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N E Weber

Publications and source records attributed to N E Weber.

9 recordsLinked to original sources
PubMed1983

Metabolism and kinetics in the regulation of animal drugs.

"Criteria and Procedures for Evaluating Assays for Carcinogenic Residues," popularly known as the "Sensitivity of the Method (SOM)" proposal for the regulation of animal drugs and feed additives, employs an initial analysis to determine whether a compound must meet the requirements as a suspect carcinogen or the requirements for general food safety (GFS). Metabolism and kinetics of drug depletion play an important role in the six-step procedure that is used for either set of regulatory criteria. The only significant difference that exists between the two sets of criteria is the degree of testing required. However, the difference will usually not be manifest until positive findings of carcinogenicity in the chronic studies in laboratory animals trigger a further evaluation of the metabolism of the drug or feed additive. For both SOM and GFS, metabolic information will be used to determine the appropriateness of the test species as well as to help select a compound for residue analysis. Residue depletion kinetics in the food animals also play an integral role in the selection of species-strains for toxicity testing selection as well as in the selection of the compound for residue analysis in food. Furthermore, depletion kinetics are used to set a safe withdrawal period. The development of guidelines is discussed.

Animal Feed↗
PubMed1982

Bioavailability of bound residues.

Due to the use of radiolabeled drugs and feed additives in residue evaluation of preclearance approval of new animal drug applications (NADAs), metabolites including those which are covalently bound are detected in the edible tissues of target food animals. Isolation and characterization of these residues is often a difficult task. The approach taken is to couple safety assessment with development of the required residue information. An outline of data development is made in the context of toxicity assessment. Unless otherwise adjusted, the sponsor's method of residue analysis and drug withdrawal time reflect responsibility of all drug residues of toxicological concern found in edible tissues. The use of bioavailability studies and how they interact with safety evaluation is developed. Focus is brought to the specific problem of covalently bound residues and a framework for their assessment is presented.

Animal Feed↗
PubMed1972

Ultrastructural studies of beef heart mitochondria. 3. The inequality of gross morphological change and oxidative phosphorylation.

The relationships between membranes and intramembrane compartments of isolated heart mitochondria are inadequately defined to express the induced morphological changes associated with the structural organization. The inner membrane and matrix are the major structural entities which undergo transformation upon alteration of metabolism or incubation conditions. To better express these morphological changes within a mitochondrion, two inner membranes plus enclosed matrix are defined as an inmerix (plural inmerices). Three general morphological forms of mitochondria can be distinguished by the size and shape of inmerices. These are distended, condensed, and coalesced inmerixal configurations. Hypotonic conditions and P(i) in isotonic sucrose generate distended configurations. This P(i) distention is apparently dependent on utilization of energy. It does not occur under anaerobic conditions. Oxidizable substrates generate condensed configurations. ADP and dADP generate coalesced configurations and stop formation of condensed and distended inmerixal configurations in the absence of inhibitors. ADP coalescence is apparently not dependent on an energy input. It occurs under aerobic and anaerobic conditions, and in isotonic and hypotonic media. Atractyloside completely inhibits the effects of ADP on inmerixal membranes whereas oligomycin does not. Distention by P(i) is unaffected by the two inhibitors. Distended inmerices, without added P(i) (12 mM and 62 mM sucrose), are coalesced by ADP. These studies indicate that coalescence of inmerixal membranes probably reflects the consequences of specific stoichiometric binding or translocation of adenine nucleotides.

Adenosine Diphosphate↗
PubMedDate not supplied

Persistent residues: interface with regulatory decisions.

The use of radiolabeled drugs and feed additives in experiments designed for preclearance approval of new animal drug applications (NADAs) demonstrates the presence of metabolites, including those which are covalently bound to macromolecules and which often persist in the edible tissues of target food animals. Isolation and characterization of these residues is often a difficult task. An outline of data development is explored in the context of toxicity assessment. Unless otherwise adjusted, the sponsor's method of residue analysis and drug withdrawal time reflect the influence of all related drug residues found in edible tissues. The use of bioavailability studies and their interaction with safety evaluation is discussed.

Animals↗