Biomedical subjects

P I Feder

Publications and source records attributed to P I Feder.

5 recordsLinked to original sources

PubMed1992

Relative bioavailability of lead from mining waste soil in rats.

The purposes of this study were to determine the extent of absorption of lead (Pb) in mining waste soil from Butte, Montana, and to investigate the effect of mining waste soil dose (g soil/day) on tissue lead concentrations. Young, 7- to 8-week-old male and female Sprague-Dawley rats (5/sex/group) were given mining waste soil that contained 810 or 3908 ppm lead mixed in a purified diet (AIN-76) at four different dose levels (0.2, 0.5, 2, and 5% dietary soil) for 30 consecutive days. Standard groups included untreated controls and dosed feed soluble lead acetate groups (1, 10, 25, 100, and 250 micrograms Pb/g feed). The test soil dose levels bracketed a pica child's soil exposure level and the lead acetate concentrations bracketed the test soil dose levels of lead. Liver, blood, and femur were analyzed for total lead concentration using graphite furnace atomic absorption spectroscopy. Clinical signs, body weight, food consumption, and liver weights for test soil and standard groups were similar to control. Tissue lead concentrations from test soil animals were significantly lower than the tissue concentrations for the lead acetate group. Relative percentage bioavailability values, based on lead acetate as the standard, were independent of the two different test soils, dose levels, and sex and were only slightly dependent on the tissue (blood > bone, liver). Mean relative percentage bioavailability values of lead in the Butte mining waste soil were 20% based on the blood data, 9% based on the bone data, and 8% based on the liver data. The results of this study will provide the information needed to determine the significance of lead exposure from Butte soils in assessing human health risks as part of the Superfund Remedial Investigation/Feasibility Study process.

Animals↗

PubMed1991

Evaluation of compounds as barriers to dermal penetration of organophosphates using acetylcholinesterase inhibition.

An efficient, objective method for evaluating the efficacy of barrier compounds in preventing dermal penetration of organophosphates (OP) in rabbits was developed using time-dependent reduction in erythrocyte (RBC) acetylcholinesterase (AChE) activity as an endpoint. Anesthetized rabbits, with or without a dermal application of a mixture of high- and low-molecular-weight polyethylene glycols (mean molecular weight of 540 daltons; PEG 540), were exposed to different percutaneous doses of 3 highly toxic OP compounds. Dose-response curves were generated for RBC AChE inhibition as a function of percutaneous dose for each OP test material over time. From data generated, a single dose of each OP was selected to challenge PEG-540-protected and unprotected animals to validate the method as a means of differentiating effective from ineffective barriers to skin penetration. Data for a complete evaluation of a PEG 540 test barrier application were obtained within 4 h and anesthesia was maintained for the entire period.

Acetylcholinesterase↗

PubMed1991

Stagewise, adaptive dose allocation for quantal response dose-response studies.

A principal design objective of many dose-response studies is to estimate extreme percentiles of a dose-response distribution, e.g., the ED95 dose for a particular drug therapy, as precisely as feasible using the smallest number of experimental subjects possible. Such a design requirement necessitates that allocation of subjects to drug doses be carried out in a stagewise fashion to maximize the information obtained from each subsequent experimental observation in light of what has previously been determined. This paper describes and illustrates specialized methods and associated computer programs to evaluate, on a stagewise basis, the anticipated relative sensitivities of alternative experimental plans in the case of dichotomous responses. Following each stage of experimentation, the current estimates of the dose-response distribution parameters, as well as the uncertainties in these estimates, are updated and are used to assign subjects to experimental dose levels for the next stage of testing. Competing dose allocations are compared with respect to anticipated improvement in estimation precision. The adoption of such a stagewise dose allocation strategy is illustrated by example.

Animals↗

PubMed1991

Stagewise, group sequential experimental designs for quantal responses. one-sample and two-sample comparisons.

The use of stagewise, group sequential experimental designs with dichotomous responses in toxicity or drug screening programs is discussed. Such designs represent a compromise between the standard, fixed sample size designs and fully sequential designs. Stagewise group sequential designs place specified numbers of animals on test at each stage, up to a maximum number of stages. The greatest increases in sample size efficiency occur with small numbers of stages, particularly when going from one stage to two. Two-stage designs can result in a 15 to 20 percent reduction in average sample size. Five-stage designs can result in a 30 to 40 percent reduction in average sample size, with no appreciable decrease in Type 1 error or power. Examples of the efficiencies that arose in actual screening programs are given. This paper demonstrates that the routine use of stagewise, group sequential designs in standardized screening protocols can result in substantial savings in animal use with virtually no sacrifice of statistical sensitivity.

Animals↗

PubMed1986

Development, evaluation and use of a pharmacokinetic model for hexachlorobenzene.

This study discusses the background, biological basis, development characteristics, application and evaluation of six physiologically based multicompartment models that describe the absorption, distribution and elimination of hexachlorobenzene (HCB) in growing rats and growing humans. The models for rats and for humans have similar structures but differ in specific physiological parameters. The goal of the modelling effort was to obtain toxicological information about HCB based on its pharmacokinetics. Comparisons were made between estimated tissue concentrations based on the rat models and observed tissue distributions based on pharmacokinetic animal studies with HCB, using both chronic and single-dose studies. The estimates from the female model agreed reasonably well with experimental results, and estimated a long half-life of approximately 180 days in all tissues; it did not, however, duplicate the biphasic tissue efflux of HCB that has been reported in the literature. The male model estimated a half-life of approximately 55 days in all tissues, shorter than that observed experimentally. The estimated yield of metabolites agreed well with values reported in the literature. A pregnancy and offspring model predicted minimal transfer of HCB to the fetal compartment during gestation and extensive mobilization of HCB to the offspring during lactation. This agrees with results reported in the literature. Correlations were obtained between experimentally observed liver toxicity and estimated yield of metabolites; between experimentally observed effects on the central nervous system and estimated HCB concentrations in the brain; and between experimentally observed offspring mortality and estimated extent of lactational HCB transfer. This paper also discusses the effects on tissue concentrations and half-lives of trapping HCB in the intestines by sequestering a large portion of it there. Various characteristics of the human models are discussed. The female model has a biphasic elimination pattern, the second elimination phase having a half-life of greater than 200 days. The pregnancy and offspring model projects extensive transfer of HCB via the milk to the nursing offspring, which correlates with the greater mortality of nursing infants whose mothers were exposed to HCB in Turkey.

Animals↗