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J Lewtas

Publications and source records attributed to J Lewtas.

At least 73 records · Page 4Linked to original sources
PubMed1989

A genotoxic assessment of environmental tobacco smoke using bacterial bioassays.

Recently, the National Research Council in the U.S.A. stated that laboratory studies of environmental tobacco smoke (ETS) should be important in identifying ETS carcinogens, their concentrations in typical daily environments, and in understanding how these compounds contribute to ETS dose-response relationships. This paper demonstrates that integrated chemical and bacterial mutagenicity information can be used to identify ETS genotoxicants, monitor human exposure, and make comparative assessments. Approximately 1/3 of the ETS constituents for which there is quantitative analytical chemistry information also have associated genotoxicity information. For example, 11 of the quantitated compounds are animal carcinogens. Work presented in this paper demonstrates that both the nonparticle-bound semivolatile and the particulate-bound organic material contain bacterial mutagens. These ETS organics give an equivalent of approximately 86,000 revertants per cigarette. In addition, this article summarized efforts to estimate ETS bacterial mutagenicity, to use bacterial tests for the monitoring of ETS-impacted indoor environments, and to use bacterial assays for the direct monitoring of human exposure.

Microbial Sensitivity Tests↗
PubMed1989

Differences in detection of DNA adducts in the 32P-postlabelling assay after either 1-butanol extraction or nuclease P1 treatment.

The use of nuclease P1 treatment and 1-butanol extraction to increase the sensitivity of the 32P-postlabelling assay for DNA adducts have been compared. Although similar results were obtained with the two methods for standard adducts formed with benzo[a]pyrene diol epoxide I (BPDE-I), nuclease P1 treatment resulted in a significant reduction in detection of major adducts from 1-amino-6-nitropyrene (1-amino-6-NP), 1-amino-8-nitropyrene (1-amino-8-NP), 2-aminofluorene (2-AF), 2-naphthylamine (2-NA) and 4-aminobiphenyl (4-ABP) modified DNAs, but not following the 32P-postlabelling analysis of 2-acetylaminofluorene (2-AAF) modified DNA. These results suggest that, at least initially, both modifications of the 32P-postlabelling assay should be used for the detection of unknown adducts or for adducts derived from nitroaromatics and aromatic amines.

1-Butanol↗
PubMed1989

Use of bioassay methods to evaluate mutagenicity of ambient air collected near a municipal waste combustor.

An ambient air sampling study was conducted around a municipal waste combustor; a primary goal was to develop procedures and methods to evaluate the emissions of organic mutagens resulting from incomplete combustion of municipal waste. The products of incomplete combustion from incineration include complex mixtures of organics, particularly polycyclic aromatic compounds, which are present after atmospheric dilution and cooling in emissions as semi-volatile or particle bound organic compounds. Combustion emissions are generally recognized as a potential cancer risk since they contain many carcinogenic and mutagenic polycyclic aromatic hydrocarbons. Analyzing such a complex mixture for the presence of even a few selected chemicals is difficult and provides risk information on only a fraction of the chemicals present. Bioassay methods, however, may be directly applied to evaluate the mutagenic and potential carcinogenic activity of the complex organics from combustion emissions. The Salmonella (Ames) assay was used to determine the mutagenicity associated with particles from ambient air collected near a municipal waste combustor. Dose-response data was generated, and mutagenicity concentrations were calculated to demonstrate the utility of bioassay in assessing the potential impact of emissions from municipal waste combustion. This phase of study quantified mutagenicity concentrations in ambient air but did not detect organic mutagens that could be attributed to incinerator emissions.

Air Pollutants, Occupational↗
PubMed1989

Home air nicotine levels and urinary cotinine excretion in preschool children.

We examined the extent of correlation between home air nicotine levels and urine cotinine/creatinine ratios (CCR) in 27 children who attended a research day care program where they were not exposed to environmental tobacco smoke (ETS) during the daytime hours. Average concentrations of nicotine in home air were determined by active air sampling during the evening and night hours on 2 consecutive days. Urine samples for cotinine and creatinine determinations were collected before, during, and after the two sampling periods. In addition, four sequential weekly urine samples for CCR were obtained from study children to determine the extent to which single determinations of CCR were representative for individual children. Fifteen children resided in homes with smokers, and 12 did not. Urine CCR consistently distinguished most exposed and unexposed children. However, three exposed children had urine CCRs that clustered routinely around the criterion CCR (30 ng/mg cotinine-creatinine) that best distinguished exposed and unexposed children. In children exposed to ETS in the home, there was a significant correlation between average home air nicotine levels and the average logarithm of urine CCR the two mornings after the home air monitoring periods (r = 0.68; p = 0.006). In study children, urine CCRs were remarkably stable over the 1-month observation period. Rank correlation coefficients for sequential weekly determinations of CCR were consistently greater than r = 0.88; p less than 0.0001.

Child, Preschool↗
PubMed1989

Emerging methodologies for assessment of complex mixtures: application of bioassays in the Integrated Air Cancer Project.

The assessment of complex mixtures of environmental pollutants requires new interdisciplinary strategies. Integration of bioassay methodologies into these strategies is an important tool that provides direct evidence of the toxicity of a mixture. Short-term genetic bioassays are now widely used in the cancer assessment of complex mixtures. New and emerging interdisciplinary methodologies for assessing complex mixtures using bioassays are illustrated by the U.S. EPA's Integrated Air Cancer Project (IACP). The goals of this project are to identify the major airborne carcinogens and their emission sources and to improve the methodology and data available for human exposure and risk assessment from airborne carcinogens. The research effort is focused primarily on characterizing the impact of complex mixtures of products of incomplete combustion, including gaseous, semi-volatile, and particle-bound organic species. Short-term genetic bioassays have been integrated into several analysis strategies, including environmental biomonitoring; bioassay-directed fractionation/characterization; transformation studies; source apportionment; and exposure, dosimetry, and risk assessment.

Air Pollutants↗
PubMed1988

Genotoxicity of complex mixtures: strategies for the identification and comparative assessment of airborne mutagens and carcinogens from combustion sources.

Two strategies for assessment of the toxicity of complex mixtures are described and illustrated with examples from genotoxicity studies of complex combustion mixtures. The first, a strategy for identifying biologically active compounds or compound classes in complex mixtures, is called bioassay-directed fractionation and characterization. The identification and assessment of mutagens and potential carcinogens in complex mixtures has been significantly advanced by the use of short-term genetic bioassays. Bioassay-directed fractionation coupled with new analytical characterization methods has provided the tools needed to more efficiently identify potential carcinogens in complex combustion emissions and urban air samples. These studies have shown that a significant portion of the mutagenicity in combustion emissions and urban air is found in fractions more polar than polynuclear aromatic hydrocarbons (PAHs). A second strategy, the comparative potency method, provides an approach to evaluating the relative toxicities of a series of mixtures. The comparative mutagenicity and carcinogenicity of a series of combustion emissions has been assessed using dose-response studies in bacteria, mammalian cells, and rodents. Comparative mutagenic and tumorigenic emission rates or emission factors provide a means to directly compare the relative hazard of the sources. This data base has also been used to develop a comparative risk assessment methodology for combustion emissions.

Air Pollutants↗
PubMed1987

Mutagenic determination of passive smoking.

The mutagenic activity of tobacco smoke has been further investigated with the plate-incorporation method and a microsuspension technique of the Ames Salmonella assay. The microsuspension test gives a higher response than the conventional plate incorporation test. It is possible to detect environmental tobacco smoke (ETS) in moderately smoky indoor environments by collection of particulate matter with personal low volume samplers followed by particle extraction and mutagenicity testing with the microsuspension assay.

Mutagenicity Tests↗
PubMed1987

Use of limited protocols to evaluate the genotoxicity of hazardous wastes in mammalian cell assays: comparison to Salmonella.

Dichloromethane extracts of four diverse hazardous wastes (coke plant, herbicide manufacturing, pulp and paper, and oil refining) were evaluated for mutagenicity in strains TA98 and TA100 of Salmonella. These extracts also were tested for biological activity in short-term mammalian cell assays, including mutagenicity in L5178Y/TK +/- mouse lymphoma cells, chromosomal aberrations and sister chromatid exchanges in Chinese hamster ovary (CHO) cells, morphological transformation in BALB/c-3T3 cells, and teratogenic potential in mouse limb bud cells. The mammalian cell assays were performed using limited protocols that consisted of a preliminary testing of the extracts for cytotoxicity in CHO cells in order to estimate the appropriate dose range for the other assays. These assays were then performed once with only a few doses of extract; all but the mouse limb bud assay were performed in the presence of metabolic activation. Although all four of the wastes were presumptively positive for either mutation or cytogenetic effects, none of the wastes transformed BALB/c-3T3 cells. Further studies are needed to establish which mammalian cell assays, if any, might be useful complements to the Salmonella assay for the purpose of screening hazardous wastes.

Animals↗
PubMed1987

Metabolism and DNA binding of 1-nitro[14C]pyrene by isolated rabbit tracheal epithelial cells.

The metabolism of 1-nitro[14C]pyrene (1-NP) and the binding of its reactive intermediates to DNA and protein was examined in rabbit tracheal epithelial cells. The tracheal cells isolated by two protease digestion methods had normal cellular morphology and viability. The digestion method which demonstrated the highest rate of 1-NP metabolism and DNA binding used a 1 h incubation of the tracheas with 1% protease at 37 degrees C. Metabolites from the incubation medium and cell lysates were extracted, analyzed and quantitated by h.p.l.c. The majority of the metabolites produced by tracheal cells were EA:AC extractable and were released to the surrounding incubation medium. The predominant metabolites identified and quantified in the medium were the ring oxidation products, a 1-NP-diol, 1-NP phenols (6- or 8-OH-1-NP), 10-OH-1-NP and 3-OH-1-NP. Major metabolites formed by nitroreduction were NAAP and 1-AMP. The metabolites retained by tracheal cells were qualitatively identical to those identified in the medium but were present at one-seventh to one-tenth of the amounts. The rate of both 1-NP metabolism and DNA binding was very high. After 4 h, 62% of the 1-NP was metabolized and 198 DNA adducts/10(6) nucleotides were formed. The rate of [14C]1-NP-DNA adducts formation was highest at 30 min of incubation (124 adducts/10(6) nucleotides/h). These high rates of metabolism and DNA binding are consistent with the possibility that tracheal cells may be a particular target tissue for tumor induction by nitrosubstituted polycyclic aromatic hydrocarbons associated with diesel and other combustion emission particles. The preponderance of highly mutagenic 1-NP phenols as metabolites suggest that ring oxidation as well as nitroreduction may result in intermediates which form DNA adducts.

Animals↗
PubMed1986

Metabolism of 1-nitropyrene by cultured rabbit alveolar macrophages and respiratory tract tissues.

The metabolism of 1-nitro[14C]pyrene (14C-1-NP; 8.1 microM) was studied in cultured (20 hr) rabbit alveolar macrophages, lung tissue, and tracheal tissue. Metabolites from the incubation medium and from the macrophages and respiratory tract tissues were extracted and then analyzed and quantified by high-pressure liquid chromatography. The following metabolites were detected in the lung and tracheal tissue incubation medium: 1-nitropyrene-4,5-dihydrodiol, N-acetyl-1-aminopyrene, 1-aminopyrene, and 10-hydroxy-1-nitropyrene. Nitropyrene phenols (4-, 5-, 6-, 8- or 9-hydroxy-1-nitropyrene) and 3-hydroxy-1-nitropyrene were only detected in the lung and tracheal tissue and not in the incubation medium for these tissues. Minor amounts of 1-aminopyrene and 10-hydroxy-1-nitropyrene were detected in the macrophage incubation medium, and only minute quantities of 1-nitropyrene-4,5-dihydrodiol, 1-aminopyrene, and 10-hydroxy-1-nitropyrene were detected in macrophages. The total percentage of 1-NP metabolism was significantly greater in the lung and tracheal tissue (28.0 and 23.0% of the recovered 14C, respectively) than in the alveolar macrophages (6.3% of the recovered 14C). The tracheal tissue was found to have the highest activity both in 1-NP metabolism and intracellular metabolite concentration. A major portion of the 1-NP metabolites produced was released into the incubation medium. The majority of the metabolites produced by tracheal and lung tissue, 70 and 84%, respectively, were ethyl acetate extractable. The metabolites retained within the cells or tissues were also predominantly ethyl acetate extractable rather than water soluble (83% for the macrophages and trachea, 95% for the lung tissue). The metabolite profiles obtained demonstrate that metabolism by both nitro reduction and ring oxidation occurs in respiratory tissue, and a degree of tissue specificity in the formation of metabolites exists. Ring oxidation was demonstrated in the lung and tracheal tissue, but very little occurred in the macrophages.

Animals↗
PubMed1986

Toxicity of particles emitted from combustion of waste crankcase oil: in vitro and in vivo studies.

The ever-rising cost of energy provides incentives for the utilization of low-cost waste crankcase oil (WCO) for space heating. Although WCO is known to contain toxic heavy metals, the potential health hazards of emissions and waste products resulting from the combustion of WCO are unknown. Thus, the toxicity of the emission particles and waste products from two different types of burners, a Dravo atomizing oil burner (AOB) and a Kroll vaporizing oil burner (VOB), is evaluated using automotive WCO. Samples are characterized by performing elemental analysis and scanning electron microscopy. Both burners emitted fine (less than or equal to 3 microns), respirable particles. The AOB emission particles contained high concentrations of toxic heavy metals, especially Pb, which showed concentrations as high as 7.5%. The VOB retained a significant amount of heavy metals in the burner residue and emitted a much smaller quantity into the air. The toxicity of AOB emission particles, VOB emission particles, and VOB waste residue is evaluated in three bioassay systems, including a rabbit alveolar macrophage (RAM) cytotoxicity in vitro assay, an intratracheal injection infectivity assay, and a peritoneal irritancy test in mice. The emission particles from both burners and leachate from VOB residue produce a dose-related reduction in viability and cellular adenosine triphosphate (ATP) in alveolar macrophages following 20-hr exposure. Acidity of the RAM medium due to the presence of VOB emission particles and waste leachate contributes to its toxicity.(ABSTRACT TRUNCATED AT 250 WORDS)

Air Pollutants↗
PubMed1986

Bioavailability of 1-nitropyrene from model coal fly ash and its uptake by alveolar macrophages.

Alveolar macrophage cultures exposed to coal fly ash vapor-coated with 1-nitropyrene were used as a model system to study the bioavailability and the uptake of a nitroaromatic hydrocarbon from coal combustion emissions. Initially, 1-nitropyrene-coated fly ash and uncoated fly ash were examined for cytotoxicity using rabbit alveolar macrophages and for mutagenicity in the Salmonella typhimurium plate incorporation assay. The results were compared to determine the effects of vapor deposition. The distribution and recovery of 1-nitropyrene from macrophage cultures treated with coated fly ash were determined by using a reverse-phase high-performance liquid chromatography-fluorescence method. 1-Nitropyrene alone was not very toxic, nor did vapor deposition of 1-nitropyrene onto coal fly ash significantly affect the toxicity of the fly ash. Most toxicity resulted from the original, uncoated fly ash particles. 1-Nitropyrene after being coated onto the particles was bioavailable in agar and aqueous culture medium. The coated fly ash showed mutagenic activity when the particles were tested directly; the uncoated fly ash did not show mutagenic activity. 1-Nitropyrene recovery from alveolar macrophage cultures exposed to the coated fly ash diminished as cell number increased. The rate of 1-nitropyrene loss was 2.7 ng/10(6) macrophages for medium and 4.1 ng/10(6) macrophages for the whole culture. The mutagenic activity recovered from these macrophage cultures also decreased with increasing cell number.

Animals↗
PubMed1986

Comparative characterization of organic emissions from diesel particles, coke oven mains, roofing tar vapors and cigarette smoke condensate.

This paper reports the characterization of the extractable organics from diesel particulate emissions compared to other complex organics which have been reported to increase the risk of human lung cancer. Class fractions of diesel, cigarette smoke condensate, roofing tar, and coke oven extracts were obtained using liquid/liquid partitioning and silica gel chromatography. Capillary GC/MS was used to identify compounds in each extract fraction. This manuscript reports the mass distribution after fractionation of each extract, all identified fraction components and quantification of selected mutagenic and carcinogenic compounds.

Air Pollutants↗