Experimental Toxicology Division
Immunotoxicology Branch Projects

Current projects include: studies of the effects of particulate air pollutants - and the role of size and component parts - on the respiratory immune responses and development of both allergic and infectious disease; the relative potency of indoor molds in the induction and exacerbation of allergic asthma and the identification of mold allergens; and effects of environmental chemicals on the developing immune system in relationship to increased risk for both infectious and allergic disease.

A mouse model of mold allergy has been developed that exhibits many of the hallmarks of allergic asthma. This model is being used to explore the relative potency of various mold species commonly found in the indoor environment with respect to both induction and exacerbation of allergic responses. The model is also being used to identify allergenic components of the mold extract, and the effects and role of in utero exposure in the induction of allergic disease. Efforts to link this work with human health effects are underway, as well as collaborations with an exposure assessment project in the National Exposure Research Laboratory.

The current emphasis is on perfluorinated chemicals. Rodent models are being used to understand the sensitivity of the developing immune system (relative to the adult) to toxic chemicals, understand the underlying mechanisms and windows of vulnerability, and develop methods for assessing the risks.

Rodent models of allergic asthma are being used to explore the relative potency and potential structure activity relationships of aldehydes in the induction and/or exacerbation of allergic asthma. This work is coordinated with studies in the National Health and Environmental Effects Research Laboratory's Human Studies Division.

Rodent models are being used to evaluate the impact of real world combustion emissions on infectious and allergic diseases in the respiratory tract, and to understand the underlying mechanisms and potential differences associated with different sources of particulate matter (PM). Current emphasis is on diesel emissions, influenza infection, and asthmatic responses to ovalbumin-induced allergy. Combustion exposures are generated in collaboration with principal investigators in the National Risk Manaqement Research Laboratory.

Rodent models are being used to understand the effects of in utero exposure to ozone and diesel emissions on the development of allergic asthma. Diesel emissions are generated in collaboration with principal investigators in the National Risk Manaqement Research Laboratory.

Efforts are underway to develop one or two mouse models for food allergy that could be used to assess the potential risks associated with plant-incorporated pesticides.

A mouse model that uses dermal sensitization, followed by respiratory challenge, is being used to explore approaches to identifying low molecular weight chemicals with the potential to cause respiratory allergy. Approaches ranging from molecular (cytokine profiling and genomics) to whole-body plethysmography are under exploration, using a variety of diisocyanates and platinum salts. This project also includes principal investigators from the Pulmonary Toxicology Branch, Stephen H. Gavett and Aimen Farraj.

This study identifies chemical components in PM samples from controlled combustion using different fuels, such as diesel and coal, with and without fuel additives, and from ambient PM collected near and far from highways. The relationship between the chemical characteristics and respiratory symptoms in mice is under investigation. This project is a collaboration with the National Risk Manaqement Research Laboratory.