Showing papers in "Environmental Health Perspectives in 1979"

N-acetyltransferase phenotype and risk in urinary bladder cancer: approaches in molecular epidemiology. Preliminary results in Sweden and Denmark.

Abstract: A variable but often significant proportion of urinary bladder cancer in urban areas can be attributed to occupational and cultural (cigarette smoking) situations associated with exposures to vario...

Exposure and accumulation of cadmium in populations from Japan, the United States, and Sweden

Abstract: Studies were carried out in Japan, United States, and Sweden regarding comparability of analytical methods for cadmium, daily intake of cadmium via food, daily amount of cadmium in feces, concentra...

Factors influencing cadmium accumulation and its toxicity to marine organisms

Abstract: The toxicity of dissolved cadmium to a variety of marine animals has been found to be related to salinity, with decreased toxicity observed at higher salinities. Recent data from our laboratory hav...

Bioaccumulation of cadmium in marine organisms.

Abstract: A general review of cadmium concentrations in marine organisms and studies of cadmium bioaccumulation is presented. Factors which influence cadmium concentrations, such as regional differences, seasonal fluctuations and salinity, are discussed and species which are likely to accumulate cadmium identified. Experimental studies designed to investigate the influence of some of these factors on cadmium bioaccumulation in a filter feeding bivalve mollusk, the American oyster (Crassostrea virginica), are presented. Field studies of seasonal dynamics of cadmium in oysters indicate patterns which may be correlated with seasonal physiological activity. The bioaccumulation of cadmium following input to estuarine systems by natural phenomena is observed. Cadmium concentrations in oysters collected from regions of different salinity suggest an inverse relationship between cadmium concentration and salinity. Laboratory experiments designed to investigate mechanisms of cadmium accumulation demonstrate that an inducible cadmium binding protein, similar to metallothiomein, is present in the American oyster.

Mortality and cancer morbidity among cadmium-exposed workers.

Abstract: Preliminary data are reported from a study of 269 cadmium-nickel battery factory workers and 94 cadmium-copper alloy factory workers. The target group comprises all workers with more than 5 years e...

Metabolic model for cadmium in man.

Abstract: A metabolic model for cadmium has been formulated in terms of a flow scheme for cadmium among eight body compartments. The mathematical description of the flow of cadmium between compartments consits of a number of differential equations, and the accumulation of cadmium may thus be calculated. Coeffcients for the flow of cadmium were estimated from empirical data both from animals and man. The modelling serves two main purposes: it provides a means of using present knowledge about metabolism in order to calculate expected accumulation in critical organs and other tissues and body fluids at certain intake levels and it makes it possible to define deficiencies in our present knowledge about metabolism. Data recently collected, partly as a result of considerations related to the model, have confirmed the assumptions of a very long biological half-time in other tissues and the small excretion of cadmium via bile.

Early cellular effects of circulating cadmium-thionein on kidney proximal tubules

Abstract: Circulating cadmium-thionein (Cd-MT) is cleared from the mammalian circulatory system by filtration through the kidney glomerulus with subsequent reabsorption by kidney proximal tubules. Damage to the tubules results following uptake of Cd-MT, which is dependent upon time and the dose level of cadmium administered. Intravenous administration of 109Cd-MT at doses of 0.017 and 0.17 mg Cd/kg body weight with examination of total renal uptake of 109Cd at 0.5, 3, and 24 hr disclosed that the rate of clearance from the blood and uptake by the kidney was significantly more rapid at the 0.017 mg Cd/kg dose. Ultrastructural changes resulting from intravenous injection of either form A or B of Cd-MT were characterized by increased numbers of pinocytotic vesicles and small, dense lysosomal structures. There was no evidence of mitochondrial swelling or cell death at either 3 or 6 hr after injection. The subcellular distribution of cadmium in kidney tissue at various times after administration of Cd-MT was determined by using differential centrifugation techniques with 109Cd and in situ by using x-ray microanalysis. At 30 min after injection of Cd-MT, significant amounts of cadmium were present in lysosomal fractions indicating an interaction between the tubular lysosome system and Cd-MT prior to the onset of overt cellular toxicity. Results suggest that Cd-MT is reabsorbed and broken down by kidney tubule cells in a physiological manner with possible subsequent release of the toxic cadmium ion.

Renal tubular dysfunction and abnormalities of calcium metabolism in cadmium workers

Abstract: Tubular proteinuria is generally accepted as the critical effect following long-term, low-level exposure to cadmium as seen in an industrial environment. This effect may not be of immediate importance to the health of the individual, but the significance, in terms of long-term morbidity and mortality, of the renal tubular defect of which it is an indicator is not fully understood, and certain sequelae may have remained unrecognized due to inadequate follow-up.Follow-up studies have been performed in nine of 12 workers who were initially investigated in 1962. In six of the men exposures ranged from 28 to 45 years to cadmium sulfide dust and for shorter periods in the earlier years to cadmium oxide fume and dust. These six men had tubular proteinuria when first seen, and this has persisted in the five survivors. All six men had hypercalciuria, and two of them became recurrent stone formers. One man whose urinary calcium excretion later fell to a low level more recently developed vitamin D resistant osteomalacia. In addition, each of the six men had exhibited some, but not all, of a variety of biochemical abnormalities related to other proximal renal tubular defects, and the worker who developed osteomalacia had additional evidence of a distal tubular defect. The five survivors also have evidence of slowly progressive deterioration in glomerular function.Follow-up of this small group has shown that renal tubular dysfunction in cadmium workers may continue symptom-free for long intervals, but in a proportion of cases serious clinical effects may develop after a number of years.

Implications for human health.

Abstract: To analyze the implications for human health, the toxicologist requires four sets of data: the results of toxicity and other studies in animals; quantitative data on actual or potential human exposure; whatever information is available on effects of exposure in man; and the statistical extrapolations from the dose-response relationships in animals to the (usually) much lower levels of human exposure. Professional expertise in toxicology is essential to assess the nature and severity of the toxic effects observed in animals, including such characteristics as potential for progression, irreversibility and production of incapacity. Given sufficient data, an estimate can be arrived at of the likelihood that such effects will be elicited in human populations of differing susceptibilities. The criteria by which the overall implications for human health can be judged comprise both the direct effects on man, as well as the indirect consequences stemming from environmental impacts.

Experimental study of biological effects of leads and aluminum following oral administration.

Abstract: A wide spectrum of the biological effects of lead and aluminum ions is noted during short-term and long-term oral administration to laboratory animals. The general toxic and gonadotoxic effects of these metals during a short-term experiment appeared to be identical, and the correlation of these effects was preserved during chronic experiments. Lead (0.03 mg/l.) and aluminum (0.5 mg/l.) concentrations in water may be dangerous to the health of the population, and hygienic standards are recommended for inclusion in the standard for drinking water quality.

Mutagenic and carcinogenic properties of polycyclic aromatic hydrocarbons.

Abstract: The rapid development of the chemical industry, combustion of fossil fuels, and smoking of tobacco have resulted in contact of the general population with benzo(a)pyrene and other carcinogenic aromatic hydrocarbons. Persons especially at risk occupationally are those engaged in thermal processing of oil shale, coal, and heavy residual petroleum. It has been shown that polycyclic aromatic hydrocarbons require metabolic activation before they can act as mutagens or carcinogens. This metabolic activation results from interaction with microsomal enzymes present in many body cells, yielding reactive epoxides which react with DNA and produce mutations in the count frame shift or participate in covalent bounding. While opinions differ regarding the relative role of these processes in mutagenesis, considerable evidence exists which links mutagenesis and carcinogenesis. Metabolites of the polycyclic aromatic hydrocarbons which are carcinogenic are usually mutagenic, which supports the hypothesis that damage to chromosomes plays an important role in carcinogenesis. These facts open the possibility to monitoring the spread of carcinogenic substances in the biosphere by relatively simple tests whose endpoint is mutagenesis.

Acute effects of cadmium on the pregnant rat and embryo-fetal development.

Abstract: In rats, of the Wistar-Porton strain, a single intravenous injection of 1.25 mg Cd2+ between days 9 and 15 of gestation results in a high incidence (80% of hydrocephalus, together with other malfor...

Statistical methods for censored survival data.

Abstract: Methods of statistical analysis of censored survival times are briefly reviewed and illustrated by application to clinical trials data. These include estimation of the survival curce, nonparametric...

Behavioral toxicology of carbon disulfide and toluene.

Abstract: Organic solvents are pervasive in the communal and industrial environments. Although many are potent central nervous system agents, clearly delineated behavioral effects have played only a minor role in the formation of exposure standards. A comprehensive behavioral pharmacology and toxicology of these compounds is one aim of US/USSR collaboration. The current report describes some actions of carbon disulfide and toulene. Earlier data about the actions of carbon disulfide on pigeon operant performance indicated disruption of schedule-controlled key-pecking. Primate data are now described from a situation designed to determine aversive thresholds to electrical stimulation. Effective concentrations of carbon disulfide produced both a rise in the amount of electric shock tolerated and a diminution of the response force exerted by the monkeys. In experiments with toluene, pigeons were shown to elevate key-pecking rate in an operant situation at certain concentrations. Toluene also was studied for its capacity to maintain self-administration in the same way as drugs of abuse. Monkeys worked to gain access to toulene vapor just as they work for opiates or amphetamines. The current experiments demonstrate how comprehensive the range of behavioral toxicology needs to be to deal with environmental health issues.

Bioavailability of Cd to Food crops in relation to heavy metal content of sludge-amended soil.

Abstract: Results of greenhouse and laboratory experiments on factors influencing uptake and accumulation of Cd by economic crops are summarized. Tolerance to Cd is highly crop-specific. For example, 21 diff...

Properties and biological significance of the ileal bile salt transport system.

Abstract: The properties of a specific transport system for bile salts, which is located in the ileum of the small intestine are described. The system operates by a sodium ion cotransport mechanism, and it f...

Analysis of pediatric blood lead levels in New York City for 1970-1976.

Abstract: A study was completed of more than 170,000 records of pediatric venous blood levels and supporting demographic information collected in New York City during 1970-1976. The geometric mean (GM) blood lead level shows a consistent cyclical variation superimposed on an overall decreasing trend with time for all ages and ethnic groups studied. The GM blood lead levels for blacks are significantly greater than those for either Hispanics or whites. Regression analysis indicates a significant statistical association between GM blood lead level and ambient air lead level, after appropriate adjustments are made for age and ethnic group. These highly significant statistical relationships provide extremely strong incentives and directions for research into casual factors related to blood lead levels in children.

Carcinogenicity of chloroform.

Abstract: Chloroform is carcinogenic in rats, mice, and probably in dogs. Chloroform induced carcinomas of the liver and kidney and malignant tumors in other organs in rats and mice. Liver neoplasms have been described in three strains of mice. Carcinomas of the kidney were found in a first study in mice and in the repeat of that study. Dogs given chloroform developed neoplasms of the liver as well as in other organs. Rats given chloroform also developed toxic changes, particularly male rats, as a result of treatment. These lesions included interstitial fibrosis of the kidney; polyarteritis of the mesenteric, pancreatic, and other arterioles and arteries; and atrophy of the testes. These toxic changes may have interfered with the development of neoplasms in male rats.

Increase in the systolic pressure of rats chronically fed cadmium.

Abstract: In our laboratory, chronically feeding cadmium to groups of rats has been reproducibly associated with average increases of 15 to 20 mm Hg in systolic pressure. A total of 497 female Long-Evans rat...

Some effects of oral ingestion of cadmium on zinc, copper, and iron metabolism.

Abstract: Data are presented to show that ingestion of cadmium chloride by rats at low levels leads to alteration of zinc metabolism in the liver, even though the formation of metallothionein is not evident....

Nutritional influences on metal toxicity: cadmium as a model toxic element.

Abstract: The nutrient quality of the diet has been shown repeatedly to be a significant factor in modifying the response of man and animals to toxic element exposure. Deficiencies of several essential nutrients have been shown to exacerbate the effects of cadmium and supplements of such nutrients have been shown to ameliorate the toxicity. Thus the effects of exposure to a toxic element, such as cadmium, may vary, depending on interactions with other elements which are present in the diet in different concentrations.

Lead toxicity and nutritional deficiencies.

Abstract: Under appropriate conditions, deficiencies of certain minerals and vitamins as well as high intakes of dietary fat increase the toxicity of a given dose of lead in experimental animals. The severity of lead poisoning can also be increased by the consumption of either deficient or excessive levels of protein. Mineral deficiencies appear to have some of the most profound effects on lead toxicity, since the consequences of plumbism can be exaggerated by feeding diets low in calcium, phosphorus, iron, zinc, and in some cases, copper. Evidence for an antagonism between lead and nutritional levels of selenium is inconclusive. Vitamin E deficiency and lead poisoning interact to produce an anemia in rats that is more severe than that caused by either treatment alone. Lead apparently exerts a pro-oxidant stress on the red cell, thereby causing its accelerated destruction. One of the biochemical mechanisms of lead poisoning may be the disruption of normal membrane architecture, thereby leading to peroxidative damage. Epidemiological surveys have suggested a negative correlation between the poor nutritional status of children with regard to calcium and the concentration of lead in blood. Other examples of potential interactions of mineral status and lead poisoning in humans include the hypothesized hazards of soft water to public health in areas with lead plumbing and the possible role of mineral deficiencies in the etiology of pica. Experimental studies have shown that in some situations combined nutritional deficiencies can have an additive effect in potentiating lead toxicity.

Influence of exposure mode on the toxicity of NO2.

Abstract: Pollutant gases are subject to a variety of physical and chemical interactions within the atmosphere due to cyclic production and various meteorological influences. In consequence there is generall...

Investigations on the lung and kidney function in workers exposed to cadmium.

Abstract: The kidney seems more sensitive to the chronic effect of cadmium than the lung. Only minor impairments of lung function (mild form of obstructive lung disease) were found after long-term occupational exposure (less than 20 yr) to moderate concentration of cadmium oxide dust and fume. This conclusion, cannot, however be extrapolated to acute or subacute inhalational exposure. The nephrotoxicity of cadmium consists in a tubular dysfunction characterized by an increased excretion of beta 2-microglobulin and giving rise to the classical tubular proteinuria and in a glomerular dysfunction evidenced by an increased excretion of high molecular weight proteins and increased levels of beta 2-microglobulin and creatinine in plasma and giving rise to a glomerular type proteinuria. These renal changes were mainly found in workers whose cadmium concentration at time of the survey exceeded 1 microgram Cd/100 ml in blood and 10 microgram Cd/g creatinine in urine. It should, however, be stressed that higher levels of Cd in blood and in urine are not necessarily associated with the presence of excessive proteinuria. In newly exposed workers, the Cd level in blood increases progressively to a plateau after several weeks. Cadmium level in urine fluctuates more. In workers exposed for several months to an airborne concentration exceeding 200 microgram/m3, Cd concentration in urine seems mainly influenced by recent exposure.

Metabolism of orally administered cadmium-metallothionein in mice.

Abstract: The main source of cadmium in the diet is cereal or meat, especially in liver and kidney. Since the cadmium in both liver and kidney is bound to metallothionein, a heat-stable protein, the gastroin...

Pulmonary and gastrointestinal exposure to cadmium oxide dust in a battery factory.

Abstract: The elimination of cadmium in feces was studied in a group of 15 male workers exposed to cadmium oxide dust in a nickel-cadmium battery factory. The elimination of cadmium in feces was on the average 619 and 268 microgram/day in seven smokers and eight nonsmokers, respectively. The corresponding ranges were 97-2577 and 31-1102 microgram/day. The cadmium concentrations in blood were significantly higher in smokers than in nonsmokers, both before and after one month of vacation. Among the smokers there was a significant decrease in the cadmium concentrations during the vacation period, but not among the nonsmokers. It was estimated that cadmium naturally occurring in food and cigarettes, cadmium excreted from the gastrointestinal tract, and cadmium transported from the lungs by mucocillary clearance to the gastrointestinal tract only could explain up to 100 microgram of the cadmium in the feces. Since even among some nonsmokers much higher values for fecal cadmium were recorded, this was interpreted as being the result of ingestion of cadmium from contaminated hands and other body surfaces. Among the smokers, direct oral contact with contaminated cigarettes or pipes is an additional factor; the smokers also inhale cadmium in the tobacco smoke from contaminated cigarettes. Part of that cadmium is transferred to the gastrointestinal tract by mucociliary clearance and also adds to the fecal cadmium.

Metallothionein synthesis and degradation: relationship to cadmium metabolism

Abstract: Metallothionein is an integral component of the mechanism that regulates the metabolism of cadmium and zinc. The synthesis of this protein can be "induced" by oral or parenteral administration of either metal. The metallothionein mRNA content of liver polysomes is increased shortly after an influx of small amounts of either metal into hepatocytes. After sufficient amounts of this poly (A+) RNA have been synthesized, there is a concomitant increase in metallothionein biosynthesis and metal binding. Unlike synthesis, the degradation of metallothionein is markedly influenced by the species of metal bound. By using in vivo and in vitro techniques, it has been possible to demonstrate that resistance of metallothionein to degradation follows the order: thionein less than zinc metallothionein less than cadmium metallothionein. Moreover, while the polypeptide chains of cadmium metallothionein are degraded, it appears that liberated cadmium ions are quickly incorporated into nascent chains of thionein. The latter explains why the cadmium content of liver and kidney increases with age and environmental exposure. Since both zinc and cadmium bind to metallothionein, it appears that the binding sites provided by this inducible species provide a locus for interaction between zinc, a nutrient, and cadmium, an environmental contaminant.

Potential health and environmental effects of trace elements and radionuclides from increased coal utilization.

Abstract: This report addresses the effects of coal-derived trace and radioactive elements. A summary of our current understanding of health and environmental effects of trace and radioactive elements releas...

Chemical induction of nondisjunction in drosophila.

Abstract: Tests for chemically induced nondisjunction and loss of the sex chromosomes in Drosophila were performed. Of 31 compounds tested four gave rise only to an increase of XO exceptions, indicating the induction of chromosome loss. Six compounds, all known spindle inhibitors (colchicine, organic mercury, lead, and tin compounds) gave rise to an increase both of XXY and XO or of only XXY. The effect by metalloorganic compounds of which methylmercury was studied particularly closely, follows a peculiar pattern. In females with structurally normal X chromosomes only an increase of XX gametes is obtained, while with X chromosomes heterozygous for long inversions only O gametes are increased. The data indicates that the effect of the metal compounds occurs at first meiosis and that the process is connected with a meiotic drive, giving rise to a preferential segregation of the two X chromosomes to the functioning pole. The increase only of O gametes with structurally heterozygous X chromosomes can tentatively be explained by a loss due to crossing over within the inversion. An increase of the effect of methyl mercury was obtained where the normal pairing of the X chromosomes was interfered with by means of autosomal inversions. Likewise a synergistic increase of nondisjunction was obtained when a temperature chock of 10 degrees C was applied together with treatment with methylmercury. It is concluded that chemical induction of nondisjunction can be studied in Drosophila, but the sensitivity of the test is rather low and large amount of material is required.

Effects of nutritional factors on metabolism of dietary cadmium at levels similar to those of man.

Abstract: Several nutrients are known to affect cadmium toxicity, but little is known about the effect of dietary nutrient levels on absorption and tissue retention of cadmium at low dietary levels, similar ...