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BACKGROUND: Open burning of anthropogenic sources can release hazardous emissions and has been associated with increased prevalence of cardiopulmonary health outcomes. Exposure to smoke emitted from burn pits in military bases has been linked with respiratory illness among military and civilian personnel returning from war zones. Although the composition of the materials being burned is well studied, the resulting chemistry and potential toxicity of the emissions are not. METHODS: Smoke emission condensates from either flaming or smoldering combustion of five different types of burn pit-related waste: cardboard; plywood; plastic; mixture; and mixture/diesel, were obtained from a laboratory-scale furnace coupled to a multistage cryotrap system. The primary emissions and smoke condensates were analyzed for a standardized suite of chemical species, and the condensates were studied for pulmonary toxicity in female CD-1 mice and mutagenic activity in Salmonella (Ames) mutagenicity assay using the frameshift strain TA98 and the base-substitution strain TA100 with and without metabolic activation (S9 from rat liver). RESULTS: Most of the particles in the smoke emitted from flaming and smoldering combustion were less than 2.5 µm in diameter. Burning of plastic containing wastes (plastic, mixture, or mixture/diesel) emitted larger amounts of particulate matter (PM) compared to other types of waste. On an equal mass basis, the smoke PM from flaming combustion of plastic containing wastes caused more inflammation and lung injury and was more mutagenic than other samples, and the biological responses were associated with elevated polycyclic aromatic hydrocarbon levels. CONCLUSIONS: This study suggests that adverse health effects of burn pit smoke exposure vary depending on waste type and combustion temperature; however, burning plastic at high temperature was the most significant contributor to the toxicity outcomes. These findings will provide a better understanding of the complex chemical and combustion temperature factors that determine toxicity of burn pit smoke and its potential health risks at military bases.
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Contaminantes Atmosféricos , Material Particulado , Contaminantes Atmosféricos/análisis , Contaminantes Atmosféricos/toxicidad , Animales , Femenino , Incineración , Pulmón , Ratones , Pruebas de Mutagenicidad , Mutágenos , Material Particulado/toxicidad , RatasRESUMEN
OBJECTIVE: Wildland firefighters (WLFFs) experience repeated exposures to wildland fire smoke (WFS). However, studies about WLFFs remain regionally limited. The objective of this study was to assess the effect of WFS exposure on urinary mutagenicity and cell oxidation among WLFFs who work at prescribed burns in the Midwestern USA. METHODS: A total of 120 spot urine samples was collected from 19 firefighters right before (pre-shift), immediately after (post-shift), and the morning (next-morning) following work shifts on prescribed burn days (burn days) and regular workdays (non-burn days). The levels of urinary mutagenicity, 8-isoprostane, malondialdehyde and oxidised guanine species (Ox-GS) were measured. Linear mixed-effect models were used to determine the difference of cross-shift changes in the concentrations of urinary biomarkers. RESULTS: Post-shift levels of creatinine-corrected urinary mutagenicity and 8-isoprostane were non-significantly higher than pre-shift levels (1.16× and 1.64×; p=0.09 and 0.07) on burn days. Creatinine-corrected Ox-GS levels increased significantly in next-morning samples following WFS exposure (1.62×, p=0.03). A significant difference in cross-shift changes between burn and non-burn days was observed in 8-isoprostane (2.64×, p=0.03) and Ox-GS (3.00×, p=0.02). WLFFs who contained the fire (performed holding tasks) had a higher pre-morning to next-morning change in urinary mutagenicity compared with those who were lighting fires during the prescribed burns (1.56×, p=0.03). CONCLUSIONS: Compared with the other regions, WLFFs who worked in Midwestern forests had an elevated urinary mutagenicity and systemic oxidative changes associated with WFS exposure at prescribed burns.
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In a recent U.S. Geological Survey/U.S. Environmental Protection Agency study assessing more than 700 organic compounds in 38 streams, in vitro assays indicated generally low estrogen, androgen, and glucocorticoid receptor activities, with 13 surface waters with 17ß-estradiol-equivalent (E2Eq) activities greater than a 1-ng/L estimated effects-based trigger value for estrogenic effects in male fish. Among the 36 samples assayed for mutagenicity in the Salmonella bioassay (reported here), 25% had low mutagenic activity and 75% were not mutagenic. Endocrine and mutagenic activities of the water samples were well correlated with each other and with the total number and cumulative concentrations of detected chemical contaminants. To test the predictive utility of knowledge-base-leveraging approaches, site-specific predicted chemical-gene (pCGA) and predicted analogous pathway-linked (pPLA) association networks identified in the Comparative Toxicogenomics Database were compared with observed endocrine/mutagenic bioactivities. We evaluated pCGA/pPLA patterns among sites by cluster analysis and principal component analysis and grouped the pPLA into broad mode-of-action classes. Measured E2eq and mutagenic activities correlated well with predicted pathways. The pPLA analysis also revealed correlations with signaling, metabolic, and regulatory groups, suggesting that other effects pathways may be associated with chemical contaminants in these waters and indicating the need for broader bioassay coverage to assess potential adverse impacts.
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Ríos , Contaminantes Químicos del Agua , Animales , Bioensayo , Monitoreo del Ambiente , Estrógenos , Masculino , Pruebas de Mutagenicidad , MutágenosRESUMEN
Background: Wildland firefighters conducting prescribed burns are exposed to a complex mixture of pollutants, requiring an integrated measure of exposure. Objective: We used urinary mutagenicity to assess if systemic exposure to mutagens is higher in firefighters after working at prescribed burns versus after non-burn work days. Other biomarkers of exposure and oxidative stress markers were also measured. Methods: Using a repeated measures study design, we collected urine before, immediately after, and the morning after a work shift on prescribed burn and non-burn work days from 12 healthy subjects, and analyzed for malondialdehyde (MDA), 8-isoprostane, 1-hydroxypyrene (OH-pyrene), and mutagenicity in Salmonella YG1041 +S9. Particulate matter (PM2.5) and carbon monoxide (CO) were measured by personal monitoring. Light-absorbing carbon (LAC) of PM2.5 was measured as a surrogate for black carbon exposure. Linear mixed-effect models were used to assess cross-work shift changes in urinary biomarkers. Results: No significant differences occurred in creatinine-adjusted urinary mutagenicity across the work shift between burn days and non-burn days. Firefighters lighting fires had a non-significant, 1.6-fold increase in urinary mutagenicity for burn versus non-burn day exposures. Positive associations were found between cross-work shift changes in creatinine-adjusted urinary mutagenicity and MDA (p = 0.0010), OH-pyrene (p = 0.0001), and mass absorption efficiency which is the LAC/PM2.5 ratio (p = 0.2245), respectively. No significant effect of day type or work task on cross-work shift changes in MDA or 8-isoprostane was observed. Conclusion: Urinary mutagenicity may serve as a suitable measure of occupational smoke exposures among wildland firefighters, especially among those lighting fires for prescribed burns.
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Contaminantes Ocupacionales del Aire/toxicidad , Biomarcadores/orina , Bomberos , Mutágenos/toxicidad , Exposición Profesional/efectos adversos , Estrés Oxidativo/efectos de los fármacos , Humo/efectos adversos , Contaminantes Ocupacionales del Aire/orina , Creatinina/orina , Dinoprost/análogos & derivados , Dinoprost/orina , Incendios , Humanos , Exposición por Inhalación/efectos adversos , Exposición por Inhalación/análisis , Malondialdehído/orina , Pruebas de Mutagenicidad , Exposición Profesional/análisis , Pirenos/orina , Salmonella/efectos de los fármacos , Salmonella/genética , South CarolinaRESUMEN
Iodinated contrast media (ICM) are nonmutagenic agents administered for X-ray imaging of soft tissues. ICM can reach µg/L levels in surface waters because they are administered in high doses, excreted largely unmetabolized, and poorly removed by wastewater treatment. Iodinated disinfection byproducts (I-DBPs) are highly genotoxic and have been reported in disinfected waters containing ICM. We assessed the mutagenicity in Salmonella of extracts of chlorinated source water containing one of four ICM (iopamidol, iopromide, iohexol, and diatrizoate). We quantified 21 regulated and nonregulated DBPs and 11 target I-DBPs and conducted a nontarget, comprehensive broad-screen identification of I-DBPs. We detected one new iodomethane (trichloroiodomethane), three new iodoacids (dichloroiodoacetic acid, chlorodiiodoacetic acid, bromochloroiodoacetic acid), and two new nitrogenous I-DBPs (iodoacetonitrile and chloroiodoacetonitrile). Their formation depended on the presence of iopamidol as the iodine source; identities were confirmed with authentic standards when available. This is the first identification in simulated drinking water of chloroiodoacetonitrile and iodoacetonitrile, the latter of which is highly cytotoxic and genotoxic in mammalian cells. Iopamidol (5 µM) altered the concentrations and relative distribution of several DBP classes, increasing total haloacetonitriles by >10-fold. Chlorination of ICM-containing source water increased I-DBP concentrations but not mutagenicity, indicating that such I-DBPs were either not mutagenic or at concentrations too low to affect mutagenicity.
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Desinfectantes , Contaminantes Químicos del Agua , Purificación del Agua , Animales , Medios de Contraste , Desinfección , Halogenación , Mutágenos , Rayos XRESUMEN
No study has evaluated the mutagenicity of atmospheres with a calculated air quality health index (AQHI). Thus, we generated in a UV-light-containing reaction chamber two simulated atmospheres (SAs) with similar AQHIs but different proportions of criteria pollutants and evaluated them for mutagenicity in three Salmonella strains at the air-agar interface. We continuously injected into the chamber gasoline, nitric oxide, and ammonium sulfate, as well as either α-pinene to produce SA-PM, which had a high concentration of particulate matter (PM): 119 ppb ozone (O3), 321 ppb NO2, and 1007 µg/m3 PM2.5; or isoprene to produce SA-O3, which had a high ozone (O3) concentration: 415 ppb O3, 633 ppb NO2, and 55 µg/m3 PM2.5. Neither PM2.5 extracts, NO2, or O3 alone, nor nonphoto-oxidized mixtures were mutagenic or cytotoxic. Both photo-oxidized atmospheres were largely direct-acting base-substitution mutagens with similar mutagenic potencies in TA100 and TA104. The mutagenic potencies [(revertants/h)/(mgC/m3)] of SA-PM (4.3 ± 0.4) and SA-O3 (9.5 ± 1.3) in TA100 were significantly different ( P < 0.0001), but the mutation spectra were not ( P = 0.16), being â¼54% C â T and â¼46% C â A. Thus, the AQHI may have some predictive value for the mutagenicity of the gas phase of air.
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Contaminantes Atmosféricos , Contaminación del Aire , Atmósfera , Pruebas de Mutagenicidad , Mutágenos , Material ParticuladoRESUMEN
Although many volatile organic compounds (VOCs) are regulated to limit air pollution and the consequent health effects, the photooxidation products generally are not. Thus, we examined the mutagenicity in Salmonella TA100 of photochemical atmospheres generated in a steady-state atmospheric simulation chamber by irradiating mixtures of single aromatic VOCs, NOx, and ammonium sulfate seed aerosol in air. The 10 VOCs examined were benzene; toluene; ethylbenzene; o-, m-, and p-xylene; 1,2,4- and 1,3,5-trimethylbenzene; m-cresol; and naphthalene. Salmonella were exposed at the air-agar interface to the generated atmospheres for 1, 2, 4, 8, or 16 h. Dark-control exposures produced non-mutagenic atmospheres, illustrating that the gas-phase precursor VOCs were not mutagenic at the concentrations tested. Under irradiation, all but m-cresol and naphthalene produced mutagenic atmospheres, with potencies ranging from 2.0 (p-xylene) to 10.4 (ethylbenzene) revertants m3 mgC-1 h-1. The mutagenicity was due exclusively to direct-acting late-generation products of the photooxidation reactions. Gas-phase chemical analysis showed that a number of oxidized organic chemical species enhanced during the irradiated exposure experiments correlated (r ≥ 0.81) with the mutagenic potencies of the atmospheres. Molecular formulas assigned to these species indicated that they likely contained peroxy acid, aldehyde, alcohol, and other functionalities.
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CONTEXT: Biodiesel and biodiesel-blend fuels offer a renewable alternative to petroleum diesel, but few data are available concerning the carcinogenic potential of biodiesel exhausts. OBJECTIVES: We compared the formation of covalent DNA adducts by the in vitro metabolic activation of organic extracts of diesel-exhaust particles (DEP) from petroleum diesel and soy biodiesel and correlated DNA adduct levels and mutagenicity in Salmonella TA100. METHODS: We examined two different DEP from petroleum diesel (C-DEP and B0), one from soy bean oil biodiesel (B100) and one from combustion of a blend of 20% B100 and 80% B0 (B20) for in vitro DNA adduct-forming potential under oxidative or nitroreductive conditions in the presence of calf thymus DNA as well as in vivo in Salmonella TA100. The modified DNA was hydrolyzed and analyzed by (32)P-postlabeling using either butanol extraction or nuclease P1 pre-enrichment. RESULTS: Multiple DNA adducts were produced with chromatographic mobilities consistent with PAH and nitro-PAH adducts. The types and quantities of DNA adducts produced by the two independent petroleum diesel DEP were similar, with both polycyclic aromatic hydrocarbon (PAH)- and nitro-PAH-derived adducts formed. Relative potencies for S9-mediated DNA adduct formation, either per mass of particulate or per MJ(th) energy consumed were B100 > B0 > B20. CONCLUSIONS: Soy biodiesel emissions induced DNA damage in the form of presumptive PAH and nitro-PAH DNA adducts that correlated with mutagenicity in Salmonella. B20 is the soy biodiesel used most commonly in the US, and it produced the lowest DNA adduct-emission factor, â¼50% that of petroleum diesel.
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Biocombustibles/toxicidad , Aductos de ADN/biosíntesis , Material Particulado/toxicidad , Salmonella/efectos de los fármacos , Salmonella/metabolismo , Emisiones de Vehículos/toxicidad , Contaminantes Atmosféricos/toxicidad , Relación Dosis-Respuesta a DrogaRESUMEN
CONTEXT: Soy biodiesel is the predominant biodiesel in the USA, but there is little understanding of the classes of chemicals responsible for the mutagenicity of its emissions. OBJECTIVE: We determined some of the chemical classes responsible for the mutagenicity of the particulate matter (PM) of the emissions from petroleum diesel (B0) and biodiesel containing increasing concentrations of soy methyl esters (B20, B50, and B100). MATERIALS AND METHODS: We subjected organic extracts of the PM to bioassay-directed fractionation by sequential elution on silica gel with solvents of increasing polarity to produce four fractions per fuel. We injected these onto high performance liquid chromatography to produce 62 sub-fractions per fraction based on chemical polarity and evaluated all fractions and sub-fractions for mutagenicity in Salmonella. We correlated the results with the concentrations of 32 polycyclic aromatic hydrocarbons (PAHs) in the fractions. RESULTS: The mutagenicity-emission factors of the fractions generally decreased with increasing concentrations of soy in the fuel. Despite the different chemical compositions of the fuels, the extractable organics of all four emissions had similar features: â¼60% of the mass was nonpolar, non-mutagenic compounds; most of the PAHs were polar; and most of the mutagenicity was due to weakly polar and polar compounds. Some of the mutagenicity of B20 was due to highly polar compounds. CONCLUSIONS: The PM from soy biodiesel emissions was less mutagenic than that from petroleum diesel, and this reduction was associated with reduced concentrations of various weakly polar, polar, and highly polar mutagens, including PAHs, aromatic amines, nitroarenes, and oxy-PAHs.
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Biocombustibles/toxicidad , Glycine max/toxicidad , Mutágenos/toxicidad , Salmonella/efectos de los fármacos , Emisiones de Vehículos/toxicidad , Contaminantes Atmosféricos/toxicidad , Bioensayo/métodos , Material Particulado/toxicidad , Salmonella/metabolismoRESUMEN
CONTEXT: Soy biodiesel is the predominant biodiesel fuel used in the USA, but only a few, frequently conflicting studies have examined the potential health effects of its emissions. OBJECTIVE: We combusted petroleum diesel (B0) and fuels with increasing percentages of soy methyl esters (B20, B50 and B100) and determined the mutagenicity-emission factors expressed as revertants/megajoule of thermal energy consumed (rev/MJ(th)). MATERIALS AND METHODS: We combusted each fuel in replicate in a small (4.3-kW) diesel engine without emission controls at a constant load, extracted organics from the particles with dichloromethane, determined the percentage of extractable organic material (EOM), and evaluated these extracts for mutagenicity in 16 strains/S9 combinations of Salmonella. RESULTS: Mutagenic potencies of the EOM did not differ significantly between replicate experiments for B0 and B100 but did for B20 and B50. B0 had the highest rev/MJ(th), and those of B20 and B100 were 50% and â¼85% lower, respectively, in strains that detect mutagenicity due to polycyclic aromatic hydrocarbons (PAHs), nitroarenes, aromatic amines or oxidative mutagens. For all strains, the rev/MJ(th) decreased with increasing biodiesel in the fuel. The emission factor for the 16 EPA Priority PAHs correlated strongly (r(2 )= 0.69) with the mutagenicity-emission factor in strain TA100 + S9, which detects PAHs. CONCLUSIONS: Under a constant load, soy-biodiesel emissions were 50-85% less mutagenic than those of petroleum diesel. Without additional emission controls, petroleum and biodiesel fuels had mutagenicity-emission factors between those of large utility-scale combustors (e.g. natural gas, coal, or oil) and inefficient open-burning (e.g. residential wood fireplaces).
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Biocombustibles/toxicidad , Glycine max/toxicidad , Mutágenos/toxicidad , Salmonella/efectos de los fármacos , Emisiones de Vehículos/toxicidad , Contaminantes Atmosféricos/toxicidad , Animales , Relación Dosis-Respuesta a Droga , Material Particulado/toxicidad , Ratas , Ratas Sprague-Dawley , Salmonella/metabolismoRESUMEN
Most studies of the health effects and chemical characterization of the dust resulting from the catastrophic collapse of the World Trade Center (WTC) on September 11, 2001, have focused on the large inorganic fraction of the dust; however, chemical analyses have identified mutagens and carcinogens in the smaller organic fraction. Here, we determined the mutagenicity of the organic fraction of WTC dust in Salmonella. Only 0.74% of the mass of the particulate matter (PM) <53 µm in diameter was extractable organic matter (EOM). Because the EOM was 10 times more mutagenic in TA100 +S9 than in TA98 +S9 and was negative in TA98 -S9, we inferred, respectively, that polycyclic aromatic hydrocarbons (PAHs) played a role in the mutagenicity and not nitroarenes. In TA98 +S9, the mutagenic potency of the EOM (0.1 revertant/µg EOM) was within the range of EOMs from air and combustion emissions. However, the EOM-based mutagenic potency of the particles (0.0007 revertants/µg PM) was 1-2 orders of magnitude lower than values from a review of 50 combustion emissions and various air samples. We calculated that 37 PAHs analyzed previously in WTC EOM were 5.4% of the EOM mass and 0.04% of the PM mass; some air contained 0.3 µg WTC EOM/m3 (0.02 µg PAHs/m3 ). Populations exposed to WTC dust have elevated levels of prostate and thyroid cancer but not lung cancer. Our data support earlier estimates that PAH-associated cancer risk among this population, for example, PAH-associated lung cancer, was unlikely to be significantly elevated relative to background PAH exposures.
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Contaminantes Atmosféricos , Neoplasias , Hidrocarburos Policíclicos Aromáticos , Humanos , Mutágenos/toxicidad , Mutágenos/análisis , Polvo/análisis , Contaminantes Atmosféricos/toxicidad , Pruebas de Mutagenicidad/métodos , Material Particulado/toxicidad , Material Particulado/análisis , Hidrocarburos Policíclicos Aromáticos/toxicidad , Hidrocarburos Policíclicos Aromáticos/análisisRESUMEN
Benzo[a]pyrene (BP) and dibenzo[a,l]pyrene (DBP) are two polycyclic aromatic hydrocarbons (PAHs) that exhibit distinctly different mutagenicity and carcinogenicity profiles. Although some studies show that these PAHs produce unstable DNA adducts, conflicting data and arguments have been presented regarding the relative roles of these unstable adducts versus stable adducts, as well as oxidative damage, in the mutagenesis and tumor-mutation spectra of these PAHs. However, no study has determined the mutation spectra along with the stable and unstable DNA adducts in the same system with both PAHs. Thus, we determined the mutagenic potencies and mutation spectra of BP and DBP in strains TA98, TA100 and TA104 of Salmonella, and we also measured the levels of abasic sites (aldehydic-site assay) and characterized the stable DNA adducts ((32)P-postlabeling/HPLC) induced by these PAHs in TA104. Our results for the mutation spectra and site specificity of stable adducts were consistent with those from other systems, showing that DBP was more mutagenic than BP in TA98 and TA100. The mutation spectra of DBP and BP were significantly different in TA98 and TA104, with 24% of the mutations induced by BP in TA98 being complex frameshifts, whereas DBP produced hardly any of these mutations. In TA104, BP produced primarily GC to TA transversions, whereas DBP produced primarily AT to TA transversions. The majority (96%) of stable adducts induced by BP were at guanine, whereas the majority (80%) induced by DBP were at adenine. Although BP induced abasic sites, DBP did not. Most importantly, the proportion of mutations induced by DBP at adenine and guanine paralleled the proportion of stable DNA adducts induced by DBP at adenine and guanine; however, this was not the case for BP. Our results leave open a possible role for unstable DNA adducts in the mutational specificity of BP but not for DBP.
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Benzo(a)pireno/toxicidad , Benzopirenos/toxicidad , Aductos de ADN , Mutágenos/toxicidad , Adenina , Guanina , Pruebas de Mutagenicidad , Mutación , Salmonella/genéticaRESUMEN
Drinking water disinfection by-products (DBPs), including the ubiquitous trihalomethanes (THMs), are formed during the treatment of water with disinfectants (e.g., chlorine, chloramines) to produce and distribute potable water. Brominated THMs (Br-THMs) are activated to mutagens via glutathione S-transferase theta 1 (GSTT1); however, iodinated THMs (I-THMs) have never been evaluated for activation by GSTT1. Among the I-THMs, only triiodomethane (iodoform) has been tested previously for mutagenicity in Salmonella and was positive (in the absence of GSTT1) in three strains (TA98, TA100, and BA13), all of which have error-prone DNA repair (pKM101). We evaluated five I-THMs (chlorodiiodomethane, dichloroiodomethane, dibromoiodomethane, bromochloroiodomethane, and triiodomethane) for mutagenicity in Salmonella strain RSJ100, which expresses GSTT1, and its homologue TPT100, which does not; neither strain has pKM101. We also evaluated chlorodiiodo-, dichloroiodo-, and dibromoiodo-methanes in strain TA100 +/- rat liver S9 mix; TA100 has pKM101. None was mutagenic in any of the strains. The I-THMs were generally more cytotoxic than their brominated and chlorinated analogues but less cytotoxic than analogous trihalonitromethanes tested previously. All five I-THMs showed similar thresholds for cytotoxicity at ~2.5 µmoles/plate, possibly due to release of iodine, a well-known antimicrobial. Although none of these I-THMs was activated by GSTT1, iodoform appears to be the only I-THM that is mutagenic in Salmonella, only in strains deficient in nucleotide excision repair (uvrB) and having pKM101. Given that only iodoform is mutagenic among the I-THMs and is generally present at low concentrations in drinking water, the I-THMs likely play little role in the mutagenicity of drinking water.
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Agua Potable/química , Mutagénesis/efectos de los fármacos , Salmonella/efectos de los fármacos , Trihalometanos/toxicidad , Animales , Cloraminas/efectos adversos , Cloraminas/farmacología , Clorofluorocarburos de Metano/efectos adversos , Clorofluorocarburos de Metano/farmacología , Desinfectantes/efectos adversos , Desinfectantes/farmacología , Glutatión Transferasa/química , Humanos , Hidrocarburos Yodados/efectos adversos , Hidrocarburos Yodados/farmacología , Mutágenos/toxicidad , Ratas , Salmonella/genética , Trihalometanos/farmacologíaRESUMEN
Regulatory agencies world-wide face the challenge of performing risk-based prioritization of thousands of substances in commerce. In this study, a major effort was undertaken to compile a large genotoxicity dataset (54,805 records for 9299 substances) from several public sources (e.g., TOXNET, COSMOS, eChemPortal). The names and outcomes of the different assays were harmonized, and assays were annotated by type: gene mutation in Salmonella bacteria (Ames assay) and chromosome mutation (clastogenicity) in vitro or in vivo (chromosome aberration, micronucleus, and mouse lymphoma Tk +/- assays). This dataset was then evaluated to assess genotoxic potential using a categorization scheme, whereby a substance was considered genotoxic if it was positive in at least one Ames or clastogen study. The categorization dataset comprised 8442 chemicals, of which 2728 chemicals were genotoxic, 5585 were not and 129 were inconclusive. QSAR models (TEST and VEGA) and the OECD Toolbox structural alerts/profilers (e.g., OASIS DNA alerts for Ames and chromosomal aberrations) were used to make in silico predictions of genotoxicity potential. The performance of the individual QSAR tools and structural alerts resulted in balanced accuracies of 57-73%. A Naïve Bayes consensus model was developed using combinations of QSAR models and structural alert predictions. The 'best' consensus model selected had a balanced accuracy of 81.2%, a sensitivity of 87.24% and a specificity of 75.20%. This in silico scheme offers promise as a first step in ranking thousands of substances as part of a prioritization approach for genotoxicity.
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The Toxic Substances Control Act (TSCA) became law in the U.S. in 1976 and was amended in 2016. The amended law requires the U.S. EPA to perform risk-based evaluations of existing chemicals. Here, we developed a tiered approach to screen potential candidates based on their genotoxicity and carcinogenicity information to inform the selection of candidate chemicals for prioritization under TSCA. The approach was underpinned by a large database of carcinogenicity and genotoxicity information that had been compiled from various public sources. Carcinogenicity data included weight-of-evidence human carcinogenicity evaluations and animal cancer data. Genotoxicity data included bacterial gene mutation data from the Salmonella (Ames) and Escherichia coli WP2 assays and chromosomal mutation (clastogenicity) data. Additionally, Ames and clastogenicity outcomes were predicted using the alert schemes within the OECD QSAR Toolbox and the Toxicity Estimation Software Tool (TEST). The evaluation workflows for carcinogenicity and genotoxicity were developed along with associated scoring schemes to make an overall outcome determination. For this case study, two sets of chemicals, the TSCA Active Inventory non-confidential portion list available on the EPA CompTox Chemicals Dashboard (33,364 chemicals, 'TSCA Active List') and a representative proof-of-concept (POC) set of 238 chemicals were profiled through the two workflows to make determinations of carcinogenicity and genotoxicity potential. Of the 33,364 substances on the 'TSCA Active List', overall calls could be made for 20,371 substances. Here 46.67%% (9507) of substances were non-genotoxic, 0.5% (103) were scored as inconclusive, 43.93% (8949) were predicted genotoxic and 8.9% (1812) were genotoxic. Overall calls for genotoxicity could be made for 225 of the 238 POC chemicals. Of these, 40.44% (91) were non-genotoxic, 2.67% (6) were inconclusive, 6.22% (14) were predicted genotoxic, and 50.67% (114) genotoxic. The approach shows promise as a means to identify potential candidates for prioritization from a genotoxicity and carcinogenicity perspective.
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Urinary mutagenicity reflects systemic exposure to complex mixtures of genotoxic/carcinogenic agents and is linked to tumor development. Coal combustion emissions (CCE) and diesel engine exhaust (DEE) are associated with cancers of the lung and other sites, but their influence on urinary mutagenicity is unclear. We investigated associations between exposure to CCE or DEE and urinary mutagenicity. In two separate cross-sectional studies of nonsmokers, organic extracts of urine were evaluated for mutagenicity levels using strain YG1041 in the Salmonella (Ames) mutagenicity assay. First, we compared levels among 10 female bituminous (smoky) coal users from Laibin, Xuanwei, China, and 10 female anthracite (smokeless) coal users. We estimated exposure-response relationships using indoor air concentrations of two carcinogens in CCE relevant to lung cancer, 5-methylchrysene (5MC), and benzo[a]pyrene (B[a]P). Second, we compared levels among 20 highly exposed male diesel factory workers and 15 unexposed male controls; we evaluated exposure-response relationships using elemental carbon (EC) as a DEE-surrogate. Age-adjusted linear regression was used to estimate associations. Laibin smoky coal users had significantly higher average urinary mutagenicity levels compared to smokeless coal users (28.4 ± 14.0 SD vs. 0.9 ± 2.8 SD rev/ml-eq, p = 2 × 10-5 ) and a significant exposure-response relationship with 5MC (p = 7 × 10-4 ). DEE-exposed workers had significantly higher urinary mutagenicity levels compared to unexposed controls (13.0 ± 10.1 SD vs. 5.6 ± 4.4 SD rev/ml-eq, p = .02) and a significant exposure-response relationship with EC (p-trend = 2 × 10-3 ). Exposure to CCE and DEE is associated with urinary mutagenicity, suggesting systemic exposure to mutagens, potentially contributing to cancer risk and development at various sites.
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Contaminantes Ocupacionales del Aire/orina , Carbón Mineral/efectos adversos , Mutágenos/análisis , Enfermedades Profesionales/epidemiología , Exposición Profesional/efectos adversos , Fumar/orina , Emisiones de Vehículos/análisis , Contaminantes Ocupacionales del Aire/efectos adversos , China/epidemiología , Carbón Mineral/análisis , Estudios Transversales , Femenino , Humanos , Masculino , Persona de Mediana Edad , Mutágenos/efectos adversos , Enfermedades Profesionales/diagnóstico , Enfermedades Profesionales/genética , Enfermedades Profesionales/orina , Exposición Profesional/análisis , Fumar/efectos adversosRESUMEN
Emissions from solid-fuel burning cookstoves are associated with 3 to 4 million premature deaths annually and contribute significantly to impacts on climate. Pellet-fueled gasifier stoves have some emission factors (EFs) approaching those of gas-fuel (liquid petroleum gas) stoves; however, their emissions have not been evaluated for biological effects. Here we used a new International Organization for Standardization (ISO) testing protocol to determine pollutant- and mutagenicity-EFs for a stove designed for pellet fuel, the Mimi Moto, and for two other forced-draft stoves, Xunda and Philips HD4012, burning pellets of hardwood or peanut hulls. The Salmonella assay-based mutagenicity-EFs (revertants/megajouledelivered) spanned three orders of magnitude and correlated highly (r = 0.99; n = 5) with EFs of the sum of 32 particle-phase polycyclic aromatic hydrocarbons (PAHs). The Mimi Moto/hardwood pellet combination had total-PAH- and mutagenicity-EFs 99.2 and 96.6% lower, respectively, compared to data published previously for the Philips stove burning non-pelletized hardwood, and 100 and 99.8% lower, respectively, compared to those of a wood-fueled three-stone fire. The Xunda burning peanut hull pellets had the highest fuel energy-based mutagenicity-EF (revertants/megajoulethermal) of the pellet stove/fuel combinations tested, which was between that of diesel exhaust, a known human carcinogen, and a natural-draft wood stove. Although the Mimi Moto burning hardwood pellets had the lowest fuel energy-based mutagenicity-EF, this value was between that of utility coal and utility wood boilers. This advanced stove/fuel combination has the potential to greatly reduce emissions in contrast to a traditional stove, but adequate ventilation is required to approach acceptable levels of indoor air quality.
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Contaminantes Atmosféricos/análisis , Contaminantes Ambientales , Culinaria , Humanos , Mutágenos , Material Particulado/análisis , Madera/químicaRESUMEN
Canola (or rapeseed) oil and waste vegetable oil (WVO) are used commonly to make biodiesel fuels composed completely from these oils (B100) or as blends with petroleum diesel (B0). However, no studies have reported the mutagenic potencies of the particulate matter with diameter ≤2.5 µm (PM2.5) or the mutagenicity emission factors, such as revertants/MJthermal (rev/MJth) for these biodiesel emissions. Using strains TA98 and TA100 with the Salmonella (Ames) mutagenicity assay, we determined these metrics for organic extracts of PM2.5 of emissions from biodiesel containing 5% soy oil (soy B5); 5, 20, 50, and 100% canola (canola B5, B20, B50, B100), and 100% waste vegetable oil (WVO B100). The mutagenic potencies (rev/mg PM2.5) of the canola B100 and WVO B100 emissions were generally greater than those of B0, whereas the mutagenicity emission factors (rev/MJth, rev/kg fuel, and rev/m3) were less, reflecting the lower PM emissions of the biodiesels relative to B0. Nearly all the rev/mg PM2.5 and rev/MJth values were greater in TA98 with S9 than without S9, indicating a relatively greater role for polycyclic aromatic hydrocarbons, which require S9, than nitroarenes, which do not. In TA100 -S9, the rev/mg PM2.5 and rev/MJth for the biodiesels were generally ≥ to those of B0, indicating that most of these biodiesels produced more direct-acting, base-substitution mutagenic activity than did B0. For B100 biodiesels and petroleum diesel, the rev/MJth in TA98 + S9 ranked: petroleum diesel > canola > WVO > soy. The diesel emissions generally had rev/MJth values orders of magnitude higher than those of large utility-scale combustors (natural gas, coal, oil, or wood) but orders of magnitude lower than those of inefficient open burning (e.g., residential wood fireplaces). These comparative data of the potential health effects of a variety of biodiesel fuels will help inform the life-cycle assessment and use of biodiesel fuels.
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Contaminantes Atmosféricos/toxicidad , Biocombustibles/toxicidad , Residuos Industriales , Aceites de Plantas/toxicidad , Aceite de Brassica napus/toxicidad , Salmonella/efectos de los fármacos , Aceite de Soja/toxicidad , Emisiones de Vehículos/toxicidad , Activación Metabólica , Animales , Microsomas Hepáticos/enzimología , Pruebas de Mutagenicidad , Tamaño de la Partícula , Material Particulado/toxicidad , Ratas , Salmonella/genéticaRESUMEN
Although chemical disinfection of drinking water is a highly protective public health practice, the disinfection process is known to produce toxic contaminants. Epidemiological studies associate chlorinated drinking water with quantitatively increased risks of rectal, kidney, and bladder cancer. One study found a significant exposure-response association between water mutagenicity and relative risk for bladder and kidney cancer. A number of studies found that several types of disinfection processes increase the level of mutagens detected by the Salmonella assay. As part of a comprehensive study to examine chlorinated and ozonated/postchlorinated drinking water for toxicological contaminants, the Salmonella mutagenicity assay was used to screen both volatile and nonvolatile organic components. The assay also compared the use of reverse osmosis and XAD resin procedures for concentrating the nonvolatile components. Companion papers provide the results from other toxicological assays and chemical analysis of the drinking water samples. The volatile components of the ozonated/postchlorinated and chlorinated water samples and a trihalomethane mixture were mutagenic to a Salmonella tester strain transfected with a rat theta-class glutathione S-transferase and predominantly nonmutagenic in the control strain. In this study, the nonvolatile XAD concentrate of the untreated water possessed a low level of mutagenic activity. However, compared to the levels of mutagenicity in the finished water XAD concentrates, the contribution from the settled source water was minimal. The mutagenicity seen in the reverse osmosis concentrates was < 50% of that seen in the XAD concentrates. Overall, mutagenic responses were similar to those observed in other North American studies and provide evidence that the pilot plant produced disinfection by-products similar to that seen in other studies.
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Desinfectantes/toxicidad , Halogenación , Pruebas de Mutagenicidad/métodos , Ozono/química , Microbiología del Agua , Contaminantes Químicos del Agua/análisis , Contaminantes Químicos del Agua/toxicidad , Purificación del Agua/métodos , Abastecimiento de Agua/análisis , Animales , Humanos , Salmonella typhimurium/efectos de los fármacos , Estados Unidos , United States Environmental Protection AgencyRESUMEN
BACKGROUND: The increasing size and frequency of wildland fires are leading to greater potential for cardiopulmonary disease and cancer in exposed populations; however, little is known about how the types of fuel and combustion phases affect these adverse outcomes. OBJECTIVES: We evaluated the mutagenicity and lung toxicity of particulate matter (PM) from flaming vs. smoldering phases of five biomass fuels, and compared results by equal mass or emission factors (EFs) derived from amount of fuel consumed. METHODS: A quartz-tube furnace coupled to a multistage cryotrap was employed to collect smoke condensate from flaming and smoldering combustion of red oak, peat, pine needles, pine, and eucalyptus. Samples were analyzed chemically and assessed for acute lung toxicity in mice and mutagenicity in Salmonella. RESULTS: The average combustion efficiency was 73 and 98% for the smoldering and flaming phases, respectively. On an equal mass basis, PM from eucalyptus and peat burned under flaming conditions induced significant lung toxicity potencies (neutrophil/mass of PM) compared to smoldering PM, whereas high levels of mutagenicity potencies were observed for flaming pine and peat PM compared to smoldering PM. When effects were adjusted for EF, the smoldering eucalyptus PM had the highest lung toxicity EF (neutrophil/mass of fuel burned), whereas smoldering pine and pine needles had the highest mutagenicity EF. These latter values were approximately 5, 10, and 30 times greater than those reported for open burning of agricultural plastic, woodburning cookstoves, and some municipal waste combustors, respectively. CONCLUSIONS: PM from different fuels and combustion phases have appreciable differences in lung toxic and mutagenic potency, and on a mass basis, flaming samples are more active, whereas smoldering samples have greater effect when EFs are taken into account. Knowledge of the differential toxicity of biomass emissions will contribute to more accurate hazard assessment of biomass smoke exposures. https://doi.org/10.1289/EHP2200.