摘要:

The process of human health risk assessment (HRA) is often judged by its ability to predict adverse outcomes of particular environmental contaminants or exposures for individual humans. Likewise, environmental scientists often examine the adverse outcomes of chemical or physical hazards on individual species. This ecotoxicological approach to ecological risk assessment (ERA) fails to encompass the potential range of adverse outcomes to populations, communities, and ecosystems. Moreover, whereas the success of HRA can be evaluated by examining the health of individual humans, success of ERA cannot because (1) populations of species are the important unit ecologically, rather than individuals, (2) the overall structure and complexity of the system is important rather than the structure or organization within one species (i.e., humans in the case of HRA), and (3) the overall functioning of the system is important rather than only the functioning of one species. I suggest that the risk assessment paradigm that includes hazard identification, dose‐response analysis, exposure assessment, and risk characterization should have a parallel phase or discipline of research: evaluation of predicted and actual outcomes. This phase, termed “predictive accuracy” in this article, is particularly critical for Ecological Risk Assessment because the potential outcomes may occur long after the initial perturbation.

ISSN:0098-4108    

DOI:10.1080/15287399409531888

出版商:Taylor & Francis Group    

年代:1994

数据来源: Taylor

摘要:

Rabbit pulmonary macrophages were exposed in vitro to particulate lead oxide (PbO) for periods of up to 72 h and then assayed for the activity of tumor necrosis factor‐alpha (TNFα) released after stimulation with lipopolysaccharide (LPS). The levels of TNFa obtained from PbO‐treated cells were decreased in a dose‐dependent manner as compared with metal‐free control cells for each time point examined. Cells treated simultaneously with both LPS and PbO yielded less monokine than did cells receiving LPS alone. In addition, incubation of cell‐free TNFα with PbO resulted in a diminution of cytotoxicity directed against TNFα‐sensitive tumor target cells. Macrophage burdens of PbO particles increased with both the length of incubation and concentration of PbO used; increases in cellular lead burdens were paralleled by reductions in cell viability. Thus, under in vitro conditions, PbO affects the levels of the immunoregulatory monokine TNFα and also disrupts its cyto‐toxic properties after release from activated macrophages.

ISSN:0098-4108    

DOI:10.1080/15287399409531889

出版商:Taylor & Francis Group    

年代:1994

数据来源: Taylor

摘要:

It has been proposed that the activation of poly(ADP‐ribose) polymerase (Papirmeister et al., 1985), which results from the presence of strand breaks in bis‐(β‐chloroethyl)sulfide (BCES) damaged DNA, causes depletion in the level of nicotinamide adenine dinucleotide (NAD) leading to cell death. This hypothesis has now been evaluated in the primary submerged culture of rat keratinocytes. The DNA content, the viable cell number, and the proliferative capability (measured by thymidine incorporation) of the culture were all reduced 48 h after exposure to 10 μM BCES. However, the total NAD level, that is, NAD+plus NADH, was not changed at a dose of BCES lower than 50 μM. This observation was the same in both proliferating and early differentiating cultures. To further test this hypothesis, the modifying effect of inhibiting poly(ADP‐ribose) polymerase on cytotoxicity in BCES‐exposed cells was investigated. After exposure to 250 μMBCES, the NAD level was reduced to approximately 26 pmol/μg DNA. This value was increased to 34–49 pmol/μg DNA at both 24 and 48 h postexposure when the cultures were incubated in medium supplemented with 1–10 mM nicotinamide. Nevertheless, the decrease in the DNA content of the culture was not reversed. These results suggest that in the rat keratinocyte culture exposed to BCES, depletion of NAD is not a prerequisite for cell death.

ISSN:0098-4108    

DOI:10.1080/15287399409531890

出版商:Taylor & Francis Group    

年代:1994

数据来源: Taylor

摘要:

Silica and ferric oxide are common industrial exposures. Studies have indicated that all commonly occurring forms of crystalline silica can cause fibrotic lung disease. There is evidence to indicate that crystalline silica is carcinogenic in humans who have not developed silicosis, while amorphous silica is not carcinogenic in humans. An important biological response to particles deposited deep in the lung is their engulfment by pulmonary alveolar macrophages (AM). To assess the role of AM in silica‐induced lung disease, particle size distribution and surface area of crystalline, gelled, precipitated, and fumed silica, ferric oxide, and aluminum oxide were characterized; the cytotoxicity of the particles to hamster and rat AM in vitro was measured at 0.0–0.5 mg/1 x 106cells at 24 and 48 h using dye exclusion procedures. The count medium diameter for aluminum oxide, ferric oxide, and amorphous silica was equal to or less than 0.38 μm, while for crystalline silica the value was 0.83 μm. The surface areas for the amorphous silicas and the aluminum oxide ranged from 253 to 125 m2lg with gelled silica having the highest value; the values for crystalline silica and ferric oxide were 4.3 and 10.8 m2/g, respectively. Crystalline silica (1.6%) was detected in the fumed silica, while none was detected in precipitated or gelled silica. With gelled silica, based on the dose of the particle, the viability of the hamster AM decreased to 27% at 0.05 mg and to zero at 0.1 mg at 24 h. At doses of 0.05 and 0.1 mg of crystalline, precipitated, or fumed silica, the percent viability decreased significantly to 76–67% and 51–42%, respectively, and to zero at 0.5 mg. Macrophages viable at 24 h decreased further at 48 h compared with the control culture. The ferric oxide and the aluminum oxide showed minimal to no changes in viability. Similar results for the particles were obtained with rat AM. The results indicate that precipitated and fumed amorphous silica tested at equivalent doses are equally as toxic to AM lavaged from two species of rodents as crystalline silica; gelled silica is more toxic than crystalline. Ferric oxide and aluminum oxide are noncytotoxic in this system. The results of this study indicate that the dose as well as the surface area and surface characterization are important determinants in the cytotoxicity of hamster and rat AM to these particles.

ISSN:0098-4108    

DOI:10.1080/15287399409531891

出版商:Taylor & Francis Group    

年代:1994

数据来源: Taylor

摘要:

Emissions generated by firing the M16 rifle with the propellant WC844 in a combustion chamber designed to simulate conditions of actual use were tested for mutagenic activity in the Salmonella/Ames assay. Dimethyl sulfoxide extracts of emissions collected from either the breech or muzzle end of the rifle were mutagenic in three strains of Salmonella (TA1537, TA1538, and TA98) both in the presence and absence of metabolic activation systems (59). The extracts were negative in strains TA100 and TA102. Aerosols generated by firing the M16 rifle were fractionated according to aerodynamic diameter. Sub‐micrometer particles were far more mutagenic than particles with aerodynamic diameters between 1 and 15 μm. The mutagens associated with the smaller particles were more active in the presence of S9, while extracts of larger particles were as active, or more active, in the absence of 59. Heavier particles, which settled rapidly out of the airstream, were not mutagenic.

ISSN:0098-4108    

DOI:10.1080/15287399409531892

出版商:Taylor & Francis Group    

年代:1994

数据来源: Taylor

摘要:

Airway hyperresponsiveness can be induced by several stimuli including antigen and ozone, both of which may be present in the air of polluted cities. Though the effect of ozone on the bronchoconstrictor response to antigen has been well described, the combined effect of these stimuli on airway hyperresponsiveness has not yet been studied. Sensitized guinea pigs with or without ozone exposure for 1 h at 3 ppm, 18 h prior to study, were challenged with a dose‐response curve to histamine (0.01–1.8 μg/kg, iv) followed by an antigen challenge (ovalbumin, 50 μg/kg, iv), and then by a second histamine dose‐response curve 1 h later. Airway responses were measured as the increase in pulmonary insufflation pressure. In sensitized guinea pigs, the histamine ED50 significantly decreased after antigen challenge, demonstrating the development of airway hyperresponsiveness. Sensitized guinea pigs exposed to ozone showed airway hyperresponsiveness to histamine when compared with nonexposed animals, and such hyperresponsiveness was further enhanced after antigen challenge. We conclude that in this guinea pig model of acute allergic bronchoconstriction both antigen challenge and ozone induce airway hyperresponsiveness, while ozone exposure does not modify the development of antigen‐induced hyperresponsiveness.

ISSN:0098-4108    

DOI:10.1080/15287399409531893

出版商:Taylor & Francis Group    

年代:1994

数据来源: Taylor

摘要:

Monoisoamyl meso‐2,3‐dimercaptosuccinate (Mi‐ADMS), a new dimercaptosuccinic acid (DMSA) analog with enhanced lipophilic properties, was evaluated for potential developmental toxicity. Intraperitoneal injections of Mi‐ADMS were given to female Swiss mice (0, 47.5, 95, and 190 mg/kg) on gestational d 6–15. The maternal clinical status was monitored daily during treatment. At termination (gestational d 18), dams were evaluated for clinical status and gestational outcome. Each live fetus was weighed and examined for external, visceral, and skeletal abnormalities. Although no maternal mortality was observed, treatment with 95 and 190 mg/kg resulted in maternal toxicity, manifested as reduced body weight gain during treatment and increased relative liver weight. Embryo/fetal toxicity, consisting of a significant increase in the number of late resorptions as well as in the percentage of postimplantation loss, reduced (nonsignificant) fetal body weight, and an increase in the incidence of skeletal defects, was also observed at 190 mg/kg/d. However, no treatment‐related external or soft‐tissue malformations or developmental variations were found in any group. The no‐observed‐adverse‐effect level (NOAEL) for maternal toxicity was 47.5 mg/kg/d, whereas the NOAEL for developmental toxicity was 95 mg/kg/d. These results indicate that Mi‐ADMS did not produce developmental toxicity in mice in the absence of maternal toxicity.

ISSN:0098-4108    

DOI:10.1080/15287399409531894

出版商:Taylor & Francis Group    

年代:1994

数据来源: Taylor

摘要:

The objective of this investigation was to determine the changes in proteins, lipids, and lipoproteins in liver and serum of rats acutely intoxicated with carbofuran (1.5 mg/kg sc). Under the influence of carbofuran acute intoxication, analysis of globulin fractions revealed remarkable changes: In liver, the levels of alpha‐2, alpha‐3, and gamma were significantly elevated while alpha‐1 was reduced; in serum, alpha‐1 and alpha‐3 fractions were elevated while alpha‐2, beta, and gamma remained unchanged. A transient increase in total protein and albumin was noted only in liver. Carbofuran produced significant increases in triglycerides and cholesterol in liver that were also seen in serum. In both the liver and serum the levels of low‐density‐lipoprotein cholesterol (LDL‐C) were reduced while the values of very‐low‐density‐lipoprotein cholesterol (VLDL‐C) were elevated. The concentration of high‐density‐lipoprotein cholesterol (HDL‐C) was drastically reduced in liver (23% of control) with a proportional rise in serum (176%). In liver, carbofuran caused marked depletion of adenosine triphosphate (ATP) and phosphocreatine (PCr) (38% and 22% of controls, respectively), resulting in increased cell membrane permeability, thereby allowing leakage of cell constituents. It was concluded that carbofuran, directly or indirectly, produced perturbations in lipoprotein metabolism.

ISSN:0098-4108    

DOI:10.1080/15287399409531895

出版商:Taylor & Francis Group    

年代:1994

数据来源: Taylor

摘要:

BIOMEMBRANE PROTOCOLS I. Isolation and Analysis. Edited byJohn GrahamandJoan HigginsVolume 19 in Methods in Molecular Biology Humana Press, Totowa, New Jersey, 1993, 313 pp., $49.50.

ISSN:0098-4108    

DOI:10.1080/15287399409531896

出版商:Taylor & Francis Group    

年代:1994

数据来源: Taylor

ISSN:0098-4108    

DOI:10.1080/15287399409531887

出版商:Taylor & Francis Group    

年代:1994

数据来源: Taylor