Dag G. Ellingsen

Gonadal hormones in long-term survivors 10 years after treatment for unilateral testicular cancer

OBJECTIVE To investigate whether unilaterally orchiectomised testicular cancer survivors (TCSs) are more likely to display reduced Leydig cell function than healthy males. METHODS A national multi-centre survey of 1235 TCSs was performed in 1998-2000 (mean age: 44 years) treated between 1980 and 1994 (mean follow-up: 11 years). Serum hormone analyses were performed on 1183 TCSs, as 52 TCSs used androgen replacement (AR). TCSs were allocated to four treatment groups: Surgery only (251); Radiotherapy only (515); Chemotherapy 1, cisplatin </=850 mg (373); Chemotherapy 2, cisplatin >850 mg (96). The Controls were represented by 200 healthy blue-collar workers (mean age: 44 years). LH >12 IU/l and testosterone <8 nmol/l and the use of AR indicated hypogonadism. RESULTS Serum testosterone was similar in TCSs and Controls (16.9 vs.17.1 nmol/l), but TCSs had higher age-adjusted LH levels than the Controls (5.2 vs. 3.5 IU/l). LH increased with treatment intensity, but was elevated even in TCSs treated with surgery only. The age-adjusted odds ratio of hypogonadism was 3.8 (95%CI: 2.0-7.3) in TCSs, and increased with treatment intensity. CONCLUSION TCSs are at risk to develop pre-mature reduced Leydig cell function and hypogonadism. They may therefore be predisposed for the syndrome of androgen deficiency of aging males (ADAM).

Low iron stores are related to higher blood concentrations of manganese, cobalt and cadmium in non-smoking, Norwegian women in the HUNT 2 study

Low iron (Fe) stores may influence absorption or transport of divalent metals in blood. To obtain more knowledge about such associations, the divalent metal ions cadmium (Cd), manganese (Mn), cobalt (Co), copper (Cu), zinc (Zn) and lead (Pb) and parameters of Fe metabolism (serum ferritin, haemoglobin (Hb) and transferrin) were investigated in 448 healthy, menstruating non-smoking women, age 20-55 years (mean 38 years), participating in the Norwegian HUNT 2 study. The study population was stratified for serum ferritin: 257 were iron-depleted (serum ferritin < 12 microg/L) and 84 had iron deficiency anaemia (serum ferritin < 12 microg/L and Hb < 120 g/L). The low ferritin group had increased blood concentrations of Mn, Co and Cd but normal concentrations of Cu, Zn and Pb. In multiple regression models, ferritin emerged as the main determinant of Mn, Co and Cd (p < 0.001), while no significant associations with Cu, Zn and Pb were found. Adjusted r(2) for the models were 0.28, 0.48 and 0.34, respectively. Strong positive associations between blood concentrations of Mn, Co and Cd were observed, also when controlled for their common association with ferritin. Apart from these associations, the models showed no significant interactions between the six divalent metals studied. Very mild anaemia (110 < or = Hb < 120 g/L) did not seem to have any effect independent of low ferritin. Approximately 26% of the women with iron deficiency anaemia had high concentrations of all of Mn, Co and Cd as opposed to 2.3% of iron-replete subjects. The results confirm that low serum ferritin may have an impact on body kinetics of certain divalent metal ions, but not all. Only a fraction of women with low iron status exhibited an increased blood concentration of divalent metals, providing indication of complexities in the bodys handling of these metals.

Speciation of mercury in human whole blood by capillary gas chromatography with a microwave-induced plasma emission detector system following complexometric extraction and butylation

Methyl- and inorganic mercury were extracted from human whole blood samples, as their diethyldithiocarbamate complexes, into toluene and butylated by using a Grignard reagent. The mercury species were then separated by gas chromatography (on a 12 m non-polar DB-1 capillary column) and detected by a microwave-induced plasma atomic emission spectrometric (GC-MPD) system. The accuracy and precision of the proposed method were established by the analysis of Seronorm lyophilized human whole blood standards for methyl- and inorganic mercury. No statistical difference (t-test) between the sum of these two species determined by the GC-MPD based method and the recommended total mercury concentrations in the Seronorm samples was observed. Results for the determination of methyl- and inorganic mercury in 60 controls and 90 previously occupationally exposed (to inorganic mercury) workers are presented to illustrate the practical utility of the proposed method. No significantly elevated inorganic mercury concentrations between the two groups were evident.

Exploration of biomarkers for total fish intake in pregnant Norwegian women

OBJECTIVE Few biomarkers for dietary intake of various food groups have been established. The aim of the present study was to explore whether selenium (Se), iodine, mercury (Hg) or arsenic may serve as a biomarker for total fish and seafood intake in addition to the traditionally used n-3 fatty acids EPA and DHA. DESIGN Intake of fish and seafood estimated by an FFQ was compared with intake assessed by a 4 d weighed food diary and with biomarkers in blood and urine. SETTING Validation study in the Norwegian Mother and Child Cohort Study (MoBa). SUBJECTS One hundred and nineteen women. RESULTS Total fish/seafood intake (median 39 g/d) calculated with the MoBa FFQ was comparable to intake calculated by the food diary (median 30 g/d, rS = 0.37, P < 0.001). Erythrocyte DHA and blood Hg, Se and arsenic concentrations were positively correlated with intake of fish and seafood, but the association for DHA was weakened by the widespread use of supplements. The main finding was the consistent positive association between the intake of fish/seafood and blood arsenic concentration. In multivariate analyses, blood arsenic was associated with blood Hg and fish and seafood intake. In these models, arsenic turned out to be the best indicator of intake of fish and seafood, both totally and in subgroups of fish/seafood intake. CONCLUSIONS While DHA reflected the intake of fatty fish and n-3 PUFA supplements, blood arsenic concentration also reflected the intake of lean fish and seafood. Blood arsenic appears to be a useful biomarker for total fish and seafood intake.

Air exposure assessment and biological monitoring of manganese and other major welding fume components in welders

In a cross-sectional study, 96 welders were compared with 96 control subjects. Also 27 former welders, all diagnosed as having manganism, were examined. Exposure to welding fumes was determined in the 96 welders, while the concentration of elements in whole blood and urine was determined in all subjects. The geometric mean (GM) concentrations of manganese (Mn) and iron in the workroom air were 97 microg m(-3) (range 3-4620 microg m(-3); n=188) and 894 microg m(-3) (range 106-20 300 microg m(-3); n=188), respectively. Thus the Mn concentration in the workroom air was on average 10.6% (GM) of that of the Fe concentration. No substantial difference was observed in the air Mn concentrations when welding mild steel as compared to welding stainless steel. The arithmetic mean (AM) concentration of Mn in whole blood (B-Mn) was about 25% higher in the welders compared to the controls (8.6 vs. 6.9 microg l(-1); p < 0.001), while the difference in the urinary Mn concentrations did not attain statistical significance. A Pearsons correlation coefficient of 0.31 (p < 0.01) was calculated between B-Mn and Mn in the workroom air that was collected the day before blood sampling. Although the exposure to welding fumes in the patients had ceased on average 5.8 years prior to the study (range 4 years-7 years), their AM B-Mn concentration was still higher than in referents of similar age (8.7 microg l(-1) vs. 7.0 microg l(-1)). However, their urinary concentrations of cobolt, iron and Mn were all statistically significantly lower.

Neuropsychological Effects of Low Mercury Vapor Exposure in Chloralkali Workers

Neuropsychological effects were examined in 47 mercury vapor exposed male chloralkali workers with current low concentrations of urinary mercury (mean U-Hg 5.9 nmol/mmol creatinine (Cr)). Their average duration of exposure was 13.3 years, and the calculated mean concentration of U-Hg was 9.0 nmol Hg/mmol Cr per year (exposure intensity) during their time of exposure. They were compared with 47 age-matched male referents in a cross-sectional study. The two groups were not statistically significantly different with respect to neuropsychological test performance or number of self-reported subjective symptoms. The test results of the Static Steadiness Test, which assesses tremor, were not associated with exposure to mercury vapor. However current smokers had more hand tremor than non-smokers. Statistically significant associations were found between indices of current exposure (the concentration of inorganic mercury in whole blood) and the results of the WAIS Digit Symbol Test and the Benton Visual Retention Test (number of correct responses). This could indicate a small effect of current exposure on visuomotor/psychomotor speed and attention, and immediate visual memory. Whether the association found between the historical exposure intensity and the Digit Symbol Test results may represent long-term consequences of exposure cannot be determined in this study.

Relation between exposure related indices and neurological and neurophysiological effects in workers previously exposed to mercury vapour.

A cross sectional study of aspects of their neurology was carried out on 77 chloralkali workers previously exposed to mercury (Hg) vapour and compared with 53 age matched referents. The chloralkali workers had been exposed for an average of 7.9 years at a concentration of 59 micrograms Hg/m3 in the working atmosphere. The individual mean urinary concentration of Hg for each year of exposure was 531 nmol Hg/1. On average the exposure had ceased 12.3 years before the examinations. Both the median sensory nerve conduction velocity and the amplitude of the sural nerve were associated with measures of cumulative exposure to Hg. An association was also found between years since first exposure to Hg and aspects of the visual evoked response. Previously exposed subjects with postural tremor or impaired coordination also had alterations in visual evoked response. These results may indicate an effect of previous exposure to mercury vapour on the nervous system, possibly in the visual pathway, cerebellum, and the peripheral sensory nerves.

Essential and toxic element concentrations in blood and urine and their associations with diet: Results from a Norwegian population study including high-consumers of seafood and game

The first aim of the study was to evaluate calculated dietary intake and concentrations measured in blood or urine of essential and toxic elements in relation to nutritional and toxicological reference values. The second aim was to identify patterns of the element concentrations in blood and urine and to identify possible dietary determinants of the concentrations of these elements. Adults with a known high consumption of environmental contaminants (n=111), and a random sample of controls (n=76) answered a validated food frequency questionnaire (FFQ). Complete data on biological measures were available for 179 individuals. Blood and urine samples were analyzed for selenium, iodine, arsenic, mercury, cadmium and lead. Principal component analysis was used to identify underlying patterns of correlated blood and urine concentrations. The calculated intakes of selenium, iodine, inorganic arsenic and mercury were within guideline levels. For cadmium 24% of the high consumer group and 8% of the control group had intakes above the tolerable weekly intake. Concentrations of lead in blood exceeded the bench-mark dose lower confidence limits for some participants. However, overall, the examined exposures did not give rise to nutritional or toxicological concerns. Game consumption was associated with lead in blood (B(ln) 0.021; 95%CI:0.010, 0.031) and wine consumption. Seafood consumption was associated with urinary cadmium in non-smokers (B(ln) 0.009; 95%CI:0.003, 0.015). A novel finding was a distinct pattern of positively associated biological markers, comprising iodine, selenium, arsenic and mercury (eigenvalue 3.8), reflecting seafood intake (B 0.007; 95%CI:0.004, 0.010). The study clearly demonstrates the significance of seafood as a source of both essential nutrients and toxic elements simultaneously and shows that exposure to various essential and toxic elements can be intertwined.

Occupational Exposure to Airborne Perfluorinated Compounds during Professional Ski Waxing

The concentration levels of 11 perfluorinated carboxylic (PFCA) and eight sulfonic (PFSA) acids were determined in the serum of 13 professional ski waxers. The same components were also determined in workroom aerosols and in fluoro containing solid ski waxes and ski wax powders. The highest median concentration (50 ng/mL) was detected for perfluorooctanoic acid (PFOA), which is around 25 times higher than the background level. For the first time perfluorotetradecanoic acid (PFTeDA) has been found in human serum. Positive statistically significant associations between years exposed as ski waxer and seven different PFCAs were observed. The serum concentrations of the PFCAs with carbon chain lengths from C(8) to C(11) were reduced by around five to 20% on average during the eight month exposure free interval, whereas the reduction was substantially larger when the carbon chain lengths were smaller than C(8) or larger than C(11). This study links for the first time PFCAs in the ski waxers serum to exposure from the work room aerosols. Not only professional ski waxers but also the significant larger group of amateur skiers and waxers are potentially exposed to these compounds.

Effects of low mercury vapour exposure on the thyroid function in chloralkali workers

Forty‐seven chloralkali workers exposed to mercury vapour for an average of 13.3 years were compared with 47 referents matched for age in a cross‐sectional study of thyroid function. The mean urinary mercury concentration in the exposed workers was low compared with other studies of chloralkali workers: 5.9 nmol mmol−1 creatinine (range 1.1–16.8) vs 1.3 nmol mmol−1 creatinine (range 0.2–5.0) in the reference group. The median serum concentration of reverse triiodothyronine (rT3) was statistically significantly higher in the exposed subjects compared with the referents (268 pmol l−1 and range 161–422 vs 240 pmol l−1 and range 129–352; P = 0.009). The difference between the exposed subjects and the referents was most pronounced in the highest exposed sub‐groups. The free thyroxine (T4)/free T3 ratio was also higher in the highest exposed subgroups compared with the referents. The median serum concentration of tumour necrosis factor alpha (TNF‐α) was lower in the exposed subjects (7.3 pg ml−1 and range 4.4–69.7 vs 8.0 pg ml−1 and range 6.0–34.6; P = 0.004). Exposed subjects with the lowest urinary iodine (<67.8 nmol mmol−1 Cr) had higher serum concentrations of reverse T3 and a higher free T4/free T3ratio than the other subjects, suggesting that a low concentration of iodine in urine may be a risk factor for increased serum concentrations of reverse T3 and the free T4/free T3 ratio in subjects exposed occupationally to mercury vapour. The study could indicate a slight effect of low mercury vapour exposure on the function of the enzyme type I iodothyronine deiodinase, possibly modified by comparatively low urinary iodine concentrations. Copyright