We propose to establish a series of methods suitable to recognize the development of pneumotoxicity in laboratory animals, rats and guinea pigs. These methods will rely on measurement of respiratory patterns of animals during ambient air breathing and during CO2 challenges. With the first method, we will be able to recognize that pulmonary toxicity is developing by repeated measurements in the same animals. This method will use a whole body plethysmograph which will permit measurement in unrestrained, unanesthetized animals in a comfortable environment. Following detection of pulmonary toxicity, the animal is then tested using other measurements to establish the type of toxicity induced. The methods proposed can be used to detect toxicity development for both airborne or systemically administered chemicals and will detect acute as well as chronic damage. The chemicals involved in evaluating how effective the methods we propose to use will include the following: cotton dust, silica, paraquat, bischloroethylnitrosourea, hexamethylene diisocyanate trimer, histamine, serotonin, carbamylcholine, propranolol and sulfuric acid mist. We propose to correlate the results obtained with the data in humans available from the literature and establish models which will have predictive power capabilities. Of particular importance, the methods proposed are adaptable in toxicological studies where it is desirable to make repeated measurements in an economical fashion. Also the number of animals required to obtain concentration-response relationships is very low in comparison to existing methods.

Agency
National Institute of Health (NIH)
Institute
National Institute of Environmental Health Sciences (NIEHS)
Type
Research Project (R01)
Project #
5R01ES002747-05
Application #
3250046
Study Section
Toxicology Study Section (TOX)
Project Start
1982-01-01
Project End
1988-12-31
Budget Start
1986-01-01
Budget End
1986-12-31
Support Year
5
Fiscal Year
1986
Total Cost
Indirect Cost
Name
University of Pittsburgh
Department
Type
Schools of Public Health
DUNS #
053785812
City
Pittsburgh
State
PA
Country
United States
Zip Code
15213
Alarie, Y (1998) Computer-based bioassay for evaluation of sensory irritation of airborne chemicals and its limit of detection. Arch Toxicol 72:277-82
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Alarie, Y; Schaper, M; Nielsen, G D et al. (1996) Estimating the sensory irritating potency of airborne nonreactive volatile organic chemicals and their mixtures. SAR QSAR Environ Res 5:151-65
Alarie, Y; Nielsen, G D; Andonian-Haftvan, J et al. (1995) Physicochemical properties of nonreactive volatile organic chemicals to estimate RD50: alternatives to animal studies. Toxicol Appl Pharmacol 134:92-9
Boylstein, L A; Anderson, S J; Thompson, R D et al. (1995) Characterization of the effects of an airborne mixture of chemicals on the respiratory tract and smoothing polynomial spline analysis of the data. Arch Toxicol 69:579-89
Vijayaraghavan, R; Schaper, M; Thompson, R et al. (1994) Computer assisted recognition and quantitation of the effects of airborne chemicals acting at different areas of the respiratory tract in mice. Arch Toxicol 68:490-9
Schaper, M M; Thompson, R D; Weil, C S (1994) Computer programs for calculation of median effective dose (LD50 or ED50) using the method of moving average interpolation. Arch Toxicol 68:332-7
Kennedy, A L; Wilson, T R; Stock, M F et al. (1994) Distribution and reactivity of inhaled 14C-labeled toluene diisocyanate (TDI) in rats. Arch Toxicol 68:434-43
Vijayaraghavan, R; Schaper, M; Thompson, R et al. (1993) Characteristic modifications of the breathing pattern of mice to evaluate the effects of airborne chemicals on the respiratory tract. Arch Toxicol 67:478-90
Kennedy, A L; Singh, G; Alarie, Y et al. (1993) Autoradiographic analyses of guinea pig airway tissues following inhalation exposure to 14C-labeled methyl isocyanate. Fundam Appl Toxicol 20:57-67

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