Table 2.

Potential lines of investigation for HAP biomarkers — ambient and ex vivo measurement

Investigation	Physiological Relevance
Exhaled CO/transcutaneous COHb: field test in HAP	High CO might explain atherosclerosis and foetal effects (through left shift in O2 dissociation curve and myoglobin binding)
Methoxyphenols, levoglucosan: field test and controlled use in HAP	Unmetabolized urinary product should reflect exposure — physiological determinants of this correlation are not well understood
1-OHP: field tests for discrimination of pyrene metabolite levels at low concentration	Polyaromatic hydrocarbons known to be carcinogenic Unknown relevance of CYP enzyme polymorphisms in terms of biomarker
DNA methylation: case control or cohort studies of effect of HAP	Epigenetic effects may explain long term effects (e.g., ischaemic heart disease) Known effects of methylation on promoters of genes for inflammatory pathways (e.g., iNOS)
Generation of robust animal models for HAP, especially chronic exposures	Chronic exposure effects are likely to be different than experimental acute exposures due to physiological responses (e.g., antioxidant upregulation, negative and positive feedback within signalling pathways)
Malondialdehyde, 8-isoprostane, 8-oxo-7,8-dihydro-2′-deoxyguanosine: Investigation of urinary and plasma performance in controlled and field tests	HAP products are known to cause oxidative stress including lipid peroxidation and DNA strand breaks. Measurement within organisms is complicated by buffering and repair mechanisms.

A summary of potential investigations and promising biomarkers: their physiological relevance.

COHb, carboxyhemoglobin;1-OHP, 1-hydroxypyrene; iNOS, inducible nitric oxide synthase.