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Overview of an integrated toxicology program for coal liquefaction materials
80 MATERIALS OVERVIEWOF AR INTEGRATEDTOXICOLDBYPROGRAM FOR COAL LIQUEFACTIONI
M$tiL~~5;.D.,BIOLOGY A CHEMISTRY DEPARTMENT,PACIFIC NORTHWESTLABORATORY.RICHLAND,
.
Productsproducedby coal liquefactionmay be used to replacepetroleun-derived fuels or as chawlcalfeedstocks. Liquefactionnay be used to decreasethe release of sulfur, flyash, and other pollutantsto the environmentfrom the use of coal. The liquefactionprocess,may, however.result in the productionof materialswhich themselveshave undesirablebiological activities. For ex&eplel, rrorkersat a coal liquefactionpilot facilityoperated in West Vlrginla in the 1950's wure reported to have had a significantlyincreasedincidenceof skin cancer. Other eplde#IIiOlCQiC data have also indicatedthat workers from coking and coal-gas facilitieshave an elevated Incidenceof lung cancer. A programwas thereforeinitiatedat Battelle,PacificNorthwestLaboratoriesto examine the potentialbiomedicaleffectsof materialsproducedIn one,of the developingcoal liquefactionprocesses,the solvent refining of coal. The elenents of this progr,aminclude: (1) chemicalcharacterization, (2) microbialutagenesis. (1) maazealian cell transfonsationand mutagenesis,(4) skin tumorigenesis, (5) teratology,(6) inhalationtoxicology,(7) pulmonaryfunction,and (8) dosimetry and wetabollsm. Many of the process stream materialswere studied in severalof the above systems. As a result,yc have been able to determinethat the mutagenic,cell-transforming, teratologic. and carcinogenicactlvitlesIncreasesharply as the boiling point of the coal liquid exceeds 7DD*P. Ye have also detenslnedthe correlationamong in vitro and in vivo assay systear for carcinogenlcityfor these oxtromely canplexmixtures. In addition,progresshas been We mrd identifyingthe componentsresponsiblefor the biologicalactivityin the variows assays. (Work supportedby the U.S. Dept. of Energy under Contract No. DE-AC0676RlD-1830).
PERCUTAREOUSABSORPTIONAN!D METABOLISM OF CARCINOGENS ASSOCIATED WITH SYNFUEL PROCESSING
E., WESTERBERG, R. B., FELICE, L. J., KELMAN, B. J.. AND SPRINGER, 0. L.,
The percutaneousabsorptionand metabolismof benzo(a)pyrene(BP) and 6-aminochrysene (AC) have been studiedas representatives of the polynucleararomatic hydrocarbonsand polynucleararmnaticamines found in some synfuel process streams. BP or AC was applied in acetone to the skin of Spnague-Dawleyrats or CD-l mice. Blood samples were collectedat intervalsup to 26 hours post-exposure. Animals were sacrificedat intervalsand skin from the applicationsite analyzed to determinethe quantityof parent compound and metabolites present. Samples obtained after dosing with 14C-BP were extractedwith ethyl acetate followedby 2:l ethyl aceDte:acetone, and the organic solvent extracts (OE) were analyzed by HPLC. HPLC fractionsand aqueous residue (AR) were counted. Counts in OE representsBP and simple phenolic metabo'lites; those in AR representhighly polar metabolitessuch as sulfates. glucuronides. ad-glutathione
conjugates.
The half-time for BP at the site of
application~3s approximately10 minutes. Metabolitesclearedmuch more slowly.with lo20% Of the dose remainingHISmetabolitesat the site of applicationafter 24 hours. At 10
minutes, 95% of the label ,in plasma was BP; in red blood cells, 710% was BP. By 60 minutes, 44% Of the label in plasma was BP. By 26 hours, all label was in AR. At all time Points, AR accountedfor essentiallyall non-BP 14-C in blood, AC was analyzed in skin samples by hanogenizing them in ethanol and analyzing the homogenates by HPLC with electrochemical detection. Initialresult?;indicatea half-timeof 10 minutes for AC at the site of application. Are detailed study of the metabolitesof BP and AC are in progress. Work supportedby the U. S.,Department of Energy under Contract DE-AC06-76RL0 lB30
M$tiL~~5;.D.,BIOLOGY A CHEMISTRY DEPARTMENT,PACIFIC NORTHWESTLABORATORY.RICHLAND,
.
Productsproducedby coal liquefactionmay be used to replacepetroleun-derived fuels or as chawlcalfeedstocks. Liquefactionnay be used to decreasethe release of sulfur, flyash, and other pollutantsto the environmentfrom the use of coal. The liquefactionprocess,may, however.result in the productionof materialswhich themselveshave undesirablebiological activities. For ex&eplel, rrorkersat a coal liquefactionpilot facilityoperated in West Vlrginla in the 1950's wure reported to have had a significantlyincreasedincidenceof skin cancer. Other eplde#IIiOlCQiC data have also indicatedthat workers from coking and coal-gas facilitieshave an elevated Incidenceof lung cancer. A programwas thereforeinitiatedat Battelle,PacificNorthwestLaboratoriesto examine the potentialbiomedicaleffectsof materialsproducedIn one,of the developingcoal liquefactionprocesses,the solvent refining of coal. The elenents of this progr,aminclude: (1) chemicalcharacterization, (2) microbialutagenesis. (1) maazealian cell transfonsationand mutagenesis,(4) skin tumorigenesis, (5) teratology,(6) inhalationtoxicology,(7) pulmonaryfunction,and (8) dosimetry and wetabollsm. Many of the process stream materialswere studied in severalof the above systems. As a result,yc have been able to determinethat the mutagenic,cell-transforming, teratologic. and carcinogenicactlvitlesIncreasesharply as the boiling point of the coal liquid exceeds 7DD*P. Ye have also detenslnedthe correlationamong in vitro and in vivo assay systear for carcinogenlcityfor these oxtromely canplexmixtures. In addition,progresshas been We mrd identifyingthe componentsresponsiblefor the biologicalactivityin the variows assays. (Work supportedby the U.S. Dept. of Energy under Contract No. DE-AC0676RlD-1830).
PERCUTAREOUSABSORPTIONAN!D METABOLISM OF CARCINOGENS ASSOCIATED WITH SYNFUEL PROCESSING
E., WESTERBERG, R. B., FELICE, L. J., KELMAN, B. J.. AND SPRINGER, 0. L.,
The percutaneousabsorptionand metabolismof benzo(a)pyrene(BP) and 6-aminochrysene (AC) have been studiedas representatives of the polynucleararomatic hydrocarbonsand polynucleararmnaticamines found in some synfuel process streams. BP or AC was applied in acetone to the skin of Spnague-Dawleyrats or CD-l mice. Blood samples were collectedat intervalsup to 26 hours post-exposure. Animals were sacrificedat intervalsand skin from the applicationsite analyzed to determinethe quantityof parent compound and metabolites present. Samples obtained after dosing with 14C-BP were extractedwith ethyl acetate followedby 2:l ethyl aceDte:acetone, and the organic solvent extracts (OE) were analyzed by HPLC. HPLC fractionsand aqueous residue (AR) were counted. Counts in OE representsBP and simple phenolic metabo'lites; those in AR representhighly polar metabolitessuch as sulfates. glucuronides. ad-glutathione
conjugates.
The half-time for BP at the site of
application~3s approximately10 minutes. Metabolitesclearedmuch more slowly.with lo20% Of the dose remainingHISmetabolitesat the site of applicationafter 24 hours. At 10
minutes, 95% of the label ,in plasma was BP; in red blood cells, 710% was BP. By 60 minutes, 44% Of the label in plasma was BP. By 26 hours, all label was in AR. At all time Points, AR accountedfor essentiallyall non-BP 14-C in blood, AC was analyzed in skin samples by hanogenizing them in ethanol and analyzing the homogenates by HPLC with electrochemical detection. Initialresult?;indicatea half-timeof 10 minutes for AC at the site of application. Are detailed study of the metabolitesof BP and AC are in progress. Work supportedby the U. S.,Department of Energy under Contract DE-AC06-76RL0 lB30