Showing papers in "Environmental Health Perspectives in 1976"
TL;DR: Theoretical models of respiratory tract deposition of inhaled particles are compared to experimental studies of deposition patterns in humans and animals, as determined principally by particle size, density, respiratory rate and flow parameters.
Abstract: Theoretical models of respiratory tract deposition of inhaled particles are compared to experimental studies of deposition patterns in humans and animals, as governed principally by particle size, density, respiratory rate and flow parameters. Various models of inhaled particle deposition make use of approximations of the respiratory tract to predict fractional deposition caused by fundamental physical processes of particle impaction, sedimentation, and diffusion. These models for both total deposition and regional (nasopharyngeal, tracheobronchial, and pulmonary) deposition are compared with early and recent experimental studies. Reasonable correlation has been obtained between theoretical and experimental studies, but the behavior in the respiratory tract of very fine (less than 0.1 micron) particles requires further investigation. Properties of particle shape, charge and hygroscopicity as well as the degree of respiratory tract pathology also influence deposition patterns; definitive experimental work is needed in these areas. The influence upon deposition patterns of dynamic alterations in inspiratory flow profiles caused by a variety of breathing patterns also requires further study, and the use of differing ventilation techniques with selected inhaled particle sizes holds promise in diagnosis of respiratory tract diseases. Mechanisms of conducting airway and alveolar clearance processes involving the pulmonary macrophage, mucociliary clearance, dissolution, transport to systemic circulation, and translocation via regional lymphatic vessels are discussed.
326 citations
TL;DR: Based on existing toxicological information, the present recommended use patterns might afford sufficient safety margin on human population, however, in extending usage to agricultural pest control, much more extensive investigations should be forthcoming from both chemical and biological aspects, since there is scant information on the fate of these pyrethroids in the environment.
Abstract: Synthetic pyrethroidal compounds undergo biodegradation in mammals both oxidatively and hydrolytically, and depending on the type of compound, either of the pathways may predominate. Thus, (+) - or (+/-) -trans isomers of the chrysanthemumate ester of primary alcohols such as fenothrin, furamethrin, proparthrin, resmethrin, and tetramethrin (and possibly permethrin, too) are metabolized mainly through hydrolysis of the ester linkage, with subsequent oxidation and/or conjugation of the component alcohol and acid moieties. On the other hand, the corresponding (+)-cis enantiometers and chrysanthemumate of secondary alcohols like allethrin are resistant to hydrolytic attack, and biodegraded via oxidation at various sites of the molecule. These rapid metabolic degradations, together with the presumable incomplete absorption from the gastrointestinal tract, would generally contribute to the low acute toxicity of synthetic pyrethroids. These compounds are neither skin irritants nor skin sensitizers, and inhalation toxicity as well as dermal toxicity are fairly low. Neither is teratogenic in rats, mice, and/or rabbits or mutagenic on various bacterial strains. Subacute and chronic feeding of higher amounts of the compounds to rats invariably causes some histopathological changes in liver; however, these are neither indicative nor suggestive of tumorigenicity. Based on existing toxicological information, the present recommended use patterns might afford sufficient safety margin on human population. However, in extending usage to agricultural pest control, much more extensive investigations should be forthcoming from both chemical and biological aspects, since there is scant information on the fate of these pyrethroids in the environment. Also several of the compounds may be very toxic to certain kinds of fish and arthropods.
205 citations
TL;DR: Oxygen-tolerant rats, which increased activities of pulmonary enzymes which combat lipid peroxidation, were also tolerant to lethal doses of paraquat as indicated by an increased paraquats LT50, and rats chronically exposed to 100 ppm paraqu at in the water had elevated pulmonary activities of glucose-6-phosphate dehydrogenase and GSH reductase.
Abstract: The purpose of this study was to investigate the hypothesis that paraquat pulmonary toxicity results from cyclic reduction-oxidation of paraquat with sequential generation of superoxide radicals and singlet oxygen and initiation of lipid peroxidation. In vitro mouse lung microsomes catalyzed an NADPH-dependent, single-electron reduction of paraquat. Incubation of paraquat with NADPH, NADPH-cytochrome c reductase, and purified microsomal lipid increased malondialdehyde production is a concentration dependent manner. Addition of either superoxide dismutase or a single oxygen trapping agent 1,3-dipheylisobenzo furan inhibited paraquat stimulated lipid peroxidation. In vivo, pretreatment of mice with phenobarbital decreased paraquat toxicity, possibly by competing for electrons which might otherwise reduce paraquat. In contrast, paraquat toxicity in mice was increased by exposure to 100% oxygen and by deficiencies of the antioxidants selenium, vitamin E, or reduced glutahione (GSH). Paraquat, given IP to mice, at 30 mg/kg, decreased concentrations of the water-soluble antioxidant GSH in liver and lipid soluble antioxidants in lung. Oxygen-tolerant rats, which hae increased activities of pulmonary enzymes which combat lipid peroxidation, were also tolerant to lethal doses of paraquat as indicated by an increased paraquat LT50. Furthermore, rats chronically exposed to 100 ppm paraquat in the water had elevated pulmonary activities of glucose-6-phosphate dehydrogenase and GSH reductase.These results were consistent with the hypothesis that lipid peroxidation is involved in the toxicity of paraquat.
190 citations
TL;DR: The toxicity of selected tin compounds is reviewed and tricyclohexyltin hydroxide, the most toxic in this group, is now registered by the Environmental Protection Agency as a miticide.
Abstract: The toxicity of selected tin compounds is reviewed. Over the years, a variety of uses has been found for organic and inorganic tin compounds, as fungicides, as stablizers in plastics, moluscicides, and miticides; they have also been suggested as insect chemosterilants and for other industrial uses. Many of these products are unpalatable when mixed into diets and have been suggested as rodent repellents. Inhaling tin as dust or fumes may cause a benign pneumoconiosis in exposed workers. The organotin compounds can be divided into alkyltin and aryltin compounds. The trimethyl and triethyltin compounds are well absorbed from the gastrointestinal tract and are the most toxic in this group. Triethyltin particularly produces status spongiosus of the white matter of the central nervous system. Most of the other alkyl and aryl tin compounds are poorly absorbed from the gastrointestinal tract, and are less toxic when given orally than when given parentally. Only one compound, tricyclohexyltin hydroxide, is now registered by the Environmental Protection Agency as a miticide. This product produces skin irritation in rabbits. Studies should be conducted to determine whether it causes contact dermatitis in humans.
152 citations
TL;DR: The formamidines, a relatively new group of acaricide-insecticides, are novel both in their range of biological activities and in their mode of action, which is presently unknown.
Abstract: The formamidines, a relatively new group of acaricide-insecticides, are novel both in their range of biological activities and in their mode of action, which is presently unknown This paper is a review of the historical development, properties, structures, uses, and chemistry of this group of pesticides, with particular emphasis on chlordimeform (Galecron or Fundal), N'-4-chloro-o-tolyl-N,N-dimethylformamidine, and amitraz, 1,3=di-(2,4-dimethylphenylimino)-2-methyl-2-azapropane Their biological activity and uses are defined by their toxicity to spider mites, ticks, and certain insects, and they are particularly effective against juvenile and resistant forms of these organisms A significant, but poorly understood feature of their field effectiveness is their breadth of toxic action which includes direct lethality, excitant-repellant behavioral effects, and chemosterilization They are generally of low hazard for nontarget species with the significant exception of predaceous mites Several aspects of the chemistry of these compounds are considered, including structure--activity relations, synthetic pathways, isomerism and configuration, and their chemical and environmental stability A significant feature of the metabolism and toxicity of these agents is the possible activation of chlordimeform by N-demethylation in vivo Strong evidence for this has been presented with the cattle tick, but recent results discussed here suggest that in other species, ie, mice, German cockroaches or black cutworm eggs, N-demethylation is neither a strong activation nor a detoxication reaction
137 citations
TL;DR: Because the initial deposition pattern of inhaled particles of various toxic agents determines their future clearance and insult to tissue, respiratory tract deposition is important in assessing the potential toxicity of inhaling aerosols.
Abstract: Because the initial deposition pattern of inhaled particles of various toxic agents determines their future clearance and insult to tissue, respiratory tract deposition is important in assessing the potential toxicity of inhaled aerosols. Factors influencing the deposition of inhaled particles can be classified into three main areas: (1) the physics of aerosols, (2) the anatomy of the respiratory tract and (3) the airflow patterns in the lung airways. In the physics of aerosols, the forces acting on a particle and its physical and chemical properties, such as particle size or size distribution, density, shape, hygroscopic or hydrophobic character, and chemical reactions of the particle will affect the deposition. With respect to the anatomy of the respiratory tract, important parameters are the diameters, the lengths, and the branching angles of airway segments, which determine the deposition. Physiological factors include airflow and breathing patterns, which influence particle deposition. Various lung models used in predicting particle deposition are reviewed and discussed. The air-way structures of various animal species are compared, showing the unique structure of the human lung compared to the animal species under study. Regional deposition data in man and dog are reviewed. Recent deposition data for small rodents are presented, showing regional difference in deposition with the right apical lobe having the highest relative deposition.
136 citations
TL;DR: Preliminary evidence is presented to support catabolic pathways in pseudomonads and micrococci that are initiated by successive hydrolyses of the diesters to give the phthalate anion.
Abstract: Recent studies on the biodegradation phthalate esters in natural ecosystems, sewage, and laboratory cultures are reviewed. There is ample evidence to demonstrate that bacteria are major elements in the biodegradative processes and that in most situations complete oxidation of the aromatic ring occurs; much less is known about the catabolism of the alcoholic moiety, e.g., 2-ethylhexanol. Evidence is presented to support catabolic pathways in pseudomonads and micrococci that are initiated by successive hydrolyses of the diesters to give the phthalate anion. Thereafter a dioxygenase catalyzes the formation of 4,5-dihydro-4,5-dihydroxyphthalate, which is oxidized by an NAD-dependent dehydrogenase to give 4,5-dihydroxyphthalate, Protocatechuate, formed by decarboxylation of 4,5-dihydroxyphthalate, is the substrate for ring cleavage enzymes. Whereas flurorescent pseudomonads use the beta-ketoadipate pathway, the nonfluorescent strains and micrococci examined use of meta-cleavage (4,5-) route. All the intermediates proposed have been accumulated by enzymes purified from Pseudomonas fluorescens. Isophthalate and terephthalate (anions) are readily used as carbon sources by aerobic bacteria, and preliminary evidence is consistent with catabolic routes for these isomers converging at the ring-cleavage substrate protocatechuate. Some possible effects and interactions of synthetic organic chemicals with the natural microflora, and the influence of other vectors, is discussed in relation to the maintenance of the carbon cycle and environmental pollution.
133 citations
TL;DR: The chemical nature, relationship of insecticidal activity to chemical structure, occurrence, production, and utilization, registered uses, metabolism, and insect and mammalian toxicity are reviewed.
Abstract: Naturally occurring insecticides are abundant and varied in their effects, though but a few are articles of commerce. Even for these, pyrethrum, nicotine, rotenone, hellebore, ryania, and sabadilla, there is a paucity of information on mammalian toxicology and environmental effects. In general, these materials are characterized favorably by low acute toxicity and ready dissipation in nature. Unfavorable aspects of natural insecticides are the contained mixture of active and inactive components and the low active ingredient content on a crop yield basis pointing to a high unit cost. Natural insecticides can serve additionally as leads to unnatural mimics, of which the commercially successful synthetic pyrethroids are prime examples. The chemical nature, relationship of insecticidal activity to chemical structure, occurrence, production, and utilization, registered uses, metabolism, and insect and mammalian toxicity are reviewed.
117 citations
TL;DR: The results indicate that the pulmonary endothelium is the initial site of injury and extensive damage to these cells could allow the drug access to interstitial and epithelial cells.
Abstract: Diffuse pulmonary fibrosis is associated with bleomycin administration to humans The sequential reactions of lung cells to this drug have now been investigated in mice following injection of 20 mg
109 citations
TL;DR: Initial tests indicate that even the more stable compounds are degraded rapidly in soil, so if the trials at present in progress reveal no toxicological or environmental hazards, within a few years synthetic pyrethroids should be available to control a wide range of domestic, veterinary, horticultural, agricultural, and forest pests at low rates of application.
Abstract: Improved understanding of the factors determining the insecticidal activity, the mammalian toxicity, and the stability in air and light of natural and synthetic pyrethroids has led to a series of n
82 citations
TL;DR: It is concluded that smoke has the ability to effect one-electron oxidations and type I signals indicate the presence of oxygenated radicals which appear to be a mixture of alkoxy radicals (RO) and aroyloxy (ArCO2-) radicals.
Abstract: The technique of spin trapping has been applied to the gas phase of cigarette smoke to identify and quantify the radicals present. It was found that radicals could be trapped only if the smoke was filtered. Three spin traps were used: N-tert-butyl-alpha-phenyl nitrone (PBN). 5,5-dimethyl-delta1-pyrroline-1-oxide (DMPO) and alpha-[3,5-di-tert-butyl-4-hydroxyphenyl)-N-tert-butyl nitrone (OHPBN). From the electron spin resonance (ESR) splitting constants of the radicals produced by the reaction of smoke radicals with the spin traps and also from the effec of varying the path length between the cigarette and the spin trap solution, it is concluded that three types of signals are observed. Type I signals indicate the presence of oxygenated radicals which appear to be a mixture of alkoxy radicals (RO) and aroyloxy (ArCO2-) radicals. Our data do not allow conclusions about the nature of the R or Ar groups in these two oxy radicals; however, considerations based on lifetimes suggest that the R group probably is tertiary. Type II and III signals are not typical spectra of spin adducts. Instead, we believe they result from reaction of smoke (and probably radicals in smoke) with the PBN spin trap and indicate that smoke has the ability to effect one-electron oxidations. Only type I signals are observed with DMPO and OHPBN. A quantitative study shows that 4 x 10(14) spins/puff are present in the smoke, in contrast with the result of a recent study which used a very different method for determining the radical content of smoke. A discussion of the nature of the radicals in smoke and some tentative conclusions are presented.
TL;DR: Blood level studies with rats illustrated uptake phenomena that were dependent on the dose and route of administration and were also affected by the vehicle used to convey the styrene monomer.
Abstract: A variety of food containers, drinking cups and cutlery, fabricated from polystyrene (PS) or polystyrene-related plastic, were analyzed for their styrene monomer content. Samples of yogurt, package...
TL;DR: Studies indicating that the production of chemically reactive metabolites by pulmonary metabolism of xenobiotics can also play a fundamental role in the pathogenesis of chemically induced lung disease are described.
Abstract: Many xenobiotics produce hepatic injury due to their metabolism in the liver to highly reactive electrophile intermediates which form covalent conjugates with nucleophilic cellular constituents. Th...
TL;DR: The role of drug metabolism in chemical-induced liver injury is reviewed, especially the chemical toxicology of the hepatic injury produced by acetaminophen, bromobenzene, furosemide, isoniazid and iproniazid.
Abstract: The role of drug metabolism in chemical-induced liver injury is reviewed. Parameters for studying the formation of chemically reactive metabolites are discussed and the factors that alter the formation and covalent binding of reactive metabolites are selectively emphasized. Some of the experimental work that led to these concepts is discussed, especially the chemical toxicology of the hepatic injury produced by acetaminophen, bromobenzene, furosemide, isoniazid and iproniazid.
TL;DR: A documented survey of the properties, metabolism, toxicology, and uses of the most commercially advanced chemical, methoprene, shows it to be environmentally acceptable and toxicologically innocuous.
Abstract: Insect growth regulators (IGRs) of the juvenile hormone type alter physiological processes essential to insect development and appear to act specifically on insects. Three natural juvenile hormones have been found in insects but not in other organisms. Future use of antagonists or inhibitors of hormone synthesis may be technically possible as an advantageous extension of pest control by IGRs. A documented survey of the properties, metabolism, toxicology, and uses of the most commercially advanced chemical, methoprene, shows it to be environmentally acceptable and toxicologically innocuous. Derivation of its current use patterns is discussed and limitations on these are noted. Residue levels and their measurement in the ppb region have allowed exemption from the requirement of tolerances in the EPA registered use of methoprene for mosquito control. Tolerances for foods accompany its fully approved use for control of manure breeding flies through a cattle feed supplement. The human health effects of using this chemical appear to be purely beneficial, but further advances through new IGR chemicals appear unlikely without major changes in regulatory and legislative policy.
TL;DR: Mercury level in RBC from cord blood appeared as the best potential indicator of this involvement of neonatal involvement, although relationships with the mother's diet and level of mercury in the placenta also appear useful.
Abstract: The potential danger of natural mercury accumulation in the diet of the Eskimo is evaluated through mercury levels determined in cord blood, placenta, maternal blood, hair, and milk of 38 maternal-infant pairs from Anchorage and the Yukon-Kuskokwim Delta. Although mercury levels are not discernably dangerous, trends to larger accumulations in maternal and fetal RBC and placental tissue with proximity to the sea and consumption of seals during pregnancy provide the basis for considering possible indicators of neonatal involvement. Mercury level in RBC from cord blood appeared as the best potential indicator of this involvement, although relationships with the mother's diet and level of mercury in the placenta also appear useful. In this area, average and maximal mercury levels in cord blood are 39 and 78 ng/ml, respectively, far below the acknowledged toxic level in infants of these mothers who eat seals or fish every day during their pregnancy.
TL;DR: Significant differences between the high and low exposure groups were found with regard to history of acute prenarcotic symptoms, acute lower respiratory symptoms, prevalence of FEV 1/FV less than 75 per cent, and elevated GCTP.
Abstract: Styrene monomer is a high volume chemical used chiefly in production of polystyrene. A clinical survey of 493 production workers was undertaken at the oldest and largest monomer production, polymerization, and extrusion facility in the U.S. Relative exposure durations and levels were obtained from occupational histories. Significant differences between the high and low exposure groups were found with regard to history of acute prenarcotic symptoms, acute lower respiratory symptoms, prevalence of FEV 1/FV less than 75 per cent, and elevated GCTP. Other liver function tests, chest x-ray, FVC less than 80 per cent, and hematological parameters showed no distinct pattern. A concomitant mortality study has been mounted and is in progress.
TL;DR: A comparison of studies in mice and rats suggests that behavioral effects of teratogens are similar in the two species and demonstrates that mice can be used successfully in a variety of behavioral evaluations.
Abstract: While mice have been used less frequently than rats in behavioral research, there use has some advantages in teratological studies. The development of the mouse CNS has been investigated more exten...
TL;DR: A detailed discussion of the tissue slice technique for evaluation of transport phenomena and the relationship of the in vitro renal transport of organic substances to in vivo renal function is discussed in detail.
Abstract: A detailed discussion of the tissue slice technique for evaluation of transport phenomena is presented. Information is given concerning the preparation of tissue slices and the advantages of this procedure over corresponding in vivo techniques. In addition, the relationship of the in vitro renal transport of organic substances to in vivo renal function is discussed in detail. Finally, certain pitfalls related to in vitro slice transport studies are presented.
TL;DR: It was shown that the toxicity parameters of compounds and the biological constants of mammals correlate with body weight, which made it possible to develop a computational method for extrapolating toxicologic data from animals to the "average" man.
Abstract: Conditions for extrapolating toxicologic data from animals to man were studied. In the search for general regularities associated with the comparative sensitivity of humans and various species of a...
TL;DR: Placentation in a number of commonly used laboratory animals and in man is described, and it is shown that dependence upon histiotroph and hemotroph varies greatly, not only between species but also at different stages of gestation in a single species.
Abstract: The distinction between histiotrophic nutrition (in which local macromolecules are chiefly responsible for the maintenance of the embryo) and hemotrophic nutrition (which results from a transfer of material between the maternal and fetal circulations) is made. Placentation in a number of commonly used laboratory animals and in man is described, and it is shown that dependence upon histiotroph and hemotroph varies greatly, not only between species but also at different stages of gestation in a single species. These facts are likely to be reflected in considerably differences in response to certain teratogens; they must be carefully considered when experimental results are extrapolated between species. The significance to man of an agent which has been shown to be teratogenic in a single species of experimental animals should be evaluated in terms of possible differences in placental function between man and that species. This is particularly so if there is a suspicion that the potential teratogen may affect the fetal membranes.
TL;DR: Chlordimeform appears to interfere with amine-mediated control of nervous and endocrine systems in a variety of ways, and antagonizes the in vivo action of reserpine in the rat (reserpine depletes amine stores in the CNS) and inhibits monoamine oxidase from rat liver in vitro.
Abstract: Chlordimeform is a relatively new acaricide/insecticide, whose mode of action we have investigated. It appears to interfere with amine-mediated control of nervous and endocrine systems in a variety of ways. Specifically, chlordimeform causes a build-up of the amines 5-hydroxytryptamine and to a lesser extent norepinephrine in the rat brain in vivo, antagonizes the in vivo action of reserpine in the rat (reserpine depletes amine stores in the CNS), inhibits monoamine oxidase from rat liver in vitro, and causes hypotension in rabbits. In the American cockroach it directly stimulates the heart in situ, acts synergistically with tryptamine in vivo, inhibits amine-N-acetyltransferase from cockroach head in vitro, causes accumulation of indolamines in cockroaches in vivo, and blocks the stimulation of adenylate cyclase by octopamine in the cockroach CNS in situ. It also inhibits tryptamine metabolism in whole mites in vitro.
TL;DR: It is shown that the gonadotoxic effect of cadmium is manifested on the same level (3 mg/kg of body weight) as the general toxic effect, and 0.001 mg/l.
Abstract: Experimental research was conducted on the study of the relationship of the general toxic and gonadotoxic effects of cadmium and boron under conditions of subacute and chronic oral intoxication on white random-bred rats, by use of biochemical, physiological, cytological, and pathomorphological methods. It is shown that the gonadotoxic effect of cadmium is manifested on the same level (3 mg/kg of body weight) as the general toxic effect. The gonadotoxic effect of boron is dominant and is manifested at a lower level (6 mg/kg of body weight) than the general toxic effect (20 mg/kg). On the basis of the results of chronic experiments, 0.001 mg/l. is recommended as the hygienic standard for cadmium in water and 0.5 mg/l. for boron.
TL;DR: Limiting food consumption to 13--15 g/rat per day from days 6 through 15 of gestation did not result in increased fetal mortality or stunting, however, fetal weight was reduced slightly, and the incidence of minor skeletal changes was approximately three to four times that among fetuses of control dams that were not pair-fed.
Abstract: The structural development of fetuses was altered when Dipterex was administered by diet to pregnant rats from days 6 through 15 of gestation. Major external and skeletal alterations occurred after consumption of 432 or 519 mg/kg body weight per day, only minor skeletal changes occurred in the 375 mg/kg dose group and the incidence of alterations in the 145 mg/kg dose group was not significantly different from that in the pair-fed controls. The malformations seen at the two highest doses did not result directly from the associated decrease in food consumed. Dipterex was not shown to have teratogenic potential when given for the same time span, once daily by gavage, even at levels that produced maternal lethality. Imidan was not teratogenic when similarly given, either by diet at concentrations that resulted in a 45% reduction in food consumption, or by gavage at dose levels that resulted in some maternal lethality. Data collected from pair-fed control females revealed that limitation of food consumption to 13--15 g/rat per day from days 6 through 15 of gestation did not result in increased fetal mortality or stunting. However, fetal weight was reduced slightly, and the incidence of minor skeletal changes was approximately three to four times that among fetuses of control dams that were not pair-fed.
TL;DR: Thiram caused hyperactivity in the nonataxic rats of both sexes and the peripheral nerve as the primary site of the lesion, and caused behavioral changes in apparently normal rats.
Abstract: Eight of 24 female rats fed 66.9 mg/kg-day of thiram developed neurotoxicity. The neurotoxic effects were characterized by ataxia and paralysis of the hind legs. There were demyelination, degeneration of the axis cylinders, and presence of macrophages in the nerve bundle of the sciatic nerve. Degeneration in the ventral horn of the lower lumbar region of the spinal cord was evidenced by chromatolysis of motorneurons, pyknosis, and satellitosis. During a second experiment, 4 of 24 females fed 65.8 mg/kg--day also developed ataxia and paralysis. An additional 9 females showed clasping of the hind feet when picked up by the tail. Nerve conduction could not be measured for one severely ataxic rat and the electromyogram indicated a loss of motor unit function. Histopathology of this rat, along with the others, suggests the peripheral nerve as the primary site of the lesion. Thiram also caused behavioral changes in apparently normal rats. The walking pattern of the hind legs was altered with decreases in stride width and the angle between contralateral steps. These rats required significantly more shock-motivations and cleared a lower height in a jump/climb ability test. An open-field study indicated that thiram caused hyperactivity in the nonataxic rats of both sexes. Three of 24 rats fed 95.8 mg/kg-day of ferbam also developed ataxia or paralysis.
TL;DR: The cohort of workers employed in a Swedish vinyl chloride/poly(vinyl chloride) plant since its start in the early 1940's has been followed for mortality and cancer morbidity patterns.
Abstract: The cohort of workers employed in a Swedish vinyl chloride/poly(vinyl chloride) plant since its start in the early 1940's has been followed for mortality and cancer morbidity patterns. Only 21 of t...
TL;DR: The role of liver microsomal enzymes in the generation of electrophilic mutagenic vinyl chloride metabolites is discussed and two of the enzyme reaction products showed potent genetic activity in microorganisms and Chinese hamster V79 cells.
Abstract: The various adverse biological effects of vinyl chloride appear to be dependent upon the metabolic conversion of this compound into chemically reactive metabolites. The metabolism of vinyl chloride...
TL;DR: Human volunteers were exposed to 0.4 ppm O3 under conditions simulating ambient pollution exposures, suggesting that exposures to elevated ambient concentrations of O3 produce adaptation in at least some residents of photochemical pollution areas.
Abstract: To test the hypothesis that adaptation protecting against acute effects of ambient ozone (O3) exposures develops in Los Angeles residents, human volunteers were exposed to 0.4 ppm O3 under conditions simulating ambient pollution exposures. Blood biochemical, pulmonary physiological, and clinical responses were assessed. Los Angeles residents (N = 6) showed only minimal clinical or physiological response to O3, while new arrivals (N = 9) showed significant losses in pulmonary function and a tendency toward increased symptoms. Most biochemical responses did not differ significantly between residents and new arrivals. These results agree with others in suggesting that exposures to elevated ambient concentrations of O3 produce adaptation in a least some residents of photochemical pollution areas. The underlying mechanisms and long-term consequences of such adaptation are unknown.
TL;DR: Initial studies, utilizing a variety of methods to assess the reproductive toxicity of environmental substances in male animals, suggest that cadmium and boron at the concentrations and dose regimens tested are without significant reproductive toxicity.
Abstract: Results of a U.S.S.R.--U.S. cooperative laboratory effort to improve and validate experimental techniques used to assess subtle reproductive effects in male laboratory animals are reported. The present studies attempted to evaluate the reproductive toxicity of cadmium as cadmium chloride and boron as borax (Na2B4O7) and to investigate the mechanism of toxicity in the rat following acute and subchronic oral exposure. In vitro cell separation techniques, in vivo serial mating tests, and plasma assays for hormones were utilized. Effects on the seminal vesicle and prostate were evaluated with chemical and enzyme assays. Clinical chemistry was monitored routinely. Acute oral doses, expressed as boron were 45, 150, and 450 mg/kg while doses for cadmium equivalent were 6.25, 12.5, and 25 mg/kg. Rats were also allowed free access to drinking water containing either boron (0.3, 1.0, and 6.0 mg/l.) or cadmium (0.001, and 0.l mg/l.) for 90 days. Randomly selected animals were studied following 30, 60, and 90 days of treatment. These initial studies, utilizing a variety of methods to assess the reproductive toxicity of environmental substances in male animals, suggest that cadmium and boron at the concentrations and dose regimens tested are without significant reproductive toxicity.
TL;DR: Behavioral effects have been found to result from the prenatal administration of substances known to be teratogenic to the CNS, but the present inability to identify potential behavioral teratogens by means other than laboratory investigation is intensified.
Abstract: Behavioral effects have been found to result from the prenatal administration of substances known to be teratogenic to the CNS. These effects occur at dose levels lower than those producing gross malformations and when the agent is administered at times other than that optimal for CNS relevant technique for detecting adverse consequences of prenatal exposure to drugs and chemicals. Behavioral testing, however, also appears to have attributes that dictate a thoughtful approach to its role as a method for assessing risk, and additional research is needed to obtain usable techniques. The need for such research is intensified by the present inability to identify potential behavioral teratogens by means other than laboratory investigation.