Health risk for children from lead and cadmium near a non-ferrous smelter in Bulgaria.

In an interdisciplinary approach the exposure to lead and cadmium of the population living in the vicinity of a Bulgarian non-ferrous metallurgical plant was studied to determine the routes of exposure. Two exposed villages situated 4 and 6 km SW and W, respectively,--in the plume of the plant's emissions--and a village for comparison situated 14 km SE of the plant were selected for the study. The blood of children aged 3-13 years from the exposed villages (n = 111) and the village for comparison (n = 18) was analyzed for lead (PbB) and cadmium (CdB) as well as for free erythrocyte protoporphyrin (FEP) and haematological parameters. A personal questionnaire concerning nutrition habits and life-style was filled in by interviewers of the children's parents. The cadmium levels in blood were within the variation range stated for Bulgaria. The exposed children had a mean CdB of 0.38 +/- 0.18 microgram/l (range 0.10-0.90 microgram/l) and the comparison group 0.31 +/- 0.35 microgram/l (0.06-1.42 micrograms/l). The mean PbB value measured in the exposed children was 240 +/- 96 micrograms/l (77-631 micrograms/l), while the mean value of PbB for the reference group was 149 +/- 57 micrograms/l (63-285 micrograms/l). Individual PbB levels > 150 and > 200 micrograms/l were found in 85% and 62%, respectively, of the exposed children and FEP > 80 micrograms/dl erythrocytes was detected in 21%. There was a concentration-response and a concentration-effect relationship (r = 0.51, D > 0.001) between PbB and FEP. According to the questionnaire only 10.3% of the interviewed families in the two exposed villages buy all food from the market, the others produce a significant part of their food themselves. The PbB levels of children who consume certain foods of local production (cabbage, cereals, poultry, and beef) were significantly higher compared to the PbB values of children whose families purchase these foods from the market. No significant relationship between lead in children's blood and the use of tin and ceramic utensils, drinking and irrigation water, hygiene habits, family tobacco smoking habits, playgrounds and traffic intensity were revealed. There was a significantly higher incidence of prematurely born babies in the exposed population. The proven relationship between lead intake via the food chain and existing significant health risks is the basis for risk communication. Measures aimed at healthier nutrition and life-style intend to contribute to decreasing the risk of the population living in the smelter region.

In vitro toxicology of heavy metals using mammalian cells: an overview of collaborative research data.

The uptake and distribution of selected heavy metals were followed and related to cytotoxicity using various parameters of proliferation and viability of cultured cells. The effects of short-term lead exposure on DNA synthesis were reversible, indicating that lead does not significantly influence genetic cellular function. In contrast, nickel effects persisted, indicating that DNA is one of the main nickel targets. Heavy metals affected all cycle phases, but those related to preparation and commencement of DNA synthesis were the most susceptible. Tolerance appeared in chronic exposure to lead and cadmium. Lead combined with X-rays had additive effect, while manganese acted synergistically and appeared to inhibit the DNA repair processes. Zinc and manganese showed a protective effect against the toxic effects of cadmium. Similar antagonistic interaction was seen for nickel v. manganese cytotoxicity. This model system makes it possible to compare heavy metal effects at the cellular level and to identify cellular targets and metabolic processes.

Pest control in public institutions.

After the spraying of insecticides against cockroaches in a kindergarten insecticide residues were detected over several months in spite of extensive decontamination. This prompted measurements in a home for asylum seekers, where insect pests had been controlled regularly by a commercial firm; here the presence of various biocides was demonstrated. As the insecticides could not be sufficiently decontaminated, the further administration was discontinued and instead cockroach traps and baits were set up. This alternative method which was well accepted by the inhabitants of the home as well as the administrative staff was subsequently successfully employed in other public institutions, e.g. a school and another kindergarten.

[Effect of microbial aerosols on the human]. / Wirkung von mikrobiellen Aerosolen auf den Menschen.

Based on numerous publications dealing with the effects of microbial emissions on workers in waste processing plants and on few papers concerning the assessment of the environmental health relevance of microbial aerosols on people living in the vicinity of composting facilities, the current state of the art in this field is presented. With regard to occupational exposure the possible health effects like infections, toxicity and allergies are specified. Since to date only few studies have been made of populations exposed to microbial aerosols in ambient air, the environmental health aspects are reviewed in the context of a study of three compost plants in Hesse, where ambient air measurements as well as epidemiological investigations were carried out. Final recommendations are given and the research needs regarding the environmental health significance of microbial aerosols are formulated.

Low dose effects of fibrous and non-fibrous mineral dusts on the proliferation of mammalian cells in vitro.

This report presents preliminary results of studies on the growth stimulating properties of mineral dusts. The studies were carried out with Syrian hamster diploid embryonic fibroblasts and Chinese hamster fibroblasts, line B14F28. Toxicity testing was done by the determination of the plating efficiency as a measure of growth and viability. The following dusts were used: the modified UICC asbestos fibres amosite, (AFF) crocidolite (KFF), chrysotile (KFF): in addition glass fibre (GFF), corundum and quartz DQ12. Concentrations > 2 microg/cm2 of AFF, CFF, KFF and GFF depressed the plating efficiency of B14F28 cells in a dose-dependent manner, but all of the fibres and corundum increased colony sizes at concentrations of 0.16-0.33 microg/cm2, in the case of corundum, AFF, KFF, and CFF also at up to 0.66 or 1.32 microg/cm2. DQ12 did not enhance colony growth. The stimulation of proliferation could be demonstrated both in terms of colony size (diameter) and cell numbers. The factor(s) responsible for proliferation stimulation reside in the supernatant, since the medium of dust-treated cell cultures was able to stimulate colony growth after removal of the dusts by filtration. The results indicate the induction of growth factors (cytokines) by low concentrations of the mineral dusts. Experiments concerning the effect of dusts on embryonic golden hamster fibroblasts yielded similar results. The plating efficiency was inhibited by concentrations of GFF and CFF > 0.25 microg cm2 and by AFF, KFF, GFF and corundum at concentrations > 5 microg/cm2, but colony counts were significantly increased by AFF, KFF and corundum at concentrations of 0.25-3 microg/cm2. This biological reaction which was observed in different cell types appears to be especially relevant in the context of environmental exposure where low dust concentrations prevail.

Testing of chelating agents and vitamins against lead toxicity using mammalian cell cultures.

Mammalian cell cultures were used to determine the capacity of antidotes to modify (a) lead uptake, (b) lead toxicity and (c) lead release from cells. The following chelating agents were tested: Na, Ca-ethylenediaminetetraacetic acid (EDTA), diethylenetriaminepentaacetic acid (DTPA), nitriloacetic acid, ethylene glycol-bis(aminoethyl)tetraacetic acid (EGTA), D,L-mercaptosuccinic acid (MSA), meso-2,3-dimercaptopropanesuccinic acid (MSA), D,L-2,3-dimercaptopropane-1-sulfonic acid (DMPS), penicillamine (PA), N-acetylpenicillamine (NAPA), and diethylcarbodithioate (DDTC). The following vitamins were tested: thiamine (B1), riboflavine (B2), pyridoxine (B6), cobalamin (B12) and ascorbic acid (C). Inhibition of lead uptake was produced by EDTA, EGTA, DMSA, DMPS, MSA, PA, NAPA and vitamins B1, B6 and C, vitamins B2 and B12 being ineffective. The same compounds reduced lead cytotoxicity. Interestingly DDTC and DTPA increased lead uptake, but did not exacerbate lead toxicity. Significant release of lead from preloaded cells was caused by DTPA, NAPA, DMPS and PA, while the other chelators were ineffective.

Improper use of an insecticide at a kindergarten.

In a German kindergarten cockroaches were destroyed by a commercial firm. A preparation containing pyrethrum and its synergist piperonyl butoxide and the organic phosphorus pesticide chlorpyriphos was sprayed. While cleaning the rooms, the staff complained of health effects. Thereupon the kindergarten was closed until further notice, samples were taken by the health authorities for chemical analysis, and an environmental medical evaluation was initiated. The analytical results are presented. The toxicological significance of the employed insecticides, their environmental persistence, and the problems associated with pest control in such institutions are discussed and recommendations given.

Reversible and irreversible immobilization of enzymes on Graphite Fibrils.

Graphite Fibrils are hollow tubes (0.01 x 1-10 microns) consisting of concentric layers of graphite. Fibrils can be chemically modified to introduce surface functionalities such as carboxyl groups. Carboxylated fibrils were further functionalized to amino alkyl derivatives which were covalently linked to an enzyme, horseradish peroxidase (HRP). HRP fibrils showed substantial catalytic activity. Additionally, carboxyl fibrils were derivatized with specific inhibitors of the enzymes beta-galactosidase (beta-Gal) and alkaline phosphatase (AP). Enzyme inhibitor-modified fibrils were used to specifically purify both beta-Gal (using beta-Gal inhibitor fibrils) and AP (using AP inhibitor fibrils) from mixtures of these two enzymes. These studies demonstrate the feasibility of using Graphite Fibrils as supports in biocatalysis and biospecific affinity chromatography.

Studies of cadmium chelator efficacy using mammalian cell cultures.

An experimental system is presented for the assessment of the efficacy of chelating agents against cadmium. Mammalian cells in vitro can be employed to screen compounds that modify metal uptake, metal toxicity and metal mobilization from metal-loaded cells and can thus identify likely, or exclude unsuitable, candidates for the therapy or prevention of metal intoxification. Examples are given of possible cadmium antidotes. As a first step the toxicity of the chelating agents for different cells lines did not show appreciable differences. For the testing of the chelating agents a highly Cd-sensitive cell line was selected, which also exhibited a well measurable Cd uptake. The influence of the chelators on cadmium incorporation was studied and correlated with the results of experiments where the metal and the antidotes were simultaneously applied. Chelating agents causing reduced Cd uptake generally also depressed Cd toxicity. However, two or the compounds which led to increased cellular Cd incorporation did not modify metal cytotoxicity in a corresponding fashion. These paradoxical findings indicate complex interactions between chelators, metals and cells. Finally, cells were pre-treated with Cd and exposed to chelating agents. Only one of the substances tested, i.e., diethyldithiocarbamate, was capable of affecting Cd release from the cells. The results obtained with this model system show good agreement with finding reported in vivo.

Cellular metabolism of arsenic studied in mammalian cellsin vitro.

The cytotoxicity of trivalent and pentavalent inorganic arsenic was studied in cultured mouse fibroblasts. Concentrations of As(III) in the µM range and approximately 10-fold higher concentrations of As(V) led to a reduction of cellular proliferation and viability with a concomitant increase of LDH release and stimulation of lactate production. Cells pretreated with a low As(III) concentration were less sensitive to toxic doses of As(III) or As(V).Uptake of As(III) by the cells was greater than that of As(V). Both forms of inorganic arsenic were converted intracellularly to monomethylarsonic (MMA) and dimethylarsinic (DMA) acids, which were subsequently released into the culture medium. In As-pretreated cells, which proved more resistant to As toxicity, biotransformation of inorganic to MMA and DMA was increased.

Cutaneous ureterostomy in cancer patients.

Twenty-four patients with malignant pelvic mass had diverting ureterocutaneostomy. Four patients (17%) developed necrosis and one (4%) required surgical correction due to stenosis. The remaining patients had a well-functioning ureterocutaneostomy until the death which occurred median 174 days later. We find that good palliation can be achieved using this simple operation, and therefore recommend it as the urinary diverting procedure to patients with obstructing pelvic malignancy.

Factors influencing cadmium uptake and cytotoxicity in cultured cells.

Cultured Chinese hamster B14F28 and HeLa cells in early lag and stationary phases accumulated less cadmium than cells in logarithmic growth. Pretreatment of the cell cultures with a non-toxic concentration of cadmium lead to adaptation of the response to subsequent high concentrations. The pretreated cells did not differ from controls in their uptake of cadmium. HeLa cell cultures accumulated more cadmium than B14F28 cultures and differed in their sensitivity to cadmium. The cytotoxicity of cadmium in the two cell lines did not correlate with uptake of cadmium. Cells accumulated more cadmium and exhibited enhanced toxicity with increasing pH of the medium. Serum and serum albumin reduced the uptake of cadmium and the cytotoxicity. Increasing concentrations of calcium ions depressed the uptake of cadmium, while magnesium and phosphate ions exerted no effect.

Arsenic uptake, cytotoxicity and detoxification studied in mammalian cells in culture.

The cytotoxicity of trivalent and pentavalent inorganic arsenic salts was determined in mouse fibroblasts in vitro. Concentrations of As (III) in the microM range led to a reduction of proliferation and viability with a concomitant increase in LDH release and stimulation of lactic acid production. Similar effects were noted with approximately 10-fold greater molar concentrations of As(V). Cells pretreated with a low As(III) concentration are less sensitive to toxic doses of As(III) or As(V). Uptake of As(III) by the fibroblasts is greater than that of As(V). Both forms of inorganic arsenic are converted intracellularly to monomethylarsonic (MMA) and dimethylarsinic (DMA) acids, which are then released into the culture medium. In As-pretreated cells, which are more resistant to As toxicity, biotransformation of inorganic arsenic to MMA and DMA is increased.

Late mortality following Billroth II resection for duodenal ulcer.

In a follow-up study of 1 000 patients subjected to Billroth II resection for duodenal ulcer in the period 1948-1956, the late mortality up to the end of 1977 (522 patients) was analyzed. The observed mortality was compared with the expected mortality calculated by the life-table method and indirectly standardized for age, sex, domicile and time and cause of death. The overall mortality rate was significantly increased, mainly due to suicide, which occurred at five times the expected rate and could be related to excessive alcohol consumption and psychiatric disturbances. Malignant neoplasms, including gastric carcinoma, were not more common than expected as causes of death. The same applied to pulmonary tuberculosis, other respiratory disorders, cardiovascular, gastro-intestinal and urogenital disease and to accidents. It is concluded that the main mortality risk factors were psychiatric disease and alcohol consumption.

Dysplasia and carcinoma in the Billroth II resected stomach 27-35 years post-operatively.

In a previous endoscopic follow-up examination of patients who 22-30 years before had undergone Billroth II resection for duodenal ulcer the prevalence of dysplasia and carcinoma of the gastric remnant was 14.8 and 0%, respectively. In this second follow-up study five years later the figures had increased to 30.3 and 5.6%. It is uncertain whether these changes result from the higher number of biopsies taken at the re-examination or reflect a time-dependent rise in the morbidity. Although the observed prevalences may seem high, we do not find prophylactic endoscopic examination of such patients indicated, as other investigations by us have shown that the series of Billroth II resected patients under study does not show excess incidence or excess mortality of gastric carcinoma.