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Biomedical subjects

O R Moss

Publications and source records attributed to O R Moss.

32 records · Page 2Linked to original sources
PubMed1994

DNA-protein cross-links and cell replication at specific sites in the nose of F344 rats exposed subchronically to formaldehyde.

Chronic exposures to high concentrations (> or = 6 ppm) of formaldehyde (HCHO) induce cell proliferation, squamous metaplasia, and squamous cell carcinomas in F344 rats. To assess the cancer risk associated with HCHO exposure, DNA-protein cross-links (DPX) formed in a single exposure of naive (previously unexposed) rats and monkeys have been used as a surrogate for the internal dose. Since the quantity of DPX may differ in subchronically exposed animals, the effects of preexposure to HCHO on the acute DPX yield (concentration of DPX following a single exposure) and the cumulative DPX yield (concentration of DPX following repeated exposures) were determined. Male F344 rats were preexposed (PE) to 0.7, 2, 6, or 15 ppm of HCHO (6 hr/day, 5 days/week, 11 weeks + 4 days). Naive (N) rats were exposed to room air. On the 5th day of the 12th week, PE and N rats were simultaneously exposed (3 hr) to H14CHO at the same concentrations used for preexposure. Acute DPX yields and cell replication (incorporation of 14C into DNA) were determined in the mucosal lining of the nasal lateral meatus (LM) (high tumor site in HCHO bioassay) and the medial and posterior meatuses (M:PM) (low tumor site in bioassay). DPX yields in the LM were approximately sixfold higher than in the M:PM. At 0.7 and 2 ppm, no differences between PE and N rats were detected in either tissue. At 6 and 15 ppm, acute DPX yields in the LM of PE rats were approximately half those of N rats, but no differences were detected in the M:PM. Cell proliferation was induced in PE rats at 6 ppm (LM only) and especially at 15 ppm (LM and M:PM). Cumulative DPX yields were measured indirectly by determining the decrease in extractability of DNA from proteins. PE rats were preexposed to 6 or 10 ppm as above, while N rats were exposed to room air. Both groups (PE and N) were then exposed (3 hr) to the same concentration of unlabeled HCHO. DPX yields increased in a concentration-dependent manner in both groups, but the yields were smaller in PE than N rats, suggesting that no accumulation of DPX occurred in PE rats. The results demonstrate that at concentrations < or = 2 ppm, N and PE rats are equivalent with respect to the formation of DPX.(ABSTRACT TRUNCATED AT 400 WORDS)

Administration, Inhalation↗
PubMed1994

Pharmacokinetics of inhaled [14C]methanol and methanol-derived [14C]formate in normal and folate-deficient cynomolgus monkeys.

Large-scale use of methanol (MeOH) as an automotive fuel may increase exposure of the public to MeOH vapor, necessitating the need for additional data for an adequate human health risk assessment. Formate is accepted as the toxic metabolite of MeOH, its metabolism is folate-dependent, and potentially sensitive folate-deficient subpopulations (e.g., pregnant women) exist that may be at higher risk to low-level methanol exposure. This study determined the pharmacokinetics of [14C]MeOH and [14C]formate in normal and folate-deficient (FD) monkeys following inhalation of environmentally relevant concentrations of [14C]MeOH. Four normal adult female cynomolgus monkeys were anesthetized (isoflurane) and exposed by lung-only inhalation to 10, 45, 200, and 900 ppm [14C]MeOH for 2 hr. Monkeys were then placed on a FD diet until folate concentrations consistent with moderate deficiency (29-107 ng/ml) developed in red blood cells and then reexposed to 900 ppm (900-FD) for 2 hr. Average (+/- SD) end-of-exposure blood [14C]MeOH concentrations were 0.65 +/- 0.3, 3.0 +/- 0.8, 21 +/- 16, 106 +/- 84, and 211 +/- 71 microM, while average (+/- SD) peak blood [14C]formate concentrations were 0.07 +/- 0.02, 0.25 +/- 0.09, 2.3 +/- 2.9, 2.8 +/- 1.7, and 9.5 +/- 4.7 microM following MeOH inhalation at 10, 45, 200, 900, and 900-FD ppm, respectively. The blood concentration of [14C]MeOH-derived formate from all exposures was 10 to 1000 times lower than the endogenous blood formate concentration (0.1 to 0.2 mM) reported for monkeys. These results suggest that low-level exposure to MeOH would not result in elevated blood formate concentrations in humans under short-term exposure conditions.

Administration, Inhalation↗
PubMed1986

Toxicity of formaldehyde vapor in B6C3F1 mice exposed for 13 weeks.

Groups of 10 male and 10 female B6C3F1 mice were exposed to 0, 2, 4, 10, 20, or 40 ppm of formaldehyde vapor 6 h/day, 5 days/week for 13 weeks. Clinical abnormalities (dyspnea, listlessness, and hunched posture), significant mortality, and body weight loss were observed in the 40 ppm groups. Pathologic changes were observed in the nose, larynx, trachea, and bronchi of treated males and females and in the uterus and ovaries of treated females. Squamous metaplasia and inflammation were present in the nasal tissues of male and female mice in the 10, 20, and 40 ppm groups and in the larynx of males and females in the 20 and 40 ppm groups. The trachea had squamous metaplasia and hyperplasia of the epithelium in addition to submucosal fibrosis and inflammation in the 20 and 40 ppm groups. In some mice, epithelial-lined, irregular connective tissue bands spanned the tracheal lumen. Metaplasia of the bronchial epithelium was confined to the 40 ppm exposure groups. These effects on the respiratory system were more prevalent in male than in female mice. Hypoplasia of the uterus and ovaries, probably secondary to body weight loss, was confined to the 40 ppm exposure group. In conclusion, 13-week inhalation exposures of B6C3F1 mice to 10, 20, and 40 ppm of formaldehyde vapor induced histologic lesions in the upper respiratory system and concentrations of 40 ppm were lethal to those mice.

Animals↗
PubMed1982

Controlled-delivery vapor generator for animal exposures.

A vapor generation system is described which provides long-term stable vapor concentrations for inhalation bioassay tests with laboratory animals. Liquid is pumped from a reservoir by a micrometering pump to the surface of a cylindrical vaporizer covered with a glass fiber wick. An 80-watt heater and temperature sensor, embedded in the cylinder, control the vaporizer temperature. Pump rates of 0.01 to 20 mL/min and surface temperatures greater than 100 degrees C can be achieved. To minimize condensation on delivery-tube walls, the vaporizer is positioned in the dilution air inlet tube leading directly into the 2-m3 exposure chamber. During exposure of rats, mice and rabbits to eleven different chemicals for periods ranging from 4 hours to over 400 daily 6-hour exposure periods, concentrations from 25 to 10,000 ppm were achieved with a dilution air flow of 280 L/min. Chamber concentrations were routinely maintained within 10% of target levels. Stable pump rates provide a method of calculating vapor concentration independent of chemical analysis. Long-term generation stability and ease of operation reduce labor requirements compared to previous generation techniques.

Animals↗
PubMed1981

An inhalation exposure chamber designed for animal handling.

A whole-body inhalation exposure chamber was designed and constructed that provided for uniform distribution of aerosols within the chamber and facilitated animal care. Animals were permanently housed in the chamber while on experiment. The entire chamber (including cage units) was sanitized in our cagewashing unit. Animals and their feed were easily observed since cages were mounted in pull-out drawers. The chamber accommodated 360 mice, 196 rats (depending on size), 312 hamsters, 60 guinea pigs, or 30 rabbits (the latter for exposure only). A special feature of the design was that cages and their associated excreta pans were equally spaced from chamber walls and arranged in vertical columns which were offset. This arrangement prevented excreta from dropping on animals in lower tiers.

Animals↗
PubMed1979

Comparison of the aerodynamic size distribution of chain-like aggregates measured with a cascade impactor and a spiral centrifuge.

Several authors have suggested that chain-like aggregates fragment in the jets of cascade impactors and that the impactor consequently underestimates the median aerodynamic diameter and overestimates the geometric standard deviation (GSD). The aerodynamic size distribution of (Pu0.14U0.86)02.2 aggregates were measured simultaneously with two Mercer cascade impactors and a LAPS spiral centrifuge to investigate this problem. Although the median aerodynamic diameters were generally in good agreement, the impactor consistently measured higher values for the GSD than did the spiral centrifuge. Based on experiments in which losses in the centrifuge inlet were measured, it was concluded that the centrifuge had measured the aerodynamic size distribution more accurately than the impactor. Interception of chain-like aggregates on the first few impactor stages may have been the primary reason for the disparity between the impactor and centrifuge measurements.

Aerosols↗
PubMedDate not supplied

Pleural lesions in Syrian golden hamsters and Fischer-344 rats following intrapleural instillation of man-made ceramic or glass fibers.

The mesothelium is a target of the toxic and carcinogenic effects of certain natural mineral and man-made fibers. Long-term inhalation of a ceramic fiber (RCF-1) results in a high incidence of pleural mesotheliomas in Syrian golden hamsters but not in identically exposed Fischer-344 rats. The present study compared the histopathology of the early pleural response in rats and hamsters instilled with artificial fibers. Groups of Syrian golden hamsters and Fischer-344 rats were instilled with ceramic (RCF-1) or glass (MMVF-10) fibers directly into the pleural space. Each species received approximately equal numbers of long, thin fibers per g body weight. Fiber-induced lesions were compared 7 and 28 days postinstillation. Both hamsters and rats developed qualitatively similar dose-dependent inflammatory lesions that were not fiber-type specific. Both species developed fibrosis in conjunction with inflammation in the visceral pleura, but a striking interspecies difference was noted in the pattern of mesothelial cell response. Hamsters developed greater surface mesothelial cell proliferation and had focal aggregates of mesothelial cells embedded deep within regions of visceral pleural fibrosis. It is hypothesized from the present study that the marked fiber-induced proliferative mesothelial cell response of the hamster visceral pleura may explain the high number of pleural mesotheliomas found in long-term fiber studies in this species.

Animals↗