Biomedical subjects

B D Naumann

Publications and source records attributed to B D Naumann.

6 recordsLinked to original sources

PubMed1996

Performance-based exposure control limits for pharmaceutical active ingredients.

For many years pharmaceutical companies have established employee exposure limits for the active ingredients used in their products. Historically these limits were derived using traditional risk assessment methods. Because the trend in the pharmaceutical industry is to identify and develop more selective drugs of increasing potency, and because of the difficulty in identifying no-effect levels for certain drugs, a new performance-based approach for setting limits was developed. This method involves assigning materials into one of five hazard categories according to their inherent toxicological and pharmacological properties. The criteria used to assign compounds into performance-based exposure control limit (PB-ECL) categories focus on the degree to which exposure impacts human health. These assignments dictate the level of containment required to assure employee safety that is achieved through the use of engineering controls and safe handling practices. Several matrices were developed to specify general design concepts and controls for unit operations in laboratory and manufacturing operations. Containment options range from conventional handling practices for low potency (PB-ECL Category 1) materials, to technologically advanced systems that result in essentially no open handling for potent or toxic (PB-ECL Category 3) materials, to state-of-the-art facilities employing closed processes and use of robotics for extremely potent (PB-ECL Category 5) materials.

Containment of Biohazards↗

PubMed1992

Setting health-based residue limits for contaminants in pharmaceuticals and medical devices.

A procedure for determining health-based residue limits for impurities in drug substances and medical devices is described. The procedure is based upon the concept of setting residue limits that correspond to the intended usage of the drug or device, i.e., short-term use, prolonged use, and/or lifetime use. Data pertaining to chemical and physical properties, occurrence and use, biodisposition, pharmacology, toxicology, and effects in people are used. After evaluation of these data, acceptable daily intake (ADI) values are derived using a safety margin approach for short-term and prolonged exposure limits. The safety margin approach combines the use of safety factors and professional judgment. ADI values for lifetime exposure are calculated using the safety margin approach for noncarcinogens and for some carcinogens, and they are calculated using risk assessment procedures that provide ADI values corresponding to no more than a 1 in 10,000 excess lifetime cancer risk based upon maximum likelihood risk levels for other carcinogens. A weight-of-evidence test determines the use of each approach. Finally, ADI values from relevant routes and endpoints are compared and a residue limit or residue limits are estimated. The standard is expressed in terms of maximum dose per exposure period and/or dose per day and is applicable to medical products intended for short-term use, for prolonged use, and/or for lifetime use as a major clinical indications dictate.

Animals↗

PubMed1986

Measurement of particle clearance from the alveolar region of the rabbit respiratory tract.

This paper describes a method for the measurement of the clearance of inert, insoluble radioactively tagged tracer particles from the alveolar region of the rabbit respiratory tract. The technique uses a fixed detector for noninvasive, external monitoring. Validation of the method is presented, as is the clearance pattern of 3.5-micron latex particles as measured for 56 days postexposure. The clearance of latex deposited within the alveolar region can be described by two phases within this time frame, having half-times of 4.9 and 30.1 days, respectively. Clearance of latex initially deposited on the tracheobronchial tree was essentially complete by 2 days after exposure.

Animals↗

PubMed1986

Assessment of early alveolar particle clearance and macrophage function following an acute inhalation of sulfuric acid mist.

Rabbits were exposed to submicrometer sulfuric acid mist at 1 mg/m3 for 1 hr to assess effects on alveolar region clearance of a polystyrene latex tracer aerosol. Bronchopulmonary lavage was performed at selected times after exposure for functional characterization of alveolar macrophages. In vivo, clearance was accelerated in acid exposed animals relative to sham controls. Acid exposure produced no change in the viability or numbers of macrophages recovered. Although an increase in the number of polymorphonuclear leukocytes, primary neutrophils, was observed by 1 hr in both acid and sham groups, compared to nonexposed controls, levels were normal by 12 hr in shams but continued elevated in the acid group through 24 hr. Reduced in vitro macrophage adherence was observed after acid exposure. In vivo uptake of the tracer particles by macrophages was enhanced during the first 3 hr after acid exposure and in vitro phagocytosis by polymorphonuclear leukocytes was increased through 48 hr post-exposure. The results indicate some functional alterations in free cells after in vivo exposure to H2SO4 and the production of a mild inflammatory response. This latter was associated with an acceleration of inert particle clearance from the alveolar region.

Aerosols↗

PubMedDate not supplied

Physiological and histological alterations in the bronchial mucociliary clearance system of rabbits following intermittent oral or nasal inhalation of sulfuric acid mist.

Rabbits were exposed to submicometer sulfuric acid mist (H2SO4) for 1 h/d, 5 d/w for 4 wk, during which time mucociliary clearance was monitored by external in vivo measurements of tagged tracer aerosol retention. One group was exposed orally to 250 micrograms/m3, another to the same concentration via the nose, and a third to 500 micrograms/m3 also via nasal breathing. Clearance was accelerated on specific individual days during the course of the acid exposures, especially at 500 micrograms/m3. In all series, clearance was significantly faster, compared to preexposure controls, during a 2-wk follow-up period after acid exposures had ceased. At the end of this period, the rabbits were sacrificed, and histological sections were obtained from the tracheobronchial tree. Significantly increased epithelial thickness of small conducting airways, compared to sham exposure controls, occurred in rabbits exposed orally at 250 micrograms/m3 or nasally at 500 micrograms/m3, and additionally the lumen of the smallest airways of the former group was narrower than control. The number of airways containing epithelial secretory cells was also significantly greater in these acid exposure groups compared to sham controls. The only change in the rabbits exposed nasally at 250 micrograms/m3 was a significant increase in the number of airways with epithelial secretory cells in the smallest airway classification. The histological alterations provide a basis for observed changes in clearance, and are similar to those found in chronic bronchitis in humans and experimental animals. Differences in site and degree of histological response and degree of physiological change between the two groups exposed to identical acid concentrations appear to have been due to differences in exposure mode, with resultant effects on breathing pattern, aerosol size distribution, and concentration penetrating beyond the upper respiratory tract to specific lung sites.

Aerosols↗

PubMedDate not supplied

Setting occupational exposure limits for pharmaceuticals.

The active ingredients used in the pharmaceutical industry's products are designed to modify biological processes; thus, if not adequately controlled, they can place employees at risk. This chapter provides an historical look at the need for occupational exposure limits, as well as an overview of the limit-setting process.

Animals↗