摘要:

Short-term exposure of rats to ozone results in lung inflammation characterized by increased permeability damage and the infiltration of neutrophils into the airways. The present study compared these ozone-induced inflammatory responses in different strains of male rat, Brown Norway rats from Charles River Laboratories, Inc. (BN-CRL), and Harlan Sprague Dawley, Inc. (BN-HSD), and Fischer 344 (F344), Sprague-Dawley (SPD), and Wistar (WSTR) male rats from Hilltop Lab Animals, Inc. Ozone-induced permeability damage was indicated by recoveries of bronchoalveolar lavage fluid (BALF) albumin 20 h following single exposures of 6 h to either air or 1 ppm or 2 ppm O3. Although BALF albumin recoveries from air-exposed rats were not significantly different between strains, ozone exposures resulted in a range of enhancements of BALF albumin of 2-, 9-, 17-, 7-, and 20-fold following exposures of BN-CRL, BN-HSD, F344, SPD, and WSTR rats to 2 ppm ozone, respectively. Concomitant strain differences in the number of ozone-induced BAL-recoverable neutrophils were not observed, except for BN-CRL rats, which demonstrated significantly lower numbers. However, the degree of ozoneinduced permeability damage did directly correspond to differences observed in the numbers of neutrophils and eosinophils in the peripheral blood and collagenase tissue digest of lavaged and perfused lungs prior to ozone exposure. Ozone-resistant BN-CRL rats exhibited the highest numbers of blood and lung tissue neutrophils and eosinophils when compared with ozone-susceptible WSTR rats exhibiting the lowest number of these granulocytes. These data suggested that the presence of high numbers of blood and tissue granulocytes at the onset of short-term ozone exposures might provide a certain degree of protection against subsequent pathological events.

ISSN:1528-7394    

DOI:10.1080/00984100050082076

出版商:Informa UK Ltd    

年代:2000

数据来源: Taylor

摘要:

No study has comprehensively compared the rate of metabolism of carbon tetrachloride (CCl4) across species. Therefore, the in vivo metabolism of CCl4was evaluated using groups of male animals (F344 rats, B6C3F1mice, and Syrian hamsters) exposed to 40-1800 ppm CCl4in a closed, recirculating gas-uptake system. For each species, an optimal fit of the family of uptake curves was obtained by adjusting Michaelis-Menten metabolic constants Km(affinity) and Vmax(capacity) using a physiologically based pharmacokinetic (PBPK) model. The results show that the mouse has a slightly higher capacity and lower affinity for metabolizing CCl4compared to the rat, while the hamster has a higher capacity and lower affinity than either rat or mouse. A comparison of the Vmaxto Kmratio, normalized for milligrams of liver protein (L/ h/ mg) across species, indicates that hamsters metabolize more CCl4than either rats or mice, and should be more susceptible to CCl4-induced hepatotoxicity. These species comparisons were evaluated against toxicokinetic studies conducted in animals exposed by nose-only inhalation to 20 ppm 14C-labeled CCl4for 4 h. The toxicokinetic study results are consistent with the in vivo rates of metabolism, with rats eliminating less radioactivity associated with metabolism ( 14CO2and urine/ feces) and more radioactivity associated with the parent compound (radioactivity trapped on charcoal) compared to either hamsters or mice. The in vivo metabolic constants determined here, together with in vitro constants determined using rat, mouse, hamster, and human liver microsomes, were used to estimate human in vivo metabolic rates of 1.49 mg/ h/ kg body weight and 0.25 mg/ L for Vmaxand Km, respectively. Normalizing the rate of metabolism ( Vma/ Km) by milligrams liver protein, the rate of metabolism of CCl4differs across species, withxhamster > mouse > rat > human.

ISSN:1528-7394    

DOI:10.1080/00984100050082085

出版商:Informa UK Ltd    

年代:2000

数据来源: Taylor

摘要:

The influence of elevated dietary zinc and/or selenium on the suppressive effect of cadmium on egg production in hens has not been previously established. To address this question, two models of cadmium administration were used to differentiate protective effects of zinc or selenium that may result from a reduced absorption of cadmium from those resulting from an elevated nutritional status of these minerals. First, cadmium-induced suppression of egg production was produced in White Leghorn hens using intraperitoneal injections of Cd in order to determine protective effects that result from prefeeding diets supplemented with 803 ppm Zn, 0.91 ppm Se, or their combination relative to a basal diet (control). Feeding elevated dietary selenium throughout the experiment, including a 6-day prefeeding period before Cd administration, resulted in significant protection from the egg suppression produced by 2 injections of cadmium (0.27 mg/ kg each) given 1 d apart. Feeding elevated dietary zinc alone or combined with +0.91 ppm Se for a similar period did not markedly protect against cadmium-induced egg suppression. After a 0.54- mg/ kg dose of Cd was administered, for a cumulative dose of 1.08 mg/ kg, no significant protection was observed from any of the supplemented diets. In a second experiment, the protective effect of the same dietary treatments on the egg-suppressive effect of dietary cadmium was determined. In contrast to cadmium injection, the suppressive effect of 153 ppm dietary cadmium was not mitigated by selenium supplementation, while supplemental zinc protected against this effect of dietary cadmium regardless of the amount of selenium in the diet. There was no significant change in plasma estrogen and vitellogenin levels as a result of cadmium administration in either model, with the exception of significant reduction in both these parameters in the dietary cadmium-exposed birds fed the basal diet. Together, the data suggest that the level of dietary zinc in food sources may be more important in influencing cadmium-induced egg suppression than the nutritional status of zinc in cadmium-exposed birds. In contrast, the nutritional status of selenium in cadmiumexposed birds may have the potential to mitigate this effect, but high exposures to dietary cadmium or zinc may preclude such protection.

ISSN:1528-7394    

DOI:10.1080/00984100050082094

出版商:Informa UK Ltd    

年代:2000

数据来源: Taylor

摘要:

Cyanazine is a member of the chloro-s-triazine class of herbicides. Other triazine herbicides have been shown to induce mammary-gland tumors in rats, although the response is unique to the Sprague-Dawley strain. Cyanazine is nongenotoxic. The present study was conducted to evaluate the chronic toxicity and oncogenic potential of cyanazine. Groups of 62 male and female rats were fed diets containing cyanazine at concentrations of 1, 5, 25, or 50 ppm for up to 2 yr. Mean body weight and body weight gain of male and female rats of the 25- and 50-ppm groups were significantly reduced over the course of the study. Food consumption and food efficiency were also reduced in these groups. Survival was not adversely affected in the treatment groups compared to controls. A significant increase in the incidence of masses of the inguinal region was noted among female rats of the 50-ppm group. These masses were correlated with a significant increase in the incidence of female rats with mammary-gland adenocarcinomas and carcinosarcomas. The incidence of rats with malignant mammary-gland tumors was elevated in the 5-, 25-, and 50-ppm groups, although the incidence within the 5-ppm group was within historical controls. There were no other toxicologically significant observations with respect to ophthalmological, clinical laboratory, or pathological evaluations. Under the conditions of this study, the no-observed-adverse-effect level was 5 ppm. Research into the mechanism of action suggests these mammary tumors are mediated through a prolactin mechanism that is thought to be of low relevance to humans.

ISSN:1528-7394    

DOI:10.1080/00984100050082102

出版商:Informa UK Ltd    

年代:2000

数据来源: Taylor