Consequent stages of developing a multi-compartmental mechanistic model for chronically inhaled nanoparticles pulmonary retention.

The paper retraces the development of a mechanistic multicompartmental system model describing particle retention in lungs under chronic inhalation exposures. This model was first developed and experimentally tested for various conditions of exposure to polydisperse dusts of SiO2 or TiO2. Later on it was successfully used as a basis for analyzing patterns in the retention of nanoparticles having different chemical compositions (Fe2O3, SiO2, NiO). This is the first publication presenting the outcomes of modeling lung retention of nickel oxide nano-aerosols under chronic inhalation exposure. The most significant adaptation of the above-mentioned model to the conditions of exposure to metal-oxide nanoparticles is associated with the need to describe mathematically not only the physiological mechanisms of their elimination but also their solubilization "in vivo" bearing in mind that the relative contribution of the latter may be different for nanoparticles of different nature and predominant in some cases. Using nickel oxide as an example, it is suggested as well that damage to the physiological pulmonary clearance mechanisms by particularly toxic nanoparticles may result in lung toxicokinetics becoming nonlinear.

Some peculiarities of pulmonary clearance mechanisms in rats after intratracheal instillation of magnetite (Fe3O4) suspensions with different particle sizes in the nanometer and micrometer ranges: are we defenseless against nanoparticles?

We studied differences between phagocytic responses to nanoparticles (NPs) versus microparticles in the pulmonary region by synthesizing magnetite of different sizes and instilling suspensions of these particles intratracheally into rats' lungs. Ten and 50 nm particles caused a greater increase in cell counts of the bronchoalveolar lavage fluid (BALF) than the instillation of microparticles. The response to 10 nm particles was weaker than to 50 nm ones, and the smaller NPs were more cytotoxic; both were more cytotoxic than the microparticles. Phagocytic activity was also studied using optical and atomic force microscopy. Phagocytes were more "loaded" in the lungs instilled with 10 nm particles as compared with those instilled with 50 nm particles; NPs of both sizes were engulfed more avidly than microparticles. We found in a separate comparative experiment that magnetite NPs were more cytotoxic than titanium dioxide and quartz suspensions having particle size distribution typical of industrial dusts.

Toxicity of monazite particulates and its attenuation with a complex of bio-protectors.

BACKGROUND: Workers employed on mining, processing and storage of monazite are at risk of exposure to dust with expected adverse health effects. OBJECTIVES: To study the adverse health effects of monazite particles in experiments on rats and to test the possibility of attenuating these effects. METHODS: Outbred white rats were injected intratracheally with a suspension of ground monazite concentrate (MC) in order to investigate the cellular response of the lower airways 24 hours later and the organism's status 6 months after the injection. The bio-protective complex (BPC) tested in these experiments consisted of glutamate, an iodine preparation, methionine, a polyvitamin-polymineral composition, and/or "Eicosavitol" (fish oil preparation rich in PUFA, predominantly of the omega 3-group). Bio-protectors were administered together with the rat food and drink daily for one month before the MC injection in the short-term experiment, or over 6 months after such injection in the long-term experiment. RESULTS: MC induced manifestations of its cytotoxicity, fibrogenicity and systemic toxicity as well as genotoxicity. The tested BPC attenuated virtually all these effects. Although a similar protective potential of "Eicosavitol" against almost all of them was lower compared with that of BPC, combining BPC with "Eicosavitol" provided, as a rule, the greatest protective effect. CONCLUSION: It may be assumed that the many-sided adverse effects of MC on the organism is due, at least partially, to the presence in its composition of not only rare earth elements but also of natural radioisotopes of the thorium and uranium families. The combination of the bio-protectors tested was highly effective and may be recommended for administering in periodic preventive programmes to exposed workers.

Prenatal and postnatal tobacco smoke exposure and respiratory health in Russian children.

BACKGROUND: Only few studies have assessed the relative impact of prenatal and postnatal exposure to tobacco smoke on the child's later asthma or chronic respiratory symptoms and to our knowledge no studies have elaborated respiratory infections and allergies in this context. OBJECTIVE: To assess the effects of prenatal and postnatal exposure to tobacco smoke on respiratory health of Russian school children. METHODS: We studied a population of 5951 children (8 to 12 years old) from 9 Russian cities, whose parents answered a questionnaire on their children's respiratory health, home environment, and housing characteristics. The main health outcomes were asthma, allergies, chronic respiratory symptoms, chronic bronchitis, and upper respiratory infections. We used adjusted odds ratios (ORs) from logistic regression analyses as measures of effect. RESULTS: Prenatal exposure due to maternal smoking had the strongest effects on asthma (adjusted OR 2.46, 95% CI 1.19-5.08), chronic bronchitis (adjusted OR 1.45, 95% CI 1.08-1.96) and respiratory symptoms, such as wheezing (adjusted OR 1.30, 95% CI 0.90-1.89). The associations were weaker for exposure during early-life (adjusted ORs 1.38/1.27/1.15 respectively) and after 2 years of age (adjusted ORs 1.45/1.34/1.18) compared to prenatal exposure and the weakest or non-existent for current exposure (adjusted ORs 1.05/1.09/1.06). Upper respiratory infections were associated more strongly with early-life exposure (adjusted OR 1.25, 95% CI 1.09-1.42) than with prenatal (adjusted OR 0.74, 95% CI 0.54-1.01) or current exposure (adjusted OR1.05, 95% CI 0.92-1.20). The risk of allergies was also related to early life exposure to tobacco smoke (adjusted OR 1.26, 95% CI 1.13-1.42). CONCLUSION: Adverse effects of tobacco smoke on asthma, chronic bronchitis, and chronic respiratory symptoms are strongest when smoking takes place during pregnancy. The relations are weaker for exposure during early-life and after 2 years of age and weakest or non-existent for current exposure.

Housing characteristics and children's respiratory health in the Russian Federation.

OBJECTIVES: We studied housing characteristics, parental factors, and respiratory health conditions in Russian children. METHODS: We studied a population of 5951 children from 9 Russian cities, whose parents answered a questionnaire on their children's respiratory health, home environment, and housing characteristics. The health outcomes were asthma conditions, current wheeze, dry cough, bronchitis, and respiratory allergy. RESULTS: Respiratory allergy and dry cough increased in association with the home being adjacent to traffic. Consistent positive associations were observed between some health conditions and maternal smoking during pregnancy, many health conditions and lifetime exposure to environmental tobacco smoke (ETS), and nearly all health conditions and water damage and molds in the home. CONCLUSIONS: Vicinity to traffic, dampness, mold, and ETS are important determinants of children's respiratory health in Russia.

Lead poisoning among young children in Russia: concurrent evaluation of childhood lead exposure in Ekaterinburg, Krasnouralsk, and Volgograd.

The Gore-Chernomyrdin Commission encouraged a binational collaboration to evaluate pediatric lead poisoning in Russia. The study evaluated children in three Russian cities: Krasnouralsk, a small city with minimal traffic centered around a copper smelter; and Ekaterinburg and Volgograd, both of which are large cities with multiple factories and heavy vehicular traffic. This project was the first international use of portable blood lead analysis instruments. In each city, at least 90% of children attending selected neighborhood kindergartens participated. We selected kindergartens on the basis of their proximity to industrial areas and major traffic corridors. We obtained capillary blood samples and analyzed for lead content and hemoglobin (Hgb) levels in the field, and collected environmental samples (i.e., indoor dust, tap water, play area soil, and interior and exterior paint) and analyzed for each participating school and in the homes of about 10% of the children who had elevated blood lead levels (BLLs; greater than or equal to 10 microg/dL). We calculated all age-, sex-, and city-specific geometric means using generalized estimating equations to account for covariance within kindergartens, and used multivariate logistic regression models to identify variables predictive of elevated BLLs. Overall, 23% of study children had elevated BLLs and 2% were anemic, defined as Hgb < 11 g/dL. Krasnouralsk had the highest geometric mean BLL (10.7 microg/dL), the highest percentage of children (60%) with elevated BLLs, and the highest percentage of anemic children (4%). All soil samples in Krasnouralsk had detectable lead levels. Volgograd was the only city that had paint samples with elevated lead levels. We found apparent city-specific differences in the percentages of children with elevated BLLs. Lead-contaminated soil and dust, which can result from lead-based automotive fuel and from lead-related industrial emissions, appear to be the most important routes of lead exposure of those evaluated in this study. Elevated lead levels found in paint samples from Volgograd may indicate old undercoats of lead-based paint that could represent a regionally rather than nationally important source of exposure.