Revisión de las metodologías sobre evaluación de riesgos en salud para el estudio de comunidades vulnerables en América Latina / Health risk assessment methodologies for the study of vulnerable communities in Latin America / Revisão das metodologias sobre avaliação de riscos na saúde para o estudo de comunidades vulneráveis na América Latina

Los métodos para evaluar el riesgo en salud se basan, en general, en el monitoreo ambiental y en la estimación de la exposición a través de modelos matemáticos. La incertidumbre de tal estrategia es grande. En consecuencia, para incrementar la certidumbre sobre la evaluación de la exposición a los contaminantes, se ha propuesto el empleo de biomarcadores. No obstante, la complejidad de los nuevos escenarios de riesgo obliga a evaluar no solamente a las poblaciones humanas sino también al resto de la biota. Asimismo, factores ambientales, sociales y de salud, al afectar la vulnerabilidad, también deben ser considerados para la caracterización del riesgo. Estos factores de vulnerabilidad pueden evaluarse a través de indicadores. Al final, con los análisis ambientales, el uso de biomarcadores y el manejo de indicadores ambientales, sociales y de salud, puede evaluarse el riesgo de manera integrada (humanos y biota). En esta revisión se presentan las diversas estrategias empleadas por este grupo de trabajo para evaluar el riesgo en sitios contaminados, comunidades marginadas y en áreas afectadas por el cambio global climático.

The most commonly used methods for risk assessment are based on environmental analysis and the use of mathematical models for the estimation of exposure. However, the uncertainty of this approach is high, as the models are based on scenarios that may be not the correct ones. In order to decrease the uncertainty, the use of biomarkers has been proposed. Furthermore, considering the complexity of pollution in some sites, these biomarkers can be used both in humans and biota in order to obtain better information for the definition of risks at those sites. In addition to biomarkers, social, health and environmental indicators have to be applied for risk characterization, as different factors of vulnerability can modify the extent of health risks in some communities. At the end, with environmental monitoring and the use of biomarkers and indicators of vulnerability, health risks in humans and biota (integrated risk assessment) can be assessed in different scenarios. In this paper we present the strategies that our group developed for the study of hazardous waste sites, vulnerable communities and areas impacted by climate change.

Os métodos para avaliar o risco na saúde se baseiam, em geral, no monitoramento ambiental e na estimação da exposição através de modelos matemáticos. A incerteza de tal estratégia é grande. Em consequência, para incrementar a certeza sobre a avaliação da exposição aos contaminantes, tem sido proposta a utilização de biomarcadores. No entanto, a complexidade dos novos cenários de risco obriga a avaliar não somente as populações humanas mas também ao resto da biota. Da mesma forma, fatôres ambientais, sociais e de saúde, ao afetar a vulnerabilidade, também devem ser considerados para a caracterização do risco. Estes fatôres de vulnerabilidade podem avaliar-se através de indicadores. Finalmente, com as análises ambientais, o uso de biomarcadores e o manejo de indicadores ambientais, sociais e de saúde, pode-se avaliar o risco de maneira integrada (humanos e biota). Nesta revisão se apresentam as diversas estratégias empregadas por este grupo de trabalho para avaliar o risco em lugares contaminados, comunidades marginalizadas e em áreas afetadas pela mudança global climática.

Exposure to arsenic and lead of children living near a copper-smelter in San Luis Potosi, Mexico: Importance of soil contamination for exposure of children.

The objective of this study was to assess the levels of soil contamination and child exposure in areas next to a primary smelter (arsenic-copper metallurgical) located in the community of Morales in San Luis Potosi, Mexico. In Morales, 90% of the soil samples studied in this work were above 400 mg/kg of lead, and above 100 mg/kg of arsenic, which are guidelines recommended by the United States Environmental Protection Agency (EPA). Bioaccessibility of these metals was studied in vitro in 10 soil samples; the median values of bioaccessibility obtained in these samples were 46.5% and 32.5% for arsenic and lead. Since the concentrations of arsenic and lead in soil were above normal values, and taking into account the bioaccessibility results, exposure to these metals was evaluated in children. Regarding lead, children aged 3-6 years had the highest mean blood lead levels; furthermore, 90% of them had concentrations above 10 microg/dl (CDC's action level). Total urinary arsenic was higher in children aged 8-9 yr; however, the percentage of children with concentrations above 50 microg/g creatinine (CDC's action level) or 100 microg/g creatinine (World Health Organization [WHO] action level) was similar among different age groups. Using the EPAs integrated exposure uptake biokinetic model for lead in children (IEUBK), we estimated that 87% of the total lead in blood is obtained from the soil/dust pathway. The exposure dose to arsenic, estimated for the children living in Morales using Monte Carlo analysis and the arsenic concentrations found in soil, was above the EPA's reference dose. With all these results, it is evident that studies are needed in order to identify adverse health effects in children living in Morales; nevertheless, it is more important to develop a risk reduction program as soon as possible.

Environmental health assessment of deltamethrin in a malarious area of Mexico: environmental persistence, toxicokinetics, and genotoxicity in exposed children.

We reported previously that children are exposed to deltamethrin in malarious areas. In the present work we explored the levels of this insecticide in soil samples and also obtained relevant toxicokinetic data of deltamethrin in exposed children. Results show that, after spraying, indoor levels of deltamethrin in soil samples were higher than outdoor levels. The mean half-life estimated with these data was 15.5 days for outdoor samples and 15.4 days for indoor samples. Children's exposure to deltamethrin was assessed using as biomarkers the urinary concentrations of the metabolites 3-phenoxybenzoic acid (3-PBA) and cis-3-(2,2-dibromovinyl)-2,2-dimethylcyclopropane-1-carboxylic acid (Br2CA). The mean level of both biomarkers reached a peak within the first 24 hr postexposure; 6 months after the initial exposure, urinary levels of 3-PBA and Br2CA were found at levels observed before exposure. Approximately 91% of the total 3-PBA or Br2CA was excreted during the first 3 days after exposure. Therefore, we estimated a half-life for this period, the values for 3-PBA and Br2CA being almost identical (13.5 vs. 14.5 hr). Finally, considering reports about the genotoxicity of deltamethrin, we assessed DNA damage in children before and 24 hr after indoor spraying of deltamethrin; we found no differences in the comet assay end points. In conclusion, we observed exposure to deltamethrin in children, but we did not find any relationship between soil concentrations of deltamethrin and urinary levels of the metabolites. At least for genotoxicity, the exposed children appeared not to be at risk.

DDT-induced oxidative damage in human blood mononuclear cells.

Recent work indicates that DDT and its metabolites induce apoptosis in different cellular types. However, the mechanism by which DDT generates apoptosis has not been elucidated. In this study, our data demonstrate that the apoptosis induction by DDT and its metabolites in human peripheral blood mononuclear cells (PBMC) is preceded by an increase in the levels of reactive oxygen species (ROS). Cells isolated from healthy individuals were incubated for different intervals of time (0-24 h) and in the presence of increasing concentrations of p'p-DDT, p'p-DDE, or p'p-DDD (0-80 microg/ml). The induction of oxidative stress was then determined by flow cytometry, using the compound 2',7'-dichlorofluorescein diacetate. The control level of ROS was 4.46+/-0.96 IFM, for DDT- and DDD-treated cells we obtained a 19.0-fold increment, whereas for DDE, the increment was 25-fold. ROS induction by DDT and DDE was observed after 1 h of incubation, while for DDD such levels began to be detected at 3 h of incubation; a maximum effect on the ROS production for the three compounds was found at 6 h of treatment. A significant level of ROS was induced by DDT, DDE, and DDD only at 60 and 80 microg/ml. Finally, to find an association between generation of ROS and apoptosis induction, cells incubated with DDT, DDE, and DDD were evaluated for apoptosis induction and generation of oxidative stress. Our results show that an increase in ROS was accompanied by apoptosis of PBMC in vitro. Moreover, N-acetyl-L-cysteine significantly inhibits the apoptosis induction.

Levels of dichlorodiphenyltrichloroethane and deltamethrin in humans and environmental samples in malarious areas of Mexico.

Mexico used dichlorodiphenyltrichloroethane (DDT) to control malaria until 1999, when it was replaced with deltamethrin for mosquito control. Thus, we performed environmental and exposure assessments to DDT and deltamethrin in the states of Chiapas and Oaxaca. In Chiapas, samples were obtained at the time when DDT was being used in the malaria control program, while in Oaxaca, samples were collected 2 years after the final spraying of DDT and 2 days after deltamethrin application. Mean concentrations of DDT and Dichlorodiphenyldichloroethylene (DDE), as measured in whole blood, were 67.8 and 86.7 microg/L for children living in Chiapas and 27.1 and 60.8 microg/L for adults, respectively. As expected, DDT levels were lower 2 years after the final application in Oaxaca (20.4 and 13.2 microg/L for children and adults, respectively). Sprayers in Chiapas had the highest levels of exposure, with 165.5 and 188.4 microg/L of DDT and DDE, respectively. Women living in Chiapas and Oaxaca also had significantly higher blood levels of DDT and DDE than those women living in areas where less DDT had been used. Deltamethrin exposure was assessed only in children living in Oaxaca; 50% of the exposed group had urinary levels of 3-phenoxybenzoic acid above the limit of detection (LOD) and 6% had levels above 25 microg/L (five times the LOD), with a negative trend with age (r=-0.33). In Chiapas we found higher DDT and DDE levels in soil than in Oaxaca. In the latter location, large amounts of DDT and DDE were found in sediment samples and deltamethrin was detected in indoor soil samples. Considering the environmental data, the blood level results can be explained by soil/dust ingestion, human milk ingestion, and consumption of fish and other contaminated foods.

Overview of human health and chemical mixtures: problems facing developing countries.

In developing countries, chemical mixtures within the vicinity of small-scale enterprises, smelters, mines, agricultural areas, toxic waste disposal sites, etc., often present a health hazard to the populations within those vicinities. Therefore, in these countries, there is a need to study the toxicological effects of mixtures of metals, pesticides, and organic compounds. However, the study of mixtures containing substances such as DDT (dichlorodiphenyltrichloroethane, an insecticide banned in developed nations), and mixtures containing contaminants such as fluoride (of concern only in developing countries) merit special attention. Although the studies may have to take into account simultaneous exposures to metals and organic compounds, there is also a need to consider the interaction between chemicals and other specific factors such as nutritional conditions, alcoholism, smoking, infectious diseases, and ethnicity.