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Showing papers in "Environmental Health Perspectives in 1977"


Journal ArticleDOI
TL;DR: The degree of permanent impairment of function in the patient was directly related to duration of intake of arsenical water and toduration of such intake at the time of onset, i.e., the higher the arsenic content of well water, the more patients with skin cancer and blackfoot disease.
Abstract: In a limited area on the southwest coast of Taiwan, where artesian well water with a high concentration of arsenic has been used for more than 60 years, a high prevalence of chronic arsenicism has been observed in recent years The total population of this "endemic" area is approximately 100,000 A general survey of 40,421 inhabitants and follow-up of 1,108 patients with blackfoot disease were made Blackfoot disease, so-termed locally, is a peripheral vascular disorder resulting in gangrene of the extremities, especially the feet The overall prevalence rates for skin cancer was 106 per 1000, and for blackfoot disease 89 per 1000 Generally speaking, the prevalence increased steadily with age in both diseases The prevalence rates for skin cancer and blackfoot disease increased with the arsenic content of well water, ie, the higher the arsenic content, the more patients with skin cancer and blackfoot disease A dose-response relationship between blackfoot disease and the duration of water intake was also noted Furthermore, the degree of permanent impairment of function in the patient was directly related to duration of intake of arsenical water and to duration of such intake at the time of onset The most common cause of death in the patients with skin cancer and blackfoot disease was carcinoma of various sites The 5-year survival rate after the onset of blackfoot disease was 763%; the 10-year survival rate was 633% and 15-year survival rate, 522% The 50% survival point was 16 years after onset of the disease

751 citations


Journal ArticleDOI
TL;DR: In this article, the concentrations of four chemical species of arsenic in urine were observed with time, after ingestion of three different chemical species, including arsenite-rich wine, arsenate-rich drinking water, and crab meat containing organo-arsenic compounds.
Abstract: The concentrations of four chemical species of arsenic in urine were observed with time, after ingestion of three different chemical species of arsenic. The arsenic-rich substances ingested, including arsenite-rich wine, arsenate-rich drinking water, and crab meat which contained organo-arsenic compounds. After ingestion of arsenite-rich wine, approximately 10% of the arsenic was excreted as arsenite, but the majority of the arsenic was methylated to methylarsonic acid and dimethylarsinic acid and excreted. After ingestion of arsenate-rich water, elevated levels of both arsenate and dimethylarsinic acid were observed. When crab meat was ingested, none of these four arsenic species were observed at elevated levels until the urine was heated in 2N NaOH. After the hot base digestion, high levels of dimethylarsinic acid were detected in these samples. The apparent biological half-lives were on the order of 10 hr for inorganic arsenic and 30 hr for the methylated arsenic forms.

332 citations


Journal ArticleDOI
TL;DR: Evaluated the working efficiency of the water treatment plant in Antofagasta, Chile, finds that contamination persists but in significantly lower levels, and results are encouraging.
Abstract: This is a second report of epidemiological and clinical investigation, related to the arsenic health problem, unique in the world, occurring in the city of Antofagasta, Chile. The arsenic problem originates in the chronic contamination of water supply in the city during 12 years. This phenomena, investigated clinically and epidemiologically and first reported in 1971, prompted the installation of a water treatment plant. This report aims to evaluate the working efficiency of the plant. The study was carried out through the examination of arsenic content in hair and nail clipping samples of the inhabitants of Antofagasta and the determination of this element in cultivated vegetables and carbonated beverages. Also a clinical study in school children, looking for cutaneous lesions attributed to arsenicism, was made. Results are encouraging. They reveal that contamination persists but in significantly lower levels.

248 citations


Journal ArticleDOI
TL;DR: A series of halogenated compounds were tested by oral intubation in 200 Osborne-Mendel rats and 200 B6C3F1 mice of both sexes as mentioned in this paper.
Abstract: A series of halogenated compounds was tested by oral intubation in 200 Osborne-Mendel rats and 200 B6C3F1 mice of both sexes. Carbon tetrachloride, used as a positive control, induced liver and adrenal tumors in mice and neoplastic nodules in the livers of rats. 1,2-Dibromoethane and 1,2-dibromo-3-chloropropane caused stomach tumors with many metastases in both rats and mice. Chloroform, known to cause hepatocellular carcinomas in mice, led in addition to kidney tumors in male rats. 1,2-Dichloroethane was much weaker than the analog, 1,2-dibromoethane, and induced only a few stomach tumors in rats. It increased liver and lung tumors in mice. Most of the compounds, namely, trichloroethylene, 1,1-dichloroethane, 1,1,2-trichloroethane, hexachloroethane, and tetrachloroethylene, increased hepatocellular carcinomas in mice but had little or no action in rats. Iodoform tended to increase thyroid tumors in male rats and hepatocellular carcinomas in male mice. The action of 3-chloropropene was questionable. No tumors could be attributed to 1,1,1-trichloroethane (methyl-chloroform).

198 citations


Journal ArticleDOI
TL;DR: Results so far show that marine organisms are able to convert inorganic arsenic into organic arsenic compounds, but no evidence points to a corresponding ability in the terrestrial ones.
Abstract: Among the trace elements, arsenic appears to possess a unique position in the environment. When comparing terrestrial and marine organisms there seems to be a significant difference between both level and chemical forms of arsenic. The level of arsenic in terrestrial organisms is seldom above 1 ppm (dry material) whereas the corresponding values for marine organisms vary from several parts per million up to more than 100 ppm. Furthermore, results so far show that marine organisms are able to convert inorganic arsenic into organic arsenic compounds. No evidence points to a corresponding ability in the terrestrial ones. In the aquatic organisms the arsenic is present as both lipid soluble and water soluble compounds. The water-soluble organic arsenic compounds have a basic character and are very stable to chemical and metabolic breakdown.

176 citations


Journal ArticleDOI
TL;DR: Increased biliary excretion of selenium caused by arsenic provides a reasonable rationale for the ability of arsenic to counteract the toxicity of seenium, although the chemical mechanism by which arsenic does this is not certain.
Abstract: In 1938, Moxon discovered that arsenic protected against selenium toxicity. Since that time it has been shown that this protective effect of arsenic against selenium poisoning can be demonstrated in many different animal species under a wide variety of conditions. Antagonistic effects between arsenic and selenium have also been noted in teratologic experiments. Early metabolic studies showed that arsenic inhibited the expiration of volatile selenium compounds by rats injected with acutely toxic doses of both elements. This was puzzling since pulmonary excretion had long been regarded as a means by which animals could rid themselves of excess selenium. However, later work demonstrated that arsenic increased the biliary excretion of selenium. Not only did arsenic stimulate the excretion of selenium in the bile, but selenium also stimulated the excretion of arsenic in the bile. This increased biliary excretion of selenium caused by arsenic provides a reasonable rationale for the ability of arsenic to counteract the toxicity of selenium, although the chemical mechanism by which arsenic does this is not certain. The most satisfactory explanation is that these two elements react in the liver to form a detoxication conjugate which is then excreted into the bile. This is consistent with the fact that both arsenic and selenium each increase the biliary excretion of the other. Several other metabolic interactions between arsenic and selenium have been demonstrated in vitro, but their physiological significance is not clear. Although arsenic decreased selenium toxicity under most conditions, there is a pronounced synergistic toxicity between arsenic and two methylated selenium metabolites, trimethylselenonium ion or dimethyl selenide. The ecological consequences of these synergisms are largely unexplored, although it is likely that selenium methylation occurs in the environment. All attempts to promote or prevent selenium deficiency diseases in animals by feeding arsenic have been unsuccessful. Over 30 years ago it was suggested that industrial hygienists use arsenic as a tonic to prevent or cure selenium poisoning in workers exposed to this hazard. Organic arsenical feed additives were tried as partial antidotes against selenium poisoning in livestock raised in seleniferous agricultural areas but were not found to be practical.

150 citations


Journal ArticleDOI
TL;DR: First void urine samples were collected from copper smelter workers exposed to inorganic arsenic and from unexposed controls and it was found that all of the subjects, including the controls excreted arsenic primarily as methylated species.
Abstract: First void urine samples were collected from copper smelter workers exposed to inorganic arsenic and from unexposed controls. Arsenic compounds (As (III), As (V), methylarsonic acid and dimethylars...

135 citations


Journal ArticleDOI
TL;DR: An As-transformation model has been constructed from rate constants derived from field observations, and the environmental factors affecting these rate constants are discussed.
Abstract: The current knowledge of arsenic (As) transformations in the environment, as well as some gaps in this knowledge, are reviewed. These transformations involve As chemical and biochemical transformat...

124 citations


Journal ArticleDOI
TL;DR: Evidence was obtained which suggests that after removal from arsenic exposure, the risk of lung cancer declines, and certain of the data which are presented suggests there may be a threshold value for airborne arsenic trioxide exposure below which no adverse effects may be expected.
Abstract: This report examines the mortality experience of 527 men who retired from a copper smelter where they were exposed to airborne arsenic trioxide. Urinary arsenic values of all plant employees were d...

91 citations


Journal ArticleDOI
TL;DR: Arsenocholine, arsenobetaine, and acetylarsenocholine have been synthesized and will serve as reference substances in the chromatography experiments and the preparation of arsenocholine-containing lipids is in progress.
Abstract: Experiments to grow Tetraselmis chuii (a marine alga) and Daphnia magna in the presence of inorganic arsenate are described. The algae incorporate arsenic rather efficiently and form a lipid-solubl...

90 citations


Journal ArticleDOI
TL;DR: Radioactive incorporation studies showed that arsenate was able to inhibit dose-dependently the incorporation of radioactively labeled nucleotide in RNA and DNA and beyond that, arsenic blocked the cells in the S- and G2-phase.
Abstract: Chromosome analysis of lymphocytes from patients who had been exposed to arsenic showed frequent structural and numerical aberrations, even with an interval of decades since the last exposure. The in vitro addition of sodium arsenate induced the same chromosome changes--even to extreme of chromosome pulverizations--upon lymphocyte cultures from healthy subjects. Radioactive incorporation studies showed that arsenate was able to inhibit dose-dependently the incorporation of radioactively labeled nucleotide in RNA and DNA. Beyond that, arsenic blocked the cells in the S- and G2-phase. A general explanation for the inhibitory effect of inorganic arsenic on cell metabolism is the known strong affinity of arsenic to enzymes, especially to those containing sulfhydryl groups.

Journal ArticleDOI
TL;DR: The effect of past applications on arsenic accumulation in soil, phytotoxicity to and uptake by plants as influenced by soil properties, and alleviation of the deleterious effects of arsenic are focused on.
Abstract: Inorganic arsenicals have been used in agriculture as pesticides or defoliants for many years and, in localized areas, oxides of arsenic have contaminated soils as a result of fallout from ore-smelting operations and coal-fired power plants. Use of inorganic arsenicals is no longer permitted in most agricultural operations, and recent air pollution controls have markedly reduced contamination from smelters. Thus, this paper will concentrate on the effect of past applications on arsenic accumulation in soil, phytotoxicity to and uptake by plants as influenced by soil properties, and alleviation of the deleterious effects of arsenic. Once incorporated into the soil, inorganic arsenical pesticides and arsenic oxides revert to arsenates, except where the soil is under reducing conditions. The arsenate ion has properties similar to that of orthophosphate, and is readily sorbed by iron and aluminum components. This reaction greatly restricts the downward movement (leaching) of arsenic in soils and the availability of arsenic to plants. Several methods of estimating plant available arsenic in soils have been developed. They involve extraction of the soil with reagents used to estimate phosphorus availability. This extractable arsenic is reasonably well correlated with reduced plant growth by, and plant uptake of arsenic. For most plants, levels of arsenic in the edible portion of the plant are well below the critical concentration for animal or human consumption, even when severe phytotoxicity occurs. Alleviation of arsenic phytotoxicity has been attempted by increasing the soil pH, by use of iron or aluminum sulfate, by desorbing arsenate with phosphate and subsequent leaching, and by cultural practices such as deep plowing. Only limited benefits have accrued from these procedures the cost of which is often prohibitively high. Since attempts to reduce arsenic toxicity have not been very successful, its excessive accumulation in soils should be avoided.

Journal ArticleDOI
TL;DR: Kidney weight and kidney weight/body weight ratios were increased by Pb alone, with no effects of Cd or As alone or as interactions, and Liver histology suggests an increased rate of cell turnover with either As compound, but few specific changes.
Abstract: Humans are exposed to a number of toxic elements in the environment; however, most experiments with laboratory animals investigate only one toxic element. To determine if concomitant exposure to le...

Journal ArticleDOI
TL;DR: Early results appear to show that some factors affecting the carcinogenic effects of chlorinated olefins act by affecting the metabolism of the tested compounds, and the need for metabolic characterization of experimental animals in chemical carcinogenesis is stressed.
Abstract: Data are presented on factors affecting the carcinogenic effects of chlorinated olefins, such as molecular structure, concentration, length of treatment, route of administration and animal species, strain, sex, and age. The observations are based upon carcinogenicity experimental bioassays of vinyl chloride and vinylidene chloride. Early results, which appear to show that some of these factors (particularly species, strain, and sex) act by affecting the metabolism of the tested compounds, are presented, and the need for metabolic characterization of experimental animals in chemical carcinogenesis is stressed.

Journal ArticleDOI
TL;DR: An organic form of arsenic is commonly encountered in marine organisms; in greysole and shrimp, it accounted for all arsenic found in muscle tissue and sea urchins, like humans, appear to be able to rapidly excrete these organic forms of arsenic.
Abstract: An organic form of arsenic is commonly encountered in marine organisms; in greysole and shrimp, it accounted for all arsenic found in muscle tissue. It has been isolated from flounder tissue by two independent procedures; it was hydrophilic, cationic, and was not decomposed to inorganic arsenic by hot nitric and sulfuric acids. NMR spectroscopy indicated all nonexchangeable protons to be equivalent; they behaved more like N-methyl protons than As-methyl protons. High-resolution mass spectroscopy from a heated probe yielded a spectrum corresponding to tetramethylarsonium (AsMe4+); the authentic ion, however, had TLC and ion-exchange behavior different from that of the natural product. Infrared spectrometry likewise produced conflicting or uninterpretable data. Decomposition of the compound for analytical purposes was accomplished by dry ashing under oxidizing conditions. Sea urchins, like trout, converted arsenic to an organic form, but to a more limited degree. Arsenic found naturally in sea urchins and in a species of macroalga was also organic. In individual containers, sea urchins were fed on the alga for 7 weeks. During this time they consumed 0.203 +/- 0.075 mg total As and excreted only 0.036 +/- 0.015 mg as feces. Measurement of inorganic As in the seawater did not account for the discrepancy, but measurements of total As did (0.202 +/- 0.095 mg). Sea urchins, like humans, appear to be able to rapidly excrete these organic forms of arsenic.

Journal ArticleDOI
TL;DR: Rats exposed in a closed system to chlorinated ethylenes vinyl chloride and trichloroethylene and to carbon tetrachloride showed irreversible binding of metabolites to tissue proteins, mainly of the liver, so it should be inferred that, unlike vinyl chloride, trich chloro methylene metabolites not only bind to sulfhydryl groups but also, to a lesser extent, to free amino groups of proteins.
Abstract: Rats have been exposed in a closed system to the chlorinated ethylenes vinyl chloride and trichloroethylene and to carbon tetrachloride as a reference compound. Data of uptake of the compounds, of urinary excretion of metabolites, and of exhalation after exposure show that the chlorinated ethylenes are metabolized much faster than carbon tetrachloride, probably due to their common ethylene structure. To eliminate differences in uptake, calculation of metabolites of the three compounds in tissues was based on the amount actually taken up by the animals. Vinyl chloride, trichloroethylene, and carbon tetrachloride showed irreversible binding of metabolites to tissue proteins, mainly of the liver. Irreversible protein binding of either of these compounds ranged within the same order of magnitude, if related to the amount of compound which had been taken up. Also, no differences in the relative portion of irreversibly bound metabolites were found after exposure to different atmospheric concentrations of the three compounds. As already shown for vinyl chloride, trichloroethylene is metabolized in vitro by rat liver microsomes in presence of NADPH-regenerating system to intermediates that irreversibly bind to proteins. Albumin (bovine and rabbit) was a preferred target for binding. In contrast to vinyl chloride, significant irreversible binding of trichloroethylene metabolites also occurred to non-SH-proteins (γ-globulin, concanavalin A) and to polylysine. Hence it should be inferred that, unlike vinyl chloride, trichloroethylene metabolites not only bind to sulfhydryl groups but also, to a lesser extent, to free amino groups of proteins.

Journal ArticleDOI
TL;DR: Arsenite decreases mutagenesis in strains containing these genes and is confirmed by the finding that arsenite has no effect on the post-irradiation survival of a recA mutant, which does not carry out post-replication repair.
Abstract: Since environmental exposure to arsenicals has been correlated with a high skin cancer risk among populations exposed to sunlight, it is possible that arsenicals might interfere with the repair of ...

Journal ArticleDOI
TL;DR: Sources of high level exposure to lead, urban street dirt, house dust, and paint are particularly common sources of high concentrations of lead, as well as factors affecting susceptibility to lead.
Abstract: Levels of lead ingestion and inhalation producing increased body burden of lead and clinical toxicity in adults and children are compared with usual levels of exposure. The magnitude of lead exposu...

Journal ArticleDOI
TL;DR: These studies indicate that decreased mitochondrial respiration is only one aspect of arsenic toxicity to this organelle and Marked arsenic-mediated perturbation of important enzyme systems localized in mitochondria which participate in the control of respiration and other normal mitochondrial functions are also important manifestations of cellular dysfunction.
Abstract: This investigation was undertaken to further delineate the subcellular manifestations of arsenic toxicity following chronic exposure using combined ultrastructural and biochemical techniques. Male ...

Journal ArticleDOI
TL;DR: A significantly higher mortality rate for lung cancer was noted in men in the exposed area, however, this increase was no longer significant when the occupationally exposed at Rönnskärsverken were excluded and the latter showed a highly significant excess mortality due to primary respiratory cancer.
Abstract: The purpose of the investigation is to study whether an increased mortality from certain causes exists in an area around the Ronnskarsverken smelter works in northern Sweden. Founded in 1928, this ...

Journal ArticleDOI
TL;DR: The pathological effects of lead on the renal, nervous, reproductive, endocrine, and immune systems have been reviewed, and emphasis is placed on reported subclinical effects due to chronic, low-level lead exposure.
Abstract: The pathological effects of lead on the renal, nervous, reproductive, endocrine, and immune systems have been reviewed. Emphasis is placed on reported subclinical effects due to chronic, low-level lead exposure. The crucial issue of whether subtle behavioral, intellectual, and developmental impairment occurs in young children, as a result of lead-induced CNS damage is discussed in detail. This issue remains unresolved. Further studies are needed in order to determine the long-term health effects of continuous, low-level lead exposure.

Journal ArticleDOI
TL;DR: The inhibition of PDH both before and after activation suggests a direct arsenic effect on pyruvate utilization which does not involve a lipoic acid moiety, and evidence is presented which indicates an arsenic effects on the regulating kinase and/or phosphatase.
Abstract: Our studies illuminate a particular site of altered pyruvate utilization by liver mitochondria isolated from arsenic-fed rats. Initially, pyruvate dehydrogenase (PDH) levels were measured before and after in vitro activation. The liver homogenates were prepared from male rats given access to deionized drinking water solutions containing 0, 20, 40, and 85 ppm arsenic as sodium arsenate (As+5) for 3 and 6 weeks. After 3 weeks, the effects of arsenic at the highest dose level were pronounced on the basal activity (before activation), with inhibition up to 48% of the control values. The total PDH (after activation) was inhibited by 14, 15, and 28% of the control values at 20, 40, and 85 ppm As+5, respectively. A similar pattern of inhibition of PDH was observed at 6 weeks, although the inhibition was lower at the highest dose. This effect is probably a reflection of mitochondrial regeneration at this time and dose. The inhibition of PDH both before and after activation suggests a direct arsenic effect on pyruvate utilization which does not involve a lipoic acid moiety. Evidence is also presented which indicates an arsenic effect on the regulating kinase and/or phosphatase. The metabolic effects of impaired mitochondrial utilization by pyruvate are also discussed.

Journal ArticleDOI
TL;DR: In this paper, all chlorinated ethylenes have been investigated in a tissue-mediated mutagenicity testing system, and the most prominent molecular feature of those with mutagenic effects (trichloro-, 1,1-dichlorofo-, and monochloroethylene) is unsymmetric chlorine substitution which renders the epoxides unstable.
Abstract: Chlorinated ethylenes are metabolized in mammals, as a first step, to epoxides. The fate of these electrophilic intermediates may be reaction with nucleophiles (alkylation), hydrolysis, or intramolecular rearrangement. The latter reaction has been studied in the whole series of chlorinated epoxiethanes. The rearrangement products found were: acyl chlorides (tetrachloro-, trichloro-, and 1,1-dichloroethylenes), or chlorinated aldehydes (1,2-dichloroethylenes, cis- and trans-, vinyl chloride). The metabolities found in vivo are identical with, or further derivatives of these rearrangment products, with one important exception: trichloroethylene. With this compound, in vivo rearrangement yields chloral exclusively. The mechanism of the different rearrangement has been identified as a Lewis acid catalysis. All chlorinated ethylenes have been investigated in a tissue-mediated mutagenicity testing system. The prominent molecular feature of those with mutagenic effects (trichloro-, 1,1-dichloro-, and monochloroethylene) is unsymmetric chlorine substitution which renders the epoxides unstable, whereas symmetric substitution confers relative stability and nonmutagenic property.

Journal ArticleDOI
TL;DR: The distribution, excretion, and possible metabolism of 14C- and/or 74As-cacodylic acid was studied in rats following a single intravenous injection, intratracheal instillation or oral gavage.
Abstract: The distribution, excretion, and possible metabolism of (14)C- and/or (74)As-cacodylic acid, an organoarsenical herbicide, was studied in rats following a single intravenous injection, intratracheal instillation or oral gavage. Male Sherman rats were dosed at levels ranging from 200 mg/kg to 120 mug/kg. The extent and rate of lung absorption was greater than gastrointestinal absorption. Concentrations in the liver and whole blood were higher after peroral dosing than intravenous administration. Levels observed in plasma and other tissues were similar after all three routes following the absorptive phase. The percent dose found in the whole blood, red blood cells, and plasma was similar for all doses given by these routes. Less than 0.1(1/2) of the administered dose was recovered as (14)CO(2) by any route at 24 hr after administration. Twenty-four hours after intravenous, intratracheal, and peroral administration, 71, 60, and 25%, respectively, was excreted in the urine. After intravenous administration of 200 mg/kg, sufficient (14)C-cacodylic acid was recovered in bile to account for the small amount excreted in the feces. Cacodylic acid is probably not metabolized to inorganic arsenic since the disposition of (14)C and (74)As-cacodylic acid were identical.Kinetic analyses of the plasma curve for (14)C-cacodylic acid (high dose) yielded three half-times; 0.014, 0.214 and 3.42 hr with an apparent volume of distribution of 15.3 ml. Highest initial concentrations were found in the whole blood, muscle, kidney, liver and lung. Levels in all tissues decreased rapidly, but remained high in whole blood. The red blood cells were found to be the major site of body burden of cacodylic acid.

Journal ArticleDOI
TL;DR: The frequency of chromosome aberrations was significantly increased among the smelter workers, but due to the simultaneous exposure to other agents the effect of arsenic per se can not be assessed with certainty.
Abstract: The occurrence of chromosome aberrations was studied in short-term cultured lymphocytes from nine workers exposed to arsenic at the Ronnskar smeltery in northern Sweden. In the smelter workers, 87 ...

Journal ArticleDOI
TL;DR: The authors conclude that the TLV concentration of 100 ppm in the workplace has a negligible margin of safety regarding unimpaired performance during repeated exposures which could be especially hazardous if the worker is physically active or is in a situation where skin absorption presents an added burden.
Abstract: There is considerable potential for worker exposure to tetrachloroethylene, both by skin contact and by inhalation, during its use in dry cleaning and degreasing operations. This paper reviews accounts of both accidental overexposures of workers and controlled exposures of human subjects by these two routes of exposure. Several reported cases of accidental overexposure to anesthetic doses of the chemical reveal that recovery was generally complete but prolonged, and accompanied by many days of measurable levels of the chemical in the patient's alveolar breath. Chronic overexposures of workmen have lessened since the general acceptance by the Western world of the recommended TLV of 100 ppm for 8 hr of daily exposure. Controlled inhalation studies with volunteer subjects at this level of exposure revealed no effects upon health but did indicate a slight decrement in performance on a coordination test. Additional behavioral and neurological tests revealed no interactive effects when alcohol or diazepam, two depressant drugs, were added singly to tetrachloroethylene exposures. Individual susceptibility to the vapor of this chemical, as evidenced by subjective complaints, was noted in approximately one of ten subjects. The authors conclude that the TLV concentration of 100 ppm in the workplace has a negligible margin of safety regarding unimpaired performance during repeated exposures which could be especially hazardous if the worker is physically active or is in a situation where skin absorption presents an added burden.

Journal ArticleDOI
TL;DR: The metabolism of the chlorinated ethylenes may be explained by the formation of chloroethylene epoxides as the first intermediate products, and monochloroacetic acid, chloral hydrate, and trichloroACetic acid have been found in reaction mixtures of 1,1-dichlorOethylene, trich chloro methylene, and tetrachloroethylenes, respectively, with rat liver microsomal systems.
Abstract: The metabolism of the chlorinated ethylenes may be explained by the formation of chloroethylene epoxides as the first intermediate products. The evidence indicates that these epoxides rearrange wit...

Journal ArticleDOI
TL;DR: The permeability of the placenta to 74As during the early critical stages of embryogenesis and the distribution of this isotope in maternal, placental and embryonic tissues is demonstrated and the teratogenic effect of sodium arsenate is shown to be significantly reduced by the simultaneous administration of selenium.
Abstract: Sodium arsenate induces developmental malformations in a variety of experimental animals. In the golden hamster, the intravenous (or intraperitoneal) administration of 20 mg/kg of sodium arsenate during day 8 to 9 of gestation induces a rather specific spectrum of congenital malformations. This period corresponds to the period of very rapid differentiation and major organogenesis in this animal. The spectrum of defects produced by arsenate in the hamster includes exencephaly, encephaloceles, skeletal defects, and malformations of the genito-urinary system. This teratogenic effect can be significantly reduced by the simultaneous administration of selenium. Recent studies in this laboratory have demonstrated the permeability of the placenta to 74As during the early critical stages of embryogenesis and the distribution of this isotope in maternal, placental and embryonic tissues. We have also recently demonstrated the marked potentiation of the teratogenic effect of sodium arsenate by subjecting the mothers to short periods of hyperthermia immediately following the administration of subteratogenic or minimal teratogenic levels of arsenate.

Journal ArticleDOI
TL;DR: The ability of a series of haloalkanes, haloethanols and haloacetaldehydes to induce mutations in Salmonella typhrimurium and preferentially to inhibit the growth of DNA polymerase-deficient E.coli is studied.
Abstract: The ability of a series of haloalkanes, haloethanols and haloacetaldehydes to induce mutations in Salmonella typhrimurium and preferentially to inhibit the growth of DNA polymerase-deficient E. coli (pol A(+)/pol A(-)) was investigated. For the haloalkanes investigated, the order of reactivities towards the E. coli pol A(+)/pol A(-), was: 1,1,2,2-tetrabromoethane > 1,1-dibromoethane > 1,1,2,2-tetrachlorethane > 1,2-dibromoethane = 1,5 dibromopentane > 1,2-dibromo-2-methylpropane > 1-bromo-2-chloroethane > 1,2-dichloroethane. In the standard Salmonella mutagenicity assay the order of these substances was 1,2-dibromoethane = 1,5-dibromopentane > 1,2-dibromo-2-methylpropane >/= 1-bromo-2-chloroethane > 1,1,2,2-tetrachloroethane = 1,1-dibromoethane > 1,2-dichloroethane. 1,1,2,2-Tetrabromoethane was negative in the standard assay but strongly mutagenic when tested in suspension. It would appear that the discrepancy between the two procedures is due to the fact that bactericidal mutagens cannot be scored reliably in the standard Salmonella assay. The order of reactivity of 2-haloethanols in E. coli pol. A(+)/pol A(-), was 2-iodo > 2-bromo-> 2-chloroethanol. In the Salmonella assay the order was 2-bromo-> 2 iodo- >2-chloro-ethanol. 2-Fluoroethanol and ethanol were devoid of activity in both assays. For the 2-haloacetaldehydes the reactivities in the E. coli system were 2-bromoethylacetate > 2-bromoacetaldehyde = acetaldehyde > 2-chloroacetaldehyde while in the Salmonella system the order was 2-bromoethylacetate > 2-chloroacetaldehyde. Acetaldehyde had minimal activity, while 2-bromoacetaldehyde was without activity but strongly bactericidal.

Journal ArticleDOI
TL;DR: The straight-line relations found between the absorbed dose of arsenic and its blood or urine concentrations could serve as baselines for exposure tests for humans.
Abstract: Pentavalent inorganic arsenic was introduced by intravenous, intratracheal, gastrointestinal, and skin application in doses 0.1 to 4.0 mg/kg in rats. Isotopic technics were applied by use of As74. ...