Cyclic exchanges and level of coupling between environmental media: intermedia feedback in multimedia fate models.

The importance of cyclic transport of chemicals between media in the environment can be expressed in terms of the Feedback correction factor--a multiplier that accounts for the fraction of an emission that returns to the medium of release after transfer to other media. This factor is calculated analytically by explicitly solving the appropriate system of mass balance equations or using matrix techniques. It generalizes the concept of stickiness, the ratio between the net and the overall deposition rate constants, to multipathway feedback, while providing a clearer view of the level of coupling between media and analyzing the importance of coupling. This paper first shows the usefulness of the total removal rate coefficient in each media (sum of degradation rate and all intermedia transfer rates) as a baseline to determine the chemical mass in different media, the characteristic travel distance and to understand the cyclic behavior, rather than starting from the degradation lifetimes or the overall persistence in the environment. Starting from this baseline, the importance of feedback is limited for most organic chemicals. The predicted media concentrations are influenced by less than 10% due to the cyclic nature of the intermedia transport for more than 90% of the 317 tested chemicals in a 4-compartment, steady-state, closed-system multimedia model. The Feedback correction factor is always less than a factor of 5 with the greatest values when transfer fractions are important in both directions for adjacent media. This corresponds to a restricted range in the K(AW) and K(OA) space with long chemical lifetimes in both adjacent media. This analysis of the importance of the Feedback correction factor, in conjunction with resultant criteria for when cyclic exchanges between media are likely to be significant, facilitates a more transparent understanding of how substance masses are distributed in the modeled system. It is one of the important criteria to determine to what extent media can be independently modeled.

Life cycle assessment part 1: framework, goal and scope definition, inventory analysis, and applications.

Sustainable development requires methods and tools to measure and compare the environmental impacts of human activities for the provision of goods and services (both of which are summarized under the term "products"). Environmental impacts include those from emissions into the environment and through the consumption of resources, as well as other interventions (e.g., land use) associated with providing products that occur when extracting resources, producing materials, manufacturing the products, during consumption/use, and at the products' end-of-life (collection/sorting, reuse, recycling, waste disposal). These emissions and consumptions contribute to a wide range of impacts, such as climate change, stratospheric ozone depletion, tropospheric ozone (smog) creation, eutrophication, acidification, toxicological stress on human health and ecosystems, the depletion of resources, water use, land use, and noise-among others. A clear need, therefore, exists to be proactive and to provide complimentary insights, apart from current regulatory practices, to help reduce such impacts. Practitioners and researchers from many domains come together in life cycle assessment (LCA) to calculate indicators of the aforementioned potential environmental impacts that are linked to products-supporting the identification of opportunities for pollution prevention and reductions in resource consumption while taking the entire product life cycle into consideration. This paper, part 1 in a series of two, introduces the LCA framework and procedure, outlines how to define and model a product's life cycle, and provides an overview of available methods and tools for tabulating and compiling associated emissions and resource consumption data in a life cycle inventory (LCI). It also discusses the application of LCA in industry and policy making. The second paper, by Pennington et al. (Environ. Int. 2003, in press), highlights the key features, summarises available approaches, and outlines the key challenges of assessing the aforementioned inventory data in terms of contributions to environmental impacts (life cycle impact assessment, LCIA).

Life cycle assessment part 2: current impact assessment practice.

Providing our society with goods and services contributes to a wide range of environmental impacts. Waste generation, emissions and the consumption of resources occur at many stages in a product's life cycle-from raw material extraction, energy acquisition, production and manufacturing, use, reuse, recycling, through to ultimate disposal. These all contribute to impacts such as climate change, stratospheric ozone depletion, photooxidant formation (smog), eutrophication, acidification, toxicological stress on human health and ecosystems, the depletion of resources and noise-among others. The need exists to address these product-related contributions more holistically and in an integrated manner, providing complimentary insights to those of regulatory/process-oriented methodologies. A previous article (Part 1, Rebitzer et al., 2004) outlined how to define and model a product's life cycle in current practice, as well as the methods and tools that are available for compiling the associated waste, emissions and resource consumption data into a life cycle inventory. This article highlights how practitioners and researchers from many domains have come together to provide indicators for the different impacts attributable to products in the life cycle impact assessment (LCIA) phase of life cycle assessment (LCA).

Evaluating multimedia/multipathway model intake fraction estimates using POP emission and monitoring data.

This paper presents a structured evaluation of a novel multimedia chemical fate and multi-pathway human exposure model for Western Europe, IMPACT 2002, using data for PCDD/F congeners. PCDD/F congeners provide an illustration of the potential use of POPs (Persistent Organic Pollutant) data for the evaluation of such models. Based on available emission estimates, model predictions with and without spatial resolution are evaluated at three different stages against monitored data: at environmental contamination levels, food exposure concentration, and in terms of human intake fractions (iF): the fraction of an emission that is taken in by the population. The iF is approximately 3.5.10(-3) for emissions of dioxin in Western Europe. This iF compares well to the traditional non-spatial multi-media/-pathway model predictions of 3.9.10(-3) for the same region and to 2.10(-3) for the USA. Approximately 95% of the intake from Western European emissions occurs within the same region, 5% being transferred out of the region in terms of food contaminants and atmospheric advective transport.

An evaluation of chemical persistence screening approaches.

A chemical's ability to persist in the environment is an important criterion in determining whether concern is warranted. Screening is commonly conducted based on the maximum degradation half-life of the chemical in any given medium (air, water, soil and sediment), or in terms of model-based estimates of the chemical's overall persistence (half-life or residence time) in the environment. In practice, however, both approaches are hindered by the limited availability of degradation data. Straightforward guidelines are therefore proposed in this paper to help predetermine which half-lives are likely to be pertinent, irrespective of the screening approach adopted. The guidelines are based on partitioning coefficients (Henry's Law constant and the octanol-water partitioning coefficient). The values selected for use in the guidelines result in a quantifiable trade-off between data acquisition requirements and uncertainty. Initial screening can be performed with whatever data is readily available. Overall persistence predictions will be conservative. False-negatives are not generated. The guideline values can then be adjusted iteratively to facilitate step-wise or tiered screening. Using this iterative approach in national and international screening initiatives will result in significant time and money savings.

Relationship of approaches and a tiered methodology for screening chemicals in the context of long-range transport.

In many national and international initiatives, where thousands of chemicals are screened, the ability of a chemical to be transported over long distances is an important criterion in determining whether environmental concern is warranted. Preliminary screening can be conducted using: (1) effective travel distance (ETD); (2) characteristic travel distance (CTD); and/or (3) the degradation half-life in air. The CTD is the distance traveled before the concentration of a chemical in air is reduced by a factor of 50%, for example. Differences in the distance traveled associated with the environmental release medium of a chemical are taken into account the ETD measure. The ETD can be defined as the distance traveled before the concentration in a stated medium (air, water, soil or sediment) is reduced to a specified level for a given mass release rate to air, to water and/or to soil. However, despite their merits, the use of multimedia screening measures like the ETD and CTD remains inhibited by both the limited availability of degradation data (particularly for soils and sediments) and release pattern information. Preliminary screening in terms of the atmospheric degradation half-life is commonly the only practical option. In this paper, straightforward guidelines based on partitioning coefficients (Henry's law constant and octanol water partitioning coefficient) are proposed to reduce the degradation data requirements of multimedia measures like the ETD and CTD. The values used in the guidelines reflect a quantifiable trade-off between data acquisition requirements and uncertainty. The relationship of the potential screening options (using all degradation data versus using only data identified as required in the CTD and ETD approaches; screening in terms of the degradation half-life in air versus the CTD versus the ETD) is derived and the consequences of the differences are illustrated. A three-tiered screening methodology is then proposed. This tiered methodology will result in significant savings in time and money in national and international screening initiatives.

Comparison of chemical screening and ranking approaches: the waste minimization prioritization tool versus toxic equivalency potentials.

Chemical screening in the United States is often conducted using scoring and ranking methodologies. Linked models accounting for chemical fate, exposure, and toxicological effects are generally preferred in Europe and in product Life Cycle Assessment. For the first time, a comparison is presented in this article of two of the prominent, but structurally different methodologies adopted to help screen and rank chemicals and chemical emissions data. Results for 250 chemicals are presented, with a focus on 12 chemicals of interest in the United Nations Environment Programme's Persistent Organic Pollutants global treaty negotiations. These results help to illustrate the significance of described structural differences and to assess the correlation between the methodologies. The scope of the comparison was restricted here to human health, although the insights would be equally useful in the context of the health of ecosystems. Illustrating the current types of chemical screening and emissions comparison approaches, the relative significance of the scenario and structural differences of the Waste Minimization Prioritization Tool (WMPT) and the Toxic Equivalency Potential (TEP) methodologies are analyzed. The WMPT facilitates comparison in terms of key physical-chemical properties. Measures for Persistence, Bioaccumulation, and Toxicity (PBT) are calculated. Each PBT measure is scored and then these scores are added to provide a single measure of relative concern. TEPs account for chemical fate, multipathway exposure, and toxicity using a model-based approach. This model structure is sometimes considered to provide a less subjective representation of environmental mechanisms, and, hence, an improved basis for screening. Nevertheless, a strong relationship exists between the two approaches and both have their limitations.

Authentic 17 kDa tumour necrosis factor alpha is synthesized and released by canine mast cells and up-regulated by stem cell factor.

BACKGROUND: Previous studies have suggested varying molecular weights for mast cell derived tumour necrosis factor alpha (TNF alpha ) and little data exist upon the factors which may regulate the control of this cytokine in these cells. OBJECTIVE: To determine the molecular weight of canine mastocytoma-derived TNF alpha, to determine whether it is pre-formed within the granule and whether is expression could be up-regulated by stem cell factor (SCF). METHODS: Molecular sizing was assessed by immunoblot. The cellular localization of the TNF alpha was determined by immunocytochemistry before and after stimulation by A23187 and passive sensitization. Subcellular localization was performed by immunogold immunocytochemistry. Changes in the level of mastocytoma mRNA for TNF alpha in response to stimulation with SCF or fibroblast conditioned media for up to 12 weeks were studied using Northern analysis and changes in the level of TNF alpha protein expression on immunoblot and immunocytochemistry. RESULTS: Mast cells contained authentic 17 kDa TNF alpha as identified by immunoblotting. Immunocytochemical studies demonstrated preformed TNF alpha which was released by stimulation with antigen after passive sensitization, or by the calcium ionophore A23187. Further confirmation of the preformed nature of this TNF alpha was provided by immunogold electron microscopy which localized this cytokine to the granule of the inactive mast cell. Northern blotting revealed a constitutive message for TNF alpha, which increased in response to fibroblast conditioned media (FCM) and to recombinant human SCF. Immunocytochemical studies of mast cells cultured long-term with FCM or with recombinant SCF showed increased expression of TNF alpha over the course of 12 weeks incubation with these stimuli. CONCLUSION: Mastocytoma derived-TNF alpha is a preformed, granule-associated 17 kDa cytokine which is released on stimulation with A23187 or passive sensitization. It is up-regulated by stem cell factor and by FCM over the course of 12 weeks.

Dog mastocytoma cells produce transforming growth factor beta 1.

Transforming growth factor-beta (TGF beta) promotes deposition of extracellular matrix and is associated with fibrotic conditions both in experimental animals and in humans. Although a role for mast cells has been suspected in the pathogenesis of fibrosis, no potent mediator capable of stimulating fibroblast growth or extracellular matrix deposition has been identified in mast cell supernatants. We report here the constitutive production of TGF beta 1 by four dog mastocytoma cell lines. TGF beta 1 was identified by characteristic biologic activity, blockade of biologic effect by specific neutralizing antibody, and by recognition of a band with the appropriate migration by western blot. TGF beta 1 mRNA, but not TGF beta 2 or TGF beta 3 mRNA, was also produced constitutively by all four cell lines. Quantitation by bioassay revealed baseline TGF beta secretion of approximately 1 ng/10(6) cells over 48 h. Stimulation of mastocytoma cells with phorbol ester increased the rate of release of TGF beta 1, most markedly in the first 30 min after stimulation, without increasing TGF beta 1 mRNA. Dog mastocytoma cells produced TGF beta 1 primarily in a latent form, inactive until treated with acid. Both pure TGF beta 1 and TGF beta-containing mastocytoma cell-conditioned media inhibited mitogenesis and proliferation in dog mastocytoma cell lines, suggesting that mast cell tumor lines would not grow preferentially based on their ability to produce TGF beta. These studies may make possible further investigation of the mechanism by which mast cells contribute to the induction of fibrosis.

Dog mastocytoma cells secrete a growth factor for fibroblasts.

It is suspected that mast cells play a part in the pathogenesis of fibrotic diseases, but the mediators that might be involved in induction of fibrosis have not been identified. We asked whether cultured dog mast cell lines produced growth factor(s) for fibroblasts. Three mastocytoma cell lines were found to secrete proliferative activity for human, hamster, and rabbit fibroblasts. Both mastocytoma cell-conditioned medium and cell extract served as competence factors for induction of DNA synthesis in confluent mouse Swiss 3T3 fibroblasts. The mitogenic activity in the conditioned medium was stable to heat, acid, and high concentrations of chaotropic agents or organic solvents but was decreased by treatment with proteases or reducing agents. The activity had an apparent molecular mass of 10 kD and did not bind to heparin. Activity eluted in a single peak from reverse-phase HPLC, and retention time differed from that of typical mesenchymal mitogens. We offer the hypothesis that mast cells produce growth factors for fibroblasts, possibly including a novel growth factor, and that this may contribute to pathologic fibrosis.

Treatment of pulmonary arteriovenous malformations by therapeutic embolization. Rest and exercise physiology in eight patients.

Pulmonary arteriovenous malformations (AVM) lead to chronic hypoxemia and systemic emboli. These lesions can now be treated by catheter embolization. In order to examine physiologic abnormalities during exercise in AVM patients, and to evaluate functional improvement after therapeutic embolization, eight patients underwent detailed physiologic studies at rest and during exercise before and after therapeutic embolization. Before treatment, six patients noted dyspnea on exertion and three had symptoms suggesting paradoxical embolism. Resting studies showed hypoxemia, abnormally increased shunt fractions, chronic alveolar hyperventilation, mild decreases in diffusing capacity, and abnormal wasted ventilation (VD). During exercise, oxygenation changed little from the resting values but VD increased markedly. Functional impairment was observed in most patients, and was correlated with shunt fraction. Obliteration of the AVM was accomplished by therapeutic embolization with placement of coils or balloons in the feeder vessels. This treatment resulted in immediate relief of dyspnea and improvement in resting PaO2 and shunt fraction. Exercise studies after embolization showed improvement in exercise capacity and gas exchange. However, chronic alveolar hyperventilation and reduced diffusing capacity remained unchanged. In summary, therapeutic embolization effectively reduces the degree of shunting, with improvement in respiratory symptoms, exercise capacity, and gas exchange at rest and during exercise. The abnormally decreased diffusing capacity and increased VD suggest the presence of a diffuse pulmonary vascular abnormality, of which further study is warranted.

Stimulation of sporulation by ppApp in a conditionally asporogenous rifampin-resistant mutant in Bacillus subtilis.

Addition of ppApp to Sterlini-Mandelstam medium stimulates sporulation of a conditionally asporogenous rifampin-resistant mutant of Bacillus subtilis to the same extent as the effect of 4 amino acids. Mutant cells sporulating in the presence of amino acids also produce 2 phosphorylated nucleotides one of which comigrated with ppApp on PEI thin layer chromatogram.