Chemical and non-chemical stressors affecting childhood obesity: a systematic scoping review.

Childhood obesity in the United States has doubled over the last three decades and currently affects 17% of children and adolescents. While much research has focused on individual behaviors impacting obesity, little research has emphasized the complex interactions of numerous chemical and non-chemical stressors found in a child's environment and how these interactions affect a child's health and well-being. The objectives of this systematic scoping review were to (1) identify potential chemical stressors in the context of non-chemical stressors that impact childhood obesity; and, (2) summarize our observations for chemical and non-chemical stressors in regards to child-specific environments within a community setting. A review was conducted to identify chemical and non-chemical stressors related to childhood obesity for the childhood life stages ranging from prenatal to adolescence. Stressors were identified and grouped into domains: individual behaviors, family/household behaviors, community stressors, and chemical exposures. Stressors were related to the child and the child's everyday environments and used to characterize child health and well-being. This review suggests that the interactions of chemical and non-chemical stressors are important for understanding a child's overall health and well-being. By considering these relationships, the exposure science research community can better design and implement strategies to reduce childhood obesity.

Assessment of biological responses of EpiAirway 3-D cell constructs versus A549 cells for determining toxicity of ambient air pollution.

CONTEXT: EpiAirway™ 3-D constructs are human-derived cell cultures of differentiated airway epithelial cells that may represent a more biologically relevant model of the human lung. However, limited information is available on their utility for exposures to air pollutants at the air-liquid interface (ALI). OBJECTIVE: To assess the biological responses of EpiAirway™ cells in comparison to the responses of A549 human alveolar epithelial cells after exposure to air pollutants at ALI. METHODS: Cells were exposed to filtered air, 400 ppb of ozone (O3) or a photochemically aged Synthetic Urban Mixture (SynUrb54) consisting of hydrocarbons, nitrogen oxides, O3 and other secondary oxidation products for 4 h. Basolateral supernatants and apical washes were collected at 9 and 24 h post-exposure. We assessed cytotoxicity by measuring lactate dehydrogenase (LDH) release into the culture medium and apical surface. Interleukin 6 (IL-6) and interleukin 8 (IL-8) proteins were measured in the culture medium and in the apical washes to determine the inflammatory response after exposure. RESULTS: Both O3 and SynUrb54 significantly increased basolateral levels of LDH and IL-8 in A549 cells. No significant changes in LDH and IL-8 levels were observed in the EpiAirway™ cells, however, IL-6 in the apical surface was significantly elevated at 24 h after O3 exposure. CONCLUSION: LDH and IL-8 are robust endpoints for assessing toxicity in A549 cells. The EpiAirway™ cells show minimal adverse effects after exposure suggesting that they are more toxicologically resistant compared to A549 cells. Higher concentrations or longer exposure times are needed to induce effects on EpiAirway™ cells.

The Gillings Sampler--an electrostatic air sampler as an alternative method for aerosol in vitro exposure studies.

There is growing interest in studying the toxicity and health risk of exposure to multi-pollutant mixtures found in ambient air, and the U.S. Environmental Protection Agency (EPA) is moving towards setting standards for these types of mixtures. Additionally, the Health Effects Institute's strategic plan aims to develop and apply next-generation multi-pollutant approaches to understanding the health effects of air pollutants. There's increasing concern that conventional in vitro exposure methods are not adequate to meet EPA's strategic plan to demonstrate a direct link between air pollution and health effects. To meet the demand for new in vitro technology that better represents direct air-to-cell inhalation exposures, a new system that exposes cells at the air-liquid interface was developed. This new system, named the Gillings Sampler, is a modified two-stage electrostatic precipitator that provides a viable environment for cultured cells. Polystyrene latex spheres were used to determine deposition efficiencies (38-45%), while microscopy and imaging techniques were used to confirm uniform particle deposition. Negative control A549 cell exposures indicated the sampler can be operated for up to 4h without inducing any significant toxic effects on cells, as measured by lactate dehydrogenase (LDH) and interleukin-8 (IL-8). A novel positive aerosol control exposure method, consisting of a p-tolualdehyde (TOLALD) impregnated mineral oil aerosol (MOA), was developed to test this system. Exposures to the toxic MOA at a 1 ng/cm(2) dose of TOLALD yielded a reproducible 1.4 and 2-fold increase in LDH and IL-8 mRNA levels over controls. This new system is intended to be used as an alternative research tool for aerosol in vitro exposure studies. While further testing and optimization is still required to produce a "commercially ready" system, it serves as a stepping-stone in the development of cost-effective in vitro technology that can be made accessible to researchers in the near future.

In vitro exposures in diesel exhaust atmospheres: resuspension of PM from filters versus direct deposition of PM from air.

One of the most widely used in vitro particulate matter (PM) exposures methods is the collection of PM on filters, followed by resuspension in a liquid medium, with subsequent addition onto a cell culture. To avoid disruption of equilibria between gases and PM, we have developed a direct in vitro sampling and exposure method (DSEM) capable of PM-only exposures. We hypothesize that the separation of phases and post-treatment of filter-collected PM significantly modifies the toxicity of the PM compared to direct deposition, resulting in a distorted view of the potential PM health effects. Controlled test environments were created in a chamber that combined diesel exhaust with an urban-like mixture. The complex mixture was analyzed using both the DSEM and concurrently collected filter samples. The DSEM showed that PM from test atmospheres produced significant inflammatory response, while the resuspension exposures at the same exposure concentration did not. Increasing the concentration of resuspended PM sixteen times was required to yield measurable IL-8 expression. Chemical analysis of the resuspended PM indicated a total absence of carbonyl compounds compared to the test atmosphere during the direct-exposures. Therefore, collection and resuspension of PM into liquid modifies its toxicity and likely leads to underestimating toxicity.

A toxicogenomic comparison of primary and photochemically altered air pollutant mixtures.

BACKGROUND: Air pollution contributes significantly to global increases in mortality, particularly within urban environments. Limited knowledge exists on the mechanisms underlying health effects resulting from exposure to pollutant mixtures similar to those occurring in ambient air. In order to clarify the mechanisms underlying exposure effects, toxicogenomic analyses are used to evaluate genomewide transcript responses and map these responses to molecular networks. OBJECTIVES: We compared responses induced by exposure to primary pollutants and photochemically altered (PCA) pollutant mixtures representing urban atmospheres to test our hypothesis that exposures to PCA pollutants would show increased modulation of inflammation-associated genes and pathways relative to primary air pollutants. METHODS: We used an outdoor environmental irradiation chamber to expose human lung epithelial cells to mixtures representing either primary or PCA pollutants for 4 hr. Transcriptional changes were assessed using microarrays and confirmed using quantitative real-time reverse-transcription polymerase chain reaction (qRT-PCR) on a subset of genes. RESULTS: We found a large difference in the cellular responses to the two pollutant exposures: Primary air pollutants altered the expression levels of 19 genes, whereas PCA pollutants altered 709 genes. Functional and molecular analyses of the altered genes revealed novel pathways, such as hepatocyte nuclear factor 4α, potentially regulating the pollutant responses. Chemical component analysis characterized and confirmed the photochemical transformation of primary air pollutants into PCA air pollutants. CONCLUSIONS: Our study shows that the photochemical transformation of primary air pollutants produces altered mixtures that cause significantly greater biological effects than the primary pollutants themselves. These findings suggest that studying individual air pollutants or primary pollutant mixtures may greatly underestimate the adverse health effects caused by air pollution.