Search PubMed⌕ Search

Biomedical subjects

H B Matthews

Publications and source records attributed to H B Matthews.

At least 91 records · Page 5Linked to original sources
PubMed1981

Comparative study of 3,4,3',4'-tetrachlorobiphenyl in male and female rats and female monkeys.

3,4,3',4'-Tetrachlorobiphenyl (TCB) is thought to be the most toxic chlorinated biphenyl present in commercial polychlorinated biphenyl (PCB) formulations. A comparative study of the distribution and excretion of TCB has been done in made and female rats and female rhesus monkeys in an effort to account for the toxicity of this PCB. The distribution and clearance of TCB were similar in male and female rats, and although TCB was cleared more slowly by monkeys than by rats, the monkeys were able to clear it at an appreciable rate so that tissue levels were negligible 6 wk after TCB administration. The results indicate that the toxicity of TCB cannot be attributed to inability of the animals to metabolize and excrete it or to its persistence in any tissue, with the possible exception of blood. TCB and/or TCB metabolites appear to be more persistent in blood than any PCB studied to date.

Animals↗
PubMed1979

Pharmacokinetics of halogenated hydrocarbons.

Pharmacokinetic modeling is being applied to chemicals posing health hazards because of their presence as contaminants in our environment. This paper presents a rationale for constructing mathematical models based on anatomic and physiological principles. Pharmacokinetic investigations incorporating such models are illustrated for two halogenated hydrocarbons that exhibit different patterns of disposition in the rat: 2,2',4,4',5,5'-hexachlorobiphenyl and Kepone. The models permit interspecies comparison and prediction of normal pharmacokinetic behavior and alterations induced by intervention measures. As an example a theoretical limit is predicted in the case of a treatment for Kepone poisoning involving oral administration of adsorbents.

Animals↗
PubMed1979

In vivo binding of 2,3,6,2',3',6'-hexachlorobiphenyl and 2,4,5,2',4',5'-hexachlorobiphenyl to mouse liver macromolecules.

The role of metabolic activation in the binding of polychlorinated biphenyls (PCBs) to cellular macromolecules was investigated in vivo by comparing the relative binding of 2,4,5,2',4',5'-[U-14C]hexachlorobiphenyl (2,4,5), a slowly metabolized PCB, with that of 2,3,6,2',3',6'[U-14C]hexachlorobiphenyl (2,3,6), a rapidly metabolized PCB, and the appropriate controls. Each hexachlorobiphenyl was administered to mice, orally for 5 days (7.28 mg/kg/day). Following the dosing schedule, animals were killed at 1, 5 and 8 days. The concentration of each PCB was determined in liver, muscle and kidney and in purified macromolecules isolated from those tissues. The concentration of 2,4,5 was consistently higher than the concentration of 2,3,6 in all tissues studied. However, the amount of 2,3,6 bound to the purified macromolecules was consistently at least one order of magnitude greater than that of 2,4,5. The greatest binding was observed in RNA followed by protein and DNA, respectively. The purity of the macromolecules and the presence of PCB-derived radioactivity at the monomer level were confirmed. This is the first report of 14C-labeled PCB being bound to purified RNA, DNA, and proteins isolated from the tissues of animals treated in vivo. The binding is thought to be covalent and to be the result of metabolic activation.

Animals↗
PubMed1977

The construction of a pharmacokinetic model for the disposition of polychlorinated biphenyls in the rat.

The construction of a preliminary pharmacokinetic model for the distribution, long-term storage sites, excretion, and metabolism of selected polychlorinated biphenyls (PCBs) in the rat is described. Following intravenous administration of radioactive PCBs, several metaboiltes of each PCB isomer were detected in urine or feces, excreted primarily as glucuronide conjugates. The relative and absolute amount of metabolites excreted depended upon the degree of chlorination and the position of the chlorine on the biphenyl molecule. Concerning long-term storage sties, an unanticipated finding was accumulation in skin, as revealed by the particularly long half-life of the 6-CB isomer in skin. A flow diagram of the model is presented, as are the differential equations, solved by computer for a given dose schedule, for the individual mass balances on parent and metabolite in each of the compartments that represent the organs or regions in which the concentration is assumed to be uniform. Low-level, long-term doses of PCBs produce a variety of toxicologic symptoms which appear only after long-time exposure. Such models should be useful in explaining and predicting the toxicities induced by exposure to PCBs and similar contaminants and the time required to reach a steady-state tissue concentration for given long-term doses.

Animals↗