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Biomedical subjects

Y Alarie

Publications and source records attributed to Y Alarie.

At least 55 records · Page 3Linked to original sources
PubMed1987

Pulmonary effects of a polyisocyanate aerosol: hexamethylene diisocyanate trimer (HDIt) or Desmodur-N (DES-N).

Desmodur-N (DES-N) or hexamethylene diisocyanate trimer (HDIt), a biuret structure of hexamethylene diisocyanate, is a viscous liquid used for durable coatings and is applied by brushing or spraying. DES-N aerosol has been shown to be primarily a pulmonary irritant following a single exposure in mice. To explore the pulmonary effects of this agent further, groups of guinea pigs were exposed to concentrations ranging from 8 to 121 mg/m3 of DES-N for 3 hr. Prior to and following exposure, each animal was challenged with 10% CO2 in 20% O2 and 70% N2 to evaluate their pulmonary performance. Following a single exposure, these animals displayed a concentration-dependent increase in respiratory rate and decrease in tidal volume, as well as coughing and apnea. Their ventilatory response to 10% CO2 was abnormal and characteristic of a lung restriction response. Some airflow limitation was seen during expiration but this occurred more often during air breathing than during CO2 challenge. With daily exposures repeated for 11 consecutive days, guinea pigs began to adapt to the exposures as indicated by a return to a normal ventilatory response to CO2. This adaptation occurred within the first 5 days of exposures. From Days 6 to 11, there was a demonstrable effect, but the level of response was much less than that following the first exposure. No cumulative effect could be demonstrated with this polyisocyanate and the effect was found to be different than that for mono- or diisocyanates. Acceptable levels of exposure to this polyisocyanate for industrial workers are suggested.

Aerosols↗
PubMed1987

Chronic pulmonary effects in guinea pigs from prolonged inhalation of cotton dust.

Inhalation of cotton dust has been associated with development of byssinosis. An animal model has been described recently in which guinea pigs exposed to cotton dust for a 6-week period demonstrated acute respiratory reactions consisting of increased breathing frequency, reduced tidal volume, and airflow fluctuations most prominent on the first day of exposure following a period without exposure, often referred to as a "Monday" response (Ellakkani et al., 1984). The current study examined the effects of cotton dust inhalation for 52 weeks in order to evaluate the animal model for ability to demonstrate more chronic effects of cotton dust exposure. Twenty guinea pigs were exposed to 21 mg/m3 cotton dust for 6 hr/day, 5 days/week, for 52 weeks. Twenty control animals received sham exposure. Parameters used to indicate chronic effects included respiratory measurements, weight gain, lung volume and weight, and histopathological evaluation. Respiratory measurements were taken while animals were breathing ambient air and also while breathing a mixture of 10% CO2, 20% O2, and 70% N2. Pulmonary effects were noted to change during the 12 months of exposure. For the first 3 months experimental animals displayed an increase in breathing frequency and a decrease in breathing volume measured as whole-body plethysmographic pressure. These effects were pronounced on the "Monday" of each week. During Months 3-6, reactions occurred on each day of exposure, although Monday responses were most severe. After 6 months, respiratory reactions were pronounced daily. Other indications of a chronic effect of exposure were increased lung volume, measured by water displacement, 15.0 +/- 3.3 ml (mean +/- SD) for the exposed group, compared with 9.8 +/- 2.0 ml for the controls; increased lung weight 9.4 +/- 1.5 g vs 7.0 +/- 0.8 g; and bronchiolar epithelial hyperplasia and hyperplasia of alveolar type II cells. Additionally, a histomorphometric study of the lungs performed by others (Coulombe et al., 1986) detected changes in the peripheral conducting airways, including increased thickness of bronchiolar epithelium and increased thickness of septa at the alveolar level, denoting chronic exposure. Taken together, these results indicated chronic respiratory effects in guinea pigs as a result of 52 weeks of continued exposure to cotton dust. The parallel in development of symptoms in guinea pigs and in humans exposed to cotton dust indicates that the guinea pig is a suitable model for byssinosis.

Animals↗
PubMed1987

Performance evaluation under intoxicating atmospheres.

A new behavioral model has been developed and used to assess the performance of mice during exposure to carbon monoxide, hydrogen chloride, or subambient levels of oxygen. The apparatus is a ventilated 150-ft series of glass tubes forming an S-shaped exposure system. Performance evaluation was obtained for two sublethal responses: distance traveled/time and incapacitation. Performance of normal mice (Type I) or mice previously fitted with a tracheal cannula (Type II) was very reproducible and similar. Concentration-response relationships were obtained showing the deterioration of performance with exposures to CO from 2500 ppm, HCl from 1095 ppm, and below 8.8% ambient O2 level. This model is likely to be sensitive to other asphyxiants and irritants. It includes both distance traveled and time of performance prior to incapacitation. Both are critical parameters to be included in escape hazard analysis in fire situations and possibly in other accidents involving chemical spills.

Animals↗
PubMed1987

Reproductive toxicity of methyl isocyanate in mice.

The effects of methyl isocyanate (MIC) vapor on pregnancy and fertility were studied in mice in view of the reported increase in reproductive complications in Bhopal following the December 3, 1984, accident. The whole-body exposure of mice to 9 and 15 ppm MIC for 3 h on d 8 of gestation led to resorption of greater than 80% of implants. In more than 75% of MIC-exposed animals, all implants were lost. At these concentrations, MIC did not cause external malformations. However, there was evidence of an increase in visceral abnormalities and a decrease in fetal and placental weights and in fetal skeleton sizes. MIC disturbed the estrus cycle and decreased the mating and pregnancy rate of female mice. The mating performance of MIC-exposed male mice was also decreased. Exposure to MIC increased serum corticosterone levels of male and nonpregnant female mice. MIC exerted no significant effects on serum corticosterone and progesterone levels of pregnant mice if the pregnancy was retained but caused a significant decrease in the serum levels of these two hormones in animals that lost all the implants. These studies show that the effects of MIC in mice mimic many of the reproductive complications in Bhopal. The mechanism of the reproductive toxicity of MIC remains to be identified.

Adrenal Cortex Hormones↗
PubMed1987

Sensory and pulmonary irritation of methyl isocyanate in mice and pulmonary irritation and possible cyanidelike effects of methyl isocyanate in guinea pigs.

Methyl isocyanate (MIC) was evaluated for sensory and pulmonary irritation in mice. MIC was found to be both a potent sensory and pulmonary irritant in this species. From these results, a safe level of exposure for a period of 8 hr was estimated to be about 0.02 ppm for humans. Guinea pigs were also exposed to MIC for a single 3-hr exposure at a concentration of 37 ppm. During exposure to MIC, coughing was observed in all animals. Pulmonary function was evaluated immediately following exposure and intermittently on the next 35 days using CO2 challenges and flow-volume loops. Highly abnormal responses to CO2 were observed immediately after exposure in all animals. Six of the eight animals exposed to MIC died. In the two survivors, an apparent recovery was seen during the 5 days following exposure, but a worsening effect was observed at days 21 and 28, with a partial recovery at day 35. The data clearly demonstrated that the primary pulmonary effect of MIC was one of airways obstruction. Oxygen uptake and carbon dioxide output were also measured in the guinea pigs following exposure to MIC. No evidence of a cyanidelike effect was observed, in contrast to a severe depression of oxygen uptake following exposure to hydrogen cyanide.

Airway Obstruction↗
PubMed1987

Evaluation of sister chromatid exchange and cytotoxicity in murine tissues in vivo and lymphocytes in vitro following methyl isocyanate exposure.

The purpose of this study was to assess sister chromatid exchange (SCE) levels and cell cycle kinetics in various murine tissues following MIC exposure. Following exposure of mice to MIC, these parameters were measured in bone marrow and alveolar macrophages labeled with BrdUrd in vivo and in peripheral blood and spleen lymphocytes cultured in the presence of BrdUrd in vitro. Target concentrations of MIC were 2, 15, and 30 ppm (3 hr). Neither elevated SCE frequencies nor inhibition of cell cycling were evident in lipopolysaccharide (LPS)- or concanavalin A (ConA)-stimulated spleen lymphocytes, or in LPS-stimulated peripheral blood lymphocyte (PBL) cultures from mice exposed for 3 hr to MIC concentrations as high as 30.5 ppm. Inhibition of cell cycling and poor culture success rates were apparent in ConA-stimulated PBLs following MIC exposures as low as 2.3 +/- 0.4 ppm for 3 hr. At the lowest MIC dose employed, the cycling characteristics of bone marrow and alveolar macrophages were not altered, and SCE frequencies were at control levels. However, severe cell cycle inhibition was observed in these tissues at MIC concentrations of 15 ppm or greater. A marker of cytotoxicity at this dose was a high frequency (approximately 33-90%) of occurrence of first division cells containing a late-replicating Y chromosome. Despite its apparent cellular toxicity, MIC is not genotoxic as measured by SCE analysis in the tissues examined in this study.

Animals↗
PubMed1986

Sensory and pulmonary irritation with exposure to methyl isocyanate.

Methyl isocyanate (MIC) was tested for its potency as a sensory irritant and as a pulmonary irritant in mice. To evaluate sensory irritation, animals were exposed to MIC at concentrations between 0.5 and 7.6 ppm for a period of 90 min. A characteristic reflex decrease in respiratory rate indicating sensory irritation was observed. The concentration evoking a 50% decrease in respiratory rate (RD50) was found to be 1.3 ppm. To evaluate pulmonary irritation, animals were first anesthetized and fitted with a tracheal cannula. Following recovery from anesthesia, they were exposed to MIC at concentrations between 0.4 and 7.3 ppm for a period of 90 min. A characteristic decrease in respiratory rate indicating pulmonary irritation in tracheally cannulated (TC) mice was observed. The concentration evoking a 50% decrease in respiratory rate (RD50TC) was found to be 1.9 ppm. Thus, MIC was found to be a potent sensory and pulmonary irritant.

Animals↗
PubMed1985

A method to classify airborne chemicals which alter the normal ventilatory response induced by CO2.

Guinea pigs inhaling 10% CO2, 19% O2, and 71 N2 increase their tidal volume (VT) by a factor of 2 to 3 and their respiratory frequency (f) by a factor of 1.2 to 1.5 above their normal values while breathing room air. While exposing guinea pigs to 10% CO2, a variety of aerosols can be added to determine how they modify the normal ventilatory response to this agent. Aerosols of carbamylcholine, serotonin, or propranolol all decreased VT of guinea pigs when added to 10% CO2. We propose here that chemicals evoking reductions in tidal volume can be classified into two groups based on the set of concurrent respiratory responses. Those chemicals evoking "obstruction," not only reduced VT but also decreased (f), increased resistance to airflow in conducting airways, and interrupted airflow. The prototype of this family would be carbamylcholine. The second group of chemicals evoked what is described as "reflex restriction." These agents reduced VT but increased f and lowered resistance to airflow. Propranolol would be the prototype for this family. Serotonin, however, evoked both types of response patterns which were time dependent. At the beginning of exposure, obstruction was prevalent while at the end of a 30-min exposure, reflex restriction was prevalent.

Aerosols↗
PubMed1985

Use of repeated CO2 challenges to evaluate the pulmonary performance of guinea pigs exposed to toluene diisocyanate.

Guinea pigs were exposed to 1.4 ppm toluene diisocyanate (TDI) for 3 h/d on 5 consecutive days to produce chemical bronchitis. Following these exposures, the ventilatory response of the animals to challenge with 10% CO2 was greatly diminished. Response recovered during the next 40 d. In contrast, animals exposed to 0.02 ppm TDI daily for 70 d showed no change in ventilatory response to challenge with 10% CO2, nor did control animals which were not exposed to TDI. These results indicated both the absence of pulmonary toxicity following exposure to low TDI concentrations for an extended time and the effectiveness of the methodology utilizing the ventilatory response to CO2 to monitor recovery from acute pulmonary toxicity.

Animals↗
PubMed1985

The effects of aerosols of carbamylcholine, serotonin and propranolol on the ventilatory response to CO2 in guinea pigs and comparison with the effects of histamine and sulfuric acid.

A new method is introduced to recognize the acute pulmonary effect of airborne contaminants in guinea pigs. The method avoids anaesthesia and invasive techniques and requires minimal restraint of the animal. To recognize the acute pulmonary effect, the inspiratory volume of the animal was increased by continuous inhalation of a mixture containing 10% CO2 in 18% O2 and 72% N2. Once a plateau increase in inspiratory volume was reached, the aerosol to be studied was added to this mixture and its effect in reducing inspiratory volume measured. By exposing the animals to different exposure concentrations of carbamylcholine, serotonin and propranolol aerosols, concentration-response relationships were obtained which permitted comparison of their potency. Comparisons were also made with histamine and sulfuric acid aerosols previously studied.

Aerosols↗
PubMed1985

Evaluation of the pulmonary effects of HCl using CO2 challenges in guinea pigs.

Pulmonary effects of inhalation exposures to hydrogen chloride were evaluated during and following exposure in male guinea pigs. During exposure, the respiratory rate and the time of onset of sensory or pulmonary irritation as evidenced by the change in respiratory pattern were measured. HCl inhalation resulted in both sensory and pulmonary irritation. The onset of sensory irritation took 6 min during HCl exposures at 320 ppm but less than 1 min at 680, 1040, and 1380 ppm. The onset of pulmonary irritation showed a concentration-response relationship, the higher the concentration the earlier the onset. Following exposure to HCl, animals were evaluated using a pulmonary performance test based on their ventilatory response (respiratory rate and tidal volume) during challenge with 10% CO2. The maximal respiratory frequency achieved during the CO2 challenge was lower in the HCl-exposed animals than in the controls in a HCl concentration-dependent fashion, but HCl had no apparent effect on the maximal tidal volume achieved during CO2 challenges. HCl exposure also affected baseline respiratory rate and tidal volume of the animals after exposure. Impairments of the respiratory function were also supported by evidence of morphological injury in both the airways and the alveolar region.

Animals↗
PubMed1984

Evaluation of the pulmonary effects of wood smoke in guinea pigs by repeated CO2 challenges.

Male, English smooth haired guinea pigs were exposed to thermal decomposition products, i.e., smoke, generated by heating Douglas fir in an open system. Various amounts of Douglas fir were placed in a furnace, at room temperature, and heated at a rate of 11 degrees C/min until completely decomposed. Major decomposition occurred between 160 and 490 degrees C, and the animals were exposed during this time for a period of 30 min. Immediately before exposure and at various times after exposure, each animal was evaluated by whole-body plethysmography to measure tidal volume and respiratory frequency during air breathing as well as during challenge with 10% CO2. Exposure to smoke from Douglas fir resulted in a diminished ventilatory response to 10% CO2. Comparing the effect of wood smoke to the effect of smoke from polyvinylchloride from previous experiments wood smoke was found to be 10 times less potent than smoke from polyvinylchloride and animals recovered much more rapidly than with smoke from polyvinylchloride.

Animals↗
PubMed1984

Induction of formaldehyde sensitivity in guinea pigs.

Occupational exposure to formaldehyde (HCHO) has been implicated in development of both dermal hypersensitivity and pulmonary hypersensitivity. The purpose of this study was to assess the route of exposure most likely to cause sensitization in animals and the potency of formaldehyde as a sensitizing chemical. Three routes of exposure were utilized: inhalation, dermal, and injection (with Freund's complete adjuvant). For inhalation exposure, groups were exposed to 6 ppm (Group I) or 10 ppm HCHO (Group II) for 6 hr/day or 8 hr/day (Group III) on 5 consecutive days. Animals were evaluated for skin sensitivity, production of anti-HCHO antibody, and respiratory sensitivity (both immediate- and delayed-onset) to HCHO. Of the animals receiving inhalation exposure, two of four animals in Group III displayed dermal sensitivity. No antibodies or pulmonary sensitivity were detected in any animals in any of these groups. Animals exposed to HCHO by injection displayed extensive dermal reactions when skin tested. In addition, two of four animals in this group developed antibodies to HCHO in low titer. No pulmonary sensitivity was detected. Animals exposed to HCHO by dermal contact developed neither pulmonary sensitivity nor antibodies to HCHO. However, all of these animals developed skin sensitivity. The severity of the contact sensitivity response, as well as the percentage of animals sensitized, increased with exposure dose. These results indicated that HCHO was a skin sensitizer in the guinea pig without causing detectable respiratory hypersensitivity.

Administration, Topical↗
PubMed1984

Evaluation of concentration-response relationships for histamine and sulfuric acid aerosols in unanesthetized guinea pigs for their effects on ventilatory response to CO2.

Through the addition of aerosols to 10% CO2 mixtures, acute respiratory responses can be detected in unanesthetized guinea pigs. This conclusion was supported by results from a previous study conducted in our laboratory in which animals were exposed to nebulized histamine or sulfuric acid while placed in a whole-body plethysmograph. In that study, only one concentration of each agent was examined. The present data were collected over a wider range of histamine and sulfuric acid exposure concentrations and the results served to reinforce the previous conclusion regarding the ease in detecting acute responses with this approach. Again, inspiratory volume (VI) and pressure changes (delta P), proportional to inspired volume, were measured continously and significant decreases in these parameters occurred during aerosol challenges. In addition, respiratory frequency (f) was evaluated during all exposures but few changes in frequency were observed other than the increases induced by 10% CO2 alone. Measurements of VI and delta P indicated similar levels of response to the tested aerosols, except during intense bronchoconstriction evoked by higher concentrations of histamine. In such constricted states, VI was a more sensitive indicator. Concentration-response relationships for histamine and sulfuric acid using VI measurements were comparable to those of other investigators who measured airflow resistance. Therefore, the new method offers many advantages over previous methods through its noninvasive and simple features yet there is comparable sensitivity to detect acute responses, as demonstrated by this study.

Aerosols↗
PubMed1984

An aerosol generator for the resuspension of cotton dust.

An aerosol generator, the Pitt 3 model, was designed, fabricated, and characterized for the resuspension of inhalable particles from bulk cotton dust. The generator was constructed around a loudspeaker whose energy is transferred into an air column through latex rubber dams. This action tumbles the bulk dust, and small particles are loosened which can then be carried out of the column with the air passing through it. Thirty to forty grams of bulk cotton dust produced a stable aerosol concentration for at least 90 min. The maximum output of about 100 mg/m3 can be reduced to lower concentrations by adding dilution air. In one application, the generator produced a stable aerosol cloud in the range of 2 to 30 mg/m3 with a mass median aerodynamic diameter (MMAD) of about 3 microns and a geometric standard deviation (sigma g) of about 1.5. In another application the concentration in an animal exposure chamber was kept at 20.8 mg/m3 with an MMAD = 2.5 microns and a sigma g = 1.8 for over 6 months. The Pitt 3 generator proved to be trouble-free and produced large amounts of inhalable particles from bulk cotton dust. The generator was also used to generate dust clouds from silica powder, fly ash, and cellulose dust. The only requirement for successful resuspension of any dust with this generator is the presence of small particles in the bulk feed dust.

Aerosols↗
PubMed1983

A method to rapidly evaluate the acute pulmonary effects of aerosols in unanesthetized guinea pigs.

A method was developed to rapidly evaluate the acute effects of aerosols on the respiratory tract in unanesthetized but slightly restrained guinea pigs. Each animal was placed in a whole body plethysmograph and was fitted with a head chamber. From the head chamber, inspiratory volume (VI) was measured by integration with time of airflow rate obtained via a pneumotachograph. From the whole body plethysmograph a pressure (delta P) proportional to inspiratory volume was measured. Both VI and delta P were measured while the animal breathed a mixture of 10% CO2, 18% O2, and 72% N2. This procedure resulted in a stable and sustained increase in both VI and delta P. With the animals still breathing 10% CO2, the aerosols to be tested were then introduced. Both sulfuric acid and histamine aerosols produced a significant decrease in VI and delta P. The method is simple and does not necessitate anesthesia or invasive techniques. It should be useful to rapidly evaluate the possible acute effects of airborne contaminants. Furthermore, measurement of delta P alone with the animal in the whole body plethysmograph, obviating the need for the head chamber and the restraint imposed by it, was found to indicate an effect similar to the measurement of VI. This step further simplifies the method to evaluate an acute effect of aerosols on the respiratory tract.

Aerosols↗