ABSTRACT
Company health and safety professionals must advise workers of the potential hazards of workplace chemicals. Yet it is difficult to develop one, consistent corporate labeling strategy for worldwide use. This chapter describes one company's approach to devising a corporate policy satisfying all criteria.
Subject(s)
Drug Industry/legislation & jurisprudence , Hazardous Substances/standards , Occupational Diseases/prevention & control , Occupational Health/legislation & jurisprudence , Product Labeling/standards , United States Occupational Safety and Health Administration/legislation & jurisprudence , Communication , Drug Industry/standards , Environmental Monitoring , Hazardous Substances/adverse effects , Humans , Risk Assessment , United StatesABSTRACT
Much of the data which have been generated on in vitro alternatives to the Draize eye irritation test have dealt with compounds within a specific chemical class or product category. However, in the pharmaceutical industry, it is often necessary to evaluate materials which are not related in structure or properties. It was thus decided to evaluate a diverse series of chemicals in seven in vitro methods for estimating ocular irritation. Thirty-seven test materials were chosen to represent a broad range of pH, solubility, and in vivo irritation potential. Assays were chosen to include as many different types of end points as practical. The group of assays was composed of TOPKAT (assessing structure-activity relationships), bovine corneal opacity-permeability (BCO-P; corneal opacity/toxicity), Eytex (protein coagulation), neutral red uptake (cytotoxicity), MTT in living dermal equivalent (cytotoxicity), Microtox (cytotoxicity in bacteria), and CAMVA (inflammation/toxicity). The results of the study indicated that, in general, the cytotoxicity end points did not correlate well with the in vivo data. The BCO-P, CAMVA, and Eytex assays had the best overall concordance (88.9, 75.8, and 75.0%, respectively) with this set of compounds. Estimation of irritation potential based on structure-activity (TOPKAT) was possible for only approximately 50% of the compounds; however, the assay showed 100% sensitivity (i.e., no false negatives), but low specificity (i.e., negatives correctly identified only 54.5% of the time). These data suggest that for screening of chemicals of diverse structure and properties, the more mechanism-based assays, as opposed to general cytotoxicity assays, hold more promise and should be further evaluated.
Subject(s)
Animal Testing Alternatives , Eye/drug effects , Irritants/toxicity , Toxicity Tests , Animals , Cattle , Cell Survival/drug effects , Chick Embryo , Evaluation Studies as Topic , Humans , In Vitro Techniques , Predictive Value of Tests , Sensitivity and Specificity , Structure-Activity RelationshipABSTRACT
Air velocity was measured at end airways of hollow replicate casts of the human tracheobronchial tree in order to determine the flow distribution within casts extending to 3 mm diameter airways. Measurements were made by hot-wire anemometry for constant inspiratory flow rates of 7.5, 15, 30 and 60 L.min-1. Average flow distribution among the lung lobes was as follows: right upper, 18.5%; right middle, 9.2%; right lower, 32.3%; left upper, 15.7%; and left lower, 24.3%. An empirical model derived from the experimental flow distribution data demonstrated the effect of various morphometric parameters of the hollow cast on the distribution of airflow. Airway cross-sectional area, branching angle and total path-length were found to have the greatest influence. As the tracheal flow rate decreased from 60 to 7.5 L.min-1, the influence of branching angle was reduced, while total path-length became more influential. These results provide evidence for the transition of flow regimes within the TB tree within normal physiological flow ranges.
Subject(s)
Bronchi/physiology , Models, Anatomic , Pulmonary Ventilation/physiology , Trachea/physiology , Adult , Humans , Male , Models, BiologicalABSTRACT
Occupational exposure limits (OELs) serve occupational health professionals as benchmarks for a healthy work environment. OELs are generally developed by manufacturers for substances which are not subject to governmental regulation or which have not been evaluated by consensus organizations such as the American Conference of Governmental Industrial Hygienists. This review is intended to serve as a practical guide to the standard-setting process. The discussion encompasses the evaluation of data, the different methods used for calculating limits, and the application of these limits to the workplace. The need for additional research to enhance the reliability of current methods is also discussed.
Subject(s)
Hazardous Substances/toxicity , Maximum Allowable Concentration , Occupational Exposure/standards , Hazardous Substances/pharmacokinetics , Humans , Occupational Exposure/analysis , Research , United States , United States Environmental Protection Agency , United States Occupational Safety and Health AdministrationABSTRACT
A simple and inexpensive dust feed mechanism has been designed for use with a two-phase fluidized bed generator (FBG). The mechanism is especially useful for generating asbestos aerosols, but may be used with other dusts as well. Using this system, a steady state concentration (39.1 fibers/cc greater than 5 microns in length +/- 6.2%) of asbestos aerosol was maintained in an inhalation chamber for five hours. In addition, FBG output concentration was easily adjusted and quickly equilibrated (within 10 minutes). The system provides a good technique for generating asbestos aerosols for day-long animal exposures.
Subject(s)
Asbestos , Aerosols , Asbestos, Crocidolite , Dust , Equipment and SuppliesABSTRACT
A computerized, nonsurgical, pulmonary function measurement method was tested for sensitivity and utility in detecting the development of fibrosis. Bleomycin, a fibrogenic agent, was intratracheally instilled into male Fisher 344 rats. Respiratory function was monitored in restrained, awake animals before treatment and for the subsequent 4 wk. In the first week, among responders, a significant (p less than 0.05) drop in body weight, tidal volume, and compliance was accompanied by a significant increase in respiratory frequency. Minute volume increased in the second week. Although body weight, tidal volume, and compliance returned to baseline values in the following weeks, respiratory frequency and minute volume remained significantly elevated. With the methods used here, respiratory rate change was the parameter most sensitive to the effects of bleomycin in vivo.