摘要:

Ecotoxicologists and ecologists have examined the effects of pollutants on individuals and populations largely in terms of one or only a few effects. Yet the recent trend toward a holistic approach to ecological risk assessment suggests that a rigorous paradigm should be applied to toxicants, from hazard identification to risk characterization. Recent discussions have recognized that an up‐front problem formulation phase is more critical in ecological risk assessment than it is for human health risk assessment. In this article a modified environmental health risk assessment paradigm is used to examine the risk of lead to birds. This risk analysis is largely conceptual, based on laboratory and field data, and incorporates information currently available. The model expands the hazard identification phase to create a target identification phase that includes the identification of receptors, endpoints, relationships, spatial and temporal scales, and indicators. The target identification phase is unique to the particular hazard, species, population, or community being examined. Lead can cause mortality, or can indirectly affect populations through effects on the food base, avian behavior, reproductive success, and recruitment. Lead can (1) decrease the abundance and availability of prey, (2) bioaccumulate in prey causing increased lead toxicosis in predators, or (3) increase prey availability by interfering with its hiding or escape behavior. Moreover, lower abundance of prey can lead to starvation or nutrient deficiencies, which amplify the absorption and retention of lead. Lead also causes decreases in clutch and egg size, mortality of embryos and nestlings, depression of growth, and deficits in behavior that affect survival. Lead decreases migratory behavior, and increases vulnerability to cold stress, hunters, and other predators. Research needs for evaluating the risk of lead in birds include obtaining data on (1) metal dynamics within various tissues as a function of dose and time since initial exposure, (2) low‐level effects on embryos, (3) effects on chicks following fledging and in the period prior to recruitment, (4) effects on adult foraging skills and reproductive behavior, and (5) the relationship between effects from exposure in the laboratory and those from exposure in the wild. This latter point is extremely important, particularly if wild birds have other means of ridding the body of lead not available or less apparent to laboratory birds.

ISSN:0098-4108    

DOI:10.1080/15287399509532003

出版商:Taylor & Francis Group    

年代:1995

数据来源: Taylor

摘要:

Metallothionein (MT) is a thiol‐rich protein that is rapidly induced by exposure to heavy metal cations. We have previously demonstrated that exogenous MT stimulates murine splenocytes to proliferate, but inhibits humoral responses to antigen. These observations suggest that metallothionein released from cells has a complex role in heavy metal‐mediated immune dysfunction. Here we examine one possible mechanism by which MT mediates suppression of humoral immunity. Exposure of macrophages to 20 μM MT did not affect their ability to engulf opsonized sheep erythrocytes, but in the presence of 20 μM MT, peritoneal macrophages were stimulated to produce increased levels of oxygen radicals. These results correlated with observations that while macrophage phagocytosis of opsonized Candida albicans was unaltered by the presence of exogenous MT, killing of the engulfed yeast cells was dramatically enhanced by 20 μM MT. Amounts of free cadmium and zinc equimolar to that added as Zn,Cd‐MT had no effect on candidacidal activity. MT was also found to significantly decrease lymphocyte proliferation mediated by macrophage activity. Biotinylated MT (MT‐b) bound specifically to the plasma membranes of these macrophages, suggesting that membrane‐associated molecules of the macrophage may transduce a signal mediated by MT binding. These results demonstrate that macrophages are a sensitive target for MT‐mediated immunomodulation and that some of the consequences of the MT interaction with macrophages may be alterations in the capacity to produce an effective immune response and increased extracellular exposure to damaging free radicals.

ISSN:0098-4108    

DOI:10.1080/15287399509532004

出版商:Taylor & Francis Group    

年代:1995

数据来源: Taylor

摘要:

Various doses of methylmercuric chloride (MMC) were administered orally to pregnant Fischer 344 rats on d 7 of gestation. On d 20 of gestation the dams were laparotomized under ether anesthesia, and the fetuses were removed. Maternal body weights were decreased for 2 d and 6 d in rats given 10 and 20 mg/kg MMC, and were continuously decreased for those given 30 mg/kg MMC. Maternal weight gain of each group was decreased to 86.2%, 78.9%, and 61.9% of control group on d 20 of gestation. The reduction of litter weight was greatly enhanced with increasing MMC doses, presumably due to postimplantation loss, which was already increased at high treatment levels. The LD50 of MMC for fetuses was determined to be 16.5 mg/kg. Mercury content in maternal organs was highest in kidney, followed by blood, spleen, liver, and brain, while in fetal organs it was highest in liver. Fetal liver and brain contained more mercury than maternal liver and brain. However, fetal kidney retained less mercury than maternal kidney. Fetal ossification center was not completely formed in sternebrae, particularly in fifth and second bones, pelvic bones, and pectoral phalanges of fetuses in rats treated with 30 mg/kg MMC. The ossified lengths of skeletal bone stained with alizarin red S were developed least in fifth sternebrae, metacarpals in the pectoral girdle, and ischium in the pelvic girdle, and were severely retarded in development as position of the ribs goes from the sixth bone (center) to the first and 13th bone (each edge). These results indicate that MMC is embryotoxic in Fischer 344 rats.

ISSN:0098-4108    

DOI:10.1080/15287399509532005

出版商:Taylor & Francis Group    

年代:1995

数据来源: Taylor

摘要:

Southwest Metropolitan Mexico City (SWMMC) preadolescent children have been exposed to a highly polluted urban atmosphere most of their lives. The main objective of this study was to determine by nasal lavage (NAL) the acute inflammatory nasal influx elicited in these children upon exposure to three different polluted days. Ozone, the main criteria pollutant for SWMMC, varied both in the number of hours above the National Ambient Air Quality Standard (NAAQS), which is 0.12 ppm as a 1‐h maximum concentration not to be exceeded more than once per year, and in the maximal concentrations in the preceding three NAL sampling dates. Nasal neutrophilic influx, the surface expression of the B2 integrin CD/ 1b on the nasal polymorphonuclear leukocytes (PMNs), rhinoscopic findings, respiratory symptoms, and nasal cytologies were evaluated in the 38 exposed children and in the 28 control children living in a nonpolluted Pacific coast port. SWMMC children had an average daily outdoor exposure of 7.7 h and complained of nasal mucus secretion, epistaxis, intermittent nasal obstruction, diurnal cough episodes, and chest discomfort. Nasal mucosal atrophy by rhinoscopy was present in 37/38, and all children had an abnormal nasal cytology. Exposed children had significantly higher nasal PMNs and nasal PMN‐CD11b expression than controls. PMN median values in exposed children were higher than controls on all sampling dates (November 12, p < .001; November 17, p < .007; and November 24, p < .00001). Interestingly, a lower nasal neutrophilic response (p < .0004) was recorded in the SWMMC children 18 h after exposure to the highest O3concentrations (up to 0.307 ppm) and the largest number of hours with O3> 0.12 ppm (7 h). The question of a competing inflammatory response at the bronchioalveolar level with structural damage is raised. These NAL findings underscore the need to restrict outdoor activity in SWMMC children during the months of greater potential exposure to ozone.

ISSN:0098-4108    

DOI:10.1080/15287399509532006

出版商:Taylor & Francis Group    

年代:1995

数据来源: Taylor

摘要:

The purpose of this study was to clarify the simultaneous administration of ethanol on styrene metabolism in the perfused rat liver under fed and fasted conditions. Styrene uptake rate, production rate of styrene glycol, oxygen consumption rate, and changes in reduced pyridine nucleotide fluorescence were monitored in the perfused rat liver. The effects of ethanol on parameters of styrene metabolism were observed in rat livers under fed and fasted conditions: fed (group I), fasted (group II), and fasted with xylitol in the per‐fusate (group III). The simultaneous administration of ethanol and styrene significantly decreased styrene uptake rate, production rate of styrene glycol, and oxygen consumption rate, and produced significant reduction of pyridine nucleotide fluorescence as compared with the single administration of styrene in groups I and III. In contrast, the simultaneous administration of ethanol and styrene significantly increased the production of styrene glycol and oxygen consumption as compared with the single administration of styrene in group II. Significant effects on the styrene uptake rate and the reduced pyridine nucleotide fluorescence were observed with regard to factors of both nutritional status and the interaction between ethanol and nutritional status by two‐way analysis of variance. These findings showed that the effects of ethanol on styrene metabolism in the liver were dependent upon the nutritional status of the animal. The fed and fasted conditions affected the effect of ethanol on styrene metabolism by changing the supply of NADPH to the mixed‐function oxidase system. In conclusion, ethanol suppressed styrene metabolism in the fed condition, but enhanced it in the fasted condition. This phenomenon should be considered in the prevention of occupational hazard of styrene exposure in industrial workers with alcohol drinking habits and nutritional problems.

ISSN:0098-4108    

DOI:10.1080/15287399509532007

出版商:Taylor & Francis Group    

年代:1995

数据来源: Taylor

摘要:

To evaluate the effects of “environmental tobacco smoke” (ETS) on developing lungs, juvenile ferrets were exposed to ETS at an average total particulate concentration of 381 ± 97 mg/m3for 2 h at the breathing zone. Twenty‐four hours after the exposure, the ferrets were sacrificed and the metabolism of (‐)‐trans‐benzo[a]pyrene‐7,8‐dihydrodiol was studied in the lung and liver homogenates. The rate of conversion of (‐)‐trans‐benzo[a]pyrene‐7,8‐dihydrodiol to the ultimate carcinogen (+)‐anti‐benzo[a]pyrene‐7,8‐dihydmdiol‐9,10‐epox‐ide was twofold higher in the liver than that observed in the lung of control ferrets. After ETS exposure, the formation of free benzo[a]pyrene‐7,8‐dihydrodiol‐9,10‐epoxide was increased by 62% in the lung (p < .01). The DNA‐bound metabolites were significantly increased only in the lung, while protein‐bound metabolites were significantly increased in the liver after ETS exposure. Although glutathione conjugates tended to be increased both in the lung and liver, sulfate conjugates were significantly decreased in the lung after ETS exposure (p < .05). (+)‐trans‐Benzo[a]pyrene‐7,8‐dihydrodiol was used to study the relative contributions of cytochrome P‐450 and peroxyl radical‐mediated formation of benzo[a]‐pyrene‐7,8‐dihydrodiol‐9,10‐epoxide. Peroxyl radical‐ and P‐450‐mediated conversion of (+)‐trans‐benzo[a]pyrene‐7,8‐dihydrodiol to benzo[a]pyrene‐7,8‐dihydrodiol‐9,10‐epoxide was proportionately equal in the ferret lung, whereas in the liver the P‐450‐mediated pathway was predominant. After ETS exposure there was a tendency for P‐450‐mediated formation of benzo[a]pyrene‐7,8‐dihydrodiol‐9,10‐epoxide to increase. These results demonstrate significant differences in the metabolism of (‐)‐trans‐benzo[a]pyrene‐7,8‐dihydrodiol by the lung and liver of juvenile ferrets and suggest a significant role of peroxyl radical‐mediated formation of (+)‐anti‐benzo[a]pyrene‐7,8‐dihydrodiol‐9,10‐epoxide in the lung, which may help explain discrepancy between the levels of P‐450 and amounts of DNA adducts of polycyclic aromatic hydrocarbons in different organs in smokers.

ISSN:0098-4108    

DOI:10.1080/15287399509532008

出版商:Taylor & Francis Group    

年代:1995

数据来源: Taylor

摘要:

Carbon tetrachloride (CCl4) induced hepatotoxicity and chloroform (CHCl3) induced nephrotoxicity were evaluated in male Sprague‐Dawley rats pretreated with acetone (A), methyl ethyl ketone (MEK), and methyl isobutyl ketone (MiBK). Dose‐response relationships for A, MEK, and MiBK potentiation of CCl4‐induced hepatotoxicity and CHCl3‐induced nephrotoxicity were compared. A, MEK, and MiBK pretreatment at a dosage of 6.8 mmol/kg, given daily for 3 d, markedly potentiated CCl4‐induced liver toxicity as indicated by a decrease in the CCI4ED50 to 3.4, 4.6, and 1.8 mmol/kg, respectively, compared to vehicle‐pretreated rats (17.1 mmol/kg). Similarly, pretreatment with these ketones (13.6 mmol/kg) potentiated CHCl3kidney toxicity but to a lesser degree; CHCl3ED50 values for vehicle‐, A‐, MEK‐, and MiBK‐pretreated rats were 3.4, 1.6, 2.1, and 2.2 mmol/kg, respectively. Our results indicate a potency ranking profile for the potentiation of CCI4hepatotoxicity of MiBK >A> MEK and of A > MEK ≥ MiBK for CHCl3nephrotoxicity. These dissimilar ranking profiles could be due to differences in mechanisms of action for the two target sites.

ISSN:0098-4108    

DOI:10.1080/15287399509532009

出版商:Taylor & Francis Group    

年代:1995

数据来源: Taylor

摘要:

The promoting activity of benzene on rat liver carcinogenesis was investigated. The chemical was tested for its ability to enhance the growth of preneoplastic foci, as detected by gamma‐glutamyl transpeptidase (CCT) staining in diethylnitrosamine (DENA) initiated hepatocytes. Two weeks after receiving a single ip dose of 200 mg/kg DENA, F344 rats were given daily oral doses of 400 mg/kg benzene (5 d/wk) for 6 wk. At wk 3 after the experiment began, all animals underwent partial hepatectomy, and at wk 8 were sacrificed. Following benzene treatment, no variation in the liver/body weight ratio was observed. After scoring of foci in liver slides, no significant difference in foci number and area could be observed between rats treated with DENA plus benzene and rats treated with DENA alone. Practically no foci were observed in the liver of rats treated only with benzene. The lack of benzene promoting activity in the liver model is discussed.

ISSN:0098-4108    

DOI:10.1080/15287399509532010

出版商:Taylor & Francis Group    

年代:1995

数据来源: Taylor

摘要:

It is well established that menadione, 2‐melhyl‐1,4‐naphthoquinone, impairs the ability of rat liver mitochondria to accumulate and retain calcium. However, it remains unclear whether this reflects inhibition of mitochondrial calcium uptake or stimulation of calcium release by menadione. The purpose of the current investigation was to determine whether interference with mitochondrial calcium homeostasis by menadione reflects a selective activation of the cyclosporine A‐sensitive pore, independent of actions on other mitochondrial calcium channels. Mitochondrial calcium flux was monitored using the metal‐lochromic dye arsenazo Ill. Treatment of mitochondria with menadione caused a concentration‐dependent decrease in net calcium accumulation followed by a delayed release of the accumulated calcium and concurrent mitochondrial swelling. Both the maximum steady‐state accumulation of calcium and the delay preceding calcium release decreased as a function of calcium concentration. The release of calcium did not occur via the Na+/Ca2+antiport or reversal of the uptake uniport, as neither diltiazem nor ruthenium red prevented the menadione‐stimulated calcium release. In contrast, cyclosporine A, a potent inhibitor of the permeability transition pore, completely inhibited menadione‐induced calcium release and the associated swelling. Furthermore, the menadione‐induced inhibition of calcium accumulation was completely prevented in the presence of cyclosporine A, indicating a selective stimulation of calcium release by menadione, rather than inhibition of calcium uptake. These data provide the first definitive description of a specific action of menadione to stimulate mitochondrial calcium release through a cyclosporine A‐sensitive pathway, independent of altering the regulation of other recognized calcium channels associated with the inner mitochondrial membrane.

ISSN:0098-4108    

DOI:10.1080/15287399509532011

出版商:Taylor & Francis Group    

年代:1995

数据来源: Taylor

ISSN:0098-4108    

DOI:10.1080/15287399509532002

出版商:Taylor & Francis Group    

年代:1995

数据来源: Taylor