-CD45RO- "virgin" lymphocytes suggesting that the metal enhances maturation of "virgin" into "memory" lymphocytes. On the whole, this study demonstrates that exposure to low levels of toxic agents, produced by vehicular traffic in an urban environment, exerts effects on immune functions of women.

Adult↗

Lymphocyte subset changes in blood and gastrointestinal mucosa after oral nickel challenge in nickel-sensitized women.

This study investigates lymphocyte subsets in both the gastrointestinal mucosa and blood, in patients with nickel allergic contact dermatitis, after 10 mg oral nickel challenge (double-blind, placebo-controlled). 6 such patients with cutaneous symptoms induced only by skin contact with nickel (group A), 6 with a flare-up of cutaneous symptoms after food nickel ingestion (group B) and 6 healthy controls (group C) were enrolled. Blood lymphocyte subsets (CD4, CD45RO, CD8) were analyzed before and after 4 and 24 h from the challenge (test 1, 2, and 3), and intestinal biopsies were performed 2 days later. Challenges were positive in group B and negative in group A and controls. Serum and urine nickel levels significantly increased after nickel ingestion, with no differences between the 3 groups. At test 3, a significant decrease of the all CDs studied was found in group B. Biopsies of this group showed higher levels of CD45RO+ cells in the lamina propria and in the epithelium and lower levels of epithelial CD8+ lymphocytes. This study confirms that ingested nickel may induce flare-up of cutaneous reactions in some nickel-allergic patients, independently of the degree of sensitization and the intake of metal. In these patients, oral nickel stimulates the immune system, inducing maturation of T lymphocytes from virgin into memory cells; these latter cells seem to accumulate in the intestinal mucosa. The immunoreaction also involves CD8+ cells, whose role is not yet clear.

Administration, Oral↗

Micronuclei assay and FISH analysis in human lymphocytes treated with six metal salts.

The capability of some metal compounds for inducing micronuclei (MN) in human lymphocytes was studied. In this investigation, Al (III), Cd (II), Hg (II), Sb (V), Te (VI), and Tl (I) salts were considered. The FISH (fluorescence in situ hybridization) technique with a centromeric probe was coupled with the MN assay in binucleated cells in order to detect both centromere-positive MN (C+ MN) due to malsegregation phenomena and centromere-negative MN (C- MN) due to chromosome breakage. The blood of two young nonsmoking male donors was employed for all experiments. In both donors, all the tested metal compounds, with the exception of Tl(2)SO(4), showed a statistically significant increase of MN compared to controls, at least at one dose. FISH analysis revealed an increase in the fraction of C+ MN for Al, Cd, and Hg compounds, and of C- MN for the Sb salt; however, this was not a statistically significant increase. A different efficiency was observed for the different metal compounds, in particular, KSbO(3) and CH(3)HgCl, which were highly genotoxic, whereas the others showed minimal effects.

Alum Compounds↗

Effects of trace metal compounds on HIV-1 reverse transcriptase: an in vitro study.

The effect of 44 different metal ions (Ag+, Al3+, As(O-)2, Au3+, Ba2+, Be2+, Bi3+, Cd2+, Ce3+, CO2+, Cr(O2-)4, Cr3+, Cs+, Cu2+, Fe3+, Fe2+, Ga3+, Ge4+, Hg2+, Ir4+, La3+, Li+, Mn2+, MO6+, Ni2+, OS4+, Pb2+, Pt4+, Rb+, Rh3+, Sb5+, Se(O2-)4, Se(O2-)3, Sn2+, Sr2+, Th4+, T1+, U(O2+)2, V(O-)3, VO2+, W(O2-)4, Y3+, Zn2+, and Zr4+) on the activity of the reverse transcriptase (RT) of the human immunodeficiency virus (HIV-1) was investigated in vitro. For this study, the RT activity assay was carried out by means of an enzyme-linked immunosorbent assay (ELISA) kit, using the template/primer hybrid poly(A) oligo(dT)15, which required some modifications: (1) possible interfering metal chelators (such as EDTA) in the original lysis buffer were avoided, and a new buffer (50 mM Tris-NO3, pH 7.8) was used throughout; (2) an amount of 2 ng of RT per well was considered to be optimal after checking the linearity of the reaction with increasing amounts of enzyme; (3) an incubation temperature of 37 degrees C and an incubation time of 1 h were chosen after preliminary studies in a wide range of temperature and time. At an incubation temperature > or = 40 degrees C, there was a dramatic loss of enzymatic activity. In addition, when RT alone was preincubated for 1 h at 5 degrees C, 25 degrees C, and 37 degrees C, there was a large (83%) loss of activity at 37 C as compared to that at 5 degrees C. These results are indicative of enzyme thermolability, which is higher in the absence of substrates. The effect of metal ions on RT activity was tested using two different metal salt concentrations (10(-4) M and 10(-5) M). Under such experimental conditions, the presence of five metal ions (Pt4+, Ag+, Rh3+, Zn2+, and Hg2+) decreased the RT activity in a dose-response fashion. The observed order of effectiveness with respect to inhibition was Pt4+ > Ag+ > Rh3+ > Zn2+ = Hg2+. Estimated mean inhibitory concentrations (IC50) were 7.8 microM for (NH4)2PtCl6, 14.1 microM for AgNO3, 46.8 microM for RhCl3, 53.7 microM for Zn(SO)4, and 56.2 microM for Hg(NO3)2. Because these data are of the same order of magnitude as the corresponding values related to other RT inhibitors used in anti-AIDS therapy, metal compounds or their derivatives could give an interesting contribution in the development of new RT inhibitors for clinical use.

Dose-Response Relationship, Drug↗

Expression of lymphocyte subpopulations, cytokine serum levels, and blood and urinary trace elements in asymptomatic atopic men exposed to an urban environment.

The objective of this study was to analyze the role of some trace metals in the immune system of nonallergic or atopic men. One of these elements (Zn) is essential for immune function, whereas others, present in the urban environment, are known to be allergenic (Ni and Cr) or toxic (Pb). Serum levels of interleukin (IL) 2, 4, 5, and 13 and of interferon-y and immunoglobulins, blood lymphocyte subsets, blood concentrations of Pb and Zn, serum levels of Zn, and urinary Cr and Ni concentrations were determined in 17 nonallergic men (mean age 34 years) and 17 healthy nonsymptomatic atopic men living in urban areas. The mean blood concentration of Pb (a marker of exposure to toxic agents) was 11 microg/dl in both groups, which showed similar levels of blood Zn and of urinary Ni and Cr, whereas the serum Zn concentration was lower in the atopic group. Serum IgE levels were much higher in atopic men than in nonallergics, whereas serum IL-2, IL-5, and IL-13 concentrations were lower, possibly due to binding to tissue receptors and cells. Moreover, in atopic subjects, numbers of blood CD4+-CD45RO-"virgin" lymphocytes were significantly lower and the CD4+ -CD45RO+/CD4+ -CD45RO- ratio was more elevated, indicating an activation of the immune system. Serum IgE levels of atopic men, in contrast to those of nonallergic subjects, were correlated with CD19+ and CD5--CD19+ B lymphocytes. Blood Pb levels of both groups of men were correlated with CD4+, CD4+-CD45RO+, and HLA-DR+ [activated T-, B-, CO4+ -C. and natural killer (NK) cells] lymphocytes; in particular, blood Pb levels of the nonallergic men were also significantly correlated with CD25+ cells activated by IL-2, whereas those of the atopic men were also correlated with CD3--HLA-DR+ (B- and NK-cells) and CD5--CD19+ lymphocytes. Besides serum Zn levels, urinary Ni and Cr of nonallergic men were correlated with several immune parameters; in particular, urinary Cr was correlated with serum IL-5 and IgE and urinary Ni was correlated with CD4+ -CD45RO+ and CD3+ -CD25+ lymphocytes. This correlation of Ni and Cr, also found in previous studies in nonallergic subjects, confirms the hypothesis that these metals are involved in mechanisms of immune response regulation and that allergy to Ni or Cr represents an alteration of physiological mechanisms. Previous experimental studies have demonstrated that Pb exerts immunomodulatory effects on CD4+ and B- lymphocytes, enhancing the production of Th2-like cytokines and IgE. These experimental results confirm those of this study, showing in atopic men the correlation of B-lymphocytes with both blood Pb and serum IgE levels. This suggests that Pb may enhance the incidence of atopy in populations exposed to an urban environment.

Case-Control Studies↗

Systemic effects of ingested nickel on the immune system of nickel sensitised women.

This study evaluates the immune response to ingestion of 10 mg of nickel (Ni) (as Ni sulphate) in 19 young non-atopic Ni-sensitised or 9 non-allergic women (group A). After Ni ingestion at 8 a.m, non-allergic and 12 Ni-sensitised women (group B) were non-symptomatic, while 7 Ni-sensitised women (group C) showed a flare up of urticaria and/or eczema. Serum and urine Ni were greatly lower before Ni administration than after 4 and 24 hours, without difference among the 3 groups. Before treatment, group B and C showed higher values of blood CD19+ and CD5--CD19+ cells than group A, while group C showed higher serum interleukin (IL) 2 and lower serum IL-5. Four hours after Ni ingestion, group C showed significant increase in serum IL-5. Twenty-four hours after treatment, group A showed a significant reduction in blood CD4+-CD45RO- "virgin" cells and an increase of CD8+ lymphocytes, while group C showed a marked decrease in total blood lymphocytes and CD3+, CD4+-CD45RO-, CD4+-CD45RO+, CD8+, CD19+ and CD5--CD19+ cell subsets. These data may be explained with migration of lymphocytes in tissues with a Th0-like immune response, as shown by the elevated serum IL-2 and the increase of serum IL-5 during the test.

Adolescent↗

Marked elevation of myocardial trace elements in idiopathic dilated cardiomyopathy compared with secondary cardiac dysfunction.

OBJECTIVES: We sought to investigate the possible pathogenetic role of myocardial trace elements (TE) in patients with various forms of cardiac failure. BACKGROUND: Both myocardial TE accumulation and deficiency have been associated with the development of heart failure indistinguishable from an idiopathic dilated cardiomyopathy. METHODS: Myocardial and muscular content of 32 TE has been assessed in biopsy samples of 13 patients (pts) with clinical, hemodynamic and histologic diagnosis of idiopathic dilated cardiomyopathy (IDCM), all without past or current exposure to TE. One muscular and one left ventricular (LV) endomyocardial specimen from each patient, drawn with metal contamination-free technique, were analyzed by neutron activation analysis and compared with 1) similar surgical samples from patients with valvular (12 pts) and ischemic (13 pts) heart disease comparable for age and degree of LV dysfunction; 2) papillary and skeletal muscle surgical biopsies from 10 pts with mitral stenosis and normal LV function, and 3) LV endomyocardial biopsies from four normal subjects. RESULTS: A large increase (>10,000 times for mercury and antimony) of TE concentration has been observed in myocardial but not in muscular samples in all pts with IDCM. Patients with secondary cardiac dysfunction had mild increase (< or = 5 times) of myocardial TE and normal muscular TE. In particular, in pts with IDCM mean mercury concentration was 22,000 times (178,400 ng/g vs. 8 ng/g), antimony 12,000 times (19,260 ng/g vs. 1.5 ng/g), gold 11 times (26 ng/g vs. 2.3 ng/g), chromium 13 times (2,300 ng/g vs. 177 ng/g) and cobalt 4 times (86,5 ng/g vs. 20 ng/g) higher than in control subjects. CONCLUSIONS: A large, significant increase of myocardial TE is present in IDCM but not in secondary cardiac dysfunction. The increased concentration of TE in pts with IDCM may adversely affect mitochondrial activity and myocardial metabolism and worsen cellular function.

Adult↗

Trace element reference values in tissues from inhabitants of the European Union. X. A study of 13 elements in blood and urine of a United Kingdom population.

Electrothermal atomic absorption spectrophotometry (ETAAS), inductively coupled plasma mass spectrometry (ICP-MS) and neutron activation analysis (NAA) were used for the quantitative determination of 13 trace elements in urine and seven trace elements in whole blood of healthy unexposed British subjects living in three regions of the United Kingdom. Careful control of pre-analytical and analytical factors have enabled the results obtained from more than 200 individuals to be used in proposing reference intervals for the following elements; Al, As, Cd, Co, Cr, Cu, Hg, Mn, Mo, Ni, Pb, Se, Tl in urine, and Cd, Cr, Hg, Mn, Pb, Se and Tl in blood.

Adolescent↗

Expression of lymphocyte subpopulations, cytokine serum levels and blood and urine trace elements in nickel sensitised women.

In this study, 20 non-allergic and 20 non-atopic women sensitised only to nickel (Ni) showed similar levels of urine and serum Ni and serum chromium (Cr). On the contrary, serum copper, a marker of inflammation, was significantly higher in the Ni-sensitised group. Sensitised women also had higher values of blood B CD19+, CD5--CD19+ and B and natural killer CD3--CD25+ lymphocytes, but not alterations of some other lymphocyte subsets and serum cytokines. Urine Ni was correlated with "memory" CD4+-CD45RO+ lymphocytes in the non-allergic women and with T CD4+-CD45RO+ and CD3+-CD25+ cells in the atopic women; these subjects also showed a statistically significant correlation of serum Ni with B CD5+-CD19+ lymphocytes and serum IL-13. Moreover, serum Cr of both groups of women was positively or negatively correlated with activated HLA-DR+ cells and/or serum IL-5 and interferon gamma. These results (confirming in part those of a previous study on non-allergic men) suggest that both Ni and Cr are involved in mechanisms regulating the immune response and that allergy to these metals could be considered an alteration of their physiological role.

Adolescent↗

Inductively coupled plasma mass spectrometric determination of molybdenum in urine from a Danish population.

Molybdenum creatinine levels in urine were measured in 128 Danish inhabitants by ICP-MS in order to establish reference intervals of molybdenum in urine for the Danish population as a part of the EURO-TERVIHT project (Trace Element Reference Values in Human Tissues). The Mo concentration was determined using the isotopes 95Mo and 98Mo. The values measured based on 98Mo were about 2% lower than those calculated using 95Mo, a negligible difference in the context of reference values. The limit of detection was 0.2 microgram l-1, the precision was 8.6% and the recovery of added NIST 1643c certified reference material was 94%. The distribution of the data, with and without correction for creatinine concentration, was long-normal. The mean concentration measured was 42.5 micrograms l-1, (3.89 micrograms Mo mmol-1 creatinine) using 95Mo and 41.5 micrograms l-1 (3.81 micrograms Mo mmol-1 creatinine) using 98Mo, with the 95% parametric reference intervals 10.0-124.0 micrograms l-1 (0.89-11.50 micrograms Mo mmol-1 creatinine) and 9.6-122.6 micrograms l-1 (0.84-11.47 micrograms Mo mmol-1 creatinine), respectively. The difference between men and women reached the level of significance only after the values were corrected for the creatinine concentration. There was no influence of age on the Mo concentration. Specific effects of different food and beverage intakes could not be demonstrated, with the exception of a positive correlation between butter consumption and Mo concentration.

Adult↗

Serum and urine nickel in nickel-sensitized women: effects of oral challenge with the metal.

15 women with a positive patch test only to nickel (Ni) and without atopy and 10 control women were selected for the study. Blood and urine specimens were collected with a standard procedure either before (at 8 a.m.) or 4 and 24 h after the ingestion of 10 mg of Ni (as Ni sulfate). 7 of the Ni-sensitized patients showed a flare-up of eczema and/or urticaria during the test, while the other women were non-symptomatic. Serum and urine Ni of controls and Ni-sensitized women did not significantly differ. Serum and urine Ni levels determined before the oral Ni challenge were in the range of reference values recently reported by other authors (0.2-2.0 micrograms/l of serum or urine). Ni was greatly augmented in urine and serum 4 h after the challenge (25th-75th percentiles: 43-264 micrograms/l urine Ni and 15-52 micrograms/l serum Ni). 24 h after Ni ingestion, urine Ni was 41-153 micrograms/l and serum Ni 4-17 micrograms/l. Our study confirms a previous investigation showing similar levels of serum and urine Ni following ingestion of the metal in control and Ni-sensitized women without atopy.

Administration, Oral↗

Toxic trace element reference levels in blood and urine: influence of gender and lifestyle factors.

This study is part of the EURO-TERVIHT project (Trace Element Reference Values in Human Tissues) which aims at establishing reference intervals for trace elements in blood, urine and other human tissues. In this study reference intervals (0.05-0.95 fractiles) were estimated for lead in blood (105-529 nmol/l for men, 80-340 nmol/l for women), manganese in blood (100-271 nmol/l) and arsenic in urine (36-541 nmol/l for men, 21-475 nmol/l for women). Upper reference limits (0.95 fractile) were established for chromium in urine (13 nmol/l), nickel in urine (52 nmol/l) and cobalt in urine (23 nmol/l for men, 31 nmol/l for women). The reference group was a Danish subpopulation (n = 189), age 40-70 years. The influence of gender, age, health status parameters, nutrition and various lifestyle factors was investigated. Urinary arsenic and blood lead levels were found to be higher for men than for women. Arsenic levels also increased with age up to 60 years, and then decreased. Alcohol intake lead to increased arsenic levels in urine as well as blood lead levels. Urinary nickel levels were higher in persons frequently eating porridge and porridge oats.

Adult↗

Critical evaluation and review of cadmium concentrations in blood for use in occupational health according to the TRACY protocol.

Cadmium in blood (B-Cd) may be used to assess recent exposure to cadmium in the working or general environment. In a paper published elsewhere pooled reference values using meta-analysis of B-Cd values in general-population studies were calculated. In the present study tentative references intervals were described which can be used for comparison with data from occupationally exposed groups or individuals. The selection of studies was done according to criteria as published by the international project TRACY. For this purpose, 800 publications covering the period 1983-1992 were reviewed on their suitability for establishing tentative reference intervals. From these 800 publications, four finally met the selection criteria. Most important criteria for selection were the check for contamination during sampling of the blood, the storage and pretreatment procedures, and the existence of internal and external quality control programs. Also, stratifications into sex, smoking habits and occupation were important selection criteria. It turned out that for non-smoking white-collar workers in the age range of 19-65 years, B-Cd values were below 0.8 micrograms/l for most areas. All other groups within this age group, e.g., white collar workers in Japan, blue-collar workers, and smokers tend to have higher B-Cd values in these sequences. Blue-collar workers not clearly exposed to Cd have higher values than white-collar workers, indicating still some minor exposure. It is not clear if this small exposure has an occupational or lifestyle (e.g., diet) origin. Geographical regions also show an influence on B-Cd levels, e.g., values in Japan are higher than elsewhere. This influence may be due to differences in diet. The conclusion will be that reference values for B-Cd in fact are area-dependent.

Adult↗