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K C Donnelly

Publications and source records attributed to K C Donnelly.

At least 19 recordsLinked to original sources
PubMed2006

In vitro models for assessing neurotoxicity of mixtures.

Rapid and inexpensive methods are needed to investigate the interactions of complex mixtures. This commentary addresses the use of cell cultures to detect neurotoxicity of simple binary mixtures, which is a first step in the development of such methods. A small number of recent studies from our laboratory are examined. Though such studies are few, they offer guidance for optimizing the value of cell cultures as systems for chemical toxicity screening and mechanistic research. The same issues that apply to in vitro neurotoxicity studies of single agents also apply to the study of mixtures, such as relevance of endpoints tested, biological usefulness and limitations of cell culture models, and relevance of exposures tested. In this commentary we will focus on several aspects of these issues.

Animals↗
PubMed2006

Biomonitoring of exposure in farmworker studies.

Although biomonitoring has been used in many occupational and environmental health and exposure studies, we are only beginning to understand the complexities and uncertainties involved with the biomonitoring process--from study design, to sample collection, to chemical analysis--and with interpreting the resulting data. We present an overview of concepts that should be considered when using biomonitoring or biomonitoring data, assess the current status of biomonitoring, and detail potential advancements in the field that may improve our ability to both collect and interpret biomonitoring data. We discuss issues such as the appropriateness of biomonitoring for a given study, the sampling time frame, temporal variability in biological measurements to nonpersistent chemicals, and the complex issues surrounding data interpretation. In addition, we provide recommendations to improve the utility of biomonitoring in farmworker studies.

Agriculture↗
PubMed2005

Chromosomal damage in two species of aquatic turtles (Emys orbicularis and Mauremys caspica) inhabiting contaminated sites in Azerbaijan.

The Caspian region and specifically the Apsheron peninsula of Azerbaijan are known to be polluted with a variety of environmental contaminants. These complex mixtures of contaminants make risk assessment difficult. We used the flow cytometry method (FCM) and the micronucleus assay (MN) to assess chromosomal damage in aquatic turtles (Emys orbicularis, the European pond turtle; and Mauremys caspica, the Caspian turtle) inhabiting contaminated wetlands in Azerbaijan. Evidence of genetic damage was found for two sites, Neftchala and Sumgayit, relative to a reference site, Ali Bairamly. Sediment samples from each site were analyzed for PAHs and mercury to evaluate potential contaminant associations with genetic damage. A significant positive correlation was documented between three-ring PAH sediment concentrations and FCM estimates of chromosomal damage in E. orbicularis. These data combine to show that the contaminated wetlands in Sumgayit and Neftchala are genotoxic and that three-ring PAHs are likely a significant influence on observed genotoxicity.

Animals↗
PubMed2005

Patterns of genotoxicity and contaminant exposure: evidence of genomic instability in the marsh frogs (Rana ridibunda) of Sumgayit, Azerbaijan.

The wetlands of Sumgayit in the Azerbaijan Republic contain complex mixtures of contaminants, including polycyclic aromatic hydrocarbons (PAHs), mercury, organochlorine pesticides, and polychlorinated biphenyls. Marsh frogs (Rana ridibunda) were collected from several contaminated wetlands within the city as well as from two reference sites outside the city. Sediment samples revealed heterogeneous patterns of PAH and mercury concentrations throughout Sumgayit, with the highest levels occurring east of the Sumgayit River, within the industrial zone. Flow cytometry and micronucleus assay revealed elevated estimates of genetic damage in frogs from the wetlands east of the Sumgayit River compared to frogs from the reference sites. Flow cytometric data showed a significant correlation with sediment mercury concentrations, whereas population micronucleus frequencies were significantly correlated with high-molecular-weight PAHs.

Animals↗
PubMed2004

Partitioning and desorption behavior of polycyclic aromatic hydrocarbons from disparate sources.

Contaminated sediments pose a unique challenge for risk assessment or remediation because the overlying water column may transport contaminants offsite or to ecological receptors. This research compares the behavior of polycyclic aromatic hydrocarbons (PAHs) on marine sediments from two sites. The first site was affected by shipping activities and the second was impacted by a creosote seep. Organic carbon:water partitioning coefficients (Koc values) were measured with three solutions. Desorption was measured using Tenax beads. PAHs from the ship channel had lower Koc values than those from the creosote facility. For example, the average logKoc value of ship channel pyrene was significantly lower than that of creosote facility pyrene (4.39 +/- 0.35 and 5.29 +/- 0.09, respectively, when tested in 5 mM calcium chloride). These results were consistent with the greater desorption of pyrene, phenanthrene and benzo(a)pyrene from the ship channel than from the creosote facility sediments. Organic compound desorption from sediments can be considered to be a two-stage process, with a labile fraction that desorbs quickly and a refractory fraction that desorbs much more slowly. In both sediments, more than 75% of the benzo(a)pyrene was found to have partitioned into the refractory phase. The amounts of phenanthrene and pyrene that partitioned into the refractory phase were lower. Linear correlations of logKoc with log(CR/CL) (where CR and CL are the fractions of the compound in the refractory and labile phases, respectively, at time zero) showed that partitioning measurements made with the US EPA's Toxicity Characteristic Leaching Procedure fluid (US EPA, 1996) most closely matched predictions of desorption behavior. The data imply that with a larger data set, it may be possible to relate simple partitioning measurements to desorption behavior. Partitioning measurements were used to predict water concentrations. Despite having higher concentrations of carcinogenic PAHs [cPAHs, the seven PAHs categorized by the US EPA (2004) as class B2 carcinogens], creosote facility sediments were predicted to produce lower aqueous concentrations of cPAHs. These results indicate that both sediment and contaminant characteristics will impact contaminant release from sediments.

Adsorption↗
PubMed2003

Neurotoxicity of polycyclic aromatic hydrocarbons and simple chemical mixtures.

Polycyclic aromatic hydrocarbons (PAHs) are a major class of environmental pollutants. These chemicals are the products of incomplete combustion and are present in every compartment of the environment. While the carcinogenic potential of these chemicals has been investigated in numerous studies, very little is known about the potential of these chemicals to produce damage to neural cells. The objective of this study was to investigate the toxicity of several model PAHs and binary mixtures of these chemicals in neural cells. Chemicals tested included benzo[a]pyrene (BaP), chrysene, anthracene, and pentachlorophenol (PCP). Four end points, including amino acid incorporation, total protein, total cell count, and viable cells (trypan dye exclusion), were measured in SY5Y human neuroblastoma cells and C6 rat glioma cells. The most sensitive measure of PAH toxicity in neural cells was amino acid incorporation into proteins. BaP was the most toxic of all PAHs tested, and anthracene failed to produce a toxic response at any concentration tested. Without metabolic activation, BaP induced a significant cytotoxic response at a concentration of 30 microM. With activation (0.25% S9), BaP induced a response at concentration levels of 3 microM and 30 microM. Minimal toxicity was observed with chrysene at the highest concentration tested, and anthracene failed to produce a toxic response at any concentration tested. With mixtures of PAHs the majority of samples induced additive responses. The minimum concentration required to induce a significant response was reduced for the mixture of chrysene and BaP when compared to BaP alone. In addition, PCP appeared to increase the inhibition of acetylcholinesterase by mipafox. The data suggest that PAHs are capable of producing damage to neural cells only at concentrations that are near their solubility limits.

Amino Acids↗
PubMed2003

Neurotoxicity induced in differentiated SK-N-SH-SY5Y human neuroblastoma cells by organophosphorus compounds.

Organophosphorus (OP) compounds used as insecticides and chemical warfare agents are known to cause potent neurotoxic effects in humans and animals. Organophosphorus-induced delayed neuropathy (OPIDN) is currently thought to result from inhibition of neurotoxic esterase (NTE), but the actual molecular and cellular events leading to the development of OPIDN have not been characterized. This investigation examined the effects of OP compounds on the SY5Y human neuroblastoma cells at the cellular level to further characterize cellular targets of OP neurotoxicity. Mipafox and paraoxon were used as OP models that respectively do and do not induce OPIDN. Mipafox (0.05 mM) significantly decreased neurite length in SY5Y cells differentiated with nerve growth factor (NGF) while paraoxon at the same concentration had no effect when evaluated after each of three 4-day developmental windows during which cells were treated daily with OP or vehicle. In contrast, paraoxon but not mipafox altered intracellular calcium ion levels ([Ca(2+)](i)), as seen in three types of experiments. First, immediately following the addition of a single high concentration of OP to the culture, paraoxon caused a transient increase in [Ca(2+)](i), while mipafox up to 2 mM had no effect. Paraoxon hydrolysis products could also increase intracellular Ca(2+) levels, although the pattern of rise was different than it appeared immediately after paraoxon administration. Second, repeated low-level paraoxon treatment (0.05 mM/day for 4 days) decreased basal [Ca(2+)](i) in NGF-differentiated cells, though mipafox had no effect. Third, carbachol, a muscarinic acetylcholine receptor agonist, transiently increased [Ca(2+)](i) in differentiated cells, an affect attenuated by 4-day pretreatment with paraoxon (0.05 mM/day), but not by pretreatment with mipafox. These results indicate that the decrease in neurite extension that resulted from mipafox treatment was not caused by a disruption of Ca(2+) homeostasis. The effects of OPs that cause or do not cause OPIDN were clearly distinguishable, not only by their effects on neurite length, but also by their effects on Ca(2+) homeostasis in differentiated SY5Y cells.

Calcium↗
PubMed2003

Porous organoclay composite for the sorption of polycyclic aromatic hydrocarbons and pentachlorophenol from groundwater.

Complex mixtures of hazardous chemicals such as polycyclic aromatic hydrocarbons (PAHs) in contaminated soil and groundwater can have severe and long-lasting effects on health. The evidence that these contaminants can cause adverse health effects in animals and humans is rapidly expanding. The frequent and wide-spread occurrence of PAHs in groundwater makes appropriate intervention strategies for their remediation highly desirable. The core objective of this research was to assess the ability of a clay-based composite to sorb and remove toxic contaminants from groundwater at a wood-preserving chemical waste site. Treatment efficiencies were evaluated using either effluent from an oil-water separator (OWS) or a bioreactor (B2). The effluent water from these units was passed through fixed bed columns containing either an organoclay composite or granular activated carbon. The sorbent columns were placed in-line using existing sampling ports at the effluent of the OWS or B2. Individual one-liter samples of treated and untreated effluent were collected in Kimax bottles over the course of 78 h (total of 50 samples). Subsequently each sample was extracted by solid phase extraction methodology, and pentachlorophenol (PCP) and PAH concentrations were quantitated via GC/MS. Columns containing porous organoclay composite, i.e. sand-immobilized cetylpyridinium-exchanged low-pH montmorillonite clay (CP/LPHM), were shown to reduce the contaminant load from the OWS effluent stream by 97%. The concentrations of benzo[a]pyrene (BaP) and PCP were considerably reduced (i.e. >99%). An effluent stream from the bioreactor was also filtered through columns packed with composite or an equivalent amount of GAC. Although the composite reduced the majority of contaminants (including BaP and PCP), it was less effective in diminishing the levels of lower ring versus higher ring PAHs. Conversely, GAC was more effective in removing the lower ring PAHs, except for naphthalene and PCP. The effectiveness of sorption of PCP from the OWS effluent by the composite was confirmed using a PCP-sensitive adult hydra bioassay previously described in our laboratory. The findings of this initial study have delineated differences between CP/LPHM and GAC for groundwater remediation, and suggest that GAC (instead of sand) as the solid support for organoclay may be more effective for the treatment of contaminated groundwater under field conditions than GAC or CP/LPHM alone. Further work is ongoing to confirm this conclusion.

Adsorption↗
PubMed2003

Chemical contaminants and their effects in fish and wildlife from the industrial zone of Sumgayit, Republic of Azerbaijan.

Sediment from a wetland adjacent to an industrial wastewater treatment plant in Sumgayit contained concentrations of total PAHs, total PCBs, aldrin, biphenyl, chlordane, DDT, mercury, beta-endosulfan, heptachlor, alpha-hexacyclohexane (alpha-HCH), gamma-HCH, and several individual PAH congeners that were elevated relative to published sediment quality guidelines. Chemical analyses of tissues from European pond turtles (Emys orbicularis) had increased levels of many of the same chemicals including aldrin, chlordane, heptachlor, alpha-HCH, total PCBs, total PAHs, and mercury, compared to reference turtles. In addition, turtle tissues contained elevated levels of DDD, hexachlorobenzene (HCB), and pentachlorobenzene that were not elevated in the sediment sample. Some differences were observed in contaminant levels between European pond turtles and Caspian turtles (Mauremys caspica) taken from the ponds in Sumgayit. Salmonella/microsome mutagenicity assays on pond sediments were negative or weakly positive. Micronuclei in European pond turtles were statistically correlated with tissue levels of mercury, heptachlor, DDD, HCB, and trans-nonachlor. Microcosm experiments using Russian sturgeon (Acipenser gueldenstaedtii) showed a positive dose-response relationship between exposure to suspended contaminated pond sediment and acute toxicity. Chemical and biological assays used in this study show the industrial area of Sumgayit is heavily contaminated with a complex mixture of toxic pollutants. Exposure to contaminated sediments produced acute effects in Russian sturgeon, but genotoxic effects appear to be slight.

Animals↗
PubMed2001

Evaluation of methods for predicting the toxicity of polycyclic aromatic hydrocarbon mixtures.

Risk assessments of polycyclic aromatic hydrocarbon mixtures are hindered by a lack of reliable information on the potency of both mixtures and their individual components. This paper examines methods for approximating the toxicity of polycyclic aromatic hydrocarbon (PAH) mixtures. PAHs were isolated from a coal tar and then separated by ring number using HPLC. Five fractions (A-E) were generated, each possessing a unique composition and expected potency. The toxicity of each fraction was measured in the Salmonella/mutagenicity assay and the Chick Embryo Screening Test (CHEST). Their abilities to induce ethoxyresorufin-O-deethylase and to inhibit gap junction intercellular communication in rat liver Clone 9 cells were also measured. In the Salmonella/mutagenicity assay, fractions were predicted to have potencies in the order C > D > E > B > A. Toxic equivalency factors (TEFs) for fractions A-E were in the order E > or = D > C > B > A. TEF values were 20,652, 20,929, 441, 306, and 74.1 micrograms of BaP equiv/g, respectively. A lack of agreement between assay-predicted potencies and chemical analysis-predicted potencies was observed with other assays and other methods of calculation. The results demonstrate the limitations of using a single method to predict the toxicity of a complex PAH mixture.

Animals↗
PubMed2001

Impacts of aging on in vivo and in vitro measurements of soil-bound polycyclic aromatic hydrocarbon availability.

Ingestion of contaminated soil is an exposure pathway at approximately one-half of the Superfund sites in the United States. This study was designed to evaluate the impacts of aging in soil on the availability of polycyclic aromatic hydrocarbons (PAHs). Two coal tar (CT)-amended soils were prepared. One was aged for 270 days and the other was not aged. Both of these treatments were incorporated into pellets and fed to male Fischer 344 rats. Excretion of 1-hydroxypyrene (1-OHP) in urine and PAH concentrations in the liver were monitored as end points. Additionally, soil:water partitioning and desorption were measured as comparisons to the in vivo results. After 5 days of ingesting their respective treatments, rats in the aged soil group excreted 4.41 +/- 1.67 ppm 1-OHP/mg of pyrene ingested while rats in the unaged soil group excreted 5.27 +/- 1.37 ppm/mg of pyrene ingested. Animals fed aged CT soil had 0.051 +/- 0.011 ppm carcinogenic PAHs in livers/mg ingested while rats fed unaged CT soil had 0.063 +/- 0.037 ppm carcinogenic PAHs in livers/mg ingested. Partitioning and desorption results revealed a similar results. These results indicate that, at high application rates, soil contact time may not play as significant a role in determining availability as simple dispersion and sorption on soil.

Animals↗
PubMed2001

Antagonistic interactions among nephrotoxic polycyclic aromatic hydrocarbons.

Although the liver and pulmonary toxicity of polycyclic aromatic hydrocarbons (PAHs) has been extensively characterized, limited data concerning the nephrotoxic potential of these chemicals are available. The present studies were conducted to define the kidney cell-specific toxic responses to anthracene (ANTH), benzo[a]pyrene (BaP), and chrysene (CHRY). Given that exposure to environmental chemicals from a specific source is rarely limited to a single compound, a second goal was to evaluate the nephrotoxic potential of binary and ternary mixtures of these chemicals. Cultured rat glomerular mesangial cells (rGMCs) and porcine cortico-tubular epithelial kidney cells (LLCPK-1) were challenged with hydrocarbon concentrations ranging from 0.03 to 30 microM for up to 24 h and were processed for measurements of mitochondrial membrane permeability, trypan blue dye exclusion, cytoplasmic enzyme leakage, and protein synthesis. BaP induced a threefold increase in mitochondrial fragility, a modest increase in cellular death, and 40% decrease in the rate of protein synthesis in rGMCs. Anthracene was also cytotoxic to rGMCs, inducing a twofold increase in mitochondrial fragility and a 40% decrease in the rate of protein synthesis, but no changes in cellular viability. Although CHRY was devoid of toxicity to rGMCs, a 40% decrease in the rate of protein synthesis was observed in LLCPK-1 cells treated with this hydrocarbon. BaP and ANTH were not overtly cytotoxic to LLCPK-1 cells at any of the concentrations tested. Binary and ternary mixtures of BaP with ANTH and CHRY in rGMCs, and mixtures of CHRY with ANTH and BaP in LLCPK-1 cells, yielded antagonistic interactions. Based on these data, it is concluded that PAHs exhibit chemical- and cell-specific nephrotoxicity, but that toxicological outcomes are influenced by the presence of multiple hydrocarbons in complex mixtures.

Amino Acids↗
PubMed2001

Pentachlorophenol potentiates benzo[a]pyrene DNA adduct formation in adult but not infant B6C3F1 male mice.

The objective of this study is to determine whether pentachlorophenol (PCP) alters benzo[a]pyrene (B[a]P)-induced DNA adduct formation in infant and adult B6C3F1 male mice. Mice were exposed intraperitoneally to 55 microg B[a]P/g body weight (BW) alone and in combination with several doses of PCP in DMSO. The 32P-postlabeling assay was used to analyze for (+/-) anti-7,8-diol-9,10-epoxide-B[a]P-N(2)deoxyguanosine (BPDE-N(2)G) adducts formed in liver and lung DNA. Hepatic DNA also was analyzed for 8-hydroxy-2'-deoxyguanosine (8-OHdG) base damage in mice exposed to PCP. 8-OHdG was not detected at any dose of PCP in infant or adult mice. PCP exhibited an antagonistic effect on BPDE-N(2)G accumulation in infant mice exposed to B[a]P in combination with 50 microg PCP/g BW at both 12 and 24 hr. Comparatively, BPDE-N(2)G adducts were increased in adult mice exposed to binary mixtures at 24 hr in both hepatic and lung DNA (P < 0.05). Multiple comparison analysis between infant and adult mice revealed that adduct levels in infants exposed to B[a]P alone or in combination with PCP were not different from those observed in adult mice exposed to B[a]P. However, a significant increase in adducts was observed in adult mice exposed to a combination of B[a]P and PCP compared to that in all other treatment groups (P < 0.05). These results suggest that PCP alters the metabolism of B[a]P in both infant and adult mice through different mechanisms, and that infants are not susceptible to the potentiating effects of PCP observed in adult mice.

Age Factors↗
PubMed2001

A study of 2,4,6-trinitrotoluene inhibition of benzo[a]pyrene uptake and activation in a microbial mutagenicity assay.

A number of in vitro and in vivo studies have determined that binary and complex mixtures may interact to produce a toxicity that could not be predicted based on the individual chemicals. The present study was conducted with a binary mixture of model compounds to investigate possible interactions affecting their mutagenicity. The compounds included Benzo[a]pyrene (BAP), a polycyclic aromatic hydrocarbon that is an indirect-acting mutagen of great environmental concern, and 2,4,6-Trinitrotoluene (TNT), a nitro-aromatic compound that is a direct-acting mutagen frequently found as a soil contaminant at munitions sites. This study indicated that a binary mixture of BAP and TNT failed to induce the positive mutagenic response in Salmonella typhimurium strain TA98 characteristic of either compound alone. Spectrofluorometric analysis of BAP, and kinetic analyses of 3HBAP uptake in the presence or absence of TNT using TA98 cells that were treated or untreated with activated rat liver microsomes were performed. In cells preloaded with BAP, cellular BAP fluorescence was rapidly suppressed in the presence of TNT. Mass spectroscopy of BAP and TNT mixtures revealed a number of products, believed to be the result of complexation and nitration, that may account for the antagonistic action of TNT on BAP-induced mutagenicity in TA98 cells. Further, kinetic studies indicated that TNT inhibited the incorporation of BAP into cells.

Animals↗
PubMed2001

Initial results of environmental monitoring in the Texas Rio Grande Valley.

Previous studies have suggested that a segment of human disease may be attributable to environmental exposures. These may include exposure to chemicals released from a broad range of natural and man-made sources. The purpose of this study was to develop the sampling methodology and prepare a preliminary database on the presence of various organic chemicals in environmental media in two South Texas counties bordered by the Rio Grande River. A third county, located approximately 150 miles north of the Rio Grande River, was also sampled. The South Texas counties were the focus of study due to an increased incidence of anencephalic births in recent years. The environmental media that was sampled included surface water and sediment from the Rio Grande River and irrigation canals, as well as soil from adjacent cropland and pastures. Samples were collected using United States Geological Survey (USGS) quadrangle maps (7.5'; 1:24,000 scale) to identify the area of interest. At least one sampling location was established in each quadrangle. A pond sampler was used for the collection of surface water samples, while soil was collected with a stainless steel trowel. Sediment samples were collected directly in a glass jar. Solid samples were extracted in a soxhlet extractor using methylene chloride. Organic chemicals were concentrated from water samples on a Sep-Pak cartridge and the organics eluted with methanol/acetonitrile. Extracts were analyzed using GC-MS. All of the surface water samples contained aliphatic hydrocarbons and plasticizers, while soil samples contained aliphatics, plasticizers, pesticides, and industrial estrogens. Specific chemicals detected in environmental samples included atrazine and benzene dicarboxylic acid. Contaminant levels in sediments were generally higher than were detected in other media. The results demonstrate the broad variability of contaminant types and concentrations in environmental samples. Although this study presents only a very preliminary characterization of a large area of South Texas, the data indicate a number of pesticides and xenobiotic estrogens that were identified in environmental samples. Additional data providing more details of spatial and temporal distribution of contaminants as well as wildlife studies are needed.

Databases, Factual↗
PubMed2000

Bioavailability of the genotoxic components in coal tar contaminated soils in Fischer 344 rats.

The effect of chemical aging on the bioavailability and subsequent genotoxicity of coal tar (CT)-contaminated soils was evaluated in a 17-day feeding study using Fischer 344 male rats. Rats consumed a control diet or diets amended with soil, 0.35% CT, or soil freshly prepared or aged for 9 months with 0.35% CT. Mild treatment-related microscopic lesions in liver tissue and elevated enzyme levels in serum were detected in all CT treatment groups. The (32)P-postlabeling assay was employed to determine DNA adduct formation in treated animals. All CT treatment groups induced DNA adducts in both the liver and lung. Adduct levels were 3-fold higher in lung DNA compared to hepatic DNA. After correcting adduct levels for total ingested polycyclic aromatic hydrocarbons (PAHs), a significant decrease (p < 0.05) in adduct levels was observed in both CT/soil treatment groups compared to CT control in liver and lung DNA. Adduct profiles of (32)P-postlabeled hepatic and lung DNA displayed several nonpolar DNA adducts that comigrated with PAH-adducted calf thymus DNA standards as determined through both thin-layer chromatography (TLC) and high-pressure liquid chromatography (HPLC). These results suggest that soil, but not aging of contaminants in soil, decreases the bioavailability of genotoxic components in CT, as evidenced by DNA adduct analysis.

Animals↗
PubMed1999

Genotoxicity of complex PAH mixtures recovered from contaminated lake sediments as assessed by three different methods.

Although human exposure generally occurs to mixtures of chemicals, limited toxicological information is available to characterize the potential interactions of the components of environmental mixtures. This study was conducted to compare the genotoxicity of chemically characterized polycyclic aromatic hydrocarbon (PAH) mixtures using in vitro and in vivo techniques. A total of three extracts (E1-E3) were selected from sediment samples collected from a lake adjacent to an abandoned coal gasification site. Sediments were collected on a grid moving downstream and away from the most likely source of PAH contamination, with E1 collected closest to the shore, E2 at an intermediate distance, and E3 furthest from the shore. The sediment samples were extracted in methylene chloride and methanol, dried, and redissolved in an appropriate solvent for evaluation in a battery of genotoxicity assays. Samples were evaluated for their ability to produce point mutations in bacteria and DNA adducts in vitro without metabolic activation or in vivo. Samples were also analyzed using GC/MS. Sample E1 had both the highest concentration of benzo(a)pyrene (BP) (46.5 ppm) and carcinogenic PAHs and, using 32P-postlabeling, induced the highest adduct levels overall in vitro and in vivo. Sample E2, which had a BP concentration of 14 ppm, induced the greatest number of revertants in the bacterial mutagenicity assay. Sample E3, which had the lowest level of carcinogenic PAHs and BP, induced the lowest adduct levels. However, E3 was capable of inducing a positive genotoxic response in bacteria (with S9), although the slope of the response at lower doses was less than that of E2. The in vivo data showed that the major adduct formed by E1 and E2 was a BP adduct. This information could not have been obtained with the Salmonella or in vitro postlabeling tests. Among internal organs, the extracts of all three samples induced the greatest adduct levels in the lung, similarly to previous complex PAH mixtures studied. These data demonstrate the limitations of predicting genotoxic or carcinogenic potential based on chemical analysis or a single biological test. The results suggest that mixture interactions, cytotoxicity and metabolism are likely to have an influence on the potential of a complex mixture of chemicals to produce a carcinogenic effect. In addition, the concentration of genotoxic PAHs and both in vitro and in vivo DNA adduct formations were decreased with increasing distance from the shoreline.

Animals↗