Showing papers in "Environmental Health Perspectives in 1975"

Metabolism and toxicity of styrene.

Abstract: The absorption, blood levels, distribution, excretion, and biotransformation of styrene in man and experimental animals are briefly reviewed. The acute toxicity of styrene appears to be unrelated t...

Developmental and behavioral changes in the rat during chronic exposure to lead.

Abstract: Young male and female Sprague-Dawley rats were given drinking water containing 5 or 50 ppm Pb for 40 days prior to mating. Pregnant females were continued on these regimens throughout gestation and lactation. After weaning the offspring were similarly exposed through adulthood. Reflex development, body weights, and locomotor activity were measured in the offspring. Significant delays were noted in the development of the righting reflex at 5 and 50 ppm and in eye opening at 50 ppm. No difference was observed in development of the startle reflex at either dose. Mean body weights of treatment groups during this developmental period were not significantly different from controls. Locomotor activity was measured in adult males utilizing a residential maze. Both levels of lead produced a significant reduction in locomotor activity. When groups were treated with d-amphetamine (4.0 mg/kg subcutaneous), lead treatment caused a dose-related diminution in the amphetamine-induced hyperactivity. These results indicate that rats exposed to low levels of lead from conception until adulthood show a delay in nervous system development. As adults, these animals exhibit hypoactivity and decreased responsiveness to amphetamine.

Environmental fate and biodegradability of benzene derivatives as studied in a model aquatic ecosystem.

Abstract: A model aquatic ecosystem is devised for studying relatively volatile organic compounds and simulating direct discharge of chemical wastes into aquatic ecosystems. Six simple benzene derivatives (aniline, anisole, benzoic acid, chlorobenzene, nitrobenzene, and phthalic anhydride) and other important specialty chemicals: hexachlorobenzene, pentachlorophenol, 2,6-diethylaniline, and 3,5,6-trichloro-2-pyridinol were also chosen for study of environmental behavior and fate in the model aquatic ecosystem. Quantitative relationships of the intrinsic molecular properties of the environmental micropollutants with biological responses are established, e.g., water solubility, partition coefficient, pi constant, sigma constant, ecological magnification, biodegradability index, and comparative detoxication mechanisms, respectively. Water solubility, pi constant, and sigma constant are the most significant factors and control the biological responses of the food chain members. Water solubility and pi constant control the degree of bioaccumulation, and sigma constant limits the metabolism of the xenobiotics via microsomal detoxication enzymes. These highly significant correlations should be useful for predicting environmental fate of organic chemicals.

Heavy metal exposure from foods.

Abstract: The Food and Drug Administration has a continuing program of monitoring foods for their content of lead, cadmium, mercury, zinc, arsenic, and selenium to determine trends of increasing or decreasing levels. The monitoring protocol is that of the Total Diet Study, in which "market baskets" of typical foods and beverages consumed by 15- to 20-year-old American males are collected in various geographical locations at regular intervals during the year, divided into food classes, composited, and analyzed. Cadmium has the most widespread distribution of the six heavy metals and mercury the most limited. The analytical values for lead may be underestimated because of limitations of the methodology; these do not apply to the other five elements. A tabulation by year shows that the levels of these elements in foods do not vary significantly from one year to the next. Average intakes of lead, cadmium, and mercury are below the WHO/FAO tolerable intakes for adults; such tolerable intakes have not been established for arsenic and selenium. Increases in concentrations of these elements in foods would be considered undesirable, however.

Toxicology of octabromobiphenyl and decabromodiphenyl oxide.

Abstract: Decabromodiphenyl oxide (DBDPO) and octabromobiphenyl (OBBP) perform well as fire-retardant additives for thermoplastics. Both compounds have low acute oral toxicity and low skin absorption toxicity. They are neither primary skin irritants or skin sensitizers and are only mildly irritating to the eyes. A 30-day dietary feeding study in rats established 8 mg DBDPO/kg-day as an unequivocal no-effect level and 80 mg/kg-day as a marginal effect level. A no-effect level was not established for OBBP in a comparative study. A 2-yr rat study providing 0.1 mg DBDPO/kg-day in the diet revealed the bromine concentration reached a plateau in the liver within 30 days, while the concentration in adipose tissue slowly increased. A comparable OBBP study revealed bromine concentration in the liver and adipose tissue increased steadily and rapidly with no attainment of a plateau during 180 days of the study. Neither compound produced an accumulation of bromine in other tissues. After administration of 14C DBDPO, all 14C activity was eliminated via the feces within 2 days. After administration of 14C OBBP, 62% was eliminated with a half-life of less than 24 hr; the half-life for the remainder was greater than 16 days. In a teratology study, 10, 100, or 1000 mg DBDPO/kg-day had no effect in rats. Reproductive capacity of rats was not effected at 3, 30, or 100 mg DBDPO/kg-day. No effects were observed on cytogenetic examination of bone marrow cells of parents and weanlings from the reproduction study.

Placental transfer of cadmium in rats: influence of dose and gestational age

Abstract: Placental transfer rates of cadmium were investigated in rats in relation to dose (0.1, 0.4, and 1.6 mg Cd/kg) and the gestational age (12, 15, and 20 days) when rats were treated. Pregnant rats were injected intravenously with a single dose of 109CdCl2 (approximately 20 muCi/animal), and animals were sacrificed after 24 hr. 109Cd concentrations were measured in the fetus, placenta, maternal liver, and blood. Cadmium crossed the placenta at all doses and at all gestational ages tested. However, higher percentages of administered cadmium accumulated in the fetus with increasing dose and increasing gestational age. For example, after pregnant rats were injected with low, middle, and high doses of Cd on day 12 of gestation, fetuses accumulated 0.0001, 0.0028, and 0.0095 per cent of the injected dose, respectively. Percentages of administered Cd detected in placental tissue did not change consistently with dose but Cd levels did increase with gestational age. Placental to maternal blood Cd concentration ratios increased with gestational age but not with dose. Maternal liver to fetal liver concentration ratios were 295, 137, and 27 for low, middle and high doses, respectively, 24 hr after pregnant rats were treated on day 20 of gestation. These results are discussed in relation to placental damage, metallothionein inducibility, and fetotoxicity.

Additives in plastics.

Abstract: The polymers used in plastics are generally harmless. However, they are rarely used in pure form. In almost all commercial plastics, they are "compounded" with monomeric ingredients to improve thei...

Structure-toxicity relationships of acrylic monomers.

Abstract: Esters of acrylic acid, in particular methyl methacrylate, have wide applications in a number of industrial and consumer products, forming very desirable nonbreakable glass-like materials. In dentistry, the monomers are used to prepare dentures and a variety of filling and coating materials for the teeth. Surgeons utilize the monomers to prepare a cement which helps anchor prosthetic devices to bone. Special types of acrylic monomers such as the cyano derivatives have found a useful application as adhesive materials. Most of the acrylic acid esters are volatile substances and can produce various levels of toxicity if inhaled. A large number of workers thus exposed to the vapors of these esters can develop clinical symptoms and signs of toxicity. This paper will discuss the toxicity of a large number of acrylic esters, and will attempt to show structure-activity relationships where such data are available. General comments will also be made as to the potential health hazards this variety of esters may present to selected segments of the population.

Distribution of metallothionein-bound cadmium and cadmium chloride in mice: preliminary studies.

Abstract: Metallothionein from livers of mice was isolated by gel chromatography and isoelectric focusing. One of two forms thus obtained contained 32 percent cysteine. This form, labeled in vitro with 109Cd...

Preliminary studies on the toxicity and metabolism of palladium and platinum.

Abstract: Preliminary data are given on the LD50 of PdCl2 following different routes of exposure and on the LD50 of PtCl4 following intravenous exposure. The retention, tissue distribution, and excretion of 103Pd and 191Pt in rats was determined following oral, intravenous, intratracheal, and inhalation exposure. The highest retention for both 103Pd and 191Pt was obtained following intravenous dosing, and the lowest retention occurred after oral dosing. Following a single oral dose, almost all of the 103Pd and 191Pt was excreted in the feces due to nonabsorption, whereas after intravenous dosing, similar quantities were excreted in both the urine and feces. Tissues containing the highest concentrations of these metals were the kidney, spleen and liver. Following intravenous dosing of pregnant rats, a small amount of 103Pd and 191Pt was found in the fetuses.

Protective value of dietary copper and iron against some toxic effects of lead in rats.

Abstract: Both dietary iron and copper were inversely related to lead absorption as indicated by erythrocyte and kidney lead levels, dietary iron having the greatest effect. Kidney copper values were depress...

Arsenic pollution at Obuasi Goldmine, town, and surrounding countryside.

Abstract: Human hair samples from mine workers and Obuasi citizens; various food items; drinking and washing water from Obuasi town; vegetation and soils from the countryside bordering on the goldmine; and g...

Physiological and toxicological aspects of smoke produced during the combustion of polymeric materials.

Abstract: Normally one expects that flame contact is the major cause of injury and death during fires. Analysis of the factors involved in numerous fires has revealed that most deaths were not due to flame contact, but were a consequence of the production of carbon monoxide, nitrogen oxides, and other combustion products, such as aldehydes, low molecular weight alcohols, hydrogen cyanide, and other noxious species. The major emphasis within the scope of this paper relates to the physiological and toxicological aspects of smoke produced during the combustion of materials. Special emphasis is directed toward laboratory procedures which have been developed to determine the qualitative and quantitative analysis of smoke, factors pertaining to smoke development, and to measure the response of laboratory animals exposed to smoke. The effects that fire retardants, incorporated into polymeric materials as a means of improving flammability characteristics, may have on smoke development, the mechanism of polymer degradation, and on the survival response of laboratory animals are also considered.

Levels of platinum, palladium, and lead in populations of Southern California.

Abstract: Results of an epidemiology study of populations living near a freeway and in the high desert area of Southern California for levels of platinum, palladium and lead are presented. Three age groups (children, young adults, and mature adults) were sampled twice for blood, urine, hair, and feces. Air, water, and soil samples were collected in the areas of the residences of the two populations. The primary objective of this study was to obtain baseline levels of these metals prior to the introduction of the catalytic muffler. The samples were collected in September 1974.

Studies on the evaluation of the toxicity of various salts of lead, manganese, platinum, and palladium.

Abstract: Preliminary studies have been conducted on various parameters in order to assess the possible and relative toxicities of a number of metallic salts. Upon oral administration in lethal-dose experiments, two soluble Pt4+ salts were more toxic than the other salts tested. Following intraperiotneal injection in lethal-dose experiments, PbCl2 was less toxic than several of the soluble or partially soluble salts of Pt4+, Pd2+, and Mn2+. An intake of a total of approximately 250 mg of Pt4+ per rat in the drinking fluid over a 30-day interval did not affect the activities of aniline hydroxylase and aminopyrine demethylase in rat liver microsomes. In rats receiving soluble Pt4+ salts in the drinking fluid, the highest concentration of Pt was found in the kidney and an appreciiable concentration was found in the liver.

Nervous system degeneration produced by acrylamide monomer.

Abstract: Acrylamide, widely employed as a vinyl monomer in the polymer industry, is a potent neurotoxin to man and to animals. The cumulative effect of prolonged, low-level exposure to acrylamide monomer is the insidious development of a progressive peripheral neuropathy. Sensory symptoms begin in the hands and feet (numbness, pins and needles), certain reflexes are lost and, with severe exposure, muscle weakness and atrophy occur in the extremities. The peripheral neuropathy may be supplemented by symptoms indicative of central nervous system damage (ataxia, tremor, somnolence and mental changes). The neuropathologic basis for this clinical picture has been determined in cats. Here, chronic acrylamide intoxication produces selective peripheral and central nerve fiber degeneration. Degeneration first occurs in the extremities of long and large nerve fibers which later undergo a progressive, seriate proximal axonal degeneration known as dying-back. Especially vulnerable are sensory axons supplying Pacinian corpuscles and muscle spindles in the hindfoot toepads, while adjacent motor nerve axons die back later. Distal central nerve fiber degeneration is seen in the medulla and the cerebellum. The neurotoxic property of acrylamide is of practical concern in two areas. One major problem is the protection of factory workers engaged in the manufacture of acrylamide. A sensitive test of neurologic function in these individuals, i.e., touch sensation, based on the experimental observation of the exquisite vulnerability of Pacinian corpuscles in acrylamide intoxicated cats, is presently under consideration. The second area for concern is the exposure of the populace to minute amounts of neurotoxic acrylamide monomer which contaminate acrylamide polymers currently deployed in the environment. Federal restrictions on the maximum permitted exposure to acrylamide, based on a largely clinical study of acrylamide neurotoxicity conducted ten years ago, may require a re-evaluation in the light of recent advances which have pinpointed the initial sites of nerve fiber degeneration.

Preliminary studies on the fate of inhaled vinyl chloride monomer (VCM) in rats

Abstract: Rats were exposed to vinyl chloride monomer gas (VCM) in a closed recirculating system. The rate at which VCM was removed from the system via metabolism was determined for rats exposed to initial concentrations of VCM ranging from 50 to 1167 ppm. Upon exposure to initial concentrations of 50 to 105 ppm, the rate of metabolism was 8.04 plus or minus 3.40 x 10(-3) min-1. Upon exposure to initial concentrations ranging from 202 to 1167 ppm, the rate constants were less; the mean value being 2.65 plus or minus 1.35 x 10(-3) min-1. Regardless of concentration, the disappearance followed apparent first order kinetics. Pretreatment of rats with pyrazole prior to exposure to initial concentrations of 65 and 1234 ppm VCM caused 71 and 87% reductions in the rate of metabolism. Ethanol caused 96% and 83% reductions in the rate of VCM metabolism by rats exposed to 56 and 97 ppm VCM, respectively. Ethanol was less effective in blocking the rate of metabolism by rats exposed to high concentrations of VCM; 46 and 36% in rats exposed to 1025 and 1034 ppm VCM. In rats exposed to an initial concentration of 65 ppm VCM, SKF-525-A administration caused no inhibition of the rate of VCM metabolism; however, a 19% inhibition was seen in rats exposed to 1038 ppm. The nonprotein sulfhydryl content of the liver (glutathione and cysteine) of rats exposed to VCM concentrations ranging from 50 to 15,000 ppm VCM is reduced without a relationship to dose. With repeated daily exposure the degree of reduction is reduced. Preliminary results indicate that the primary metabolites of VCM react with the nonprotein sulfhydryl. Final metabolic products excreted in the urine appear to be S-(2-hydroxyethyl) cysteine and S-(2-carboxymethyl)cysteine and the respective N-acetyl derivatives. Monochloroacetic acid was identified as another potential metabolite. Considering the results in toto, it is hypothesized that VCM is readily and extensively metabolized. Metabolism via the primary pathway, postulated to involve alcohol dehydrogenase, is swamped by exposures to concentrations exceeding 220 ppm. In rats exposed to concentrations at and exceeding this level, metabolism occurs via a secondary pathway(s), postulated to be epoxidation and/or peroxidation. These results are considered pertinent is assessing the potential hazard at low level exposures to VCM.

Epidemiology of toluene diisocyanate (TDI)-induced respiratory disease.

Abstract: This paper describes our experience with the respiratory effects of TDI. Five respiratory reactions attributable to TDI are described with supporting evidence. The reactions are sensitization, irritation from overexposure, acute loss of ventilatory capacity, accelerated loss of pulmonary function and induction of a general asthmatic state. Evidence is presented that suggests a safe exposure level.

Public health implications of components of plastics manufacture. Flame retardants.

Abstract: The four processes involved in the flammability of materials are described and related to the various flame retardance mechanisms that may operate. Following this the four practical approaches used...

Heavy metal contamination from geothermal sources.

Abstract: Liquid-dominated hydrothermal reservoirs, which contain saline fluids at high temperatures and pressures, have a significant potential for contamination of the environment by heavy metals. The design of the power conversion cycle in a liquid-dominated geothermal plant is a key factor in determining the impact of the installation. Reinjection of the fluid into the reservoir minimizes heavy metal effluents but is routinely practiced at few installations. Binary power cycles with reinjection would provide even cleaner systems but are not yet ready for commercial application. Vapor-dominated systems, which contain superheated steam, have less potential for contamination but are relatively uncommon. Field data on heavy metal effluents from geothermal plants are sparse and confounded by contributions from "natural" sources such as geysers and hot springs which often exist nearby. Insofar as geothermal power supplies are destined to multiply, much work is required on their environmental effects including those caused by heavy metals.

Aging of polymers.

Abstract: This paper provides background on the basic chemical processes which can occur during the exposure of polymers to typical end-use environments such as air, sunlight, water vapor, and various atmospheric pollutant gases.

Noble metals: a toxicological appraisal of potential new environmental contaminants.

Abstract: The public health benefits expected by reducing known hazardous emissions from mobile sources should not be compromised by increasing levels of other potentially hazardous unregulated emissions. Ca...

Biochemical toxicology of unsaturated halogenated monomers.

Abstract: Previous inhalation toxicity studies from our laboratory have shown that 1,1-dichloroethylene (1,1-DCE), 1,1-dibromoethylene (1,1-DBE), and 2-chloro-1,3,-butadiene (2-CBD) are more toxic to fasted ...

Toxicity of platinum (IV) salts for cells of pulmonary origin.

Abstract: The acute toxicity of tetravalent platinum was studied in vitro by use of rabbit alveolar macrophages and human lung fibroblasts (strain WI-38). Alveolar macrophages were exposed in tissue culture for 20 hr to platinum dioxide (PtO2) or platinum tetrachloride (PtCl4). There was no evidence of dissolution of PtO2 and no decrease in viable cells at concentrations as high as 500 mug/ml. PtCl4 was soluble in the macrophage system and after a 20-hr exposure, resulted in loss of viability in 50% of the cells originally present at a concentration of 0.30mM (59 mug Pt/ml). After a 20-hr exposure, rapidly growing human lung fibroblasts were rendered nonviable by PtCl4 at comparable concentrations. A decrease in total cellular ATP was observed at lower concentrations in macrophages and fibroblasts along with a reduction in phagocytic activity of macrophages as compared to controls. With the fibroblasts, a 50% decrease in incorporation of 14C-thymidine was observed after a 22-hr exposure to PtCl4 at a concentration of 0.007mM; higher concentrations were required to inhibit the incorporation of 14C-uridine and 14C-leucine. Time-course studies indicated that the inhibition of 14C-thymidine incorporation was nearly complete (90%) after 7 hr in the presence of 0.06mM PtCl4. Under the same conditions, there was little inhibition (15%) of 14C-leucine incorporation and moderate inhibition (50%) of 14C-uridine incorporation. Higher concentrations of PtCl4 were required to inhibit 14C-thymidine incorporation into the acid-soluble fraction than were required to inhibit incorporation into the acid-precipitable fraction. Hence, the preferential inhibition of DNA synthesis by PtCl4 may result from an impairment of the incorporation process.

Mass balance of trace elements in Walker branch watershed: relation to coal-fired steam plants.

Abstract: A mass balance study of trace element flows at the TVA Allen Steam Plant at Memphis showed that most of the released Hg, some Se, and probably most Cl and Br are discharged to the atmosphere as gases. The elements As, Cd, Cu, Ga, Mo, Pb, Sb, Se, and Zn were concentrated in fly ash compared to slag and were more concentrated in the ash discharged through the stack than in that collected by the precipitator, while Al, Ba, Ca, Ce, Co, Eu, Fe, Hf, K, La, Mg, Mn, Rb, Sm, Sr, Ta, Th, and Ti showed little preferential partitioning between the slag and the collected or discharged fly ash. The elements Cr, Cs, Na, Ni, U, and V exhibited behavior intermediate between the latter two groups. This information about stack emissions of trace elements from the Allen Plant was used to estimate the likely range of air concentrations and input (dry and wet deposition) to the Walker Branch Watershed. The watershed, which is on the ERDA reservation at Oak Ridge, is within 20 km of three coal-fired steam plants, two in the TVA system and one belonging to ERDA. The estimated input values are compared to measurements of Cd, Cr, Cu, Hg, Mn, Ni, Pb, and Zn in wet precipitation falling on the watershed during 1973 and 1974. Dry deposition of these elements could not be measured directly but estimates indicated that this could be of the same order of magnitude as the rainwater input. A six-month mass balance indicated that the watershed efficiently retains Pb (97-98% of the atmospheric input,) Cu (82-84%), while Cr (69%), Mn (57%), Zn (73%), and Hg (69%) are less well retained.

Structure-activity relationships for ulcerogenic and adrenocorticolytic effects of alkyl nitriles, amines, and thiols.

Abstract: In rats, a single administration of acrylonitrile (vinyl cyanide) produces a rapidly occurring bilateral adrenal apoplexy. Structure-activity studies have shown that a close derivative, propionitrile (ethyl cyanide), causes duodenal ulcer without markedly affecting the adrenal glands. Prolonging the two-carbon chain of propionitrile by a methyl group (n-butyronitrile) enhances, replacing the methyl by bromide or nitrile decreases, while substitution by an amino group abolistes the ulcerogenic potency and variably affects the adrenocorticolytic action. On assaying a large number of nonnitrile compounds as well for ulcerogenic effect, such as thiols and amines, this effect was found to be related to a two-carbon structure bearing electronegative radicals on one or both ends of the chain.

Whole body retention in rats of different 191Pt compounds following inhalation exposure.

Abstract: The whole body retention, excretion, lung clearance, distribution, and concentration of 191Pt in other tissues was determined in rats following a single inhalation exposure to different chemical fo...

Interactions of platinum metals and their complexes in biological systems

Abstract: Platinum-metal oxidation catalysts are to be introduced in exhaust systems of many 1975 model-year automobiles in the U.S. to meet Clean Air Act standards. Small quantities of finely divided catalyst have been found issuing from prototype systems; platinum and palladium compounds may be found also. Although platinum exhibits a remarkable resistance to oxidation and chemical attack, it reacts chemically under some conditions producing coordination complex compounds. Palladium reacts more readily than platinum. Some platinum-metal complexes interact with biological systems as bacteriostatic, bacteriocidal, viricidal, and immunosuppressive agents. Workers chronically exposed to platinum complexes often develop asthma-like respiratory distress and skin reactions called platinosis. Platinum complexes used alone and in combination therapy with other drugs have recently emerged as effective agents in cancer chemotherapy. Understanding toxic and favorable interactions of metal species with living organisms requires basic information on quantities and chemical characteristics of complexes at trace concentrations in biological materials. Some basic chemical kinetic and thermodynamic data are presented to characterize the chemical behavior of the complex cis-[Pt(NH3)2Cl2] used therapeutically. A brief discussion of platinum at manogram levels in biological tissue is discussed.

Methylmercury in the environment: a review of current understanding.

Abstract: The danger of methylmercury poisoning appears to be slight when the environment is not directly contaminated with methylmercury. Sediments rapidly bind mercury and decrease its availability to aquatic organisms. Sediments further have a greater propensity to demethylate than to methylate mercury. In noncontaminated aquatic ecosystems, the concentrations of methylmercury and inorganic mercury are many times lower than those that have been found to cause toxicity, even in the most sensitive organisms. Methylmercury bound to protein is comparatively less toxic than methylmercury salts, and selenium present in this protein appear to be one of the major detoxifying agents for methylmercury. This is particularly important in seafood, where there is an excess of selenium compared to methylmercury.

Effect of nickel chloride on primary antibody production in the spleen.

Abstract: Mice immunized intraperitoneally with sheep erythrocytes were treated with nickel chloride, a common particulate air pollutant. Primary antibody production in the spleen was examined using a hemoly...