Case study aggregate exposure

The methodology in the case study for chronic exposure, as well as several advances in probabilistic assessment methodology for acute exposure (e.g., a person s exposure on a single day), are being incorporated into the Cumulative and Aggregate Risk Evaluation System (CARES) begun in 2000 and being further developed with the International Life Sciences Institute (ILSI) in 2004. 

A fairly detailed case study illustrating a probabilistic approach to both aggregate and cumulative assessments is described in the first part of this chapter. This case study focuses on chronic exposure (that is, a person s long-term average dose). The case study was prepared as part of a submission to the US Environmental Protection Agency (USEPA) in 1996. 

A number of studies have examined the anti-inflammatory aetivities of CO (Abraham et al, 1988 Mannaioni et al, 2006). An activation of the heme oxygenase system and exposure to CO in vitro (Chauveau et al, 2005 Gibbons and Farrugia, 2004 Otterbein et al, 1999, 2000 Pae et al, 2004 Sethi et al, 2002) and in vivo (Dolinay et al, 2004 Nakao et al, 2003 Neto et al, 2004 Otterbein et al, 1999) revealed anti-inflainmatory activity in animal models but not in humans (Mayr et al, 2005). CO can inhibit apoptosis of endothelial cells (Soares et al, 2002). There is some evidence that upregulation of HO-1 might be beneficial in inflammatory diseases (Willis et al, 1996). In any case, the ability of CO to inhibit platelet aggregation and inflammation has important therapeutic implications and needs to be explored. 

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