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Renal effects of cadmium body burden of the general population.

In a cross-sectional population study to assess whether environmental exposure to cadmium is associated with renal dysfunction, 1699 subjects aged 20-80 years were studied as a random sample of four areas of Belgium with varying degrees of cadmium pollution. After standardisation for several possible confounding factors, five variables (urinary excretion of retinol-binding protein, N-acetyl-beta-glucosaminidase, beta 2-microglobulin, aminoacids, and calcium) were significantly associated with the urinary excretion of cadmium (as a marker of cadmium body burden), suggesting the presence of tubular dysfunction. There was a 10% probability of values of these variables being abnormal when cadmium excretion exceeded 2-4 micrograms/24 h. Excretion reached this threshold in 10% of non-smokers. There was also evidence that diabetic patients may be more susceptible to the toxic effect of cadmium on the renal proximal tubule.

Acetylglucosaminidase↗

Effect of cadmium body burden on immune response of school children.

The effects of cadmium on measures of immune-system function were determined from a health survey of school children in heavily polluted regions of eastern Germany. A representative sample of 842 students, aged 5-14 y, was included in logistic regression analyses in which the relationship between urinary cadmium content and blood immunoglobulin levels was examined. Investigators further evaluated a subsample of 807 students to determine cadmium's effect on the immediate hypersensitivity reactions elicited by skin-prick challenges with 12 common aeroallergens. Several potentially confounding factors were controlled for, after which investigators found that increasing body burdens of cadmium were associated consistently with dose-dependent suppression of immediate hypersensitivity and of immunoglobin G, but not immunoglobulins M, A, or E levels. The immunoglobulin pattern observed in exposed children led investigators to suggest that secondary humoral responses were impaired by cadmium.

Adolescent↗

Side-effects: mercury contribution to body burden from dental amalgam.

The purpose of this paper is to examine and report on studies that relate mercury levels in human tissues to the presence of dental amalgams, giving special attention to autopsy studies. Until recently, there have been few published studies examining the relationship between dental amalgams and tissue mercury levels. Improved and highly sensitive tissue analysis techniques have made it possible to measure elements in the concentration range of parts per billion. The fact that mercury can be absorbed and reach toxic levels in human tissues makes any and all exposure to that element of scientific interest. Dental amalgams have long been believed to be of little significance as contributors to the overall body burden of mercury, because the elemental form of mercury is rapidly consumed in the setting reaction of the restoration. Studies showing measurable elemental mercury vapor release from dental amalgams have raised renewed concern about amalgam safety. Mercury vapor absorption occurs through the lungs, with about 80% of the inhaled vapor being absorbed by the lungs and rapidly entering the bloodstream. Following distribution by blood circulation, mercury can enter and remain in certain tissues for longer periods of time, since the half-life of excretion is prolonged. Two of the primary target organs of concern are the central nervous system and kidneys.

Alzheimer Disease↗

Reduction of the human body burdens of hexachlorobenzene and polychlorinated biphenyls.

Adipose-tissue concentrations of hexachlorobenzene (HCB), four other pesticides and 10 polychlorinated biphenyl congeners were significantly reduced by enhanced mobilization and excretion through the method developed by Hubbard. Electrical workers paired by age, sex and potential for polychlorinated biphenyl exposure were divided into treatment and control groups. Adipose-tissue concentrations were determined pre- and post-treatment, and 3 months post-treatment. Daily treatment was provided for 3 weeks, consisting of heat stress and niacin administration to enhance mobilization and polyunsaturated-oil administration to enhance excretion, with other components administered to provide protection from mobilized chemicals. Adjusted for re-exposure as represented in the control group, HCB body burdens were reduced by 30% at post-treatment and 28% 3 months post-treatment. Mean reduction of polychlorinated biphenyl congeners was 16% at post-treatment and 14% 3 months post-treatment. Analysis of variance indicates these reductions are statistically significant (f less than 0.001). Enhanced excretion appeared to keep pace with mobilization, as blood-serum levels in the treatment group did not increase during treatment. Post-treatment remission of symptoms associated with chemical exposure has been summarized according to reports from related studies.

Adipose Tissue↗

Reduced cadmium body burden in cadmium-exposed calves fed supplemental zinc.

The objectives of this study were to evaluate the use of practical supplemental dietary zinc to modify the cadmium content in edible bovine tissues and to identify copper interactions with cadmium and zinc. The effect of supplemental zinc (200 or 600 micrograms/g) on the concentrations of cadmium, zinc, and copper in liver, kidney cortex, muscle, and blood of calves fed 50 micrograms/g cadmium for 60 days was evaluated. Blood samples were collected before and eight times after starting to feed cadmium or cadmium plus zinc. Liver, kidney, and muscle samples were collected when calves were slaughtered (baseline, at beginning of experimental feeding; cadmium-fed, at end of 60 days feeding). The cadmium concentrations of all sample types collected were markedly increased by the feeding of cadmium. Feeding 600 micrograms/g supplemental zinc significantly increased the zinc concentrations of liver, kidney cortex, and blood and decreased the cadmium accumulation in these organs as well as muscle. The copper concentrations of muscle or blood were not altered by feeding cadmium with or without zinc but those of liver and kidney cortex were significantly increased by higher dietary levels of zinc and cadmium. The potential use of dietary zinc salts in reducing cadmium body burden in food animals suspected or known to have high cadmium intakes is suggested.

Animals↗

DMPS (2,3-dimercaptopropane-1-sulfonate, dimaval) decreases the body burden of mercury in humans exposed to mercurous chloride.

DMPS (2,3-dimercaptopropane-1-sulfonate, Na salt), when used as a challenge test for mercury in workers involved in the production of a calomel skin-bleaching lotion and in direct contact with mercurous chloride, elevated urine levels of mercury. A DMPS treatment regimen was devised and initiated. Three days after the challenge test, DMPS was administered p.o. (400 mg per day) for 8 days, followed by a no-treatment period of five days. A new cycle of DMPS treatment for 7 days was initiated and followed by 5 days without treatment. A third period of treatment was begun for 6 days, followed by a 5-day no-treatment period. The urinary mercury greatly increased during those periods when DMPS was administered (1754, 314, and 173 microgram/24 h for the periods 1, 2 and 3, compared with 106, 48 and 53 microgram/24 h on the corresponding no-treatment periods). One of the workers presented signs of drug intolerance and was discharged after receiving the first cycle of treatment. DMPS treatment was effective in lowering the body burden of mercury and in decreasing the urinary mercury concentration to normal levels.

Adult↗

An evaluation of hexachlorobenzene body-burden levels in the general population of the USA.

Hexachlorobenzene (HCB) is a chemical of concern to the US Environmental Protection Agency. Although the use of HCB as a fungicide has virtually been eliminated, detectable levels of HCB are still found in nearly all people in the USA. This paper describes an examination of HCB-residue levels from the US National Human Adipose Tissue Survey, which is an annual programme to collect a nationwide sample of adipose-tissue specimens and analyse them for the presence of toxic compounds. The specimens are collected from surgical patients and autopsied cadavers according to a multistage statistical survey design that allows identification of geographic and demographic subpopulations with elevated HCB levels, and thus may help to indicate sources of human exposure to this chemical. Data on HCB body-burden levels are available for the years 1974-1983, excluding 1980 and 1982. The estimated average residue level of 6115 specimens is 0.053 ppm, the ninetieth percentile value is 0.09 ppm and the range is 'not detected' to 4.33 ppm. The analysis reveals that while the percentage of individuals with detectable levels is increasing, the annual average level is decreasing. A large percentage of specimens with elevated HCB levels comes from the Pacific census division and the oldest age group. In comparison, world-wide detectable levels are approaching 100% and average residue levels tend to increase with age. World-wide HCB levels are higher in females, which contrasts with findings from the National Human Adipose Tissue Survey.

Adipose Tissue↗

High body burdens of 2,2',4,4'-tetrabromodiphenyl ether (BDE-47) in California women.

Following our first report on elevated polybrominated diphenyl ether (PBDE) concentrations in California women, we expanded our investigation to include diverse groups of local women. We analyzed additional adipose and serum samples collected in the late 1990s from San Francisco Bay Area women participating in a breast cancer study and in a reproductive study, respectively. Adipose samples (n = 32) were analyzed by low-resolution mass spectrometry in negative-ion chemical ionization mode, whereas serum samples (n = 50) were analyzed by dual-column gas chromatography with electron capture detection. The results confirmed our earlier findings. Concentrations of 2,2,4,4 -tetrabromodiphenyl ether (BDE-47) in contemporary California women ranged between 5 and 510 ng/g lipid, with a median (16.5 ng/g lipid) 3-10 times higher than those reported from Europe. In contrast, PBDEs were not measurable in any of 420 archived serum samples collected in the 1960s from San Francisco Bay Area women participating in a study of child development. BDE-47 concentrations did not increase with age or with concentrations of a polychlorinated biphenyl (PCB-153), suggesting other routes of exposure in addition to diet. Rising body burdens of endocrine-disrupting chemicals such as PBDEs may pose a potential public health threat.

Adipose Tissue↗

Human milk as a bioindicator for body burden of PCDDs, PCDFs, organochlorine pesticides, and PCBs.

In the State Laboratory of North Rhine-Westphalia for Food, Pharmaceutical and Environmental Chemistry (Chemisches Landesuntersuchungsamt), more than 600 individual human milk samples have been analyzed for polychlorinated dibenzo-p-dioxins (PCDDs) and polychlorinated dibenzofurans (PCDFs), and more than 1400 individual milk samples have been analyzed for organochlorine pesticides (OCPs) and polychlorinated biphenyls (PCBs) since 1984. All samples were collected on a voluntary basis from nursing mothers mostly living in North Rhine Westphalia, a federal state in Germany. The samples analyzed so far show a typical pattern of PCDDs and PCDFs. Out of the 210 possible congeners, only those with 2,3,7,8-chlorine substitution were found. While OCDD normally shows the highest concentration, the levels of the other dioxin congeners decrease with decreasing number of chlorine atoms. A different pattern was found for PCDFs. Within this group 2,3,4,7,8-P5CDF is the most abundant congener, followed by the hexachlorodibenzofurans. The mean level of tetrachlorodibenzodioxin (TCDD) was found to be of 3.2 pg/g on a fat basis and for total PCDDs and PCDFs, calculated as I-TEq (NATO/CMMS), 29.3 pg/g on a fat basis. The investigations of the past 2 years have revealed somewhat lower levels compared to former years. This might be an indication that the efforts undertaken to minimize dioxin emissions and to shut down known sources have already had an effect on the body burden of humans. Although mostly banned for a considerable period of time now, some lipophilic persistent pesticides such as DDT, dieldrin, hexachlorobenzene (HCB), and hexachlorocyclohexanes (HCH) can still be found in human milk.(ABSTRACT TRUNCATED AT 250 WORDS)

Benzofurans↗

Oral benzo[a]pyrene in Cyp1 knockout mouse lines: CYP1A1 important in detoxication, CYP1B1 metabolism required for immune damage independent of total-body burden and clearance rate.

CYP1A1 and CYP1B1 metabolically activate many polycyclic aromatic hydrocarbons (PAHs), including benzo[a]pyrene, to reactive intermediates associated with toxicity, mutagenesis, and carcinogenesis. Paradoxically, however, Cyp1a1-/- knockout mice are more sensitive to oral benzo[a]pyrene exposure, compared with wild-type Cyp1a1+/+ mice (Mol Pharmacol 65:1225, 2004). To further investigate the mechanism for this enhanced sensitivity, Cyp1a1-/-, Cyp1a2-/-, and Cyp1b1-/- single-knockout, Cyp1a1/1b1-/- and Cyp1a2/1b1-/- double-knockout, and Cyp1+/+ wild-type mice were analyzed. After administration of oral benzo[a]pyrene (125 mg/kg/day) for 18 days, Cyp1a1-/- mice showed marked wasting, immunosuppression, and bone marrow hypocellularity, whereas the other five genotypes did not. After 5 days of feeding, steady-state blood levels of benzo[a]pyrene were approximately 25 and approximately 75 times higher in Cyp1a1-/- and Cyp1a1/1b1-/- mice, respectively, than in wild-type mice. Benzo[a]pyrene-DNA adduct levels were highest in liver, spleen, and marrow of Cyp1a1-/- and Cyp1a1/1b1-/- mice. Many lines of convergent data obtained with oral benzo[a]pyrene dosing suggest that: 1) inducible CYP1A1, probably in both intestine and liver, is most important in detoxication; 2) CYP1B1 in spleen and marrow is responsible for metabolic activation of benzo[a]pyrene, which results in immune damage in the absence of CYP1A1; 3) both thymus atrophy and hepatocyte hypertrophy are independent of CYP1B1 metabolism but rather may reflect long-term activation of the aryl hydrocarbon receptor; and 4) the magnitude of immune damage in Cyp1a1-/- and Cyp1a1/1b1-/- mice is independent of plasma benzo[a]pyrene and total-body burden and clearance. Thus, a balance between tissue-specific expression of the CYP1A1 and CYP1B1 enzymes governs sensitivity of benzo[a]pyrene toxicity and, possibly, carcinogenicity.

Administration, Oral↗

Food contamination with polychlorinated biphenyls and dioxins in Belgium. Effects on the body burden.

The core paper of this debate shows that persistent organic pollutant residues of the 12 chemicals targeted for a phase out under the Stockholm Convention are present in almost all categories of food in the US food supply. For dioxins, the study does not use measured data, but is based upon potential dioxin residues in selected food items. Polychlorinated biphenyls are not included in the study. In this paper we discuss selected data of polychlorinated biphenyl and dioxin concentrations in Belgian food. Some of these exposures are chronic, others are attributable to incidents. Both result in high body burdens in Belgium. The paper also compares the current concentrations in food with the recent standards launched by the EU for dioxins in food, and discusses whether these values adequately protect European citizens.

Belgium↗