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L R Pohl

Publications and source records attributed to L R Pohl.

At least 91 records · Page 5Linked to original sources
PubMed1980

Differing degrees of coal-tar shampoo-induced mutagenesis in the Salmonella/liver test system in vitro.

Hexane extracts of four commercial preparations of coal tar shampoos were studied for their mutagenic properties in the Salmonella/liver test system in vitro. Three of the four shampoos were highly mutagenic, whereas the fourth was not - under our experimental conditions. By high-performance liquid chromatographic, gas-liquid chromatographic, and gas-liquid chromatography-mass spectrometric analyses, more than 35 distinct fractions could be resolved; seven polycyclic aromatic chemicals believed to be present in coal tar were tentatively assigned as the major component of some of these fractions. The shampoo extract that was most mutagenic had a greater number of distinct fractions and contained approximately 50 times more benzo[a]pyrene, compared with the one shampoo extract that was not mutagenic under our experimental conditions. The possible clinical hazards of this observed mutagenicity of certain coal tar shampoos are presently not known.

Animals↗
PubMed1980

Comparison of the biotransformation and hepatotoxicity of halothane and deuterated halothane.

To investigate the effect of deuterium substitution on the biotransformation and hepatotoxicity of halothane, male, phenobarbital-pretreated rats were exposed for 2 hr to 1% halothane or deuterated halothane (d-halothane) delivered in 14% O2-85% N2. The exposures were performed at mildly hypoxic conditions (14% O2) since it was previously established that the decreased oxygen tension promotes both the reductive metabolism of halothane and halothane-induced liver injury. At the end of anesthesia or at 24 hr, the rats were sarificed so that blood, liver and urine samples could be obtained for measurement of metabolites and assessment of liver damage. Deuterium substitution did not affect the levels of reductive metabolites of halothane (fluoride, CF3CH2Cl and CF2CHCl) nor did it alter the degree of hepatotoxicity as assessed by serum glutamic-pyruvic transaminase levels and morphological examination. The levels of oxidative metabolites (CF3COOH and bromide) were significantly reduced at the end of anesthesia and at 24 hr. It is concluded that halothane-induced hepatotoxicity is initiated by reactive intermediates formed during its reductive metabolism and that cleavage of the C-H bond is not involved in this pathway. The oxidative biotransformation of halothane proceeds by an oxygen insertion reaction at the C-H bond. Thus, the increased stability of the C-D bond explains the reduction in oxidative metabolities observed after exposure to d-halothane.

Animals↗
PubMed1980

Bioactivation and covalent binding of halothane in vitro: studies with [3H]- and [14C]halothane.

To determine if the hydrogen atom of halothane (CF3CHBrCl) is retained on the reactive intermediates that covalently bind to microsomal lipids and protein, [3H]halothane and [14C]halothane were incubated with rat hepatic microsomes and a NADPH generating system. Both [3H]- and [14C]halothane were bioactivated and bound to a greater degree when incubations were performed in a N2 atmosphere rather than an O2 atmosphere. Binding of [3H]- and [14C]halothane equivalents was significanty enhanced when heaptic microsomes from phenobarbital- or Aroclor 1254-treated rats were used in the incubations. Omission of NADPH or incubation with CO was inhibitory to the binding of both [3H]- and [14C]halothane. The apparent kinetic constants for binding or halothane equivalents, Km and Vmax, indicate a significantly higher Km but lower Vmax for the formation and/or binding of 3H-binding equivalents. The results indicate tht halothane is primarily bioactivated under conditions that promote its reductive metabolism and that this reactive metabolism does not involve cleavage of the carbon-hydrogen bond of halothane. Differences in binding under N2 and O2 as well as between [3H]- and [14C]halothane suggest that multiple reactive intermediates may form during the biotransformation of halothane.

Animals↗
PubMed1977

A prospective on covalent binding and toxicity.

In this paper are discussed (1) the three general mechanisms by which radioisotopes may be retained in animal tissues long after labeled drugs are administered, (2) ways of differentiating these mechanisms, and (3) possible relationships between the toxic effects of drugs and their metabolism. It is emphasized, however, that studies on the disposition of drugs should be coordinated with toxicity studies in order to make the results of bioavailability and pharmacokinetic studies more meaningful in setting limits for food residues.

Animals↗