Toxicity for cats of methylmercury in contaminated fish from Swedish lakes and of methylmercury hydroxide added to fish.
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Biomedical subjects
Publications and source records attributed to S Skerfving.
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The effect on kidney function was studied in 22 smelter workers with concomitant exposure to lead and cadmium. One active and five retired workers showed early signs of kidney dysfunction. They all had a long-term and high lead exposure, while their kidney cadmium concentrations measured in vivo by XRF techniques were low to moderate. Thus, the exposure to lead has been a greater risk, although an interaction between lead and cadmium could not be excluded.
In this study of the effects of lead on the endocrine system, 77 secondary lead-smelter workers (i.e., 62 active and 15 retired) were compared with 26 referents. Lead concentrations were determined in plasma with inductively coupled plasma mass spectrometry (i.e., index of recent exposure), in blood with atomic absorption spectrophotometry, and in fingerbone with K x-ray fluorescence technique (i.e., index of long-term exposure). In addition, pituitary hormones were determined in serum by fluoroimmunoassay, and thyroid hormones and testosterone in serum were determined with radioimmunoassay. Nine lead workers and 11 referents were challenged with gonadotrophin-releasing hormone and thyrotrophin-releasing hormone, followed by measurements of stimulated pituitary hormone levels in serum. Median levels of lead in plasma were 0.14 microg/dl (range = 0.04-3.7 microg/dl) in active lead workers, 0.08 microg/dl (range = 0.05-0.4 microg/dl) in retired lead workers, and 0.03 microg/dl (range = 0.02-0.04 microg/dl) in referents (1 microg/dl = 48.3 nmol/l). Corresponding blood lead concentrations were 33.2 microg/dl (range = 8.3-93.2 microg/dl), 18.6 microg/dl (range = 10.4-49.7 microg/dl), and 4.1 microg/dl (range 0.8-6.2 microg/dl), respectively. Respective bone lead levels were 21 microg/gm (range = -13 to 99 microg/gm), 55 microg/gm (range = 3-88 microg/gm), and 2 microg/gm (range = -21 to 14 microg/gm). Concentrations of basal serum hormone (i.e., free thyroid hormones, thyrotrophin, sex hormone binding globulin, and testosterone) were similar in the 3 groups. There were no significant associations between the hormones mentioned herein and blood plasma, blood lead, and bone lead levels. In the challenge test, stimulated follicle-stimulating hormone levels were significantly lower in lead workers (p = .014) than in referents, indicating an effect of lead at the pituitary level. Also, there was a tendency toward lower basal stimulated follicle-stimulating hormone concentrations in lead workers (p = .08). This effect, however, was not associated with blood plasma level, blood lead level, or bone lead level. In conclusion, a moderate exposure to lead was associated with only minor changes in the male endocrine function, particularly affecting the hypothalamic-pituitary axis. Given that sperm parameters were not studied, the authors could not draw conclusions about fertility consequences.
Lead levels in finger bone were monitored using an in vivo X-ray fluorescence technique in retired lead workers. Eight subjects followed for 2-5 yr directly after end of exposure all displayed a decrease. Their average half-time was 7 (range 3-15) yr. In a second group of six persons, followed from year 7 to year 13 after finishing lead work, a decrease was seen in all but one. The average half-time for this group was 8 (range 2 infinity) yr. The mean value for both groups was 7 yr. The results show that there is a decrease of lead in bone after the end of exposure and that it is considerably faster than estimated earlier from various data on lead metabolism.
Samples of vertebral bone were obtained by skeletal biopsy and lead concentrations were determined by atomic absorption spectroscopy. The median level of lead in bone in 27 active lead workers was 29 micrograms/g wet weight (range 2-155), corresponding to 370 micrograms/g calcium (range 30-1,120). In 9 retired workers, the corresponding levels were 19 micrograms/g (5-76) and 250 micrograms/g calcium (60-700); in 14 reference subjects without occupational exposure, 1.3 micrograms/g (1-4) and 13 micrograms/g calcium (8-40). The bone lead content rose with time of exposure. Comparison of levels in vertebra with those in fingerbone, as measured by in vivo x-ray fluorescence in the same subjects, strongly suggested the presence of lead pools with different kinetics. The accumulation pattern, as well as the relation between levels in vertebra and fingerbone, suggests a much shorter half-time of lead in the mainly trabecular vertebral bone as compared to the mainly cortical fingerbone. Further, there was an association between vertebral and blood lead levels in the retired workers, which shows a considerable endogenous lead exposure from the skeletal pool.
The geometric mean of the blood lead concentrations in 1,781 samples obtained from children during 1978 to 1988 was 46.9 micrograms/l (0.23 mumol/l) (range: 14-250 micrograms/l [0.07-1.2 mumol/l]). There was a significant (p less than .001) decrease in blood lead concentrations of 7%/y in rural and urban areas. In 134 children who were sampled twice, the decrease over 2-y periods was 14%. The striking decrease in blood lead levels is most likely the result of a reduction of lead additives in motor fuel during this period.
Urinary mercury (U-Hg) and plasma mercury (P-Hg) levels were higher in 244 dental personnel than in 81 matched referents (U-Hg: 1.8 and 1.1 mumol/mol creatinine, respectively; p less than .001; P-Hg: 6.7 and 6.2 nmol/l, respectively; p = .03). The amalgam in the mouth influenced mercury levels in whole blood (B-Hg), plasma, and urine. The association was nonlinear: the more amalgam, the larger the relative increase in mercury levels. The number of amalgam surfaces accounted for more of the variance in blood and urine mercury levels than did the number of fillings (e.g., U-Hg: 44% and 36%, respectively). The estimated increases in mercury level with rising amalgam load were 3.0%, 2.0%, and 0.8% per filled surface for U-Hg, P-Hg, and B-Hg, respectively (p less than .0001 in all cases). The impact of occupational exposure on U-Hg in the dental personnel corresponded to approximately 19 amalgam surfaces. Ceramo metallic restorations were associated with higher (31%) U-Hg.
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.
Fatty fish species, e.g., salmon and herring, in the Baltic Sea have high levels of polychlorinated biphenyls (PCBs) and 1,1,1-trichloro-2,2-bis(p-chlorophenyl)ethane (p,p'-DDT), and its main metabolite: 1,1-dichloro-2,2-bis(p-chlorophenyl)-ethylene (p,p'-DDE). We determined levels of 10 different PCB congeners, including non- and mono-ortho-PCBs, as well as DDT and DDE, in human blood plasma from 37 subjects with varying intake of fish (0-1 750 g/wk) from the Baltic Sea. With respect to all of the PCB congeners we investigated, as well as for DDT and DDE, there were statistically significant associations with fish intake. Thus, fish from the Baltic Sea is a major source of exposure to these compounds in Swedes. Polychlorinated dibenzo-p-dioxins (PCDD) and dibenzofurans (PCDF) had been determined earlier in 29 of the subjects. The PCB contribution to "dioxin-like" effects among high consumers of fish (calculated as Nordic TCDD equivalents) was almost 80%, whereas that from PCDD and PCDF was only 20%.
Urinary cotinine (U-cotinine) as a biomarker of environmental tobacco smoke exposure was evaluated in 14 children (age 4-11 y) and in 7 adults who were exposed to environmental tobacco smoke at an air nicotine level of 110 mg/m3 for 2 h in a bus. Nicotine in air and U-cotinine were measured by gas chromatography/mass spectrometry before, during, and after the experiment. U-cotinine rose rapidly to a maximum after a median of 6 h following the end of exposure; remained at an apparent plateau for half a day; and then decreased exponentially, with a mean half-time of 19 h (95% confidence interval 18-20 h; no significant difference between children and adults). The maximum U-cotinine was higher in the children (mean = 22 mg/l) than in the adults (13 mg/l; p = .005); decreased with age among the children (r = -.74; p = .002); and increased as the estimated inhaled nicotine dose increased. Therefore, the findings of the present study showed that young children had higher U-cotinine than adults at the same experimental environmental tobacco smoke exposure, probably because they had a higher relative nicotine dose because of a higher relative ventilation rate, and possibly also because of metabolic differences; the elimination rate did not differ. The long half-time makes U-cotinine a good biomarker of environmental tobacco smoke exposure; the time of sampling is not very critical. Dilution-adjusted concentrations should be employed, and in children, preferably by density correction. A certain urinary cotinine level indicates a lower environmental tobacco smoke exposure in a small child than in an adult.
Total mercury concentrations (mean +/- standard deviation) in breast milk, blood, and hair samples collected 6 wk after delivery from 30 women who lived in the north of Sweden were 0.6 +/- 0.4 ng/g (3.0 +/- 2.0 nmol/kg), 2.3 +/- 1.0 ng/g (11.5 +/- 5.0 nmol/kg), and 0.28 +/- 0.16 microg/g (1.40 +/- 0.80 micromol/kg), respectively. In milk, an average of 51% of total mercury was in the form of inorganic mercury, whereas in blood an average of only 26% was present in the inorganic form. Total and inorganic mercury levels in blood (r = .55, p = .003; and r = .46, p = .01 6; respectively) and milk (r = .47, p = .01; and r = .45, p = .018; respectively) were correlated with the number of amalgam fillings. The concentrations of total mercury and organic mercury (calculated by subtraction of inorganic mercury from total mercury) in blood (r = .59, p = .0006, and r = .56, p = .001; respectively) and total mercury in hair (r = .52, p = .006) were correlated with the estimated recent exposure to methylmercury via intake of fish. There was no significant between the milk levels of mercury in any chemical form and the estimated methylmercury intake. A significant correlation was found between levels of total mercury in blood and in milk (r = .66, p = .0001), with milk levels being an average of 27% of the blood levels. There was an association between inorganic mercury in blood and milk (r = .96, p < .0001); the average level of inorganic mercury in milk was 55% of the level of inorganic mercury in blood. No significant correlations were found between the levels of any form of mercury in milk and the levels of organic mercury in blood. The results indicated that there was an efficient transfer of inorganic mercury from blood to milk and that, in this population, mercury from amalgam fillings was the main source of mercury in milk. Exposure of the infant to mercury from breast milk was calculated to range up to 0.3 microg/kg x d, of which approximately one-half was inorganic mercury. This exposure, however, corresponds to approximately one-half the tolerable daily intake for adults recommended by the World Health Organization. We concluded that efforts should be made to decrease mercury burden in fertile women.
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.