Biotransformation

Many species, especially vertebrates, are capable of substantial metabolism of PAHs leading to high variability in effect concentrations (e.g., the LC50), precluding the determination of a toxic tissue concentration, which can be useful for assessing toxicity. Interestingly, PAHs can cause adverse effects in some species even though measured tissue concentrations are extremely low. One of the most important considerations is the amount of accumulated PAH that is metabolized, especially for species that have strong biotransformation capabilities for PAHs. These species may accumulate large amounts of these compounds, show effects, but not contain any measurable concentration of the parent compounds. In those species that are able to metabolize these compounds, mutagenic metabolites are often formed, which can be more toxic than the parent compounds.

Biotransformation of PAHs by various species has been well studied. The metabolites produced from PAH biotransformation are changed chemically and are rapidly excreted. For example, many studies have shown that a high percentage (>75%) of the total PAH dose given to different species was found in the bile after a short time due to biotransformation. Once the PAHs have been transformed to more water soluble metabolites, they are accumulated in bile and excreted. Because of the increase in polarity for these hydrophobic compounds, the rate of excretion is expected to increase greatly leading to the elimination of metabolites. This is supported by studies showing a large increase in clearance of PAH metabolites by the kidney.

Invertebrates, which are a very diverse group, exhibit a great deal of variability in their ability to metabolize PAHs. Among invertebrates, species of crustacea generally possess some of the highest rates of biotransformation for PAHs, whereas mollusks frequently have weak to nonexistent activation of detoxifying enzymes. Even within taxa, high variability exists. A few studies have reported that annelid and crustacean species display highly differential rates of biotransformation for PAHs. For example, one study of four annelid species found a large range in the percentage of benzo[tf]pyrene (BaP) converted to metabolites, with one species at 7%, two species at around 40%, and one species able to convert 96% of the total BaP. Additionally, this study found high variability for two crustacean species, with metabolites accounting for 20% and 60% of the BaP accumulated after 7 days.

One of the most pressing problems for PAH toxicity assessment is the determination of exposure. Because most species can effectively metabolize PAHs, determining ifindividuals have been exposed is often very difficult. In some species (mostly invertebrates) that do not extensively metabolize PAHs, a tissue concentration-response relationship can be established. Future work linking biological responses to biomarkers of exposure or specific metabolites found in bile may be valuable in defining dose-response relationships for vertebrates exposed to PAHs. For example, the determination of fluorescent aromatic compounds (FACs) in bile as a biomarker for PAH exposure may be a useful way to link exposure and response metrics. Other biomarkers of exposure include DNA adducts in various tissues and activation of certain enzymes, such as cytochrome P450—1A. At this point, there are no generalized correlations between the actual dose (mgg-1 or mgml-1 in water, food, or sediment/soil) and biomarkers of exposure. For most of these biomar-kers, such correlations have rarely been explored. For compounds that are metabolized extensively, such as PAHs, the administered dose or throughput of a compound (e.g., microgram of toxicant/gram organism/day) may be a more important factor than the actual whole-body tissue concentration or the amount present at the site of toxic action and should be considered as a viable dose metric.

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