摘要:

The presence of organochlorine pesticides, such as p,p’-DDT[2,2-bis(p-chlorophenyl)-l, 1,1-trichloroethane], and of polychlorinated biphenyls (PCBs) in human serum and adipose tissue has been reported in many studies over the last four decades. Recently, debate has heightened concerning the link of these compounds to breast cancer. To clarify and resolve this issue, accurate analytical residue data must be obtained. Separation of the organochlorine pesticides from the PCBs in breast tissue is critical to obtaining valid residue data. Based on methods refined in the Analytical Laboratory at Colorado State University, accurate residue levels were established for nine individual PCB congeners and eight organochlorine pesticides. The breast adipose tissue method used was a modification of the Mills et al. and de Faubert Maunder et al. methods. The serum method employed was a modification of the Burse et al. method. Both breast adipose tissue and serum from 36 women were analyzed, and correlations of the residues from the two substrates were evaluated. Serum concentrations of p,p’-DDE, the primary metabolite of p,p’-DDT, were correlated (α = .05) with the concentrations of p,p’-DDE in human breast adipose tissue (r = .808). Serum concentrations of the PCB congener BZ 153 were also significantly correlated to the human breast adipose tissue concentrations of BZ 153 (r = .377). No significant relationship was found between serum concentrations and tissue residues for 15 of the 17 compounds analyzed. This lack of correlation between breast adipose tissue and serum, as well as an absence of the compound residues in serum, emphasized that adipose tissue should be analyzed in addition to serum to fully understand the relationship of the organochlorine compounds to breast cancer.

ISSN:0098-4108    

DOI:10.1080/00984109708984065

出版商:Taylor & Francis Group    

年代:1997

数据来源: Taylor

摘要:

This article estimates the potential exposure ofestuarine organisms to two pesticides (azin-phosmethyl and fenvalerate) in a tidal stream of Leadenwah Creek near the Edisto River, South Carolina, during four runoff episodes. Exposure is calculated from simulation runs of the one-dimensional transport equation solved by an implicit finite difference method. Calibration was done for each episode by adjusting three conditions (runoff starting time, duration, and flow) and a correction to the dispersion coefficient in order to match the continuously measured salinity transients. First-order rate constants used by the fate component were calculated from half-life values reported in the literature. Baseline scenarios for each episode and each pesticide were derived by using the same conditions obtained in the salinity runs and adjusting the pesticide loading in order to mimic the few data points of measured pesticide concentrations. In all baseline scenarios, pesticide concentration rises following the initial burst of runoff (also noticeable as an abrupt drop in salinity) and then oscillates, forced by the tidal cycle. These oscillations are dominated by transport, while fate imposes a secular decaying trend. Ten additional scenarios for each episode were obtained from the baseline scenario by randomly varying three pesticide load parameters (starting time and duration of runoff, and pesticide discharge) using a Latin hypercubes design. Two exposure metrics were calculated from the simulated and the measured pesticide concentration: maximum and time average, which was obtained by integrating the curve and dividing by the time period. The metrics calculated from the baseline runs are relatively close to the data-derived metrics, because the baseline runs attempted to mimic the data. For each one of the two metrics and all pesticide-episode combinations, several statistics of the set of 1 I scenarios were also calculated: minimum and maximum, mid-range, mean, standard deviation, and median. The mean ± standard deviation interval of the simulation-derived value consistently brackets the data-derived value for the maximum metric, but not for the time-average metric. This may indicate that even if the maximum value is correctly captured in the field sample, the time-average exposure could be in error when calculated directly from the field data due to undersampling of the pesticide time series. The methodology developed here attempts to reconstruct the possible exposure from the sparse sampling of the pesticide concentration during the runoff episodes; only when the number of field samples is high and regularly spaced is it possible to have confidence in the reconstruction.of the curve. The shape of the curve cannot be inferred from the field measurements alone; as expected, tidal movement makes the pesticide concentration swing up and down. This result has important implications because the biological community would be subject to repetitive pulses of exposure to the chemicals. The baseline simulations can be used to derive a pulse-exposure metric by calculating the sum of ratios of the time average of the threshold-exceeding concentrations to the time average of the toxic threshold during intervals of above-threshold concentration. This metric is species specific and extrapolates laboratory toxicity data in order to compare pulse exposure to mortality rates measured in the field.

ISSN:0098-4108    

DOI:10.1080/00984109708984066

出版商:Taylor & Francis Group    

年代:1997

数据来源: Taylor

摘要:

The stability of the saliva/plasma (SIP) concentration ratio of atrazine was determined under varying conditions of salivary flow rate and plasma concentration of atrazine in Sprague-Dawley rats. In the salivary flow study, whole saliva samples were collected at different salivary flow rates while the plasma concentration of atrazine was maintained at a steady-state level of approximately 150 μgll. In the plasma level study, whole saliva samples were collected at two steady-state plasma concentrations of atrazine (50 and 250 μgll), while salivary flow rate was maintained at a relatively constant level. In both studies, atrazine concentrations in whole saliva and arterial plasma demonstrated a consistent rela tionship, but salivary concentrations were always lower than those of arterial plasma. Linear regression analysis demonstrated that the SIP concentration ratio of atrazine was not significantly different for salivary flow rates ranging from 23 to 92 pLIminlkg body weight, and did not vary for atrazine plasma concentrations between 30 and 433 μglL. The SIP concentration ratio of atrazine was relatively constant throughout each experimen tal period (0.68 ± 0.7 and 0.70 ± 0.11 for salivary flow and plasma level studies, respec tively) and did not differ significantly between rats. When data from both studies were pooled, salivary concentrations were highly correlated with plasma concentrations (r2 = .94). It is concluded that under these experimental conditions, the stability of the SIP con centration ratio of atrazine is not affected by variations in salivary flow rate or atrazine plasma concentrations. The results from this study support the conclusion that atrazine salivary concentrations can be used to predict plasma levels of atrazine in rats.

ISSN:0098-4108    

DOI:10.1080/00984109708984067

出版商:Taylor & Francis Group    

年代:1997

数据来源: Taylor

摘要:

Among the elements of toxicological relevance, inorganic arsenic (As) probably exhibits the most complex metabolism, and we deemed it interesting to identify and quantify the different As species excreted after an occupational acute intoxication with arsine. For this purpose total As and five As species were determined using an hybrid analytical method coupling liquid chromatography with inductively coupled plasma mass spectrometry. The highest urinary elimination of total As was observed in the first 5 d after admission. The As species mostly excreted were monomethylarsonate (MMA), dimethylarsinate (DMA), As3+, arsenobetaine (AsB), and to a lesser extent As5+. The amount of AsB excreted in urine by the subject does not appear to be completely justified by AsB intake through food. Arsenic is excreted mainly via the urine with a clearance of 7.8 ml/h/kg and follows a triphasic model with periods of 28 h, 59 h, and 9 d, respectively. The evidence that DMA excretion culminates after a few days, when the excretion of the inorganic form is substantially reduced (while that of MMA is still elevated), seems to confirm the existence of two successive methylating enzyme activities. Furthermore, the elimination rate of As from blood follows a three-phase model and the half-lives of different species vary from about 27 to 86 h with the following gradient As5+< MMA < As3+< DMA < AsB.

ISSN:0098-4108    

DOI:10.1080/00984109708984068

出版商:Taylor & Francis Group    

年代:1997

数据来源: Taylor

摘要:

In order to investigate how endogenous iron can be deposited in vivo on inhaled mineral fibers during early stages of formation of asbestos bodies, in vitro experiments were per formed on the adsorption of ferritin onto amosite asbestos. The mineral dust was found to adsorb the protein from an aqueous solution containing 0.3 mg/ml horse spleen ferritin. In order to simulate physiological conditions the aqueous solution was adjusted with 150 mM saline. Polyacrylamide-SDS gel electrophoresis of the desorbed protein showed sub-units of approximately 13 and 15 kD, aside from the 20-kD subunit present in the native protein. This suggests that as a result of interactions between ferritin molecules and the solid surface of the mineral fibers, the protein iron core may be released or partially exposed. Data indicate these interactions may have implications in the observed mineral fiber toxicities.

ISSN:0098-4108    

DOI:10.1080/00984109708984069

出版商:Taylor & Francis Group    

年代:1997

数据来源: Taylor

摘要:

Amiodarone is an antiarrhythmic drug with numerous side effects, the most serious being the development of pulmonary toxicity. We have previously reported that a single intratra cheal instillation of amiodarone to Fischer 344 rats results in pulmonary fibrosis within 6 wk of treatment. Presently, the mechanism of amiodarone-induced pulmonary toxicity is unknown. Cytokines that stimulate fibroblast proliferation and/or collagen production may play a role in amiodarone-induced pulmonary toxicity. To investigate this possibility, female rats were given a single intratracheal instillation of amiodarone (6.25 mg/kg), its metabolite desethylamiodarone (5 mg/kg), or vehicle (sterile water). At I, 2, 3, or 6 wk after treatment the lungs were lavaged and the recovered cells were counted and identi fied. The alveolar macrophages were isolated by attachment to plastic petri dishes, cul tured overnight, and the spent media collected for tumor necrosis factor alpha (TNF-α) and transforming growth factor beta (TGF-β) analyses. Desethylamiodarone treatment resulted in a neutrophilic alveolitis, but the levels of TNF-α and TGF-β were not signifi cantly different from control animals. In contrast, amiodarone treatment resulted in a lym phocytic alveolitis and significantly higher amounts of TNF-α were observed at 3 and 6 wk after treatment. A trend toward higher levels of TCF-β was also noted in the amio-darone-treated group at wk 1-3 but the values were not significantly different from those of controls. In conclusion, the release of TNF-α may play a role in the development of amiodarone-induced pulmonary toxicity.

ISSN:0098-4108    

DOI:10.1080/00984109708984070

出版商:Taylor & Francis Group    

年代:1997

数据来源: Taylor

摘要:

Haloacetates are a common class of water chlorination by-products. Depending on the amount of bromide in the source water, varying amounts of chlorinated, brominated, and mixed bromochloro haloacetates are produced. When administered to rodents, halo acetates have been shown to increase formation of thiobarbituric acid-reactive substances and 8-hydroxydeoxyguanosine levels in the liver. These responses appear to be modified by prior treatment. To examine potential mechanisms that account for these modifications in oxidative stress, the ability of trichloroacetate (TCA) or dichloroacetate (DCA) pretreat-ment to alter the metabolism of bromodichloroacetate (BDCA) and the disposition of its metabolites was examined in male B6C3F1 mice. Two-week pretreatment with I g/L DCA and TCA in the drinking water of mice alters the initial hepatic metabolism of BDCA and the further metabolism of its metabolite DCA. DCA pretreatment inhibits cytosolic metabo lism of both I raM DCA or BDCA up to 70%. In contrast, DCA pretreatment stimulates hepatic microsomal BDCA metabolism 1.3-fold but has little effect on microsomal metabo lism of DCA. Increased microsomal metabolism of BDCA appears to be attributable to the induction of a metabolic pathway that produces CO2and bromodichloromethane (BDCM) as metabolites. TCA pretreatment inhibits BDCA metabolism up to 70% in the cytosol and 30% in microsomes but has little effect on DCA metabolism. These results indicate that the hepatic metabolism of the haloacetates becomes quite complex at the high doses that have been employed in cancer bioassays. BDCA serves as a good exam ple, because it is metabolized to at least two carcinogenic metabolites that have different modes of action, BDCM and DCA. As doses approach those that induce cancer in mice, the proportion of and amounts of these metabolites as a fraction of the dose administered will change substantially. This article demonstrates that those interactions will occur from mixed treatment with haloacetates as well.

ISSN:0098-4108    

DOI:10.1080/00984109708984071

出版商:Taylor & Francis Group    

年代:1997

数据来源: Taylor