SEARCH · Search PubMed
Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.
Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.
The exposure of council and forestry workers to 2,4,5-T, a plant poison, has been monitored for a period of two years. It was found that the excessive urine levels of 2,4,5-T fell dramatically once the exposure was minimized. Therefore, the use of protective clothing and adoption of measures to prevent inhalation exposure are essential.
An exposure facility was tested with regard to the information obtainable from short-term animal experiments for the assessment of health hazards from automotive engine exhausts. Indicators of immunotoxicity and genotoxicity were studied in guinea pigs and mice, respectively, exposed for 2 weeks, 8 h/day, to ten times diluted exhausts from a one-cylinder research diesel engine running at constant load. Regulated and non-regulated pollutants were determined. Besides increased number of lavageable cells in the airways, exposed guinea pigs exhibited, after immunization and challenge to ovalbumin, reduced leukotrienes B4 and C4 in lavage fluid and reduced anti-ovalbumin IgG in serum. Absence of increased CYP1A activity indicated that the exposure was below the threshold for induction of these enzymes. Instead a certain reduction of this activity indicated interaction with active enzyme sites. In vivo doses of some reactive metabolites of low molecular mass were measured by adducts to hemoglobin. Doses from aliphatic epoxides were low, in accordance with low hydrocarbon levels in the exhaust. The levels of hemoglobin adducts from aldehydes showed no clearcut influences of exposure. Genetic effects determined by DNA fingerprint analysis were indicated. It is concluded that repeated dose inhalation exposure of small numbers of animals is a useful mode of exposure for studying parameters that may elucidate toxic effects of air pollutants emitted from automotive engines, with a possibility to evaluate engine and fuel with regard to health hazards.
The effects of chronic exposure to new inhalation anesthetics (sevoflurane and isoflurane) on spermatogenesis and sperm morphology were examined in 23 rabbits, randomly divided in 3 groups. Rabbits received 20 exposure hours (four hours/day x 5 days), as follows: group I: 2.3% (1.2 MAC) sevoflurane + 2L/min oxygen, group II: 1.3% (1.2 MAC) isoflurane + 2L/min oxygen, and group III (control): 2L/min oxygen. Semen was collected on the 12th, 19th, 26th, 33rd, and 41st days of exposure. Sperm concentration, motility and morphological changes were evaluated. On the 41st day, testicular biopsies were taken and observed with light microscopy. Sperm concentration and motility significantly decreased in the sevoflurane and the isoflurane groups, compared to control. There were no significant changes in the control group. It is concluded that chronic exposure to the new inhalational anesthetics had negative effects on spermatogenesis and sperm morphology.
The effects of subchronic inhalation exposure to toluene (80 ppm, for 4 weeks, 5 days/week, 6 h/day) was studied on spatial learning (postexposure days 3-6) and memory (postexposure day 14) using a water maze, on spontaneous and apomorphine-induced (1 mg/kg, subcutaneously (s.c.)) locomotor activity (postexposure day 17) and on the binding parameters of the dopamine D2 agonist S(-)[N-propyl-3H(N)]propylnorapomorphine ([H]NPA) in membrane preparations of the neostriatum of the rat. Toluene treatment was found to cause a statistically significant impairment in acquisition and retention of the spatial learning task. Furthermore, toluene significantly increased (2-fold) apomorphine-induced locomotion and caused a trend for a 50-60% increase in motility without any significant effect on rearing. Spontaneous locomotion, motility and rearing were not affected by toluene. Toluene treatment produced a significant 30-40% increase in the Bmax values of [3H]NPA and a trend for a 20-30% increase in the KD values. These results indicate that subchronic exposure to toluene in low concentrations causes a slight but persistent deficit in spatial learning and memory, a persistent increase in dopamine-mediated locomotor activity and an increase in the number of dopamine D2 receptors in the rat.
The chronic toxicity and carcinogenic potential of morpholine were evaluated in 60 Sprague-Dawley rats/sex/group receiving morpholine at mean inhalation exposure concentrations of 0, 10, 50 and 150 ppm for 6 hr/day, 5 days/week, for 104 weeks. Survival, body weight gains, organ weights, hematology, and clinical chemistries were normal in exposed groups and comparable to those of the control animals. The incidences of palpable tissue masses and of histologically confirmed neoplasia were comparable among all groups, including the control groups, and were typical of the strain and age of the rats tested. In-life clinical examinations revealed increased incidences of irritation around the eyes and nares, chromadacryorrhea, and urine stains on the fur, predominantly in high-dose animals. Morpholine exposure was associated with corneal irritation seen by ophthalmoscopic examination and confirmed microscopically as keratitis limited to the highest exposure group. Irritation of the maxillary and nasoturbinates as indicated by infiltration of neutrophils, focal squamous metaplasia of the turbinate epithelium, and necrosis of the turbinate bone was observed in high-dose animals. Therefore, chronic exposure of rats to morpholine for 2 years at concentrations of 150 ppm or less revealed no carcinogenic potential or chronic systemic toxicity. Consistent with its known irritating properties, morpholine produced only local irritation, which was limited almost exclusively to high-dose animals.
The effect of tail pinch on acetylcholine release in the striatum of freely moving rats was studied by microdialysis immediately after inhalation exposure to toluene (2000 ppm, 2 h) or exposure to air only. It has recently been found that toluene increases extracellular dopamine levels while decreasing acetylcholine release, and that dopamine uptake inhibition increases both extracellular dopamine levels and acetylcholine release, suggesting that toluene decreases acetylcholine release by a dopamine-independent mechanism. The present experiment was an attempt to study if a behaviourally induced increase of extracellular dopamine differs from that induced by toluene in affecting striatal acetylcholine release. Acetylcholine released increased during tailpinch in the unexposed as well as the toluene exposed group. No difference between the two groups in the acetylcholine release response to tailpinch was demonstrated. The result supports the conclusion that acute toluene exposure decreases acetylcholine release via a dopamine independent mechanism, and suggests that toluene exposure does not affect the striatal acetylcholine response to an acute stressful stimulus.
During twenty applications with a spray pistol of methomyl to chrysanthemums, inhalation exposure as well as potential and actual dermal exposure were monitored using the 'whole-body'-method. On the basis of the exposure data, in terms of exposure to the liquid formulation and the spray liquid, the possible health risk for methomyl and thirteen other pesticides, frequently used in ornamentals, was indicatively assessed. From the No-Observed-Adverse-Effect-Level (NOAEL) in animal experiments an Indicative Limit Value (ILV) was derived. The ILV is considered indicative for the limit of daily exposure for a worker which probably gives no rise to adverse health effects. This value is a rough approximation since the database for a proper assessment of such a value is generally incomplete. Assuming that exposure is independent of the pesticide, using a suitable format, the actual observed exposure can be compared with the ILV. To reduce the dermal exposure levels below the ILV the exposure of especially the hands has to be reduced e.g. by using impermeable gloves.
Physiological models are useful tools in the understanding of organic solvent toxicokinetics. An approach is presented where a physiological model is designed and solved by means of a spreadsheet macro instruction on a personal computer. The spreadsheet template is easy to use. Model parameters are entered and stored in tabular form, and any parameters and variables may be plotted. The model may be changed by editing the spreadsheet template, allowing compartments to be added, nonlinear metabolism to be introduced, etc. Accordingly, the kinetics of any substance and its metabolites, and any route of exposure may be modeled. The spreadsheet approach of physiologically based kinetic modeling is illustrated by simulating inhalation exposure to four organic solvents (acetone, 2-butoxyethanol, methylene chloride and styrene) in humans at various work loads. The results of the simulations are graphically compared with experimental data. By separating resting and working muscle tissue, the model successfully predicted the solvent concentrations not only in arterial but also in venous blood samples at various work loads (shown for acetone and methylene chloride).
New analytical gas chromatographic-tandem mass spectrometric approaches have been developed for assessing both potential and actual exposure of agricultural workers to malathion. The metabolites alpha- and beta-malathion monocarboxylic acids have been determined after a derivatisation process in order to obtain their hexafluoroisopropyl esters. Whole body dosimetry was used for potential dermal exposure assessment. Potential exposure by inhalation was estimated using personal air samplers and polyurethane foam plugs as sorbents. The intern dose measurements were carried out by analysing samples of urine after solid-phase extraction with C18. The recoveries of the analytes of the three matrices were between 90 and 102%. Quantification limits were lower than 0.24 ng L(-1). The proposed methods have been applied to evaluate potential and actual exposure of applicators spraying malathion in greenhouses.
The effect of toluene on the preference of ethanol was studied in rats. Toluene was administered orally by stomac tube in doses of 200, 400 or 800 mg/kg daily for 5 weeks or by inhalation at a concentration of 2000 p.p.m. 6 or 8 hr daily for 5 or 6 days per week for 2 weeks in rats of different age. During toluene inhalation exposure the rats had access to either tap water or ethanol-containing water (6 or 10%). After the exposure and during oral administration the rats had access to both ethanol-free and ethanol-containing water. Toluene inhibited the body weight gain in the highest oral dose group and in rats exposed to toluene and forced to drink ethanol in the inhalation experiments. In these experiments, the intake of fluid was reduced in the exposure period in rats forced to drink ethanol-containing water and further reduced in rats exposed to both ethanol and toluene. Exposure to toluene alone increased the fluid consumption. The preference of ethanol defined as consumed ethanol-containing water in per cent of the total water intake was not influenced by oral administration of toluene. It was, however, reduced by toluene given by inhalation to rats forced to drink ethanol-containing water during the exposure period. Toluene exposure alone or forced ethanol intake alone caused in these experiments a short-lasting reduction of the ethanol preference. It is concluded that toluene decreases the preference of ethanol in rats forced to drink ethanol during exposure to toluene.
Although hydrogen sulfide (H2S) is a known neurotoxic hazard, only a limited number of experimental animal studies have examined its neurochemical or behavioral effects. Our aim was to determine if short-term inhalation exposure of rats to H2S would result in altered brain catecholamnine levels or impaired learning and memory. Three groups of adult male CD rats were tested; two groups were exposed by nose-only inhalation (0, 30, 80, 200, or 400 ppm H2S) and one group was exposed by whole-body inhalation (0, 10, 30, or 80 ppm H2S) for 3 h per day forfive consecutive days. The first group (n = 10 rats per concentration) was tested immediately following each daily nose-only H2S exposure for spatial learning with a Morris water maze. Core body temperatures were also monitored in these animals during and after the last H2S exposure. The second group of rats (n = 10 rats per concentration) was tested for spontaneous motor activity immediately following the fifth exposure. These rats were then euthanized and striatal, hippocampal, and hindbrain catecholamnine levels determined. A third group of rats (n = 5-7 rats per concentration) was pretrained on a multiple fixed- interval (FI) schedule and exposed whole-body. Daily performance on the FI schedule was compared for the week pre-exposure, for the exposure week immediately following daily exposures, and for the week postexposure. We observed significant reductions in motor activity, water maze performance, and body temperature following exposure only to high concentrations (> or = 80 ppm) of H2S. Exposure to H2S did not affect regional brain catecholamine concentrations or performance on the FI schedule. Additional studies using other measures of behavior and longer-term exposure to H2S may be required to more definitively address conditions under which H2S exposure results in behavioral toxicity.
Iron and manganese share structural, biochemical, and physiological similarities. The objective of this study was to determine whether iron, like manganese, is transported to the rat brain via the olfactory tract following inhalation exposure. Eight-week-old male CD rats were exposed to approximately 0.31 mg Fe per m(3) (mass median aerodynamic diameter = 2.99 microm; geometric standard deviation = 1.15) via inhalation for a target duration of 90 min. Following exposure, rats were euthanized immediately (0) or at 1, 2, 4, 8, or 21 days postexposure. In addition to nasal and regional brain tissues, blood, and viscera were also collected. 59Fe concentrations were determined by gamma spectrometry. Further, heads were collected and frozen, and autoradiograms were prepared to visualize the location of 59Fe from the nose to the brain. Finally, olfactory mucosa samples collected at 0, 2, 4, and 21 days postexposure were further analyzed using high-performance liquid chromatography (HPLC) plus gamma spectroscopy to determine the association between 59Fe and transferrin. Data obtained from gamma spectrometry revealed that most of the iron remained in the nasal regions of the olfactory system and that less than 4% of iron deposited on the olfactory mucosa was observed in the olfactory bulb. Autoradiograms confirmed the data obtained from gamma spectrometry. 59Fe activity was absent in the olfactory regions of the brain even 4 days postexposure. Further, HPLC-gamma spectroscopy analyses indicated that 59Fe in the olfactory mucosa was coeluted with transferrin. Hence iron, unlike manganese, is not readily transported to the brain via the olfactory tract.
Most previous reports of ototoxicity following exposure to several volatile organic solvents have restricted testing to the low- and mid-frequencies (2-20 kHz) of the hearing range in the rat (0.25-80 kHz). We report here that inhalation exposure to styrene, mixed xylene, toluene, and 1,1,2-trichloroethylene resulted in hearing dysfunction only in the mid-frequency range and spared function at lower and higher frequencies. Adult male Long Evans rats were exposed via inhalation (whole body) in flow-through chambers. The following exposures were used: styrene, 1600 ppm; 1,1,2-trichloroethylene, 3500 ppm; toluene, 2500 ppm; mixed xylenes, 1800 ppm (N = 7-8 per group, 8 h/day for 5 days), and n-butanol, 4000 ppm (N = 10/group, 6 h/day for 5 days). Testing of auditory function was conducted 5 to 8 weeks after exposure using reflex modification audiometry (RMA). RMA thresholds were determined for frequencies from 0.5 to 40 kHz. Results indicated increased RMA thresholds for the mid-frequency tones (e.g., 8 and 16 kHz), but not higher or lower tones, for all solvents except n-butanol. Toluene and xylene also increased thresholds at 24 kHz. These data indicate that for those solvents reported thus far to cause hearing loss, the deficit is restricted to mid-frequencies in rats.
To accurately assess the potential therapeutic effects of airborne drugs, the deposition sites of inhaled particles must be known. Herein, an original theory is presented for physiologically based pharmacokinetic modeling and related prophylaxis of airway diseases. The mathematical model describes the behavior and fate of particles in the lungs of adult human subjects under various breathing conditions. Their deposition patterns are calculated via superposition of the separate but not independent processes of inertial impaction, sedimentation, and diffusion. The related computer code is designed to calculate total and compartmental (tracheobronchial and pulmonary) distributions of inhaled aerosols. In this manuscript, the model is first tested via comparisons of predicted deposition patterns with laboratory data from human inhalation exposure experiments and then it is applied to determine which factors most influence the dosimetry of inhaled particles. In this format, deposition patterns are explicitly related to particle characteristics, ventilatory parameters, and intersubject variabilities of lung morphologies. The dosimetric model was developed to improve the efficacy of aerosol therapy via the selective deposition of inhaled pharmaceuticals at prescribed lung locations to elicit optimum effects.
Exposure assessment, a component of risk assessment, links sources of pollution with health effects. Exposure models are scientific tools used to gain insights into the processes affecting exposure assessment. The purpose of this paper is to review the process and methodology of estimating inhalation exposure to particulate matter (PM) using various types of models. Three types of models are discussed in the paper. Indirect type of models are physical models that employ inventories of outdoor and indoor sources and their emission rates to identify major sources contributing to exposure to PM, and use fate and transport and indoor air quality models to estimate PM concentrations at receptor sites. PM concentrations and time spent by a subject at each receptor site are input variables to the conventional exposure model that estimates the desired exposure levels. Direct type models use measured exposure or exposure concentrations in conjunction with information obtained from questionnaires to formulate exposure regression models. Stochastic models use exposure measurements, estimates can also be used, to formulate exposure population distributions and investigate associated uncertainty and variability. Since models developed using databases from western countries are not necessarily applicable in developing countries, the difference in requirements among western and developing countries is highlighted in the paper. Employment of exposure modeling methods in developing countries requires development of local information. Such information includes local outdoor and indoor source inventories, local or regional meteorological conditions, adjustment of indoor models to reflect local building construction conditions, and use of questionnaires to obtain local time budget and activity patterns of the subject population.
Dermal exposure assessment and modeling is still in early phases of development. This article presents the results of a workshop organized to harmonize the future needs in this field. Methods for dermal exposure assessment either assess the mass of contaminant that is transferred to the skin, or the transfer of contaminant through the skin. Models for dermal exposure are either knowledge-based or deterministic. Any method or model should be transparent, validated, and open to further development. Some (partly) validated and standardized methods are available for measuring or modeling permeation of the skin or of personal protective equipment (PPE). Further validation and standardization is necessary. More research is needed on permeation of dusts and aerosols and more realistic tests should be developed and used for PPE. Several methods have been developed to measure contamination of surfaces or skin, but they are not validated or standardized. A number of non-validated models exist to assess dermal exposure. A clear need exists for more studies of dermal exposure, regarding measurement methods, models and actual exposure levels. A running four-year European study will greatly expand the knowledge in this field. Simple tools to assess and control the risks of dermal exposure in small and medium sized enterprises are also needed. Increasing the general knowledge of practitioners (e.g., safety professionals, occupational hygienists and physicians) in the field of dermal exposure is a first requirement. Available data, for example, on the permeation of PPE, should be made more readily available, using modern information technology. When information on dermal exposure is gathered and stored, the core information needs are partly the same as those for inhalation exposure. Some elements of process and activity, substance and product or worker, specific for dermal exposure, have been suggested by the workshop.
A screening health risk assessment was performed to assess the upper-bound risks of cancer and noncancer adverse health effects among wildland firefighters performing wildfire suppression and prescribed burn management. Of the hundreds of chemicals in wildland fire smoke, we identified 15 substances of potential concern from the standpoints of concentration and toxicology; these included aldehydes, polycyclic aromatic hydrocarbons, carbon monoxide, benzene, and respirable particulate matter. Data defining daily exposures to smoke at prescribed burns and wildfires, potential days of exposure in a year, and career lengths were used to estimate average and reasonable maximum career inhalation exposures to these substances. Of the 15 substances in smoke that were evaluated, only benzene and formaldehyde posed a cancer risk greater than 1 per million, while only acrolein and respirable particulate matter exposures resulted in hazard indices greater than 1.0. The estimated upper-bound cancer risks ranged from 1.4 to 220 excess cancers per million, and noncancer hazard indices ranged from 9 to 360, depending on the exposure group. These values only indicate the likelihood of adverse health effects, not whether they will or will not occur. The risk assessment process narrows the field of substances that deserve further assessment, and the hazards identified by risk assessment generally agree with those identified as a concern in occupational exposure assessments.
Exposure assessment is a poorly understood component of the science of epidemiology. The relationship between exposure to chemicals and ill-health outcomes is often calculated using crude exposure measures such as ever/never exposed or duration. When investigating subtle effects, exposures need to be characterized much more fully in terms of intensity, frequency, duration and route. While occupational exposures tend to be much greater than those experienced from the wider environment there is a need to remember that, for many chemicals, exposure can occur occupationally, environmentally and through consumer use of products containing the material of interest. Inhalation exposure has generally been the traditional focus for most epidemiological investigations but there is now growing awareness of the importance of the dermal and ingested routes of contact and internalization. Quantification of the exposure also needs to be related to a biological mechanism of action and exposure metrics need to be selected accordingly. Occupational exposures can generally be measured using simple well-validated techniques. Environmental exposures require much more sensitive instruments and are more difficult to assess. Exposure modelling, particularly for the environmental fate of chemicals has undergone many recent developments and Monte Carlo techniques can be used to characterize model uncertainty and variability. This approach to exposure assessment can now be used in the setting of the wider environment and will enable a far better understanding of the relationship between exposure and disease.