- Retired USEPA researcher in genetic toxicology.edit
Diurnal ozone and volatile organic compounds (VOCs) were measured at the 610 meter television tower 10 km southeast of downtown Raleigh at three different levels: Surface, Mid (240 m), and Top (460 M) sampling level in July and August of... more
Diurnal ozone and volatile organic compounds (VOCs) were measured at the 610 meter television tower 10 km southeast of downtown Raleigh at three different levels: Surface, Mid (240 m), and Top (460 M) sampling level in July and August of 1993 and 1994. These measurements revealed very high ozone concentrations at Mid and Top. Of the VOCs measured, only arene concentrations were significantly elevated at Mid and Top. The combined presence of ozone, arenes and nitrogen oxides (NO{sub x}) at Mid and Top suggested possible nitration of arenes. A subsequent preliminary study in a mutagenicity assay analyzed the presence of nitroaromatic-like activity, which supports the possibility of long-range transport of arenes. 33 refs., 2 figs.
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The environmental release of microorganisms has prompted the investigation of potential health effects associated with their release. In this study, survival and translocation to the spleen and liver of several environmental Pseudomonas... more
The environmental release of microorganisms has prompted the investigation of potential health effects associated with their release. In this study, survival and translocation to the spleen and liver of several environmental Pseudomonas spp. were investigated in antibiotic-treated mice. Pseudomonas aeruginosa BC16 and P. maltophilia BC6, isolated from a commercial product for polychlorinated biphenyl degradation; P. aeruginosa AC869, a 3,5-dichlorobenzoate degrader; and P. cepacia AC1100, an organism that metabolizes 2,4,5-trichlorophenoxyacetic acid were examined for their survival capabilities in the intestines of mice dosed with clindamycin, kanamycin, rifampin, or spectinomycin. A mouse intestinal isolate, strain PAMG, was included in the study. Following antibiotic pretreatment (1 mg twice daily for 3 days), mice were dosed by gavage with 10(9) CFU of each Pseudomonas strain. At the end of the 5-day test period, strains AC869 and PAMG survived in kanamycin-, rifampin-, spectino...
Research Interests: Microbiology, Environmental microbiology, Biology, Medicine, Multidisciplinary, and 15 moreSpleen, Liver, Mice, Animals, Applied Environmental Microbiology, Male, Pseudomonas, Polychlorinated Biphenyls, Pseudomonas aeruginosa, Antibiotics, Intestines, Anti-Bacterial Agents, Pseudomonas Aeruginosa, Clindamycin, and Sensitivity and Specificity
Chemical mutagens are recognized as prevalent in the environment and a potential threat to the health of future generations. This paper presents an overview of chemical mutagenesis as an issue for public health. Several problems in the... more
Chemical mutagens are recognized as prevalent in the environment and a potential threat to the health of future generations. This paper presents an overview of chemical mutagenesis as an issue for public health. Several problems in the determination of risk to human populations are discussed, including difficulties of extrapolating scientific data to humans, the latency period between exposure and recognizable genetic damage, and the large number of chemicals which must be tested. Test systems are described. Possibilities of control through federal regulation are discussed.
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When introduced intranasally, P. cepacia AC1100 (approximately 10(8) CFU/animal) and P. aeruginosa AC869 (approximately 10(3) CFU/animal) were readily cleared from the mouse. However, a approximately 10(7)-CFU dose of AC869 persisted for... more
When introduced intranasally, P. cepacia AC1100 (approximately 10(8) CFU/animal) and P. aeruginosa AC869 (approximately 10(3) CFU/animal) were readily cleared from the mouse. However, a approximately 10(7)-CFU dose of AC869 persisted for 14 days. Strain AC869 had a 50% lethal dose of 2.7 x 10(7) CFU. Slight morbidity occurred in animals treated with approximately 10(7) CFU of AC869 or approximately 10(8) CFU of AC1100.
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Description/Abstract Using a modified version of the TLC/Salmonella assay developed by Bjorseth et al.(1982), 10 complex hazardous wastes were tested for mutagenic activity. The method couples thin-layer chromatography (TLC) with the... more
Description/Abstract Using a modified version of the TLC/Salmonella assay developed by Bjorseth et al.(1982), 10 complex hazardous wastes were tested for mutagenic activity. The method couples thin-layer chromatography (TLC) with the Salmonella/mammalian-microsome (Ames) assay for the detection of mutagenic constituents in complex mixtures. Crude hazardous wastes and selected hazardous-waste extracts were fractionated on commercially available cellulose TLC plates. Mutagenicity testing was performed by ...
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This article presents a toxicologically-based risk assessment strategy for identifying the individual components or fractions of a complex mixture that are associated with its toxicity. The strategy relies on conventional component-based... more
This article presents a toxicologically-based risk assessment strategy for identifying the individual components or fractions of a complex mixture that are associated with its toxicity. The strategy relies on conventional component-based mixtures risk approaches such as dose addition, response addition, and analyses of interactions. Developmental toxicity data from two drinking-water concentrates containing disinfection by-products (DBP) mixtures were used to illustrate the strategy. The results of this study showed that future studies of DBP concentrates using the Chernoff-Kavlock bioassay need to consider evaluating DBP that are concentrated more than 130-fold and using a rat strain that is more sensitive to chemically-induced pregnancy loss than Sprague-Dawley rats. The results support the planned experimental design of a multigeneration reproductive and developmental study of DBP concentrates. Finally, this article discusses the need for a systematic evaluation of DBP concentrates obtained from multiple source waters and treatment types. The development of such a database could be useful in evaluating whether a specific DBP concentrate is sufficiently similar to tested combinations of source waters and treatment alternatives so that health risks for the former may be estimated using data on the latter.
Research Interests: Toxicology, Water Purification, Risk assessment, Fetal development, Environmental Sciences, and 23 moreBladder Cancer, Pregnancy, Water Supply, Humans, United States, Female, Animals, Salmonella Typhimurium, Glutathione, Drinking Water, Disinfectants, Chemical Analysis, CHEMICAL SCIENCES, Reverse osmosis, Ozone, Mental health public policy & practice, Risk Assessment, Water Microbiology, North American, Pilot Plant, Epidemiologic Studies, Halogenation, and Relative Risk(Bladder Cancer, Pregnancy, Water Supply, Humans, United States, Female, Animals, Salmonella Typhimurium, Glutathione, Drinking Water, Disinfectants, Chemical Analysis, CHEMICAL SCIENCES, Reverse osmosis, Ozone, Mental health public policy & practice, Risk Assessment, Water Microbiology, North American, Pilot Plant, Epidemiologic Studies, Halogenation, and Relative Risk)
(Bladder Cancer, Pregnancy, Water Supply, Humans, United States, Female, Animals, Salmonella Typhimurium, Glutathione, Drinking Water, Disinfectants, Chemical Analysis, CHEMICAL SCIENCES, Reverse osmosis, Ozone, Mental health public policy & practice, Risk Assessment, Water Microbiology, North American, Pilot Plant, Epidemiologic Studies, Halogenation, and Relative Risk)
... 182 JH DRIVER, HW ROGERS, AND LD CLAXTON 30000 ~ 28900 28OOO 2600O 24~0 22O60 2OOOO 18OOO F ... 17. Andrews, AA, Thibault, LH, and Linjinsky, W. The relationship between carcinogenicity and mutagenicity of some polycyclic... more
... 182 JH DRIVER, HW ROGERS, AND LD CLAXTON 30000 ~ 28900 28OOO 2600O 24~0 22O60 2OOOO 18OOO F ... 17. Andrews, AA, Thibault, LH, and Linjinsky, W. The relationship between carcinogenicity and mutagenicity of some polycyclic hydrocarbons. Mutat. Res. ...
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Description/Abstract As EPA, industry, and others promote the use of bioremediation as a treatment alternative for environmental contamination, the health risks of such cleanup efforts must be assessed. Conversions of toxic constituents... more
Description/Abstract As EPA, industry, and others promote the use of bioremediation as a treatment alternative for environmental contamination, the health risks of such cleanup efforts must be assessed. Conversions of toxic constituents to metabolic intermediates and byproducts can result in fluctuations in toxicity over time. We have examined this process by studying the microbial degradation of petroleum products in the field and in the laboratory. For the field study, we evaluated 2 accidental releases (a coastal oil spill and a refinery ...
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The metabolism of [14C]‐1‐nitropyrene by human, rat, and mouse intestinal microflora and a bioassay‐directed chemical analysis of the isolated metabolites by assaying HPLC fractions with a microsuspension reverse mutation assay were... more
The metabolism of [14C]‐1‐nitropyrene by human, rat, and mouse intestinal microflora and a bioassay‐directed chemical analysis of the isolated metabolites by assaying HPLC fractions with a microsuspension reverse mutation assay were examined.[14C]‐1‐Nitropyrene was metabolized by human, rat, and mouse intestinal microflora to 1‐aminopyrene, N‐acetyl‐1‐aminopyrene, N‐formyl‐1‐aminopyrene, and two unknown metabolites identified as A and B. The predominant metabolite produced by human, rat, or mouse intestinal microflora ...
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In previous papers, the synthesis and chemical properties of iron-complexed azo and formazan dyes were reported. It was shown that in certain cases iron could be substituted for the traditionally used metals such as chromium and cobalt,... more
In previous papers, the synthesis and chemical properties of iron-complexed azo and formazan dyes were reported. It was shown that in certain cases iron could be substituted for the traditionally used metals such as chromium and cobalt, without having an adverse effect on dye stability. While these results suggested that the iron analogs were potential replacements for the commercially used chromium and cobalt prototypes, characterization of potentially adverse environmental effects of the new dyes was deemed an essential step in their further development. The present paper provides results from using the Salmonella/mammalian microsome assay to determine the mutagenicity of some important commercial metal complexed dyes, their unmetallized forms, and the corresponding iron-complexed analogs. The study compared the mutagenic properties of six unmetallized azo dyes, six commercial cobalt- or chromium-complexed azo dyes, six iron-complexed azo dyes, six unmetallized formazan dyes, and six iron-complexed formazan dyes. The results of this study suggest that the mutagenicity of the unmetallized dye precursors plays a role in determining the mutagenicity of the iron-complexes. For the monoazo dye containing a nitro group, metal complex formation using iron or chromium decreased or removed mutagenicity in TA100; however, little reduction in mutagenicity was noted in TA98. For the formazan dye containing a nitro group, metal-complex formation using iron increased mutagenicity. Results varied for metal-complexes of azo and formazan dyes without nitro groups, but in general, the metal-complexed dyes based on mutagenic ligands were also mutagenic, while those dyes based on nonmutagenic ligands were nonmutagenic.
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The primary objective of this study is to characterize the genotoxic potential of the ambient air aerosols collected within an air shed impacted primarily by wood smoke and automotive emissions. The study also examines the relative merits... more
The primary objective of this study is to characterize the genotoxic potential of the ambient air aerosols collected within an air shed impacted primarily by wood smoke and automotive emissions. The study also examines the relative merits of a microsuspension assay and the standard plate assay for monitoring the presence of airborne particle-bound mutagens. Wintertime ambient air particulate samples collected from Boise, Idaho, USA, were shown to contain extractable organic matter that is mutagenic in the Salmonella typhimurium microsuspension and plate-incorporation assays. Differences in the results from the primary sites, auxiliary sites and the background site demonstrate that the particle-bound mutagens are not evenly distributed within the air shed and are more associated with the location of sampling than with the time of sampling or the type of bioassay used to evaluate the samples. This study also demonstrates that the bioassay protocol used in such studies should depend upon the characteristics of the air shed's mutagens and the purpose of the study. For example, the microsuspension assay gave somewhat more variable results between samples but was approximately threefold more sensitive than the plate assay. When strain TA98 was used in the microsuspension assay, the mutagenic response was greater without an exogenous activation system. The reverse was true for the plate assay in which the use of an exogenous activation system increased the mutagenicity response. TA100 in the microsuspension assay provided results comparable to those with TA98. This is important because TA100 can also be used to bioassay semivolatile and volatile organics associated with ambient air mutagenicity. This, in turn, allows a comparison of the mutagenicity of organics collected by differing methods due to their volatility. Future studies should be directed toward correlation of mutagenicity results with other analytical results in order to further develop methods for better characterization of the genotoxicity of ambient air.
Research Interests: Air Quality, Environmental Monitoring, Multidisciplinary, Aerosols, Toxicity, and 10 moreLiver, Wood, Animals, Salmonella Typhimurium, IDAHO, Rats, Time Factors, Mutagens, Fine Particles, and Air Pollutants(Liver, Wood, Animals, Salmonella Typhimurium, IDAHO, Rats, Time Factors, Mutagens, Fine Particles, and Air Pollutants)
(Liver, Wood, Animals, Salmonella Typhimurium, IDAHO, Rats, Time Factors, Mutagens, Fine Particles, and Air Pollutants)
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For a number of years, investigators have recognized that humans potentially are exposed to large numbers of genotoxicants. Many efforts have attempted to validate various short-term bioassays for use as rapid, inexpensive screens for... more
For a number of years, investigators have recognized that humans potentially are exposed to large numbers of genotoxicants. Many efforts have attempted to validate various short-term bioassays for use as rapid, inexpensive screens for genotoxicants--especially carcinogens. In this analysis, we examine Salmonella mutagenicity as an indicator of potential carcinogenicity by comparing published (and when possible, evaluated) Salmonella results with the evaluated Gene-Tox animal carcinogen data base. The Salmonella bioassay does especially well in those cases where the level of evidence for carcinogenicity is the strongest. Analysis shows that except for specific classes of compounds, the plate-incorporation protocol and the preincubation protocol are equally efficient at detecting mutagens. This paper also demonstrates how validation values (sensitivity, specificity, etc.) vary with chemical class. Overall, this analysis demonstrates that when used and interpreted in a meaningful chemical class context, the Salmonella bioassay remains extremely useful in identifying potential animal carcinogens.
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The mutagenic activity of sidestream cigarette smoke particles was estimated by testing sidestream cigarette smoke particles which had been collected under controlled burning conditions in the laboratory. Two different extraction methods... more
The mutagenic activity of sidestream cigarette smoke particles was estimated by testing sidestream cigarette smoke particles which had been collected under controlled burning conditions in the laboratory. Two different extraction methods (Soxhlet and ultrasonic agitation) and 3 different solvents (dichloromethane, methanol, and acetone) were compared for their efficiencies in the extraction of compounds from sidestream cigarette smoke particles which are mutagenic in the Ames test. The mutagenic activity of the sidestream smoke particles was estimated to be 15,000-20,000 revertants per cigarette in TA98 with metabolic activation and 12,000-17,000 revertants per cigarette in TA100 without metabolic activation. Only weak mutagenic activity was detected in TA98 without activation and in TA100 with activation. Under test conditions used, ultrasonic agitation produced the most consistent results and acetone extraction produced the highest levels of mutagenic activity.
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Abstract A wide variety of combustion sources produce soot, ie, carbon aerosols containing variable quantities of organic matter. The most significant transportation-related sources of such materials are diesel engines. Diesel power has... more
Abstract A wide variety of combustion sources produce soot, ie, carbon aerosols containing variable quantities of organic matter. The most significant transportation-related sources of such materials are diesel engines. Diesel power has been used for railway locomotives, long haul trucks, and earthmoving equipment for many years. However, recently a strong trend has developed toward use of diesel engines in urban service vehicles and also taxicabs. In the near future substantial numbers of diesel-powered automobiles may be ...
ABSTRACT: During the winter of 1985, the US Environmental Protection Agency (EPA) collected air quality data and samples in residential locations in Albuquerque, New Mexico and Raleigh, North Carolina as part of its Integrated Air Cancer... more
ABSTRACT: During the winter of 1985, the US Environmental Protection Agency (EPA) collected air quality data and samples in residential locations in Albuquerque, New Mexico and Raleigh, North Carolina as part of its Integrated Air Cancer Project (IACP). One of the major objectives of these field monitoring studies was to evaluate new sampling, analysis, and receptor modeling procedures and to apportion the fine particle mass and mutagenic activity of the organic fraction of the fine particles to the appropriate sources. Samples ...
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Research Interests: Genetics()
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The mutagenic activities of 1-nitropyrene (1-NP), 2,7-dinitrofluorenone (2,7-DNF), and a diesel-exhaust extract were compared using the Salmonella typhimurium plate-incorporation assay. Each sample was tested with and without a 9000 X g... more
The mutagenic activities of 1-nitropyrene (1-NP), 2,7-dinitrofluorenone (2,7-DNF), and a diesel-exhaust extract were compared using the Salmonella typhimurium plate-incorporation assay. Each sample was tested with and without a 9000 X g liver homogenate (S9), both with and without an NADPH-generating system. The samples were also treated with the microsome fraction of S9, cytosol fraction of S9, boiled S9, bovine serum albumin (BSA), and boiled BSA. Salmonella tester strains TA98 and TA98FR1 were used in all treatments; TA98/1,8DNP6 was used to test mutagenic activity without activation. Without the NADPH-generating system, the samples generally had less mutagenic activity than samples treated with the NADPH-generating system. The addition of the NADPH-generating system resulted in marked increases in mutagenic activity of 1-NP in the microsome and S9 treatments, and of all 3 samples in the cytosol fraction treatment. These results indicate that although protein binding reduced the ...
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As research expands the types of energy sources for the future, there is a need to understand the health impacts of fuels and their emissions and to understand what health-research data gaps exist so that in the future proper and... more
As research expands the types of energy sources for the future, there is a need to understand the health impacts of fuels and their emissions and to understand what health-research data gaps exist so that in the future proper and informative research and decision-making can be done. In that regard, this series of papers will explore what is known about the history, carcinogenicity, and genotoxicity of fuels and their emission products and attempt to identify major data gaps and areas of interest for future research. The reviews will concentrate on petroleum-derived fuels and biofuels. Although the length of these papers may cause the reader to think otherwise, the coverage of published works is intended to be illustrative rather than exhaustive and is intended for a multidisciplinary audience. This series of papers is not a risk assessment; instead, it is an attempt to introduce the reader with the history and terminology needed when examining fuels and emissions for genotoxic effec...
Research Interests: History, Genetics, Transformation, Cancer, Transportation, and 10 moreHealth, Biofuels, Humans, Wood, Air, Animals, Regulations, Laws, Fuel Oils, and Air Pollutants
One of the issues often associated with scientific misconduct is conflict of interest. Although there is a lack of uniformity in the definition of conflict of interest, many express concerns that competing interests may bias research... more
One of the issues often associated with scientific misconduct is conflict of interest. Although there is a lack of uniformity in the definition of conflict of interest, many express concerns that competing interests may bias research methods and the interpretation of data and conclusions. In extreme cases, conflict of interest activity could contribute to scientific misconduct, hinder the training of scientists, delay the dissemination of research results, lead to the harming of human health and the environment, and misdirect society's decisions that rely on science. This article is not a commentary or editorial but an attempt to supply an overview of what has been said, researched, and accomplished in the area of conflict of interest for toxicologists. Discussion of the financial, professional, and philosophical concerns associated with conflict of interest will be followed by brief discussion of general management approaches and the roles of scientists and organizations from a...
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In previous papers, the synthesis and chemical properties of iron-complexed azo and formazan dyes were reported. It was shown that in certain cases iron could be substituted for the traditionally used metals such as chromium and cobalt,... more
In previous papers, the synthesis and chemical properties of iron-complexed azo and formazan dyes were reported. It was shown that in certain cases iron could be substituted for the traditionally used metals such as chromium and cobalt, without having an adverse effect on dye stability. While these results suggested that the iron analogs were potential replacements for the commercially used chromium and cobalt prototypes, characterization of potentially adverse environmental effects of the new dyes was deemed an essential step in their further development. The present paper provides results from using the Salmonella/mammalian microsome assay to determine the mutagenicity of some important commercial metal complexed dyes, their unmetallized forms, and the corresponding iron-complexed analogs. The study compared the mutagenic properties of six unmetallized azo dyes, six commercial cobalt- or chromium-complexed azo dyes, six iron-complexed azo dyes, six unmetallized formazan dyes, and ...
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Pseudomonas aeruginosa AC869, a 3,5-dichlorobenzoate degrader, is a mouse pathogen and has a reported 50% lethal dose (LD50) of 1.05 x 10(7) CFU when given intranasally to C3H/HeJ mice (S.E. George, M.J. Kohan, M.I. Gilmour, M.S. Taylor,... more
Pseudomonas aeruginosa AC869, a 3,5-dichlorobenzoate degrader, is a mouse pathogen and has a reported 50% lethal dose (LD50) of 1.05 x 10(7) CFU when given intranasally to C3H/HeJ mice (S.E. George, M.J. Kohan, M.I. Gilmour, M.S. Taylor, H.G. Brooks, J.P. Creason, and L.D. Claxton, Appl. Environ, Microbiol. 59:3585-3591, 1993). AC869 was serotyped as O6 when grown in CD-1 mouse cecal and lung mucus but could not be assigned an O serotype when grown in Luria broth (LB). After growth in mouse cecal mucus, a less virulent mutant, AC869-11, was isolated from AC869 by using bacteriophage E79, which adsorbs to the O side chain of lipopolysaccharide (LPS). AC869-11 produced significantly less O antigen on its LPS than AC869 when grown in mouse lung and cecal mucus. The mutant also produced half the amount of exoenzyme S and 16-fold less extracellular protease than AC869 and was more sensitive than its parent to a number of antibiotics when grown either in LB or in mouse lung mucus. AC869-1...
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The environmental release of engineered microorganisms has caused health and environmental concerns. In this study, an animal model was used to examine health effects following pulmonary exposure to environmental and clinical isolates. In... more
The environmental release of engineered microorganisms has caused health and environmental concerns. In this study, an animal model was used to examine health effects following pulmonary exposure to environmental and clinical isolates. In order to rule out the possibility that an adverse response was caused by endotoxin, 50% lethal doses (LD50) were determined, when possible, with endotoxin-sensitive (C3HeB/FeJ) and endotoxin-resistant (C3H/HeJ) mice by using both environmental isolates (Pseudomonas aeruginosa BC16, BC17, BC18, and AC869 and Pseudomonas maltophilia BC6) and clinical isolates (P. aeruginosa PAO1 and DG1). The LD50 of strains AC869, DG1, and PAO1 are 1.05 x 10(7), 6.56 x 10(6), and 1.02 x 10(7) CFU, respectively, in C3HeB/FeJ mice and 1.05 x 10(7), 1.00 x 10(7), and 2.75 x 10(6) CFU, respectively, in C3H/HeJ mice. Strains BC17 and BC18 were not lethal to the animals. On the basis of the LD50 data, an appropriate sublethal dose (approximately 10(6) CFU) was selected. A...
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This study was designed to detect the effect that different environmental conditions have upon diesel-exhaust organics. In this study, diesel exhaust was injected into the Calspan smog chamber under different conditions, and the resulting... more
This study was designed to detect the effect that different environmental conditions have upon diesel-exhaust organics. In this study, diesel exhaust was injected into the Calspan smog chamber under different conditions, and the resulting particles were collected upon Pallflex glass-fiber filters. After extraction from the particles with methylene chloride, the organics were solvent exchanged to dimethyl sulfoxide and tested in the Salmonella typhimurium plate-incorporation test. Results demonstrate that the irradiation of propylene, SO2, NO and NO2 produces ozone and a mutagenic moiety. Unless another mitigating factor (e.g., ozone) was present or formed, irradiation did not alter the mutagenic response of the organics. The production or injection of ozone into chamber tended to reduce the mutagenic response of the collected organics. In summary, this study demonstrates that ambient conditions can alter the mutagenic response of diesel-exhaust organics.
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The mutagenicity and activation requirements of purified synthetic derivatives and potential metabolites of 1-nitropyrene have been characterized in the Ames plate incorporation assay with the Salmonella tester strains TA98, TA98NR and... more
The mutagenicity and activation requirements of purified synthetic derivatives and potential metabolites of 1-nitropyrene have been characterized in the Ames plate incorporation assay with the Salmonella tester strains TA98, TA98NR and TA98/1,8-DNP6, in the presence or absence of exogenous metabolic activation provided by Aroclor-induced rat liver S9. All the compounds tested (1-aminopyrene, N-acetyl-1-aminopyrene, N-hydroxy-N-acetyl-1-aminopyrene, 3-hydroxy-1-nitropyrene, 6-hydroxy-1-nitropyrene, and 8-hydroxy-1-nitropyrene) exhibited mutagenic activity under one or more assay conditions. 1-Nitropyrene was metabolized to 3-hydroxy-1-nitropyrene, 6- or 8-hydroxy-1-nitropyrene, 1-aminopyrene, N-acetyl-1-aminopyrene and other unidentified products (including some bound to protein) by an S9 preparation analogous to that used for exogenous metabolic activation in the Ames assay. 1-Nitropyrene and 3-hydroxy-1-nitropyrene were activated primarily by the 'classical' nitroreductase,...
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The microsomal metabolites and mutagenic activity of four cyclopenta-fused benz(a)anthracenes, benz(j)aceanthrylene [B(j)A], benz(e)aceanthrylene [B(e)A], benz(l)aceanthrylene [B(l)A], and benz(k)acephenanthrylene [B(k)A], have been... more
The microsomal metabolites and mutagenic activity of four cyclopenta-fused benz(a)anthracenes, benz(j)aceanthrylene [B(j)A], benz(e)aceanthrylene [B(e)A], benz(l)aceanthrylene [B(l)A], and benz(k)acephenanthrylene [B(k)A], have been studied. Aroclor 1254-induced rat liver microsomes metabolized B(j)A to B(j)A-1,2-dihydrodiol, B(j)A-9,10-dihydrodiol, B(j)A-11,12-dihydrodiol, and 10-hydroxy-B(j)A; B(e)A-1,2-dihydrodiol, B(e)A-3,4-dihydrodiol, and B(e)A-5,6-dihydrodiol; B(l)A to B(l)A-1,2-dihydrodiol, B(l)A-4,5-dihydrodiol, and B(l)A-7,8-dihydrodiol; and B(k)A to B(k)A-4,5-dihydrodiol and B(k)A-8,9-dihydrodiol. With each polycyclic aromatic hydrocarbon, metabolism occurred on the cyclopenta ring. All four isomers were active as gene mutagens in Salmonella typhimurium and in Chinese hamster V79 cells. In the S. typhimurium mutation studies, using Aroclor 1254-induced rat liver S9, B(j)A, B(e)A, and B(l)A required significantly less microsomal protein for maximal mutation response than B...
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In summary, the work presented demonstrates that rapid, in vitro indicators of genotoxicity have been and will continue to play a valuable role in understanding the toxicity of mobile source emissions. Bacterial assays have had tremendous... more
In summary, the work presented demonstrates that rapid, in vitro indicators of genotoxicity have been and will continue to play a valuable role in understanding the toxicity of mobile source emissions. Bacterial assays have had tremendous value in the characterization of mobile source emissions. Specifically they have had four major uses: 1) comparative screening, 2) analyzing factors that alter the genotoxicants found in emission products, 3) directing the chemical fractionation of emission organics for the identification of specific genotoxicants, and 4) analyzing the interaction of complex emission products with various mammalian systems.
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Exposures of Salmonella typhimurium strain TA100 with and without S9 metabolic activation to low ppm levels of pure peroxyacetyl nitrate (PAN) in the gas phase were conducted. Measurements of the gas-phase PAN exposure concentration and... more
Exposures of Salmonella typhimurium strain TA100 with and without S9 metabolic activation to low ppm levels of pure peroxyacetyl nitrate (PAN) in the gas phase were conducted. Measurements of the gas-phase PAN exposure concentration and the concentration of its decomposition products in surrogate test media led to a measured mutagenic activity of 34 +/- 5 revertants/mumole. The data indicate that PAN is a relatively weak direct-acting mutagen with TA100.
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The purpose of this research was to develop and characterize a sensitive test method to detect mutagenic activity of volatile liquid organic chemicals (i.e, volatiles) in the Ames/Salmonella assay. A Tedlar bag vaporization technique was... more
The purpose of this research was to develop and characterize a sensitive test method to detect mutagenic activity of volatile liquid organic chemicals (i.e, volatiles) in the Ames/Salmonella assay. A Tedlar bag vaporization technique was developed, which increased contact time between the volatiles and bacterial test system, circumvented volatilization limitations in the standard plate incorporation and preincubation methods, allowed chemical analysis during incubation, and was flexible in design. The vaporization technique was evaluated concurrently against the plate incorporation and preincubation techniques with eight liquid volatile mutagens in the Ames/Salmonella mutagenicity assay with Salmonella typhimurium strains TA100 and TA102. Results suggested that when volatile organic chemicals with boiling points below 63 degrees C were tested for mutagenic activity, the most sensitive test conditions were the vaporization technique with TA100. GC analysis of epichlorohydrin and buty...
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Study of the relationship between mutagenicity and molecular structure for a data set of nitrogenous cyclic compounds is reported. A computerized SAR system (ADAPT) was utilized to classify a data set of 114 nitrogenous cyclic compounds... more
Study of the relationship between mutagenicity and molecular structure for a data set of nitrogenous cyclic compounds is reported. A computerized SAR system (ADAPT) was utilized to classify a data set of 114 nitrogenous cyclic compounds with 19 molecular descriptors. All of the descriptors represented at least 10% of the compounds in the data sets. The average correct predictability of the data base was calculated to be 89% after evaluating 100 training/prediction subsets. The actual predictive ability of the discriminants generated by the ADAPT system was demonstrated by predicting the mutagenicity of structurally similar compounds not in the data set. Weight vectors generated in the pattern recognition programs were used to predict the bacterial mutagenicity of 10 compounds which were not included in the data set. All of the compounds were predicted correctly which was actually better than the 89% calculated by the system. This displayed the ability of the system of classify compo...
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The Salmonella/microsome assay with strains TA97, TA98, TA100 and TA102 was used to examine the potential mutagenicity and structure-activity of 16 mono- and di-halogenated pyridines. The chemical reactivity of the halopyridines suggests... more
The Salmonella/microsome assay with strains TA97, TA98, TA100 and TA102 was used to examine the potential mutagenicity and structure-activity of 16 mono- and di-halogenated pyridines. The chemical reactivity of the halopyridines suggests that nucleophilic displacement of halogens can occur with halogens at positions 2, 4 and 6 being displaced in addition-elimination reactions. 2-Chloropyridine gave a positive result with rat-liver metabolic activation, and 2-fluoropyridine gave equivocal results under these conditions. Mutagenic responses were also obtained with 2-chloromethyl pyridine and 3-chloromethyl pyridine, in both the presence and absence of rat-liver S9. These results suggest that the halogenated pyridines, especially with halogens at the 2-position, and singly on a methyl substituent, have mutagenic activity in the Salmonella assay.
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10 complex hazardous wastes were tested for mutagenic activity using a modified version of the TLC/Salmonella assay developed by Bjørseth et al. (1982). This fractionation/bioassay scheme couples thin-layer chromatography (TLC) with the... more
10 complex hazardous wastes were tested for mutagenic activity using a modified version of the TLC/Salmonella assay developed by Bjørseth et al. (1982). This fractionation/bioassay scheme couples thin-layer chromatography (TLC) with the Salmonella/mammalian-microsome (Ames) assay for the detection of mutagenic constituents in complex mixtures. Crude (unadulterated) hazardous wastes and selected hazardous waste extracts were fractionated on commercially available cellulose TLC plates. Mutagenicity testing was performed in situ by applying a single overlay of minimal growth agar, tester strain TA98 or TA100, and the optional metabolic activation system directly onto the developed chromatogram. A mutagenic effect was indicated either by the appearance of localized clusters of revertant colonies or by an increase in total revertant growth vis-à-vis control plates. 7 of 10 hazardous wastes (including tars, emulsions, sludges, and spent acids and caustics) demonstrated mutagenic activity ...
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7 laboratories participated in a collaborative study to evaluate an EPA standard protocol for the Ames test. The study utilized Salmonella typhimurium (strains TA98 and TA100) and 3 metabolic activation levels (0%, 2%, and 10% S9 in the... more
7 laboratories participated in a collaborative study to evaluate an EPA standard protocol for the Ames test. The study utilized Salmonella typhimurium (strains TA98 and TA100) and 3 metabolic activation levels (0%, 2%, and 10% S9 in the S9 mix). 6 pure chemicals and 2 complex mixtures were tested as coded unknowns. Ability to obtain qualitative results in agreement with published data was less (% agreement) than that reported in an earlier study (% agreement) by de Serres and Ashby (1981) in which each laboratory used its own protocol. The conclusion from analysis of the quantitative data from this interlaboratory Ames study was that both intralaboratory and interlaboratory variations were substantial. Results for the same substance varied by an order of magnitude or more (CV of 115%) when the mutagenic response was measured as the slope of the dose response in revertants/microgram. Taking interlaboratory variation into account, one chemical must be more than an order of magnitude m...