摘要:

Observations have been performed on peripheral blood lymphocytes from a patient having ingested 200 mg thallium sulfate, in order to evaluate the ability of the compound to produce cytogenetic damage in vivo in humans. Our results demonstrate that neither the yield of structural chromosome aberrations nor sister chromatid exchanges were significantly modified. The drastic increase of binucleated cells with micronuclei indicates that thallium sulfate has in common with many metallic compounds the ability to interfere with chromosome distribution.

ISSN:0098-4108    

DOI:10.1080/009841097160500

出版商:Informa UK Ltd    

年代:1997

数据来源: Taylor

摘要:

Current biological monitoring techniques are often unable to provide accurate estimates of pesticide dose in exposed worker populations. This study was conducted to investigate the feasibility of pesticide biomonitoring using saliva. Atrazine [2-chloro-4-ethylamino-6-(isopropylamino)-s-triazine], a member of the triazine herbicides, was selected to investigate salivary excretion following direct gastric administration in rats. Concentrations of atrazine in whole saliva and arterial plasma samples were determined by enzyme-linked immunosorbent assay (ELISA). Atrazine reached its highest level in both arterial plasma (238 g/L) and whole saliva (157 g/L) 35 min after administration of 105 mg/kg of atrazine, and then decreased with time in a parallel fashion. Although saliva atrazine levels were lower than levels in arterial plasma, there was a very high correlation between whole saliva and 2 arterial plasma atrazine concentrations (r = .95). In addition, pharmacokinetic analysis suggested that salivary levels of atrazine can be used to predict concentrations of atrazine in plasma. The mean whole saliva/arterial plasma atrazine concentration ratio (S/P) was 0.66 0.11 (n = 20). The S/P ratios did not vary significantly over time, and were not affected by salivary flow rate. This study demonstrates that atrazine is transported into saliva, and that a relatively constant concentration ratio between whole saliva and arterial plasma is maintained. Because the salivary concentrations of atrazine are independent of variation in salivary flow rate, salivary monitoring of atrazine in humans may prove useful and practical. Finally, this study suggests that other pesticides with chemical and physical properties similar to those of atrazine can be monitored in saliva.

ISSN:0098-4108    

DOI:10.1080/009841097160519

出版商:Informa UK Ltd    

年代:1997

数据来源: Taylor

摘要:

This study investigated the lethalinteraction of pyridostigmine bromide (PB), permethrin, and DEET when given to adult male rats by gavage and was separated into two phases. Phase I determined the acute orallethaldose-response relationship of each compound with the vehicle, propylene glycol. Phase II was divided into two portions: a dose-response study using probit units obtained from phase I [lethal dose (LD) 16, 30, 50, 70, and 84], and an interaction study that contained low levels (calculated LD16, additive LD32) of the two compounds while the concentration of the third compound was varied. Rats were fasted overnight, dosed, and observed for 14 d. A significant increase in lethality occurred when PB, permethrin, and DEET were given concurrently when compared to expected additive values. Furthermore, solutions containing PB and permethrin or PB and DEET also caused a significant increase in lethality when compared to expected additive values. This information suggests that lethality in this study was more than an additive effect.

ISSN:0098-4108    

DOI:10.1080/009841097160528

出版商:Informa UK Ltd    

年代:1997

数据来源: Taylor

摘要:

In vivo exposures to fibrous silicates are characterized by the formation of asbestos bodies. These structures consist of the original fiber with a coating of inexact composition, but it will include iron and protein. We tested the hypothesis that this iron, accumulated on asbestos bodies, participates in electron transport and oxidant generation. Thirty-day-old, male guinea pigs were intratracheally instilled with 1.0 mg crocidolite. Six months later, the animals were anesthetized, euthanized, and the fibers were isolated from the lungs. Energy-dispersive x-ray analysis and x-ray photoelectron spectroscopy confirmed an accumulation of metal onto the fiber after in vivo exposure. Stains for iron demonstrated a heterogeneous distribution of the metal on the silicate, while the uptake of a commercially available polyclonal antibody to ferritin localized to beaded enlargements along the coated 3+ fibers. Chelatable [Fe ] associated with the fiber increased after in vivo exposure. However, oxidant generation by asbestos bodies was decreased relative to uncoated fibers despite the elevation in the concentration of metal associated with the crocidolite. We conclude that iron is accumulated onto fibers in the lungs of guinea pigs. Some portion of this accumulation of iron is in the form of ferritin, and this metal is not chemically reactive in oxidant production. Asbestos bodies may represent a successful attempt by the host to sequester the metal adsorbed to the surface of a fiber and diminish the oxidative challenge introduced by a fibrous silicate. Subsequently, the generation of free radicals by the fibrous silicate is diminished.

ISSN:0098-4108    

DOI:10.1080/009841097160537

出版商:Informa UK Ltd    

年代:1997

数据来源: Taylor

摘要:

Inhalation exposure to ozone (O3) is known to induce epithelial and inflammatory changes in the lungs, characterized by neutrophilia and changes in epithelial permeability. Several cell types and their soluble mediators, including interleukin-1 (IL-1) and tumor necrosis factor- (TNF- ), are involved in the evolution of these responses. In this study, we have compared the effects of the combination of anti-IL-1 and anti-TNF- on in vitro and in vivo responses to inhaled O3. Male, Sprague-Dawley rats were exposed, nose-only, to 0.8 ppm O3 for 3 h and the in vitro and in vivo parameters were measured 8-12 h following exposure. The in vitro studies revealed that the adherence of inflammatory cells, primarily macrophages, harvested from the lungs of O3-exposed rats to cultured lung epithelial cells (ARL-14) was significantly greater than the adherence of macrophages from air-exposed controls. Furthermore, this adherence was significantly reduced in antibodytreated cells as compared to cells treated with preimmune rabbit serum. In vivo, elevations were found in the percentage of neutrophils in bronchoalveolar lavage fluid (BALF), 99m transport of Tc-diethylenetriaminepentaacetate (DTPA) across the tracheal epithelium, and concentrations of total protein and albumin in BALF following O3 exposure. However, these effects were not significantly altered by treatment with the anti-IL-1 /anti-TNFcombination. Therefore, it was concluded that O3 affects the early stages of the inflammatory response, particularly with respect to macrophage activation and adherence to epithelial cells, and that this early response may be mediated by IL-1 and/or TNF- . The results also suggest that the in vivo effects of O3 are controlled by complex mechanisms involving factors other than IL-1 and TNF- , even though these cytokines are capable of modifying macrophage function as revealed by the in vitro adherence studies.

ISSN:0098-4108    

DOI:10.1080/009841097160546

出版商:Informa UK Ltd    

年代:1997

数据来源: Taylor

摘要:

Treatment of rats with p-chlorotoluene (PCT, 1 g/kg, ip) resulted in peak PCT blood and lung concentrations at 4 h, which declined to very low levels at 12 h. The concentration of PCT in the liver attained its highest value at 1 h and also declined to low levels at 12 h. In the dose-response study, PCT significantly decreased hepatic and pulmonary AHH activities at 0.5 g/kg, 1 h. Maximum inhibition was attained at 1 g/kg, 1 h, and further increase in the dose did not enhance the enzyme inhibition. In the time-course investigation, PCT (1 g/kg) maximally inhibited hepatic and pulmonary arylhydrocarbon hydroxylase (AHH) activities at 1 h and the decrease in enzyme activity was sustained through 12 h. Administration of PCT (1 g/kg, 1 h) also markedly decreased pulmonary cytochrome P-450 content, while hepatic cytochrome P-450 content was only slightly reduced. The partial decrease in cytochrome P450 content indicated altered levels of the P-450 isozymes, which may have profound effects on the metabolic disposition of benzo[a]pyrene [BaP]. BaP is regioselectively metabolized by two major isoforms of P-450 to toxic dihydrodiols and nontoxic phenol derivatives and there is a balance between these two metabolite groups. PCT (1 g/kg, 1 h) significantly inhibited the phenolic 3-OH BaP formation in both lung (52%) and liver (56%). The formations of BaP 7,8-dihydrodiol (146%) and 9,10-dihydrodiol (90%) were significantly elevated in the lung. The toxication to detoxication ratios were significantly elevated in both organs. Total quinone formation was markedly enhanced in the liver. Since PCT inhibited phenolic metabolite formation and increased dihydrodiol production, the activities of the isozymes that are responsible for their formations were determined. PCT (1 g/kg, 1 h) significantly inhibited cytochrome P-4502B1 in the lung (50%) and 2B1/2B2 in the liver (40%), while cytochrome P-4501A activity was not altered in either lung or liver. PCT increased phospholipid (PL) levels (45%) and conjugated diene (CD) formation (58%) in lung but not in liver, while membrane fluidity was increased [phospholipid/cholesterol (PL/CL) ratio; diphenylhexatriene (DPH) and trimethylammonium DPH (TMA-DPH) fluorescence polarization] in both organs. There was no apparent relationship between these membrane changes and alterations in MFO activity. Taken together the results suggest that PCT is capable of nonselectively inactivating the hepatic and pulmonary isozymes of P-450 that are responsible for the detoxication of BaP. The observed shift in the metabolism of BaP toward potentially more toxic metabolites suggests that concurrent exposure to BaP and PCT may result in greater toxicity, compared to exposure to BaP alone.

ISSN:0098-4108    

DOI:10.1080/009841097160555

出版商:Informa UK Ltd    

年代:1997

数据来源: Taylor

摘要:

In the present study, pretreatment with p-aminohippurate (PAH) and induction of stopflow conditions (by ureteral ligation) were used as tools to determine whether the enhanced accumulation of injected inorganic mercury that occurs in the renal outer stripe of the outer medulla in rats following uninephrectomy and compensatory renal growth is due to a luminal and/or basolateral mechanism. The effects of these pretreatments on the disposition of mercury in the liver and blood were also evaluated as a secondary aim. Pretreatment of both uninephrectomized (NPX) and control rats with a 7.5 mmol/kg dose of PAH 5 min prior to the injection of a nontoxic 0.5 mol/kg iv dose of mercuric chloride caused a significant decrease in the renal accumulation of mercury in both control and NPX rats during the initial 3 h after the injection of inorganic mercury. However, the concentration of mercury in the renal outer stripe of the outer medulla was significantly greater in the NPX rats than in the corresponding control rats. Induction of stop-flow conditions (by iv bolus injection of 2.0 mmol/kg mannitol followed 5 min later by ureteral ligation) approximately 75 min prior to the injection of inorganic mercury also resulted in decreased renal accumulation of mercury in both NPX and control rats. In contrast to the effects of PAH, induction of stop-flow conditions resulted in the concentration of mercury in the renal outer stripe of the outer medulla in the NPX rats being statistically equivalent to that in the corresponding control rats 3 h after the injection of mercury. Assuming that glomerular filtration rate was reduced to negligible levels in these animals, the fraction of mercury that was not taken up and accumulated in the outer stripe of both groups of rats represents the fraction of mercury that is taken up by a luminal mechanism. Thus, on the basis of the findings in this study, it appears that the increased accumulation of mercury that occurs in the renal outer stripe of the outer medulla in NPX rats is linked to a luminal mechanism, presumably localized in the epithelial cells lining the proximal tubule. Finally, when pretreatment with PAH and induction of stop-flow conditions were combined, there was additivity with respect to decreased renal accumulation of mercury. This additivity provides further support for the current hypothesis that there are both luminal and basolateral mechanisms involved in the renal uptake of inorganic mercury.

ISSN:0098-4108    

DOI:10.1080/009841097160564

出版商:Informa UK Ltd    

年代:1997

数据来源: Taylor