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PubMed1980

Occupational exposure to hexachlorocyclohexane. I. Body burden of HCH-isomers.

In a lindane (gamma-hexachlorocyclohexane = gamma-benzenehexachloride)-producing factor 57 workers were studied with regard to their blood levels of the three hexachlorocyclohexane isomers: alpha-, beta-, and gamma-HCH. The TLV-TWA (MAK value 1979) for gamma-HCH of 0.5 mg/m3 was not exceeded at any of the workplaces where HCH is synthesized and purified to lindane. Additionally, in some of the workers samples of s.c. adipose tissue were taken for determination of HCH-isomer content. An external group of 20 clerks was examined in the same way for control purposes. In contrast to the control persons, none of whom had HCH-concentrations in serum above the respective detection limits, the values determined in serum of the exposed workers were in the following ranges: alpha-HCH: 10-273 microgram/1, beta-HCH: 17-760 microgram/l, and gamma-HCH: 5-188 microgram/1. Of special interest is the observation of a significant increase of beta-HCH-concentration in serum with the time of employment in lindane production, indicating a pronounced accumulation of this substance in the human organism. Concentrations of this isomer in s.c. adipose tissues were about 300-fold higher than in serum. A significant correlation between both parameters could be established. The results of this study show that adherence to the TLV-TWA of gamma-HCH is not sufficient for control of HCH-exposure. Furthermore, biological monitoring of exposed workers is necessary taking into account the three more important isomers alpha-, beta-, and gamma-HCH.

Adipose Tissue↗
PubMed1991

Biological half-time and body burden of cadmium in dogs after a long-term oral administration of cadmium.

To investigate the kinetic behavior of cadmium, we conducted a long-term oral administration experiment, using beagle dogs. The experimental animals were given a commercial diet and pelleted food containing 1, 3, 10, 50, and 100 mg of cadmium per day in the form of cadmium chloride for 8 yr. A single injection of cadmium (as CdCl2) into dogs was also performed in order to obtain fundamental kinetic information for a dog. The kinetic behavior of cadmium in chronic experiment is described theoretically, using a two-compartment model. The model was selected based on the elimination pattern of cadmium from the blood in the single injection experiment. The parameters of the model were estimated from the acute and chronic experimental data. The theoretical value of the cumulative amount of cadmium excreted in urine agreed with the experimental one. This result suggests that the two-compartment model used in this study is useful to elucidate the kinetic behavior of cadmium after a long-term exposure to cadmium. The terminal biological half-time in the two-compartment model was estimated at about 1 to 2 yr for both male and female dogs given 1, 3, 10, and 50 mg of cadmium, and for the male dog given 100 mg of cadmium, but only 0.3 to 0.5 yr for the female dog given 100 mg of cadmium. The amount of cadmium in the central compartment and tissue compartment increased continuously and then gradually reached a steady state. The amount of tissue compartment was much higher than that of the central compartment for each beagle dog.

Administration, Oral↗
PubMed2002

Modes of action in ecotoxicology: their role in body burdens, species sensitivity, QSARs, and mixture effects.

In contrast to the general research attitude in the basic sciences, environmental sciences are often goal-driven and should provide the scientific basis for risk assessment procedures, cleanup, and precautionary measures and finally provide a decision support for policy and management. Hence, the prominent role of mechanistic studies in ecotoxicology is not only to understand the impact of pollutants on living organisms but also to deduce general principles for the categorization and assessment of effects. The goal of this review is, therefore, not to provide an exhaustive coverage of modes of toxic action and their underlying biochemical mechanisms but rather to discuss critically the application of this knowledge in ecotoxicological risk assessment. Knowing the mechanism or, at least the mode of toxic action is indispensable for developing descriptive and predictive models in ecotoxicology. This review seeks to show the crucial role of target sites, interactions with the target site(s), and mechanisms for an adequate and efficient ecotoxicological risk assessment. Emphasis in the discussion is on target effect concentrations (or target occupancy), species selectivity and species sensitivity, time perspective of effect studies, Quantitative Structure-Activity Relationships (QSAR), and mixture toxicity. A particular focus of this review is on multiple mechanisms. Although the illustrative examples were mainly taken from studies in aquatic ecotoxicology, the proposed conceptual approach is also in principle applicable and even particularly useful for soil and sediment systems. Recommendations for further research and developments include the use of internal effect concentrations and target site concentrations in site-specific risk assessment and as a mixture toxicity parameter as well as general considerations for the derivation of mechanistically meaningful QSAR and other predictive models.

Body Burden↗
PubMed2004

Noninvasive assessment of liver detoxification capacity of children, observed in children from heavily polluted industrial and clean control areas, together with assessments of air pollution and chloro-organic body burden.

The liver is an important target organ in exposure to foreign substances or their metabolites. Early changes in the metabolic capacity of the liver may be a first sign of the effect of an exposure and an indication of an early (pre)pathological process. For the noninvasive testing of this metabolic capacity, a special diagnostic tool has been developed and demonstrated under real exposure conditions. The main questions investigated were (1) whether the liver detoxification capacity of children is affected by long-term low exposure in a highly polluted area and (2) to what extent redevelopment in once heavily polluted industrial areas contributes to improvement in the health measured in the children from the changed detoxification capacity. Kindergarten children from a heavily polluted industrial area and a control area were observed over a prolonged period during redevelopment of the industrial area. The liver's detoxification capacity was assessed with a stable-isotope-based diagnostic test, the [(15)N]methacetin test. In addition, the region-specific external exposure (indicator components were chlorinated compounds) and internal load were measured. The difference in the children's internal load between the exposed and control groups reflected the differences in exposure (exposed children had an internal load 2.3 times greater than that of the control children). The exposed children showed a 6% lower liver detoxification capacity. A reduction in pollution by about 70% as a result of remediation was reflected in improved liver detoxification capacity, and the difference between the polluted and control areas was no longer significant. Prolonged exposure to low concentrations of xenobiotics can disturb hepatic functioning. The proposed test can be used as a tool to determine the effects of multicomponent exposure and is well suited for bioeffect monitoring.

Acetamides↗
PubMed1994

Control of the body burden of M. avium complex is associated with improved quality of life and prolonged survival of patients with AIDS: a prospective trial with rifabutin combined with isoniazid, clofazimine, ethambutol.

The objectives of this study were to assess whether culture conversion affects quality of life (QoL), survival and Mycobacterium avium complex (MAC)-associated morbidity in patients with AIDS. Data from an open, multicenter, noncomparative trial were analyzed to test the benefit of suppressing mycobacteria: measures of QoL, clinical outcomes and quality-adjusted survival are compared on occasion of culture-negative and positive assessments. The study was conducted at AIDS clinics in France, coordinated by the GETIM, with the participation of 51 AIDS patients with culture-proven Non-Tuberculous Mycobacteria (NTM) disease. Patients underwent a quadruple drug-regimen. The following parameters were investigated: (i) Culture conversion to a negative finding (= suppression) or on > 2 occasions, including each patient's last valid observation (= conversion); (ii) survival after treatment start; (iii) QoL by using the ECOG score, re-coded 0 to 4 for worst to best performance status; (iv) quality-adjusted survival. On treatment, > 1 negative culture was recorded for 69% of the evaluable patients, corresponding to 111 person-months of observation. Positive culture findings accounted for 42 person-months only. Patients' performance status (mean 1.8 at entry) worsened or improved according to whether culture was positive or negative (means 1.2 and 2.2; total scores 109 and 217 person-months, respectively). Similarly, MAC-attributable morbidity was significantly reduced when culture was negative. Mean survival was 195 days longer in treatment success patients. These analyses suggest that, in patients with NTM disease occurring as a late complication of AIDS, treatment was effective in improving clinical status and survival, and in suppressing bacterial growth.(ABSTRACT TRUNCATED AT 250 WORDS)

AIDS-Related Opportunistic Infections↗
PubMed2005

Mercury body burdens in Gambusia holbrooki and Erimyzon sucetta in a wetland mesocosm amended with sulfate.

This study used an experimental model of a constructed wetland to evaluate the risk of mercury methylation when the soil is amended with sulfate. The model was planted with Schoenoplectus californicus and designed to reduce copper, mercury, and metal-related toxicity in a wastestream. The sediments of the model were varied during construction to provide a control and two levels of sulfate treatment, thus allowing characterization of sulfate's effect on mercury methylation and bioaccumulation in periphyton and two species of fish--eastern mosquitofish (Gambusia holbrooki) and lake chubsucker (Erimyzon sucetta). After one year in the experimental model, mean dry-weight normalized total mercury concentrations in mosquitofish from the non-sulfate treated controls (374+/-77 ng/g) and the reference location (233+/-17 ng/g) were significantly lower than those from the low and high sulfate treatments (520+/-73 and 613+/-80 ng/g, respectively). For lake chubsucker, mean total mercury concentration in fish from the high sulfate treatment (276+/-63 ng/g) was significantly elevated over that observed in the control (109+/-47 ng/g), the low sulfate treatment (122+/-42 ng/g), and the reference population (41+/-2 ng/g). Mercury in periphyton was mostly inorganic as methylmercury ranged from 6.6 ng/g (dry weight) in the control to 9.8 ng/g in the high sulfate treatment, while total mercury concentrations ranged from 1147 ng/g in the control to a high of 1297 ng/g in the low sulfate treatment. Fish methylmercury bioaccumulation factors from sediment ranged from 52 to 390 and from 495 to 3059 for water. These results suggest that sulfate treatments add a factor of risk due to elevated production of methylmercury in sediment and porewater which biomagnified into small fish, and may potentially increase through the food web.

Analysis of Variance↗
PubMed1997

Baseline studies in the Slave River, NWT, 1990-1994: Part II. Body burden contaminants in whole fish tissue and livers.

The Northwest Territories section of the Slave River is the recipient of chemical compounds from a variety of sources, including upstream industry and agriculture. In 1990, concerned government agencies formulated a practical, focussed, and comprehensive environmental monitoring program to assess contamination in the river and the Slave River Environmental Quality Monitoring Program was established. The program was designed to respond to the distinct requirements of two major monitoring goals. The first priority was to ascertain whether the fish in the Slave River were safe to eat. The second goal was to establish a baseline data set with which to compare future effects from upstream activities and long-range transport of contaminants. From the data gathered in the present study, it appears that whole tissue of fish (muscle) is fit for human consumption. Throughout the monitoring period, consistently low concentrations of organochlorine pesticides, PCBs, dioxin and furan isomers, PAHs, chlorinated phenolics, and heavy metals have been observed and median concentrations have all been below federal fish consumption advisories. Also, the numerous data values below analytical detection limits attest to the relatively uncontaminated nature of the fish. These results were comparable with other studies conducted on arctic animals. The heavy metals observed in fish tissue are probably of natural origins, since inorganic analyses of suspended sediment in the Slave River indicated relatively elevated levels, with no known anthropogenic source. While the present study concluded that contaminant levels in whole fish are low, toxaphene levels in burbot livers should continue to be monitored since concentrations were consistently above fish consumption advisories during the monitoring and are eaten extensively by the native peoples. The second goal of the monitoring program was to develop a baseline data set and the values tabled in the current paper are useful in establishing a foundation for future comparison.

Animals↗
PubMed2000

Mobilization of mercury by DMPS in occupationally exposed workers and in model experiments on rats: evaluation of body burden.

The aim of the study was to evaluate the efficacy of DMPS (sodium-2,3-dimercapto-1-propane sulfonate) (Dimaval) administration for mobilizing mercury from the body in occupationally exposed people and experimental animals. Two doses of DMPS were administered at a 24-h interval to: (a) groups of people occupationally exposed to merkury--workers of the chloralkali industry (n = 43), and dentists (n = 12), (b) non-exposed individuals (n = 20), and (c) rats chronically exposed to mercury vapour at the concentration of 0.8 mg/m3 Hg degree (6 h/day, 5 days/week) for 15 weeks. In an out-patient mobilizing test, the urinary excretion of mercury 48 h after the administration of the first dose reached 1513 micrograms in the group of industrial workers, 132.6 micrograms in dentists, and 3.78 micrograms in controls. In rats, two consecutive doses of DMPS decreased kidney content of mercury by about 30% and 50% after oral and intraperitoneal administration, respectively. Kidney mercury burden was calculated on the basis of the data from animal and human studies of the mobilization of mercury via urine after DMPS treatment: 61, 2800 and 28,000 ng/g in controls, dentists and workers, respectively. It was estimated that two doses of DMPS mobilized 17-20% (after oral administration) and 25-30% (after intramuscular administration) of kidney mercury burden, both in the control and exposed subjects.

Adult↗
PubMed2005

Cortical and amygdalar Lewy body burden in Parkinson's disease patients with visual hallucinations.

Visual hallucinations (VH) are among the most common non-motor complications of Parkinson's disease (PD). A few studies on their etiopathogenesis have suggested involvement of cortical and amygdalar areas. In order to investigate the possible association between extranigral Lewy Body (LB) distribution across cortical and amygdalar regions and the presence of VH in PD brain donors, we conducted a clinico-pathological comparison of 10 PD patients with VH vs 10 closely matched PD patients without VH. The LB burden was significantly higher across the amygdala and the frontal, temporal and parietal cortical areas in patients with VH. Although our results suggest significant extranigral involvement, the precise etiopathologic mechanisms responsible for the development of VH need further clarification.

Aged↗