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Automated inhalation exposure system for small animals
T I M E . C O U R S E OF P E R F L U O R O - n - D E C A N O I C ACID ( P F D A ) - I N D U C E D C H A N G E S IN [14CI.PALMITATE O X I D A T I O N M E A S U R E D IN V I V O IN M A L E F I S C H E R - 3 4 4 R A T S
Gary D. Pilcher,*MarilynE. George,and Melvin E. Andersen Harry G. Armstrong Aerospace Medical Research Laboratory~Toxic Hazards Division Biochemistry Branch, Wright-Patterson Air Force Base, Ohio 45433
Perfluorocarboxylic acids and related compounds are commercially i m p o r t a n t because of their unusual surfactant properties and high chemical stability. Certain perfluorinated surfactants are found in aqueous film-forming foams used as fire extinguishants. One chemical in this class, perfluoro-n-decanoic acid (PFDA,) CF3(CF2)8COOH, causes toxic signs similar to those of 2,3,7,8-tetrachlorodibenzodioxin (TCDD), a toxic contaminant of trichlorophenoxyacetic acid-based herbicides such as "Agent Orange." The mechanism of toxicityfor these chemicals is unknown; however, both P F D A a n d T C D D are reported to cause alterationsin lipidmetabolism. Studies were initiatedto examine PFDA's effectson the dispositionof a radiolabeled fatty acid substrate, [14C]-palmitate. At 2, 4, 8, and 12 days after a single i.p.dose of 50 m g P F D A / k g body weight, rats were injectedi.v.with [14C]-palmitate and placed in a flow-through chamber system. [14C]~CO2 in the expired air was collected for a 12-h period. Results of this work indicate that palmitate oxidation as measured by cumulative 12-h [14C]-CO2 elimination was unchanged at 2 and 4 days postexposure in PFDA-dosed rats compared to pair-fed controls. At 8 and 12 days after dosing, [14C]-CO2 elimination in PFDA-dosed rats was significantly reduced by 39% and 33%, respectively, when compared to pair-fed controls. These data suggest t h a t PFDA partially interferes with fatty acid oxidation over a delayed timecourse; however, the relevance of this observation to the toxicity of PFDA is unknown.
A U T O M A T E D I N H A L A T I O N E X P O S U R E SYSTEM F O R S M A L L A N I M A L S
John R. Decker,* H.S. DeFord, E.G. Kuffel, and R.D. Swannaek Biology and Chemistry Department, Battelle Pacific Northwest Laboratories, R ichIand, Washington 99352
A n automated data acquisition and control system has been constructed for inhalation studies. By multiplexing monitoring devices and control elements, the
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system is capable of handling three separate test chemicals (vapors or aerosols) in three separate rooms using up to 30 Battelle-designed Hazleton 2000 exposure chambers (10 per room). The system monitors and controls chamber air flow, vacuum, temperature, and relative humidity, as well as test chemical concentration and generator functions. All data acquisition and control originates from a Hewlett-Packard Model 216 computer located in a control center. Experimental protocols reside in this computer and are entered into software tables accessed by menus. All protocol entries and changes are automatically recorded on the daily printout. Operators must enter passwords to access the menus. Data from each of the three test chemical exposures are stored immediately upon completion of m e a s u r e m e n t on separate magnetic micro-floppy diskettes and are printed as a daily log by separate printers located in the control center. Operator comments may also be entered in the computer and printed in the daily log. At the end of the 24-h period, the daily data are automatically analyzed, and summary reports are printed. A six-point alarm system with user-definable set points is available for each parameter and measurement location. Alarm conditions that may be a threat to the health of the animals alert security personnel who call the on-duty system operator.
H I S T O P A T H O L O G I C C H A N G E S IN T H E L U N G S OF R A T S E X P O S E D TO I N H A L A T I O N OF T O B A C C O SMOKE OR M A R I H U A N A
Mohan K u m a r , t , 2. S. Poddar,l Louise Cardenas, 1 and B.N. Rao l
l University of West Indies, Faculty of Medicine, Kingston, Jamaica and 2Cleveland College, Los Angeles, California 90004-2196
The histopathologicchanges caused by tobacco and marihuana smoke in the lungs were evaluated by exposing two lots of healthy rats to smoke u n d e r controlled experimental conditions for periods ranging from 6 to 36 weeks. Two groups of 120 rats each were exposed to tobacco and marihuana smoke, respectively. The animals were placed in a compartmentalized grilled cage within a sealed polythene bag. The animals in one group were exposed to tobacco smoke, and the second group to m a r i h u a n a smoke. Twelve cigarettes of either toxic substance were used for each lot over an 8-h period each day. The animals were exposed to smoke for 5 min, after which they were exposed to fresh air for 10 rain, and the the experiment was repeated, in order to simulate actual h u m a n smoking conditions. Control animals for each group were subject to similar
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Gary D. Pilcher,*MarilynE. George,and Melvin E. Andersen Harry G. Armstrong Aerospace Medical Research Laboratory~Toxic Hazards Division Biochemistry Branch, Wright-Patterson Air Force Base, Ohio 45433
Perfluorocarboxylic acids and related compounds are commercially i m p o r t a n t because of their unusual surfactant properties and high chemical stability. Certain perfluorinated surfactants are found in aqueous film-forming foams used as fire extinguishants. One chemical in this class, perfluoro-n-decanoic acid (PFDA,) CF3(CF2)8COOH, causes toxic signs similar to those of 2,3,7,8-tetrachlorodibenzodioxin (TCDD), a toxic contaminant of trichlorophenoxyacetic acid-based herbicides such as "Agent Orange." The mechanism of toxicityfor these chemicals is unknown; however, both P F D A a n d T C D D are reported to cause alterationsin lipidmetabolism. Studies were initiatedto examine PFDA's effectson the dispositionof a radiolabeled fatty acid substrate, [14C]-palmitate. At 2, 4, 8, and 12 days after a single i.p.dose of 50 m g P F D A / k g body weight, rats were injectedi.v.with [14C]-palmitate and placed in a flow-through chamber system. [14C]~CO2 in the expired air was collected for a 12-h period. Results of this work indicate that palmitate oxidation as measured by cumulative 12-h [14C]-CO2 elimination was unchanged at 2 and 4 days postexposure in PFDA-dosed rats compared to pair-fed controls. At 8 and 12 days after dosing, [14C]-CO2 elimination in PFDA-dosed rats was significantly reduced by 39% and 33%, respectively, when compared to pair-fed controls. These data suggest t h a t PFDA partially interferes with fatty acid oxidation over a delayed timecourse; however, the relevance of this observation to the toxicity of PFDA is unknown.
A U T O M A T E D I N H A L A T I O N E X P O S U R E SYSTEM F O R S M A L L A N I M A L S
John R. Decker,* H.S. DeFord, E.G. Kuffel, and R.D. Swannaek Biology and Chemistry Department, Battelle Pacific Northwest Laboratories, R ichIand, Washington 99352
A n automated data acquisition and control system has been constructed for inhalation studies. By multiplexing monitoring devices and control elements, the
223
system is capable of handling three separate test chemicals (vapors or aerosols) in three separate rooms using up to 30 Battelle-designed Hazleton 2000 exposure chambers (10 per room). The system monitors and controls chamber air flow, vacuum, temperature, and relative humidity, as well as test chemical concentration and generator functions. All data acquisition and control originates from a Hewlett-Packard Model 216 computer located in a control center. Experimental protocols reside in this computer and are entered into software tables accessed by menus. All protocol entries and changes are automatically recorded on the daily printout. Operators must enter passwords to access the menus. Data from each of the three test chemical exposures are stored immediately upon completion of m e a s u r e m e n t on separate magnetic micro-floppy diskettes and are printed as a daily log by separate printers located in the control center. Operator comments may also be entered in the computer and printed in the daily log. At the end of the 24-h period, the daily data are automatically analyzed, and summary reports are printed. A six-point alarm system with user-definable set points is available for each parameter and measurement location. Alarm conditions that may be a threat to the health of the animals alert security personnel who call the on-duty system operator.
H I S T O P A T H O L O G I C C H A N G E S IN T H E L U N G S OF R A T S E X P O S E D TO I N H A L A T I O N OF T O B A C C O SMOKE OR M A R I H U A N A
Mohan K u m a r , t , 2. S. Poddar,l Louise Cardenas, 1 and B.N. Rao l
l University of West Indies, Faculty of Medicine, Kingston, Jamaica and 2Cleveland College, Los Angeles, California 90004-2196
The histopathologicchanges caused by tobacco and marihuana smoke in the lungs were evaluated by exposing two lots of healthy rats to smoke u n d e r controlled experimental conditions for periods ranging from 6 to 36 weeks. Two groups of 120 rats each were exposed to tobacco and marihuana smoke, respectively. The animals were placed in a compartmentalized grilled cage within a sealed polythene bag. The animals in one group were exposed to tobacco smoke, and the second group to m a r i h u a n a smoke. Twelve cigarettes of either toxic substance were used for each lot over an 8-h period each day. The animals were exposed to smoke for 5 min, after which they were exposed to fresh air for 10 rain, and the the experiment was repeated, in order to simulate actual h u m a n smoking conditions. Control animals for each group were subject to similar
224