SEARCH · Search PubMed

Results for “Inhalation Exposure”

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.

SourceResearch connectionFrom yearThrough year

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 1,783 records · Page 99Linked to original sources

PubMedDate not supplied

Neurotoxicity of organic solvent mixtures: embryotoxicity and fetotoxicity.

The toxicity of organic solvents at different concentrations was examined to determine their effect on pregnant rats and their offspring. A very serious effect which inhalational exposure to n-hexane, methyl-ethyl-ketone and a mixture of the two organic solvents produced in pregnant rats was a concentration-dependent increase of intrauterine mortality. In cases of only prenatal exposure, the persistence of reduced body growth was an important result obtained at all concentrations we investigated (first solvent experiment, 500 ppm; second solvent experiment, 800 ppm; and third solvent experiment, 1000 to 1500 ppm; 23 hr day). In these cases, a delay in the maturation of cerebellar cortex was also observed. In cases of pre- and postnatal solvent exposure, the effects of malnutrition were added to the solvent-induced retardation. This resulted in an extreme delay in tissue maturation accompanied by a retarded cell maturation. The solvents examined had no teratogenic effect in pregnant rodents and their offspring. Neurotoxicity was restricted to the known structures of the adult animals, whose axons were damaged. They did, however, show a concentration-dependent embryotoxic and fetotoxic effect.

Administration, Inhalation↗

PubMed1997

Immunologic specificity of lymphocyte cell lines from dogs exposed to beryllium oxide.

We have reported that dogs exposed twice to aerosols of beryllium oxide (BeO) developed Be-specific immune responses within the lung, along with granulomatous and fibrotic lung lesions. To evaluate the specificity of the immune response, lymphocytes from lungs and blood of BeO-exposed dogs were co-cultured over an irradiated blood monocyte layer, alternately with interleukin 2 and BeSO4. Resultant cell lines were then tested for their response to different metal cations, common canine recall antigens, and BeSO4 in an in vitro cell proliferation assay. The cell lines responded to BeSO4 in a dose-dependent fashion, with mean stimulation indices of 7, 58, 119, and 112 at concentrations of 0.01, 1.0, 10, and 100 microM BeSO4 respectively. Cells not proliferate when incubated with ZnSO4 or NiSO4, or with canine distemper, leptospira, adenovirus 2, parvovirus, or parainfluenza antigens. Lymphocytes from normal vaccinated dogs proliferated markedly when cultured with these antigens. Cells from the cultured cell lines (91%) stained with Thy-1 (a pan T-cell marker) and 96% stained with DT2 (a helper T-cell marker). Furthermore, the Be-induced proliferative response was restricted by major histocompatibility (MHC) class II antigens. These data reinforce the premise that inhalation exposure of dogs to BeO produces lung lesions and MHC class II restricted immunologic responses mediated by Be-specific, helper T-Cells. These data further confirm the hypothesis that antigen localized to the lung results in the recruitment of T-cells to the lung, followed by localized antigen-specific, cell-mediated immune responses.

Administration, Inhalation↗

PubMed1990

[Health aspects of sodium salts of sulfurous and sulfuric acids as environmental pollutants].

For the first time hygienic characteristics of long-term inhalation exposure effects of sodium salts of sulphurous and sulphuric acids in low concentrations on animals is given. The most sensitive organs and organism systems have been identified. MACs of the substances under study for the ambient air are proposed. The degree of contamination and the distance of spreading of sodium sulfate from the source have been determined in field studies. The size of the sanitary-protective zone has been substantiated.

Administration, Inhalation↗

PubMed2002

Dose-response modeling of cytochrome p450 induction in rats by octamethylcyclotetrasiloxane.

Inhalation of octamethylcyclotetrasiloxane (D4) induces CYP2B1/2 protein and causes liver enlargement. We have developed a pharmacodynamic (PD) extension to a physiologically based pharmacokinetic (PBPK) model to characterize these dose-response behaviors. The PD model simulates interactions of D4 with a putative receptor, leading to increased production of cytochrome P450 2B1/2. Induction was modeled with a Hill equation with dissociation constant, Kd, and Hill coefficient, N. Both a 1- and a 5-compartment liver model were evaluated. The PBPK model provided excellent simulations of tissue D4 and hepatic CYP2B1/2 protein concentrations following 6 h/day, 5-day inhalation exposures to 0, 1, 7, 30, 70, 150, 300, 500, 700, or 900 ppm D4. Either the 1- or 5-compartment liver model could accurately simulate increases in CYP2B1/2 protein in the liver. With a 1-compartment liver, Kd and N were 0.67 microM (free liver concentration) and 1.9, respectively. The 5-compartment model used higher N-values (approximately 4.0) and varied Kd between compartments. The fitted 5-compartment model parameters were Kd = 0.67 microM in the midzonal compartment with geometric differences in Kd between compartments of 2.9. On the basis of unbound (free) plasma concentrations, D4 appeared to be a higher potency inducer than phenobarbital (PB). Dose-response curves for increased liver weights had N/mS 1.0 and Kd/mS 3.4 microM, very different values from those for enzyme induction. Exposure concentration leading to a 0.1% increase in CYP2B1/2 protein predicted by the 1- and 5-compartment models were 2.1 ppm and 5.1 ppm, respectively. The 1- and 5-compartment liver models provided very similar fits to the whole liver induction data, excluding the lowest dose, but the 5-compartment liver model had the additional advantage of simultaneously describing the regional induction of CYP2B1/2.

Adjuvants, Immunologic↗

PubMed1995

A critical review of 55Fe dosimetric models.

The available literature on 55Fe dosimetry has been devoted to environmental exposures and medical iron kinetic studies. For occupational dosimetry, ICRP (1979, 1988) published a non-recycling dosimetric model for iron. These ICRP publications do not provide information on iron excretion. Johnson and Dunford (1985) published dose conversion factors and urinary excretion curves based on the ICRP (1980) and MIRD (1983) iron metabolic models. A critical review of these models was undertaken to select a model for occupational dose assignment. The review indicated that the information and recommendations in ICRP (1988) and Johnson and Dunford (1985) are dependent on unrealistic assumptions that do not agree with known iron metabolism. Therefore, an alternative model is proposed for dosimetric application. Calculations of dose conversion factors and urinary excretion curve for class W55Fe inhalation exposure (1 micron AMAD) using the proposed model are compared with predictions based on ICRP (1980) and Johnson and Dunford (1985) models. The difference in the practical outcome (i.e., dose assignment) is examined by applying the proposed and reviewed models to a realistic bioassay case. The Johnson and Dunford (1985) model yields a dose estimate which is roughly a factor of ten higher than values predicted by ICRP (1980) and the proposed model. Some of the disagreement is due to uncertainty in the fraction of radio-iron excretion via urine. Further research on this subject is recommended. In the interim, the proposed model is recommended for occupational dose assignment.

Animals↗

PubMed1994

Mesothelial cell proliferation induced by intrapleural instillation of man-made fibers in rats and hamsters.

Long-term inhalation exposure to a biopersistent man-made ceramic fiber (RCF 1) results in a high incidence of pleural mesotheliomas in Syrian golden hamsters but not in identically exposed rats. To understand better the mechanisms involved in the intraspecies pathobiology of fiber-exposed mesothelium, the ability of the two different man-made fibers to induce cell proliferation in hamster and rat pleural mesothelial cells was investigated. Three dose levels of either glass fibers (MMVF 10) or ceramic fibers (RCF 1) were instilled intrapleurally into male Fischer 344 rats and male Syrian Golden hamsters. Rats and hamsters were exposed to approximately equal numbers of long thin fibers per kilogram of body weight using a single intrapleural instillation. Bromodeoxyuridine (BrdU) was administered via an implanted osmotic pump, and mesothelial cell proliferation was assessed at 7 and 28 days postinstillation (PI) using immunocytochemical visualization of labeled S-phase cells. Both rats and hamsters exhibited dose-dependent increases in proliferation of pleural mesothelial cells following exposure to both fiber types. Interspecies differences in mesothelial cell proliferation were noted for fiber type and pleural site. At 28 days PI, RCF-induced mesothelial cell proliferation was found to be more pronounced in hamsters than in rats in the caudal visceral pleural. Comparing both fibers either by equal mass or by equal fiber numbers, mesothelial cell proliferation in RCF 1-treated animals was higher than in animals exposed to MMVF 10, especially in hamsters, and may be a factor in the difference in mesothelioma induced by the two fibers. The higher sustained (28 day) mesothelial cell proliferation in the visceral pleural of hamsters exposed to RCF may contribute to the species-specific differences in mesothelioma incidence found in long-term rodent inhalation studies.

Analysis of Variance↗

PubMed1996

Comparative proliferative and histopathologic changes in rat lungs after inhalation of chrysotile or crocidolite asbestos.

Patterns of cell proliferation in lung and pleura and development of histopathologic lesions were studied in lungs from Fischer 344 rats after inhalation exposure to chrysotile or crocidolite asbestos at average airborne concentrations of approximately 8 mg/m3 air for 5 and 20 days and after 20 days of exposure followed by an additional 20 days in room air (20 + 20 days). To assess cell proliferation rats were injected with 5-bromo-2'-deoxyuridine (BrdU) at various time points after initiation of exposure to asbestos. Image analysis was used to quantitate the effects of chrysotile and crocidolite on BrdU labeling indices in the following lung compartments: (1) interstitium, (2) alveolar duct region, (3) bronchial epithelium, and (4) visceral mesothelium. With the exception of mesothelium, which exhibited significant increases in BrdU incorporation in rats exposed to crocidolite at 20 + 20 days, asbestos-induced elevations in BrdU uptake in other compartments were transient with labeling comparable to sham controls at later time points. Histopathology of rat lungs revealed fibrotic lesions of a greater extent and severity at 20 days in rats exposed to crocidolite, but fibrosis occurred in both asbestos-exposed groups after an additional 20 days in clean air (20 + 20). Quantification of fiber burden in rat lung after inhalation of comparable airborne concentrations of either fiber type demonstrated that inhalation of crocidolite asbestos led to a higher fiber retention when compared to chrysotile asbestos. Our results indicate that chrysotile and crocidolite asbestos induce different patterns of cell proliferation in lung and pleural cells. The protracted increases in BrdU labeling of mesothelial cells by crocidolite may reflect increased retention of fibers and/or inherent differences between types of asbestos.

Administration, Inhalation↗

PubMed1975

Histamine induction and release following proteolytic enzyme exposure.

The mechanism of biologic response from exposure to a 12% subtilisin Carlsberg preparation is shown to be one of histamine release in the guinea pig. Three groups of guinea pigs were pretreated by intradermal injections withsaline solution of (1) the commercial proteolytic enzyme preparation containing 12% subtilisin Carlsberg, (2) an alkaline protease preparation obtain from Aspergillus oryzae that was isolated from cotton dust, or (3) a nonproteolytic mixture of proteins and lipases obtained from cotton seeds. The histamine content of the ling, liver, and ear tissues of guinea pigs that were pretreated with any one of the three preparations showed an in untreated animals. Following challenge by intratracheal injection of a saline solution containing the subtilisin preparation, the guinea pigs pretreated with the same preparation showed a markedly reduced liver histamine level. Challenge by inhalation exposure to the subtilisin preparation of guinea pigs that were pretreated with any one of the above preparations resulted in a lower histamine concentration in the lungs and livers.

Aerosols↗

PubMed1987

Pulmonary gas trapping in the guinea pig and its application in pharmacological testing.

Airway constriction produced by bronchoconstrictive aerosols in vivo can result in substantial postmortem pulmonary gas trapping in the guinea pig. In order to use gas trapping responses for the evaluation of potential antiasthma agents, we developed a multiple animal inhalation exposure apparatus and an accurate system for quantitating excised lung gas volumes in the guinea pig. Aerosols of histamine, methacholine, and leukotriene D4 were shown to produce gas trapping responses that were inhibited in a dose-dependent fashion by appropriate antagonists. The approach described provides an objective and sensitive measure of the severity of airway obstruction, does not require surgery or anesthesia, and allows excellent control of unwanted sources of experimental variation.

Administration, Inhalation↗

PubMed2002

[Specific parameters for the calculation of dose after aerosol inhalation of transuranium elements].

A review on specific parameter measurements to calculate doses per unit of incorporation according to recommendations of the International Commission of Radiological Protection has been performed for inhaled actinide oxides. Alpha activity distribution of the particles can be obtained by autoradiography analysis using aerosol sampling filters at the work places. This allows us to characterize granulometric parameters of "pure" actinide oxides, but complementary analysis by scanning electron microscopy is needed for complex aerosols. Dissolution parameters with their standard deviation are obtained after rat inhalation exposure, taking into account both mechanical lung clearance and actinide transfer to the blood estimated from bone retention. In vitro experiments suggest that the slow dissolution rate might decrease as a function of time following exposure. Dose calculation software packages have been developed to take into account granulometry and dissolution parameters as well as specific physiological parameters of exposed individuals. In the case of poorly soluble actinide oxides, granulometry and physiology appear as the main parameters controlling dose value, whereas dissolution only alters dose distribution. Validation of these software packages are in progress.

Actinoid Series Elements↗

PubMed1995

Differential pulmonary responses in rats inhaling crystalline, colloidal or amorphous silica dusts.

Pulmonary responses in rats were compared after short-term inhalation exposure to polymorphs of silica dust. Groups of CD rats were exposed 6 h a day for 3 d to crystalline silica or amorphous silica. Another group was exposed to Ludox colloidal silica for 6 h a day, 5 d a week for two or four weeks. Thereafter the groups were killed, and the lungs washed at several postexposure times. The crystalline silica produced persistent pulmonary inflammatory responses characterized by neutrophil recruitment and consistently elevated biomarkers of cytotoxicity in bronchoalveolar lavage fluids, and progressive histopathological lesions were observed within one month of the exposure. Amorphous silica produced a transient pulmonary inflammatory response, and Ludox elicited transient pulmonary inflammatory responses at 50 or 150 mg center dot m-3 but not at 10 mg center dot m-3. After three months most of the biochemical values of the Ludox-exposed animals had returned to the control level. These results demonstrate that crystalline silica dust is more potent in producing pulmonary toxicity when compared with amorphous or colloidal silica particles.

Administration, Inhalation↗

PubMed1988

Mediators of pulmonary injury induced by inhalation of bacterial endotoxin.

The purpose of this study has been to further define the pathophysiologic aspects of lung injury caused by the inhalation of endotoxin (LPS) using the morphometric approach to identify mediators that influence distal lung structure and function. Hamsters were divided into 3 groups 24 h prior to low dose LPS inhalation exposure (4 micrograms/m3 for 5 h): (1) pretreated with cobra venom factor to deplete complement in vivo, (2) pretreated with indomethacin to block prostaglandin production, and (3) untreated control group. Both pretreatments abolished LPS-induced decreases in lung volume as well as increases in capillary PMN and platelets seen in untreated control animals. Neither pretreatment had any effect on the LPS-induced decreases of other capillary leukocytes. Similarly, both methods of pretreatment failed to block increases in cellular interstitium of distal capillary septa induced with LPS alone. LPS provoked changes in capillary endothelium, especially seen as an increase in numerical density of endothelial pinocytotic vesicles. Decomplementation failed to alter this increase, but indomethacin pretreatment blocked the effect. Neither treatment had any effect on their size. Low dose LPS inhalation also altered pulmonary capillary permeability to a 125I-BSA probe, which was found in significantly greater amounts in LPS-exposed lungs than in those of saline aerosol control lungs, but was not present in the air space as evidenced by negligible counts in bronchoalveolar lavages. It is evident that endotoxin on the epithelial side of the air-blood barrier leads to changes on the other side of that barrier.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1993

Sequential analysis of the pathogenesis of plutonium-induced pulmonary neoplasms in the rat: morphology, morphometry, and cytokinetics.

Light microscopy, morphometry, and cytokinetic techniques were used to examine the dynamics of plutonium-induced pulmonary proliferative lesions and neoplasms in rats at several intervals to 450 days after inhalation exposure to aerosols of 239PuO2. Maximal increases in alveolar and bronchiolar epithelial cell labeling were seen at 30 days; decreasing subsequently, the levels remained elevated above control indices. Focal proliferative epithelial lesions developed in the lung by 180 days and before the onset of pulmonary neoplasms. Pulmonary neoplasms, predominantly adenocarcinomas and squamous cell carcinomas, were initially observed at 308 days. The proliferative lesions progressed through a succession of morphological changes leading to the development of neoplasms. The volume density (fraction) and epithelial surface area of foci of alveolar epithelial hyperplasia increased progressively between 180 and 450 days after exposure, in contrast to the other proliferative lesions. We conclude that plutonium-induced pulmonary neoplasms develop through a succession of focal proliferative lesions that represent developmental preneoplastic lesions. Progressive increases in volume and epithelial surface area of the alveolar epithelial hyperplasias suggest that they may be more at risk for neoplastic transformation than the other histological types of proliferative foci.

Adenocarcinoma↗

PubMed1983

Evaluation of heart malformations in B6C3F1 mouse fetuses induced by in utero exposure to methyl chloride.

C57BL/6 female mice impregnated by C3H males mice to produce B6C3F1 fetuses were exposed daily for six hr to atmospheres containing 0, 250, 500, or 750 ppm methyl chloride, from gestation day 6 to gestation day 18. There were 74 to 77 females with copulation plugs per exposure concentration. Females exposed to 750 ppm ethyl chloride exhibited ataxia commencing on the seventh day of exposure (gestation day 12). They also showed hypersensitivity to touch or sound, tremors and convulsions. Six females in the 750 ppm group died and one was euthanized in extremis prior to scheduled sacrifice. On gestation day 18, all other females were euthanized for evaluation. Only dams exposed to 750 ppm exhibited significant decrease in body weight by gestation day 18, weight gain during the gestation period, and absolute weight gain (weight gain minus gravid uterine weight) versus controls. There were no treatment related-effects on these parameters in the other exposure groups. None of the groups exhibited exposure-related differences in pregnancy rate, gravid uterine weight, or maternal liver weight. There were no differences in the numbers of implantations, resorption, dead fetuses, nonlive (dead plus resorbed) fetuses, live fetuses, sex-ratio, or mean fetal body weight per litter. There was a significant exposure-related increase in the number and percentage of affected (nonlive plus malformed) fetuses per litter with the incidence of affected fetuses in the 750 ppm group significantly higher than controls. There was a statistically significant increase in the incidence of heart defects in the 500 and 750 ppm group relative to controls. Of the 37 fetuses in the study with heart defects, 23 were females, 14 were males. The heart defects observed included: absent or abnormal tricuspid valve, reduced number of papillary muscles and/or chordae tendineae on the right side, small right ventricle, globular heart, and white spots in the left ventricular wall. Multiple malformations were observed in one fetus from the 500 ppm group and in three fetuses in the 750 ppm group. It is concluded that methyl chloride inhalation exposure to pregnant C57BL/6 mice from gestation day 6 through gestation day 17 resulted in maternal toxicity only at the 750 ppm exposure concentration and was teratogenic to B6C3F1 conceptuses at exposure concentrations of 750 and 500 ppm, leading to fetal heart malformations. No evidence of embryo or fetotoxicity other than teratogenicity was seen at any of the exposure concentrations employed. No maternal, embryo or fetotoxicity or teratogenicity was associated with exposure of mice, during critical periods of embryo and fetal development, to 250 ppm of methyl chloride.

Abnormalities, Drug-Induced↗

PubMed1988

Assessment of the developmental risks resulting from occupational exposure to select glycol ethers within the semiconductor industry.

This risk assessment evaluates the potential human hazards of adverse developmental effects posed by exposure to 2-ethoxyethanol (2-EE), 2-ethoxyethanol acetate (2-EEA), 2-methoxyethanol (2-ME), and 2-methoxyethanol acetate (2-MEA) as they are currently used in semiconductor manufacturing. These glycol ethers are contained in positive photoresists used in the wafer fabrication process. The available data on the developmental toxicology of these glycol ethers indicates that each can selectively affect the offspring of pregnant animals that have been exposed to relatively low vapor concentrations. For these chemicals, the ratio of the lowest dose which adversely affected the pregnant animals (A) and the lowest dose which produced developmental effects in offspring (D), e.g., A/D ranged from 1-5. Approximately 400 workplace air samples of 4-8 h duration, both personal and area, from seven different companies were used to assess the degree of inhalation exposure during the manufacture of wafers. The geometric mean results obtained during personal sampling of workplace air for 2-EE, 2-EEA, 2-ME, and 2-MEA were 0.36, 0.02, 0.10, and 0.01 ppm, respectively. These levels are 14- to 500-fold lower than the applicable threshold limit value (TLV) currently recommended by the American Conference of Governmental Industrial Hygienists (ACGIH). Specifically, the margins of safety between the typical occupational exposure and the TLV for 2-ME, 2-EE, 2-MEA, and 2-EEA are 50, 14, 500, and 250, respectively. The TLVs for these chemicals were set at levels considered sufficiently low to protect workers and their offspring from adverse effects and are about 2- to 10-fold lower than the various no-observed-effect levels (NOELs) obtained in animal tests. Based on more recent data, lower TLVs are indicated. The safety-factor approach, rather than mathematical models developed for estimating cancer risks, was used in this analysis. Historical data have shown that the application of safety factors of 10-100 to the NOEL, as determined in Segment II developmental toxicology tests in animals, should be adequate to protect humans. In its risk assessment guidelines, the U.S. Environmental Protection Agency (EPA) selected the uncertainty-factor approach as the most reasonable one for evaluating the hazards of developmental toxicants. This assessment indicates that the airborne concentrations of these glycol ethers in the semiconductor industry are, in general, sufficiently low to protect employees against their adverse developmental and reproductive effects as well as any other toxic effects as long as dermal exposure is minimal.

Air Pollutants, Occupational↗

PubMed1993

Relative developmental toxicities of inhaled aliphatic mononitriles in rats.

The developmental toxicities of eight aliphatic mononitriles were studied in Sprague-Dawley rats after inhalation exposure for 6 hr/day, during Days 6 to 20 of gestation. The range of exposure concentrations for acetonitrile was 900 to 1800 ppm; for propionitrile and n-butyronitrile, 50 to 200 ppm; for isobutyronitrile, 50 to 300 ppm; for acrylonitrile and methacrylonitrile, 12 to 100 ppm; for allylnitrile 12 to 50 ppm; and for 2-chloroacrylonitrile, 1 to 12 ppm. Embryolethality was observed after exposure to 1800 ppm acetonitrile, 200 ppm propionitrile, 300 ppm isobutyronitrile; fetotoxicity was observed after exposure to 200 ppm propionitrile, n-butyronitrile, or isobutyronitrile, or to 25 ppm acrylonitrile in the presence of overt signs of maternal toxicity. In the absence of significant maternal toxicity, allylnitrile caused embryolethality, fetotoxicity, and clear teratogenicity at 50 ppm, and n-butyronitrile and methacrylonitrile caused fetotoxicity at 200 ppm and 100 ppm, respectively. While maternal toxicity was observed for 2-chloroacrylonitrile, it did not cause significant embryonal or fetal toxicity up to 12 ppm.

Acetonitriles↗

PubMed1997

Inhalation of high concentrations of low toxicity dusts in rats results in impaired pulmonary clearance mechanisms and persistent inflammation.

This study was carried out to assess the time course of pulmonary clearance impairment and persistence of inflammation following high-dose inhalation exposures to titanium dioxide (TiO2) or carbonyl iron (CI) particles. Male rats were exposed to air, TiO2 or CI particles 6 hr/day, 5 days/week, for 4 weeks at concentrations of 5, 50, and 250 mg/m3 and evaluated at selected intervals through 6 months postexposure. Indices of pulmonary inflammation as well as alveolar macrophage clearance functions (i.e., morphology, in vivo and in vitro phagocytosis, and chemotaxis), cell proliferation, and histopathology endpoints were measured at several postexposure time periods through 6 months. In addition, amounts of TiO2 or CI in lungs and tracheobronchial lymph nodes were measured to allow an evaluation of particle clearance and translocation patterns. Four-week exposures to TiO2 or CI particles at concentrations of 250 mg/m3 resulted in lung burdens of 12 mg titanium and 17 mg iron, respectively, with particle retention half-times ranging from 68 days for 5 mg/m3 TiO2 to approximately 330 days for 250 mg/m3. The impact of this TiO2 dust load and similar lung burdens of CI particles produced a sustained pulmonary inflammatory response measured through a period of 3-6 months postexposure concomitant with increases in BrdU cell labeling of terminal airway and pulmonary parenchymal cells. The impairment of particle clearance mechanisms was accounted for by deficits in in vitro phagocytic and chemotactic potential of alveolar macrophages recovered from the lungs of high-dose, TiO2- or CI-exposed rats. Free granular pigment (TiO2 or CI) was present on the hypertrophic mucosal surfaces of bronchioles and bronchi, and particle-laden macrophages, found individually, were numerous throughout alveoli and within lymphoid tissues immediately after exposure. Aggregates of particle-laden macrophages were present within alveoli and alveolar ducts from 1 week postexposure through the entire 6-month recovery period. Macrophage accumulations increased in size and number from 1 week through 1 month postexposure and then appeared to remain constant through the remaining 5-month postexposure period. Minimal cellular hypertrophy and hyperplasia were evident at alveolar duct bifurcations adjacent to macrophage aggregates, and this effect was most prominent at 3 to 6 months postexposure. The results of this study clearly demonstrate that exposure to high dust concentrations of two different innocuous particle types produced sustained pulmonary inflammation, enhanced proliferation of pulmonary cells, impairment of particle clearance, deficits in macrophage function, and the appearance of macrophage aggregates at sites of particle deposition. In addition, the mass deposition rate determination appears to be a less sensitive indicator of "overload" when compared to biomarkers of pulmonary toxicity, such as macrophage function and cellular inflammation and proliferation indices.

Administration, Inhalation↗

PubMed1992

Inhalation toxicity of methylisocyanate: assessment of germ cell mutagenicity and reproductive effects in rats.

Adult male Wistar rats were exposed to methylisocyanate (MIC, 3.2 mg/l, single inhalation exposure for 8 min under static condition) or ethyl methanesulphonate (EMS, 150 mg/kg, single ip dose) for the assessment of germ cell mutagenicity and reproductive effects. Sequential matings of treated males with normal females on days 1-7, 8-14 and 15-21 post-exposure did not indicate any induction of dominant lethal mutation (increased frequency of preimplantation losses and early fetal deaths) by MIC but it was significantly induced by EMS as compared to respective controls. Males, necropsied after 21 days of exposure, showed no effect of MIC on epididymal sperm density and morphology. EMS also had no effect on sperm density but it significantly induced morphological abnormalities in sperm as compared to untreated controls. There was an acute and transitional reduction in reproductive performance (10-21%) of MIC-exposed males during days 1-14 post-exposure followed by recovery to the normal level during days 15-21 post-exposure. The progeny of MIC-exposed males was also normal in terms of litter size, litter weight, neonatal survival and body weight gain in litters up to 10 days post-partem. It is concluded with the evidence at hand that the observed failure of MIC to cause germ cell mutagenicity is related to its poor biodistribution to the target site(s) and a transient reduction in the reproductive performance of MIC-exposed males is a result of general stress and disconsolate copulation.

Administration, Inhalation↗