Increased blood cadmium levels were not associated with increased fracture risk but with increased total mortality in women: the Malmö Diet and Cancer Study.

This study aimed to investigate if high levels of blood cadmium at baseline were associated with increased fracture risk during follow-up in middle-aged women. No increased fracture risk was observed during follow-up, but women with higher levels of cadmium had an increased overall mortality. INTRODUCTION: Exposure to high levels of cadmium has been associated with an increased fracture risk. The aim was to investigate a perceived association between low levels of blood cadmium (B-Cd) at baseline and risk of first incident fracture. METHODS: From the population-based Malmö Diet and Cancer Study Cardiovascular cohort, 2920 middle-aged women with available background questionnaire and B-Cd measurements were included. Women were divided into quartiles (Q) according to their cadmium levels (Cd-Q1 <0.18 µg/L, Cd-Q2 0.18-0.28 µg/L, Cd-Q3 0.28-0.51 µg/L, and Cd-Q4 >0.51 µg/L). National registries were analysed for prospective risk of fractures or death. Associations between B-Cd and fracture risk were assessed by survival analysis (Cox regression analysis). RESULTS: In total, 998 first incident fractures occurred in women during a follow-up lasting 20.2 years (median) (12.5-21.2 years) (25th-75th percentile). Women in Cd-Q4 were more often current smokers than in Cd-Q1 78.4 vs. 3.3% (p < 0.001) and the number of cigarettes smoked per day correlated with B-Cd (r = 0.49; p < 0.001). The risk of fracture was not associated with baseline B-Cd in adjusted models. The hazard ratio (HR) Cd-Q4 vs. Cd-Q1 was 1.06 (95% confidence interval (CI) 0.89-1.27). In the multivariate Cox regression, independent variables for increased fracture risk were history of gastric ulcer and increasing age, whereas increasing body mass index (BMI) lowered fracture risk. Overall mortality was significantly higher for women with high B-Cd, HR 2.06 (95% CI 1.57-2.69). CONCLUSIONS: Higher blood levels of cadmium did not increase fracture risk in middle-aged women but reduced overall survival.

Low personal exposure to benzene and 1,3-butadiene in the Swedish petroleum refinery industry.

PURPOSE: Petroleum refinery workers are exposed to the carcinogens benzene and 1,3-butadiene. Declining exposures have been reported internationally but information on current exposure in the Swedish refinery industry is limited. The aim was to examine refinery workers' personal exposure to benzene and 1,3-butadiene and increase awareness of exposure conditions by collaboration with involved refineries. METHODS: Altogether 505 repeated personal exposure measurements were performed among workers at two refineries. Full-shift measurements were conducted in different exposure groups using Perkin Elmer diffusive samplers filled with Carbopack X. Mean levels were calculated using mixed-effects models. A large fraction of measurements below the limit of detection (LOD) required imputation of computer-generated data. RESULTS: Mean benzene exposure among process technicians was 15.3 µg/m3 (95% CI 10.4-22.5 µg/m3) and 13.7 µg/m3 (95% CI 8.3-22.7 µg/m3) for Refinery 1 and 2, respectively. Process technicians working outdoors had higher exposure than maintenance workers (20.7 versus 5.9 µg/m3, p < 0.01). Working in the harbour and tank park (Refinery 1), compared with the process area, was associated with higher exposure. The 1,3-butadiene exposure was low, 5.4 and 1.8 µg/m3, respectively. The total variation was generally attributed to within-worker variability. CONCLUSIONS: Low benzene and 1,3-butadiene levels were found among refinery workers. Mean benzene exposure was about 1% of the Swedish occupational limit (1500 µg/m3) and for 1,3-butadiene, exposure was even lower. A large fraction of values below the LOD can be managed by carefully modelled, computer-generated data.

8-isoprostane in exhaled breath condensate after experimental exposure to wood smoke in humans.

Wood smoke, a well-known indoor and outdoor air pollutant, may cause adverse health effects through oxidative stress. In this study 8-isoprostane, a biomarker of oxidative stress, was measured in exhaled breath condensate (EBC) and urine before and after experimental exposure to wood smoke. The results were compared with measurements of other biomarkers of oxidative stress and inflammation. Thirteen subjects were exposed first to clean air and then, after 1 week, to wood smoke in an exposure chamber during 4-hour sessions. Exhaled breath condensate, exhaled nitric oxide, blood and urine were sampled before and at various intervals after exposure to wood smoke and clean air. Exhaled breath condensate was examined for 8-isoprostane and malondialdehyde (MDA), while exhaled air was examined for nitric oxide, serum for Clara cell protein (CC16) and urine for 8-isoprostane. 8-isoprostane in EBC did not increase after wood smoke exposure and its net change immediately after exposure was inversely correlated with net changes in MDA (r(s)= -0.57, p= 0.041) and serum CC16 (S-CC16) (r(p)= -0.64, p= 0.020) immediately after the exposure. No correlation was found between 8-isoprostane in urine and 8-isoprostane in EBC. In this study controlled wood smoke exposure in healthy subjects did not increase 8-isoprostane in EBC.

Personal exposure to benzene and 1,3-butadiene during petroleum refinery turnarounds and work in the oil harbour.

PURPOSE: Petroleum refinery workers' exposure to the carcinogens benzene and 1,3-butadiene has decreased during normal operations. However, certain occupational groups or events at the refineries still involve a risk of higher exposures. The aim of this study was to examine the personal exposure to benzene and 1,3-butadiene at refinery turnarounds and during work in the oil harbour. METHODS: Personal exposure measurements of benzene and 1,3-butadiene were taken during work shifts, with a priori assumed higher benzene exposure, using PerkinElmer diffusive samplers filled with Carbopack X. Mean exposure levels were calculated, and repeated exposure measurements, when available, were assessed using mixed effect models. Group and individual compliance with the Swedish occupational exposure limit (OEL) was tested for the different exposure groups. RESULTS: Mean benzene exposure levels for refinery workers during the three measured turnarounds were 150, 610 and 960 µg/m3, and mean exposures for oil harbour workers and sewage tanker drivers were 310 and 360 µg/m3, respectively. Higher exposures were associated with handling benzene-rich products. Most occupational groups did not comply with the Swedish OEL for benzene nor did the individuals within the groups. The exposure to 1,3-butadiene was very low, between <1 and 3 % of the Swedish OEL. CONCLUSIONS: Work within the petroleum refinery industry, with potential exposure to open product streams containing higher fractions of benzene, pose a risk of personal benzene exposures exceeding the OEL. Refinery workers performing these work tasks frequently, such as contractors, sewage tanker drivers and oil harbour workers, need to be identified and protected.

Experimental exposure to wood smoke: effects on airway inflammation and oxidative stress.

BACKGROUND: Particulate air pollution affects cardiovascular and pulmonary disease and mortality. A main hypothesis about the mechanisms involved is that particles induce inflammation in lower airways, systemic inflammation and oxidative stress. OBJECTIVES: To examine whether short-term exposure to wood smoke in healthy subjects affects markers of pulmonary inflammation and oxidative stress. METHODS: 13 subjects were exposed first to clean air and then to wood smoke in a chamber during 4-hour sessions, 1 week apart. The mass concentrations of fine particles at wood smoke exposure were 240-280 mug/m(3), and number concentrations were 95 000-180 000/cm(3), about half of the particles being ultrafine (<100 nm). Blood and breath samples were taken before and at various intervals after exposure to wood smoke and clean air and examined for exhaled nitric oxide and Clara cell protein in serum and urine, and malondialdehyde in exhaled breath condensate. RESULTS: Exposure to wood smoke increased alveolar nitric oxide 3 hours post-exposure while malondialdehyde levels in breath condensate were higher both immediately after and 20 hours after exposure. Serum Clara cell protein was increased 20 hours after exposure. CONCLUSIONS: Wood smoke at levels that can be found in smoky indoor environments caused an inflammatory response and signs of increased oxidative stress in the respiratory tract, especially in the lower airways.

Variability in airborne and biological measures of exposure to mercury in the chloralkali industry: implications for epidemiologic studies.

Exposure assessment is a critical component of epidemiologic studies, and more sophisticated approaches require that variation in exposure be considered. We examined the intra- and interindividual sources of variation in exposure to mercury vapor as measured in air, blood, and urine among four groups of workers during 1990-1997 at a Swedish chloralkali plant. Consistent with the underlying kinetics of mercury in the body, the variability of biological measures was dampened considerably relative to the variation in airborne levels. Owing to the effects of intraindividual variation, estimating workers' exposures from a few measurements can attenuate measures of effect. To examine such effects on studies relating long-term exposure to a continuous health outcome, we evaluated the utility of each exposure measure by comparing the necessary sample sizes required for accurate estimation of a slope coefficient obtained from a regression analysis. No single measure outperformed the others for all groups of workers. However, when workers were evaluated together, creatinine-corrected urinary mercury better discriminated workers' exposures than airborne or blood mercury levels. Thus, pilot studies should be conducted to examine variability in both air and biomonitoring data because quantitative information about the relative magnitude of the intra- and interindividual sources of variation feeds directly into our efforts to design an optimal sampling strategy when evaluating health risks associated with occupational or environmental contaminants.

Cadmium, mercury, and lead in kidney cortex of the general Swedish population: a study of biopsies from living kidney donors.

Cadmium, mercury, and lead concentrations were determined in deep-frozen kidney cortex biopsies taken from 36 living, healthy Swedish kidney donors (18 males and 18 females), who were 30-71 (mean 53) years of age. Information about occupation, smoking, the presence of dental amalgam, and fish consumption could be obtained for 27 of the donors. The samples (median dry weight 0.74 mg) were analyzed using inductively coupled plasma mass spectrometry, and the results were transformed to wet-weight concentrations. The median kidney Cd was 17 micrograms/g (95% confidence interval, 14-23 micrograms/g), which was similar in males and females. In 10 active smokers, the median kidney Cd was 24 micrograms/g, and in 12 who never smoked, it was 17 micrograms/g. The median kidney Hg was 0.29 micrograms/g, with higher levels in females (median 0.54 micrograms/g) than in males (median 0.16 micrograms/g). Subjects with amalgam fillings had higher kidney Hg (median 0.47 micrograms/g, n = 20) than those without dental amalgam (median 0.15 micrograms;g/g, n = 6), but kidney Hg was below the detection limit in some samples. Nearly half of the samples had kidney Pb below the detection limit. The median kidney Pb was estimated as 0. 14 micrograms/g. This is the first study of heavy metals in kidney cortex of living, healthy subjects, and the results are relatively similar to those of a few previous autopsy studies, indicating that results from autopsy cases are not seriously biased in relation to kidney metal concentrations in the general population. Cd concentrations in those who never smoked were relatively high, indicating considerable Cd intake from the diet in Sweden. The effect of dental amalgam on kidney Hg was as expected, although the reason for the difference in Hg levels between males and females is unclear.

Long-term use of nicotine chewing gum and mercury exposure from dental amalgam fillings.

In experimental studies, chewing gum has been shown to increase the release rate of mercury vapor from dental amalgam fillings. The aim of the present study was to investigate the influence of long-term frequent chewing on mercury levels in plasma and urine. Mercury levels in plasma (P-Hg) and urine (U-Hg), and urinary cotinine were examined in 18 subjects who regularly used nicotine chewing gum, and in 19 referents. Age and number of amalgam surfaces were similar in the two groups. Total mercury concentrations in plasma and urine were determined by means of cold vapor atomic absorption spectrometry. Urinary cotinine was determined by gas chromatography-mass spectrometry. The chewers had been using 10 (median) pieces of gum per day for the past 27 (median) months. P-Hg and U-Hg levels were significantly higher in the chewers (27 nmol/L and 6.5 nmol/mmol creatinine) than in the referents (4.9 nmol/L and 1.2 nmol/mmol creatinine). In both groups, significant correlations were found between P-Hg or U-Hg on the one hand and the number of amalgam surfaces on the other. In the chewers, no correlations were found between P-Hg or U-Hg and chewing time per day or cotinine in urine. Cotinine in urine increased with the number of pieces of chewing gum used. The impact of excessive chewing on mercury levels was considerable.

Exposure to mercury vapor and impact on health in the dental profession in Sweden.

Possible adverse effects of mercury exposure in dentistry have been discussed in several studies. The objective of the present study was to carry out detailed measurements of mercury exposure in the dental profession in Sweden, and to search for adverse health effects from such exposure. We examined 22 dentists and 22 dental nurses, working in teams, at six Swedish dental clinics. Measurements of air mercury, performed with personal, active air samplers, showed a median air Hg of 1.8 micrograms/m3 for the dentists, and 2.1 micrograms/m3 for the dental nurses. Spot measurements with a direct reading instrument displayed temporarily elevated air Hg, especially during the preparation and application of amalgam. The average concentration of mercury in whole blood (B-Hg) was 18 nmol/L, in plasma (P-Hg) 5.1 nmol/L, and in urine (U-Hg) 3.0 nmol/mmol creatinine. Possible effects on the central nervous system (CNS) were registered with three questionnaires: Q16, Eysenck Personality Inventory (EPI), and the Profile of Mood Scales (POMS). In the Q16, the number of symptoms was statistically significantly higher in the dentistry group compared with an age- and gender-matched control group (n = 44). The urinary excretion of albumin and urinary activity of the tubular enzyme N-acetyl-beta-glucose-aminidase (NAG) did not differ between the two groups. The results confirm that exposure to mercury in the dental profession in Sweden is low. The air Hg levels were mainly influenced by the method of amalgam preparation and inserting, and by the method of air evacuation during drilling and polishing.

In vivo XRF analysis of mercury: the relation between concentrations in the kidney and the urine.

The objective of this study was to determine the concentrations of mercury in organs of occupationally exposed workers using in vivo x-ray fluorescence analysis. Twenty mercury exposed workers and twelve occupationally unexposed referents participated in the study. Their mercury levels in kidney, liver and thyroid were measured using a technique based on excitation with partly plane polarized photons. The mercury levels in blood and urine were determined using atomic absorption spectrophotometry. The detection limit for mercury in the kidney was exceeded in nine of the exposed workers, but in none of the referents. The mean kidney mercury concentration (including estimates below the detection limits) was 24 micrograms g-1 in the exposed workers, and 1 microgram g-1 in the referents. The association between mercury in the kidney and in urine was statistically significant, but it was unclear whether the relation was linear. The measurements on liver (n = 10) and thyroid (n = 8) in the exposed workers showed mercury levels below the detection limit. The study shows that it is now possible to measure the mercury concentrations in kidneys of occupationally exposed persons, using in vivo x-ray fluorescence. The estimated concentrations are in reasonable agreement with the limited human autopsy data, and the results of animal studies.

A small dose of ethanol increases the exhalation of mercury in low-level-exposed humans.

Inorganic mercury is mainly eliminated by urinary and fecal excretion, but it is also eliminated by exhalation and sweat. There are only a few reports on exhalation of mercury in humans. In volunteers with short-term mercury exposure, an increased exhalation of mercury was found after alcohol intake. The aim of this study was to determine mercury in end-exhaled air and the influence of ethanol on mercury exhalation in subjects with long-term mercury exposure from diet, amalgam fillings, or the work environment. Fourteen subjects, with different grades of mercury exposure, were given 0.2 g ethanol/kg body weight. Measurements of mercury in end-exhaled air were performed before and after alcohol intake. Mercury in end-exhaled air could be detected in all subjects. In 10 individuals without amalgam fillings the mercury concentration was 3 to 12 pg/L. A marked increase, in general about fivefold, in mercury concentrations in end-exhaled air was seen in all subjects 30 min after intake of alcohol, regardless of the level of mercury exposure. Higher ethanol doses resulted in higher mercury levels in end-exhaled air and longer time periods before a return to background levels. An increase was seen even after an ethanol dose of only 0.1 g ethanol/kg body weight (about 0.08 L wine). The decrease in exhaled mercury at higher alcohol doses followed approximately zero-order kinetics and probably reflects the elimination of ethanol in tissues. In conclusion, low levels of mercury can be detected in end-exhaled air also in individuals without amalgam fillings. About a fivefold increase was seen 30 min after alcohol intake, and the relative increase seemed to be independent of the body burden of mercury. Exhalation of mercury represents only a small percentage of the total elimination of mercury.

Polyneuropathy possibly caused by 30 years of low exposure to n-hexane.

A slowly developing, mainly sensory, polyneuropathy was found in a 60-year-old man exposed to n-hexane (10-100 mg/m3) for 30 years in a mountain fuel stockpile. The nerve damage was verified by electromyography and sural nerve biopsy, and it is proposed that also a low-grade, but prolonged, exposure to n-hexane may cause polyneuropathy.

Effects of occupational exposure to mercury vapor on lymphocyte micronuclei.

For 26 chloralkali workers exposed to inorganic mercury and 26 age-matched, occupationally unexposed referents, the frequency and size distribution of micronuclei were determined in peripheral lymphocytes stimulated with either phytohemagglutinin or pokeweed mitogen. For the exposed workers the mean concentrations of mercury in urine, plasma, and erythrocytes were 16 nmol/mmol of creatinine, 48 nmol/l, and 78 nmol/l, respectively, and their mean exposure time was 10 years. Neither the frequency nor the size of micronuclei was significantly different in the two groups; nor were there any correlations to current mercury levels. However, in the exposed group, and with phytohemagglutinin as the mitogen, a statistically significant correlation between previous exposure to mercury (cumulative exposure or number of blood mercury peaks) and the frequency of micronuclei was found. This association was also present when the effects of age and smoking were allowed for, and it may indicate an accumulation of cytogenetic effects in T-lymphocytes.

Cerebrospinal fluid proteins in men with chronic encephalopathy after exposure to organic solvents.

Cerebrospinal fluid was examined for 23 patients with chronic toxic encephalopathy after heavy exposure to organic solvents and 23 healthy age-matched referents. No differences were found between the patients and referents with respect to the levels of albumin, immunoglobulin, prealbumin, alpha-1-antitrypsin, beta-2-microglobulin, haptoglobin, or the astroglial cell proteins S100 and glial fibrillary acidic protein in the cerebrospinal fluid. The albumin ratio was normal for both the patients and the referents. The patient group had had heavy exposure to organic solvents, but its members had not been exposed for at least one year before the study. It was concluded that, if exposure to organic solvents affects proteins in cerebrospinal fluid, such effects are probably reversible.

Kinetics of mercury in blood and urine after brief occupational exposure.

The decrease in mercury (Hg) levels in whole blood (B), plasma (P), erythrocytes (Ery), and urine (U) was investigated in nine men after 3 d of intense (greater than 100 micrograms/m3) exposure to metallic Hg vapor. In a model in which common half-times for all subjects were used, the best fit for B-Hg was obtained with half-times of 3.1 d for a fast phase and 18 d for a slow phase. P-Hg seemed to decay more rapidly than Ery-Hg. Peak U-Hg (morning, creatinine-corrected samples) was not observed until 2-3 wk after exposure. Thereafter, the median half-time was 40 d (assuming individual one-compartment models). In a model for which common half-times were used, the point estimates were 59 d for a one-compartment model and 28 and 141 d for a two-compartment model. The fractions of the fast phases (i.e., two-compartment models with common half-times) were 80% for B-Hg and 84% for U-Hg.

Self-reported symptoms and their effects on cognitive functioning in workers with past exposure to solvent-based glues: an 18-year follow-up.

OBJECTIVES: To examine to what extent exposure to organic solvents during the working life affects general well-being in the long term, and to explore the relationship between self-reported symptoms and cognitive functioning in previously solvent-exposed floor layers. METHODS: The study included 41 solvent-exposed floor layers and 40 unexposed referents participating in a longitudinal follow-up study 18 years after the baseline assessment. Symptom prevalence and level of spare time activities were studied using the same methods as in the initial study. These include a general health examination, the Q16 symptom questionnaire, and a questionnaire for spare time activities. Relationships between symptoms and cognitive functioning were analysed based on recently published data on cognitive functioning of the participants at follow-up. RESULTS: At follow-up neuropsychiatric symptoms such as need to check things, depressive mood, and abnormal fatigue, were more prevalent among floor layers, particularly the most exposed individuals, than among referents. In addition, the most highly exposed floor layers reported more concentration difficulties and irritability. Fatigue and depressive mood increased over the follow-up time in the most exposed floor layers but not in the referents. Memory difficulties, although more frequent among floor layers than among referents, had decreased in floor layers while increased in referents. Floor layers also reported some negative effects on intimate relations and activity level. Neuropsychiatric symptoms were related to poorer performance chiefly in memory tasks and tests of complex attention and perceptual speed, more seldom in visuospatial tasks. CONCLUSIONS: Findings of exposure-related, long-lasting, partly deteriorating neuropsychiatric complaints indicate that general well-being later in life has been affected in floor layers with past heavy solvent exposure. We also found frequent associations between symptom prevalence and the cognitive functioning. Together with previous findings of dose-related cognitive decrements, the present results strengthen the evidence that long-term heavy occupational solvent exposure may negatively interact with the normal ageing process.

Urinary excretion of mercury, copper and zinc in subjects exposed to mercury vapour.

The excretion of mercury, copper and zinc in urine, and mercury in whole blood and plasma, was determined in 40 chloralkali workers exposed to mercury vapour and 40 age-matched referents. The Hg concentrations in whole blood, plasma and urine were higher in the exposed group (35 nmol l-1, 30 nmol l-1, and 11.5 nmol mmol-1 creatinine, respectively) in comparison with the reference group (15 nmol l-1, 6.3 nmol l-1, and 1.8 nmol mmol-1 creatinine, respectively). The urinary copper excretion was similar in the two groups, while U-Zn excretion was significantly higher (P = 0.04) in the exposed group, median 0.83 mumol mmol-1 creatinine versus 0.76 munmol mmol-1 creatinine in the reference group. In a subgroup of exposed workers with current U-Hg above 11.5 nmol l-1 mmol-1 creatinine (20 micrograms g-1 creatinine) the median U-Zn was 1.1 mumol mmol-1 creatinine. In both groups smokers had high U-Zn levels than non smokers. When both U-Hg and smoking were taken into account in a linear regression model, there was a significant association between U-Hg and U-Zn in the combined group of exposed and referents (P = 0.002). This study indicates that mercury exposure in humans, as in animals, causes increased urinary excretion of zinc. The mechanisms may be induced synthesis of metallothionein in the kidneys, displacement of Zn from preexisting metallothionein by Hg, or a decreased reabsorption of zinc in the kidneys owing to a slight tubular dysfunction.

People with high mercury uptake from their own dental amalgam fillings.

OBJECTIVES: To describe people with high mercury (Hg) uptake from their amalgam fillings, and to estimate the possible fraction of the occupationally unexposed Swedish population with high excretion of urinary Hg. METHODS: Three case reports are presented. The distribution of excretion of urinary Hg in the general population was examined in pooled data from several sources. RESULTS: The three cases excreted 23-60 micrograms of Hg/day (25-54 micrograms/g creatinine), indicating daily uptake of Hg as high as 100 micrograms. Blood Hg was 12-23 micrograms/l, which is five to 10 times the average in the general population. No other sources of exposure were found, and removal of the amalgam fillings resulted in normal Hg concentrations. Chewing gum and bruxism were the probable reasons for the increased Hg uptake. Extrapolations from data on urinary Hg in the general population indicate that the number of people with urinary excretion of > or = 50 micrograms/g creatinine could in fact be larger than the number of workers with equivalent exposure from occupational sources. CONCLUSION: Although the average daily Hg uptake from dental amalgam fillings is low, there is a considerable variation between people; certain people have a high mercury uptake from their amalgam fillings.