Biomedical subjects

B R Broxup

Publications and source records attributed to B R Broxup.

5 recordsLinked to original sources

PubMed1995

Acute and subchronic neurotoxicity studies with tri-N-butyl phosphate in adult Sprague-Dawley rats.

Male and female adult Sprague-Dawley rats received tributyl phosphate (TBP) in corn oil by gavage in acute (single-dose) and subchronic (three-month) studies. Dosage levels in the acute study were 100, 325, and 1000 mg/kg; they were 32.5, 100, and 325 mg/kg/day in the subchronic study. Behavioral evaluations were performed in both studies, and neuropathological evaluations were performed in the three-month study only. The methods used in the studies are as described in the U.S. Environmental Protection Agency neurotoxicity guidelines. Mean body weight decreases were statistically significant compared to controls for male rats at the high-dosage level only in the acute study. Transient changes only, attributable to the general toxicity of the material, were noted in forelimb grip strength and mean activity level during the first 24 hours after dosing for 1000 mg/kg rats. In the subchronic study high-dose males and females had statistically significant body weight decreases; some mortality also was observed at this dosage level. The motor activity levels and qualitative and quantitative functional observational battery measurements were comparable between treatment and control groups, and there were no gross or neurohistopathological findings in the rats indicative of treatment-related effects. Based on these study results, TBP was not neurotoxic to rats following either acute or subchronic exposures.

Animals↗

PubMed1990

Distribution of the bispyridinium oxime [14C] HI-6 in male and female rats.

Female rats poisoned with multiple LD50s of soman or tabun have been shown previously to respond to the protective effects of HI-6 more positively than male rats. This present study was designed first to determine the distribution pattern and concentration of [14C] HI-6 in rats, and secondly, to determine the possibility that HI-6 might be located in high concentrations in critical tissues in the female as opposed to the male. To these ends, [14C] HI-6 was administered to groups of male and female rats and its radiolabelled distribution determined by whole body autoradiography and/or by measurement of its actual concentration, by scintillation spectrometry. The experiments were repeated in the presence of 2 x LD50 soman and supporting therapy with atropine. In both sexes, HI-6 levels were highest in the kidney, followed in order by cartilage greater than plasma greater than liver greater than heart greater than or equal to lung greater than or equal to diaphragm greater than brain and spinal cord. The relative distribution in the two sexes was confirmed by both methods and was not significantly altered in the presence of soman and atropine. The lack of a measurable difference in tissue distribution of [14C] HI-6 derived radioactivity between males and females suggested that the hormone-dependent difference in the protective effects previously observed was not due to selective accumulation of [14C] HI-6 in organs believed to be important in its therapeutic activity, such as brain or diaphragm.

Animals↗

PubMed1990

Quantitative techniques in neuropathology.

In the future, quantitative techniques will probably be used in industry as part of Tier II studies for the evaluation of chemicals and drugs for their neurotoxic potential. Movement towards quantifying some structures or neuropathological changes will be made possible by advances in tissue preparation and computer technology. Emphasis will need to be placed on standardized techniques, good quality samples and sampling techniques in order to produce good quantitative data in a reasonable time. In this paper, different sampling techniques are evaluated using a cross section of rat sural nerve as the tissue for quantitative investigation.

Animals↗

PubMed1988

Morphometric evaluation of hepatocellular proliferative lesions in the rat liver.

Classification of rat hepatocellular proliferative lesions can vary between pathologists as the many qualitative histologic criteria have not been satisfactorily evaluated and ranked for prognostic value. Computer-assisted morphometry offers an objective method to evaluate certain cellular features. The Solt-Farber resistant hepatocyte model was used in this study to produce populations of rats with a full range of hepatocellular proliferative lesions. Cellular features within the lesions were then measured morphometrically and the data were analyzed by animal age and by subjective lesion diagnosis. The nuclear/cytoplasmic ratio followed by the cell area and nuclear area were found to be the most important parameters for separating microscopic foci and islands of cellular alteration, an early hyperplastic lesion, from other hepatocellular proliferative lesions. The coefficient of variation, as a relative measure of heterogeneity, increased in a linear manner for cell, nuclear and nucleolar areas as the animals aged and was significantly higher for cell and nuclear area in hepatocellular carcinoma compared to other hepatocellular proliferative lesions. Hepatocyte nodules (representing primarily late hyperplastic lesions) and persistent hepatocyte nodules (lesions with similarities to hepatocellular adenoma) could not be satisfactorily separated within the limits of this study. As these borderline lesions show a continuum of cytologic change, other features, such as architectural change, are necessary to satisfactorily classify them on a subjective basis. An alternative approach is to use discriminant functions derived from morphometric studies.

Animals↗

PubMedDate not supplied

Subchronic oral toxicity of tributoxyethyl phosphate in the Sprague-Dawley rat.

The effects of the widely used alkyl phosphate, tributoxyethyl phosphate (TBOP), were investigated in male and female Sprague-Dawley rats. This chemical was administered (low dose: 0.25 ml/kg X day; high dose: 0.50 ml/kg X day) by gavage once a day for 5 days/wk, over a period of 18 wk. Histopathological examination of tissues in treated male rats showed the presence of cardiac lesions, including myocardial necrosis with inflammatory cell infiltration. This study indicated that oral administration of TBOP may have caused or contributed to the early onset of a common background finding in this rat strain.

Administration, Oral↗