Biomedical subjects

R W O'Connor

Publications and source records attributed to R W O'Connor.

15 recordsLinked to original sources

PubMed1994

Cytogenetic and germ cell effects of phosphine inhalation by rodents: II. Subacute exposures to rats and mice.

Phosphine (PH3) is a highly toxic grain fumigant to which there is significant human workplace exposure. To determine the in vivo cytogenetic effects of inhalation of PH3, male F344/N rats and B6C3F1 mice were exposed to target concentrations of 0, 1.25, 2.5, or 5 ppm PH3 for 6 hr/day for 9 days over an 11-day period. Approximately 20 hr after the termination of exposures, blood was removed from the mice and rats by cardiac puncture and the lymphocytes cultured for analyses of sister chromatid exchanges and chromosome aberrations in rats and mice, and micronuclei (MN) in cytochalasin B-induced binucleated lymphocytes from mice. In addition, bone marrow (rats) and peripheral blood (mice) smears were made for the analysis of MN in polychromatic and normochromatic erythrocytes. No significant increase in any of the cytogenetic endpoints was found at any of the concentrations examined. These results indicate that concentrations of PH3 up to 5 ppm are not genotoxic to rodents when administered by inhalation for 9 days during an 11-day period as measured by several cytogenetic assays. To evaluate the effects of PH3 on male germ cells, a dominant lethal test was conducted in male mice exposed to 5 ppm PH3 for 10 days over a 12-day period and mated to groups of untreated females (2 females/male) on each of 6 consecutive 4-day mating intervals. None of the 6 groups of females exhibited a significant increase in percent resorptions. These results indicate that exposure to 5 ppm PH3 by inhalation does not induce dominant lethality in male mouse germ cells at steps in spermatogenesis ranging from late differentiating spermatogonia/early primary spermatocytes through mature sperm.

Administration, Inhalation↗

PubMed1994

Pulmonary response of Fischer 344 rats to acute nose-only inhalation of indium trichloride.

We have previously shown that rats dosed intratracheally with indium trichloride (InCl3) develop severe lung damage and fibrosis. However, it is not clear what pulmonary effects would result following accidental occupational exposure to low concentrations of indium by inhalation. The present study uses a model of acute lung injury based on single 1-hr nose-only exposures to 0.2, 2.0, or 20 mg InCl3/m3. Exposure to 0.2 mg InCl3/m3 was capable of initiating an inflammatory response. Seven days following inhalation of 20 mg InCl3/m3 the total cell number, fibronectin, and TNF alpha levels in the bronchial alveolar lavage fluid were 8, 40, and 5 times higher than the control, respectively. Commensurate with the level of lung injury 7 days after exposure, an acute restrictive lung lesion and increased airway responsiveness to acetylcholine were observed. Forty-two days after exposure a compensatory increase in lung volume and carbon monoxide diffusing capacity in the 20 mg InCl3/m3 group suggested recovery from the lung injury. Lung collagen levels were increased in a concentration-dependent manner 42 days postexposure. These data indicate that inhalation of InCl3/m3 causes acute inflammatory changes in the lung.

Administration, Inhalation↗

PubMed1993

Styrene inhalation toxicity studies in mice. II. Sex differences in susceptibility of B6C3F1 mice.

Styrene is a commercially important chemical used in the production of plastics and resins. In initial short-term styrene inhalation studies, toxicity was significantly greater in male B6C3F1 mice than in females, suggesting that males may metabolize styrene more extensively and/or may be less able to detoxify reactive metabolites. In addition, a nonlinear dose-response was observed where toxicity and mortality were greater in mice exposed to 250 ppm than in those exposed to 500 ppm. These studies were conducted to investigate potential mechanism(s) for sex differences and the nonlinear dose-response in styrene toxicity by evaluating the effects of repeated styrene exposure on styrene oxide production, hepatic GSH availability, and hepatotoxicity in male and female B6C3F1 mice. Mice (36/sex/dose) were exposed to 0, 125, 250, or 500 ppm styrene 6 hr/day for up to 3 days. Styrene exposure caused increased mortality and hepatotoxicity (centrilobular necrosis, increased serum liver enzymes) in males and females after one or two exposures to 250 and 500 ppm. Hepatic GSH levels were decreased in a dose-dependent manner in males and females. After one exposure, GSH levels in males rebounded above controls in all dose groups. After three exposures to 125 or 250 ppm males appeared to maintain GSH levels; GSH was still decreased in the 500 ppm group. GSH levels in females were decreased after each exposure in all dose groups to lower levels than in males, and did not rebound above controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Inhalation↗

PubMed1993

Styrene inhalation toxicity studies in mice. III. Strain differences in susceptibility.

Inhalation toxicity studies were conducted to evaluate mouse strain differences in the susceptibility to styrene vapors. Male and female B6C3F1, C57BL/6, Swiss, and DBA/2 mice (8 weeks old) were exposed to 0, 125, 250, or 500 ppm styrene 6 hr/day, for 4 days (20/sex/dose). Histopathological changes and changes in liver weights were evaluated as a measure of hepatotoxicity. Styrene uptake and styrene-7,8-oxide (SO) formation were estimated by measuring levels of styrene and SO in blood. An estimate of SO detoxification by conjugation with GSH was obtained by measuring hepatic GSH depletion. In general, mortality, increased liver weights, and hepatocellular necrosis were observed in the 250 and 500 ppm dose groups for all strains and both sexes. Considerable sex and strain differences were observed. Mortality, increased liver weights, and hepatocellular necrosis were greatest in B6C3F1 and C57BL/6 mice in the 250 ppm dose group and in males; hepatotoxicity was similar in both strains. Swiss mice exhibited dose-dependent increases in mortality, liver weights, and in hepatocellular necrosis, with only slight sex differences at early time points. Hepatotoxicity in DBA/2, B6C3F1, and C57BL/6 strains was greater at 250 than 500 ppm; however, toxicity was less severe in DBA/2 than in other strains based on absence of mortality in either sex and less extensive liver necrosis at both 250 and 500 ppm. Blood styrene and SO levels did not correlate well with strain differences in toxicity.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Inhalation↗

PubMed1987

Managing data quality through automation.

Traditional definitions of data quality deal primarily with individual data sets and the data collection process. Today's standards for ensuring data quality have not changed with respect to the desired results, but have simply been expanded to take advantage of modern technology. Computers are used to acquire, review, store, analyze, and report data. Because each of these steps can be automated, the need for human intervention and manual review is minimized. As a result, the potential for invalid data to reach the data analysis stage has increased significantly. To reduce this potential, efforts must be devoted to developing automated procedures that cover every conceivable validation possibility. Relationships between data and data sets must be well defined [1], and data base support that facilitates ready access to the data for the purpose of analysis must be provided. For small data sets, automation may therefore be impractical; but for large, interrelated data sets, automation is highly desirable. Computer automation has therefore expanded the traditional concept of ensuring data quality to include a complex array of interrelated tasks that must be properly managed to achieve the desired results.

Animals↗

PubMed1987

Inhalation exposure system used for acute and repeated-dose methyl isocyanate exposures of laboratory animals.

Laboratory animals were exposed by inhalation for 2 hr/day (acute) or 6 hr/day (four consecutive days, repeated dose) to methyl isocyanate (MIC). Exposures were conducted in stainless steel and glass inhalation exposure chambers placed in stainless steel, wire mesh cages. MIC was delivered with nitrogen via stainless steel and Teflon supply lines. Chamber concentrations ranged from 0 to 60 ppm and were monitored continuously with infrared spectrophotometers to 1 ppm and at 2-hr intervals to 20 ppb with a high performance liquid chromatograph equipped with a fluorescence detector. Other operational parameters monitored on a continuous basis included chamber temperature (20-27 degrees C), relative humidity (31-64%), static (transmural) pressure (-0.3 in.), and flow (300-500 L/min). The computer-assistance system interfaced with the inhalation exposure laboratory is described in detail, including the analytical instrumentation calibration system used throughout this investigation.

Animals↗

PubMed1983

Characterization of three types of chrysotile asbestos after aerosolization.

Jeffrey Mine and Coalinga Mine chrysotile, two asbestos samples prepared for experimental research by the National Institute of Environmental Health Sciences, and the UICC B chrysotile reference sample have been characterized in the aerosolized state using gravimetric measurements, light microscopy, scanning electron microscopy, and x-ray energy spectrometry. These methods revealed (1) a greater "respirable" mass fraction in the Jeffrey and UICC B preparations compared to the Coalinga sample, (2) for fibers greater than 5 microns in length and less than 3 microns in diameter, Jeffrey Mine chrysotile contained a significantly greater fraction of fibers longer than 40 microns in length compared to the UICC B or Coalinga Mine chrysotiles, and (3) Jeffrey and UICC B chrysotile contained no fibers or fiber clusters which exceeded 2 microns in diameter while Coalinga chrysotile contained numerous fibers and fiber clusters which were greater than 2 microns in diameter. The characterization of these chrysotile preparations in the aerosolized state, in particular the Coalinga Mine chrysotile, demonstrated different fiber length and fiber width distributions when compared with previous characterizations of samples that had been dispersed in a liquid medium by ultrasonification. These observations emphasize the importance of determining size distribution of fibers in the aerosolized state for inhalation studies and the size distribution of fibers in a liquid suspension for oral ingestion, instillation, or injection studies. Because of differences in length-width distributions, each of the studied chrysotile preparations would be expected to have different patterns of deposition in the alveolar regions of the lung after an inhalation exposure.

Aerosols↗

PubMed1981

Chrysotile asbestos inhalation in rats: deposition pattern and reaction of alveolar epithelium and pulmonary macrophages.

The initial deposition and subsequent translocation of chrysotile asbestos were studied in the lungs of rats exposed for 1 h in inhalation chambers. Using scanning and transmission electron microscopy of tissue fixed by vascular perfusion, we determined that the majority of fibers that pass through the conducting airways deposits at the bifurcations of alveolar ducts. The farther an alveolar duct bifurcation was from its terminal bronchiole, the less asbestos were observed. The amount of asbestos present on the alveolar duct surfaces was significantly decreased 5 h after cessation of the 1-h exposure. Some fibers were taken up by Type I epithelial cells during the first hour of dusting, and this process continued through the 8-day period in which the animals were studied. As early as 24 h after exposure, there was an accumulation of macrophages at the sites of initial asbestos deposition. This may be a significant cellular response in the early pathogenesis of asbestosis.

Animals↗

PubMed1975