摘要:

Concentrations of Aroclor mixtures and specific polychlorinated biphenyl (PCB) congeners were measured in surface sediments and aquatic biota (striped bass fillet, mummi-chog, and blue crab muscle and hepatopancreas) collected from the lower Passaic River. Several of the 47 surface sediment samples contained Aroclor concentrations that exceeded a National Oceanic and Atmospheric Administration (NOAA) benchmark level for “total PCBs” (22.7 pg/kg). Each of the 18 PCB congeners analyzed in aquatic biota was detected in one or more tissue samples, and numerous congeners were detected in every sample (IUPAC numbers 77, 105, 114, 118, 123, 126, 156, 157, 167, and 189). PCB congener concentrations were similar to those that have been reported in fish from other waterways that contain elevated levels of PCBs. Congener 118 was present at the highest concentration in almost all samples, and constituted 14–60% of the total PCB mass (sum of all congener masses) measured in any given tissue sample. In spite of the prevalence of PCB congeners in biota tissues (up to 1314 pg/kg total PCBs), Aroclors were not detected in bass or crab samples at a limit of detection of 33–55 pg/kg. This anomaly may be due to selective degradation of certain PCB congeners that are used to analytically recognize and quantitate Aroclors. Using the measured sediment concentrations, a food web model accurately predicted blue crab muscle concentrations of individual PCB congeners (typically within a factor of two) and was also fairly accurate for mummichog (typically within an order of magnitude). Concentrations in striped bass fillet were underestimated by factors of approximately 20–140. Increased cancer risk estimates associated with fish and crab consumption were obtained using four different methods. Using Aroclor tissue concentrations (one-half the limit of detection) and an Aroclor slope factor, total risks were 2.6×10∼6; using the “total PCB” measurements, and an Aroclor slope factor, total risks were 1.9×10−5; the “PCB-TEQ” method yielded total risks of 6.5×10−4and USEPA'S recent suggested approach for evaluating “dioxin-like” and non-“dioxinlike” effects resulted in a total risk of 6.6×10−4. This wide range in risk estimates indicates that it is critical to the risk management decision-making process that data requirements and risk assessment objectives be carefully evaluated early in the investigation process.

ISSN:0098-4108    

DOI:10.1080/00984109708984055

出版商:Taylor & Francis Group    

年代:1997

数据来源: Taylor

摘要:

N,N-Diethyl-m-toluamide (DEET), the active ingredient in many commercial mosquito repellents, is thought to be responsible for a wide range of local and systemic adverse reactions following its use. Many investigators have studied the dermal absorption of pure DEET; however, there is only one report in the literature on the absorption of DEET from commercial mosquito repellents and the effect of concentration of DEET on its absorption through skin. The first objective of the present study was to evaluate the permeation characteristics of DEET from four commercial products, Everglades (95%), Repel Deerhunters (52.25%), Off Skintastic (6.65%), and Skedaddle (6.2%), as compared to pure DEET (∼100%). The second objective was to study the effects of ethanol, the solvent for DEET, on the permeation of DEET and investigate its potential for enhancing the dermal absorption of DEET. Permeation studies of DEET from commercial mosquito repellents and from solutions containing various percentages of ethanol were conducted across human skin using an infinite dose technique with a Franz diffusion cell. Permeation parameters such as steady-state flux (Jss, lag time (tL), diffusion coefficient (D), permeability (?), and skin/ vehicle partition coefficient (K) were obtained from the permeation profiles in each case. The cumulative amount of DEET permeated can be ranked according to the following order: neat DEET(100%) = Everglades (95%)>Repel (52.25%)>Skedaddle (6.2%)=Off Skintastic (6.65%). Pure DEET exhibited the highest flux value of 63.20±24.52 µg/cm2-h, while Off Skintastic had the lowest value of 21.12±14.75 pg/cm’-h. The lL and D values for each of the products were similar to that of pure DEET. The total amount of DEET permeated from 30-45% ethanolic solutions at the end of 36 h was significantly higher than that from pure DEET and from the 60–90% ethanolic solutions. The J, P, and K values of DEET from the 30–45% ethanolic solutions were significantly higher than those from the 75–90% ethanolic solutions, while the tL and D values were similar for each solution. Therefore, there is potential for significant absorption of DEET after the dermal application of commercial mosquito repellents, and ethanol, used as a solvent, may enhance the permeation of DEET.

ISSN:0098-4108    

DOI:10.1080/00984109708984056

出版商:Taylor & Francis Group    

年代:1997

数据来源: Taylor

摘要:

The genotoxicity of nitroaromatic compounds was examined in two cultured cell lines, namely, a human hepatoma cell line, HepC2, and a brown bullhead fibroblast cell line, BB. Furthermore, the role of the quinone-reducing enzyme DT diaphorase [NAD(P)H:(quinone acceptor) oxidoreductasel was examined with respect to its influence on the genotoxic effects of model nitroaromatic pollutants. The nitroreductive characteristics of these two cell lines were examined using an acetylated cytochrome c reduction assay for enzymatic nitroreductase activity. Subsequently, the influence of DT diaphorase on the genotoxicity of two model nitroaromatics, 4-nitroquinoline 1-oxide (4NQ) and nitrofurantoin (NF), revealed that DT diaphorase was the predominant 4NQ reductase in cytosols of both cell lines, but played a lesser role in NF reduction in both species. Despite these interspecific similarities, results revealed marked qualitative differences between the two species in terms of the influence of DT diaphorase on quinone-mediated genotoxicity. When pre-treated with the DT diaphorase inhibitor dicoumarol, HepC2 cells exhibited an exacerbation of genotoxicity in the presence of 4NQ, indicating a protective influence of the enzyme. In contrast, 4NQ genotoxicity in BB cells was reduced in the presence of dicoumarol, indicating a deleterious effect of DT diaphorase activity. Conversely, dicoumarol pretreatment was moderately protective against NF-mediated genotoxicity in HepC2 cells but exacerbated NF toxicity in BB cells. This study illustrates the manner in which functionally analogous enzymes may have markedly distinct influences on xenobiotic toxicity in different cellular systems.

ISSN:0098-4108    

DOI:10.1080/00984109708984057

出版商:Taylor & Francis Group    

年代:1997

数据来源: Taylor

摘要:

Cadmium-induced apoptosis is shown to occur, in vivo, in several organs of the male Wistar rat urogenital system, 48 h after cadmium administration ip at a dose of 0.03 mmol/kg. Characteristic DNA fragmentation (as measured by an enzyme-linked immunosorbent assay, ELISA) and histopathologically observed changes characteristic of apoptosis are found in the kidney, prostate, seminal vesicles, testes, and epididymis. TUNEL assay also demonstrates the apoptosis. Such changes are absent from bladder and vas deferens tissue. Timely administration of an appropriate chelating agent capable of reaching intracellular cadmium binding sites can suppress the processes leading to apoptosis. Administration of monoisoamyl meso-2,3-dimercaptosuccinate (M\-ADMS, 0.5 mmol/kg ip) to cadmium-treated rats is effective in greatly reducing typical histopathologic signs of apoptosis and the associated chromatin DNA fragmentation as revealed by ELISA when the antagonist is administered I h after cadmium. Administration of the chelating agent at later times results in greater degradation of DNA into oligonucleotides and more prominent histopathological evidence of apoptotic changes in the affected organs of the rat urogenital system. There is also a progressive increase in apoptotic changes indicated by TUNEL assay, as the antagonist is administered at progressively greater intervals after cadmium.

ISSN:0098-4108    

DOI:10.1080/00984109708984058

出版商:Taylor & Francis Group    

年代:1997

数据来源: Taylor

摘要:

Hyperthyroidism potentiates the in vivo hepatotoxicity of 1,1-dichloroethylene (DCE) in rats, with a concomitant increase in [14C]-DCE covalent binding. The enhanced injury produced in hyperthyroid livers by DCE could be due to alterations in either the bioactivation or detoxication phases of DCE metabolism. Previous in vitro studies suggested that hyperthyroidism did not potentiate DCE hepatotoxicity by increasing DCE oxidation to intermediates which were able to covalently bind. Several factors, however, that could contribute to the magnitude of DCE bioactivation or covalent binding were not examined. Our objectives were to characterize the effects of hyperthyroidism in male Sprague-Dawley rats on: (1) covalent binding of [14C]-DCE to microsomes and other subcellular fractions, (2) microsomal mixed-function oxidase (MFO) and glutathione S-transferase (GST) activities, and (3) inactivation of microsomal enzyme activities by presumptive DCE reactive intermediates. Hyperthyroid (HYPERT) and euthyroid (EUT) rats received 3 sc injections of thyroxine (100 µg/100 g) or vehicle, respectively, at 48-h intervals; microsomes and other subcellular fractions were isolated from HYPERT and EUT livers 24 h after the last injection. [l4C]-DCE-derived covalent binding was consistently greater in EUT than HYPERT microsomes. The absence of NADH, and the addition of low concentrations (0.1 and 0.5 mM), but not higher concentrations (>l mM), of glutathione (CSH) diminished covalent binding to a greater extent in HYPERT than EUT microsomes. Covalent binding in mitochondrial, nuclear, and cytosolic fractions of EUT and HYPERT livers was equivalent. Regression analysis of covalent binding to liver cell fractions from both EUT and HYPERT rats showed a significant correlation with P-450 content. Hyperthyroidism decreased microsomal, but not mitochondrial, cytochrome P-450 content, and MFO activities for 7-ethoxycoumarin and benzphetamine were similarly decreased. Hyperthyroidism also diminished microsomal CST activity, and altered CST kinetics for both CSH and 1-chloro-2,4-dinitrobenzene (CDNB). The magnitude of inactivation of MFO and CST activities in the presence of DCE (presumably by DCE reactive intermediates) was comparable between EUT and HYPERT microsomes. When covalent binding was standardized to cytochrome P-450 concentrations in microsomes and mitochondria, HYPERT fractions exhibited slightly greater covalent binding than EUT fractions, suggesting that hyperthyroidism does not reduce the capacity of P-450 hemoproteins to bioactivate DCE. Thus, potentiation of DCE hepatotoxicity by hyperthyroidism may be predominantly due to diminished Phase II constituents, and major increases in reactive intermediate/conjugates that covalently bind to and impair critical cellular molecules.

ISSN:0098-4108    

DOI:10.1080/00984109708984059

出版商:Taylor & Francis Group    

年代:1997

数据来源: Taylor