Health impact assessment of decreases in PM10 and ozone concentrations in the Mexico City Metropolitan Area: A basis for a new air quality management program / Evaluación de impacto en salud ante reducciones de PM10 y ozono en la Zona Metropolitana del Valle de México: Base para un nuevo programa de calidad del aire

Objective. To conduct a health impact assessment (HIA) to quantify health benefits for several PM and O3 air pollution reduction scenarios in the Mexico City Metropolitan Area (MCMA). Results from this HIA will contribute to the scientific support of the MCMA air quality management plan (PROAIRE) for the period 2011-2020. Materials and methods. The HIA methodology consisted of four steps: 1) selection of the air pollution reduction scenarios, 2) identification of the at-risk population and health outcomes for the 2005 baseline scenario, 3) selection of concentration-response functions and 4) estimation of health impacts. Results. Reductions of PM10 levels to 20 μg/m³ and O3 levels to 0.050ppm (98 µg/m³) would prevent 2300 and 400 annual deaths respectively. The greatest health impact was seen in the over-65 age group and in mortality due to cardiopulmonary and cardiovascular disease. Conclusion. Improved air quality in the MCMA could provide significant health benefits through focusing interventions by exposure zones.

Objetivo. Realizar una evaluación de impacto en salud (EIS) que documente los beneficios en salud ante diversos escenarios de reducción de PM10 y O3 en el aire de la Zona Metropolitana del Valle de México (ZMVM). Los resultados contribuyen al sustento científico del plan de gestión de calidad del aire (PROAIRE 2011-2020). Material y métodos. La metodología de EIS comprende cuatro pasos: 1) selección de los escenarios de reducción, 2) identificación de la población en riesgo y de los eventos en salud para el año basal 2005, 3) selección de las funciones de concentración-respuesta y 4) estimación del impacto en la salud. Resultados. Reducciones de PM10 a 20μg/m³ y de O3 a 0.050ppm (98 µg/m³) evitarían, respectivamente, cerca de 2 300 y 400 muertes por año. El mayor impacto se observa en el grupo de más de 65 años y en la mortalidad por causas cardiopulmonares y cardiovasculares. Conclusiones. Mejorar la calidad del aire en la ZMVM podría reflejar importantes beneficios para la salud focalizados por zonas o áreas de exposición.

1,3-Butadiene: I. Review of metabolism and the implications to human health risk assessment.

1,3-Butadiene (BD) is a multisite carcinogen in laboratory rodents following lifetime exposure, with mice demonstrating greater sensitivity than rats. In epidemiology studies of men in the styrene-butadiene rubber industry, leukemia mortality is associated with butadiene exposure, and this association is most pronounced for high-intensity BD exposures. Metabolism is an important determinant of BD carcinogenicity. BD is metabolized to several electrophilic intermediates, including epoxybutene (EB), diepoxybutane (DEB), and epoxybutane diol (EBD), which differ considerably in their genotoxic potency (DEB >> EB > EBD). Important species differences exist with respect to the formation of reactive metabolites and their subsequent detoxification, which underlie observed species differences in sensitivity to the carcinogenic effects of BD. The modes of action for human leukemia and for the observed solid tumors in rodents are both likely related to the genotoxic potencies for one or more of these metabolites. A number of factors related to metabolism can also contribute to nonlinearity in the dose-response relationship, including enzyme induction and inhibition, depletion of tissue glutathione, and saturation of oxidative metabolism. A quantitative risk assessment of BD needs to reflect these species differences and sources of nonlinearity if it is to reflect the current understanding of the disposition of BD.

Quantitative assessment of the distributions of membrane conductances involved in action potential backpropagation along basal dendrites.

Basal dendrites of prefrontal cortical neurons receive strong synaptic drive from recurrent excitatory synaptic inputs. Synaptic integration within basal dendrites is therefore likely to play an important role in cortical information processing. Both synaptic integration and synaptic plasticity depend crucially on dendritic membrane excitability and the backpropagation of action potentials. We carried out multisite voltage-sensitive dye imaging of membrane potential transients from thin basal branches of prefrontal cortical pyramidal neurons before and after application of channel blockers. We found that backpropagating action potentials (bAPs) are predominantly controlled by voltage-gated sodium and A-type potassium channels. In contrast, pharmacologically blocking the delayed rectifier potassium, voltage-gated calcium, or I(h) conductance had little effect on dendritic AP propagation. Optically recorded bAP waveforms were quantified and multicompartmental modeling was used to link the observed behavior with the underlying biophysical properties. The best-fit model included a nonuniform sodium channel distribution with decreasing conductance with distance from the soma, together with a nonuniform (increasing) A-type potassium conductance. AP amplitudes decline with distance in this model, but to a lesser extent than previously thought. We used this model to explore the mechanisms underlying two sets of published data involving high-frequency trains of APs and the local generation of sodium spikelets. We also explored the conditions under which I(A) down-regulation would produce branch strength potentiation in the proposed model. Finally, we discuss the hypothesis that a fraction of basal branches may have different membrane properties compared with sister branches in the same dendritic tree.

Development of a combined biological and chemical process for production of industrial aromatics from renewable resources.

Production of industrial aromatic chemicals from renewable resources could provide a competitive alternative to traditional chemical synthesis routes. This review describes the engineering of microorganisms for the production of p-hydroxycinnamic acid (pHCA) and p-hydroxystyrene (pHS) from glucose. The initial process concept was demonstrated using a tyrosine-producing Escherichia coli strain that overexpressed both fungal phenylalanine/tyrosine ammonia lyase (PAL) and bacterial pHCA decarboxylase (pdc) genes. Further development of this bioprocess resulted in uncoupling the pHCA and pHS production steps to mitigate their toxicity to the production host. The final process consists of a fermentation step to convert glucose to tyrosine using a tyrosine-overproducing E. coli strain. This step is followed by a single biotransformation reaction to deaminate tyrosine to pHCA through immobilized E. coli cells that overexpress the Rhodotorula glutinis PAL gene. Finally, chemical decarboxylation of pHCA produces pHS. This multifaceted approach, which integrates biology, chemistry, and engineering, has allowed development of an economical process at scales suitable for industrial applications.

Assessment of styrene oligomers eluted from polystyrene-made food containers for estrogenic effects in in vitro assays.

Recently, several substances from among the huge numbers of chemicals used by mankind have been implicated as instigators of disrupted endocrine function and related human health problems. Polystyrene (PS) is one of the most frequently used resins in the world, and the styrene oligomer dissolved out from PS has been designated as a potential trigger of estrogen-like activity in the Wingspread Declaration and the Japan Environment Agency's SPEED98 [JEA (Japan Environment Agency) Strategic Problem on Environmental Endocrine Disruptors '98 (SPEED) '98), http://www.env.go.jp/en/pol/speed98/sp98.html]. In order to assess the endocrine disrupting effect of styrene oligomers, we tested one styrene monomer (SM), three styrene dimers (SDs) and seven styrene trimers (STs), newly isolated from optical isomers, known to dissolve in small amounts from cup noodle containers made of polystyrene by the estrogen receptor binding assay, luciferase reporter gene assay, and human breast cancer cell MCF-7 proliferation assay. In all three tests, none of the SM, SDs and STs showed any significant activity. Accordingly, we concluded that these substances have no estrogenic activity.

Use of covalent binding in risk assessment.

Risk characterization comprises hazard identification describing the intrinsic toxic potential of a chemical, toxicokinetics, as well as the toxic mechanisms, information about dose response and exposure assessment. Compounds that induce reversible effects, which are repaired during and after exposure, are considered thresholded and allow definition of a NOEL. If damage is not repaired, the effect persists and accumulates upon repeated exposure. In such cases a NOEL cannot be determined. Biological reactive intermediates of chemicals have the potential to bind covalently to cellular macromolecules like proteins and DNA. Such interaction is not repaired completely and may persist. Thus, data on covalent binding (CB) are of qualitative and quantitative significance in the risk assessment process. Qualitatively, CB, especially with DNA and in correlation with this to proteins, is indicative for an irreversible and non-thresholded mutagenic and carcinogenic effect. Absence or presence of CB assists to differentiate between primarily genotoxic and thresholded non-genotoxic carcinogens. Quantitatively, CB is used to understand internal exposure and target dose, which is a prerequisite for species-species extrapolation, and to justify extrapolation from high dose to low dose. The reactive intermediates of ethylene, propylene and styrene have been determined in rodents and humans and modeled to predict dose responses of internal exposure. It is described in this communication that such information, together with other parameters like cell proliferation as a result of cytotoxicity, is the basis for quantitative risk assessment of human exposure to these compounds.

Styrene toxicity: an ecotoxicological assessment.

Although other aromatic compounds (e.g., benzene, toluene, polycyclic aromatic hydrocarbons (PAH), etc.) have been thoroughly studied over the years, styrene has been given little attention probably due to its lower rate of industrial use. In addition, it is less toxic than benzene and PAH, proven carcinogens. However, it is classified as a mutagen and thus potentially carcinogenic. Its main use is in the production of the polymer polystyrene and in the production of plastics, rubber, resins, and insulators. Entry into the environment is mainly through industrial and municipal discharges. In this review, the toxicological effects of styrene on humans, animals, and plants are discussed. Its mode of entry and methods of monitoring its presence are examined. Although its effects on humans and aquatic life have been studied, the data on short- or long-term exposures to plants, birds, and land animals are insufficient to be conclusive. Since exposure to workers can result in memory loss, difficulties in concentration and learning, brain and liver damage, and cancer, development of accurate methods to monitor its exposure is essential. In addition, the review outlines the present state of styrene in the environment and suggests ways to deal with its presence. It might appear that the quantities are not sufficient to harm humans, but more data are necessary to evaluate its effect, especially on workers who are regularly exposed to it.

Risk assessment extrapolations and physiological modeling.

The process of assessing the risk associated with human exposure to environmental chemicals inevitably relies on a number of assumptions, estimates and rationalizations. One of the more challenging aspects of risk assessment involves the need to extrapolate beyond the range of conditions used in experimental animal studies to predict anticipated human risks. The most obvious extrapolation required is that from the tested animal species to humans; but others are also generally required, including extrapolating from high dose to low dose, from one route of exposure to another and from one exposure timeframe to another. Several avenues are available for attempting these extrapolations, ranging from the assumption of strict correspondence of dose to the use of statistical correlations. One promising alternative for conducting more scientifically sound extrapolations is that of using physiologically based pharmacokinetic models that contain sufficient biological detail to allow pharmacokinetic behavior to be predicted for widely different exposure scenarios. In recent years, successful physiological models have been developed for a variety of volatile and nonvolatile chemicals, and their ability to perform the extrapolations needed in risk assessment has been demonstrated. Techniques for determining the necessary biochemical parameters are readily available, and the computational requirements are now within the scope of even a personal computer. In addition to providing a sound framework for extrapolation, the predictive power of a physiologically based pharmacokinetic model makes it a useful tool for more reliable dose selection before beginning large-scale studies, as well as for the retrospective analysis of experimental results.