Metabolites analyses, risk assessment

Despite this clearly outlined procedure, scientific progress in the field has been slow, as very few authors have as yet attempted environmental risk assessment of PhCs in water, focussing their attention, furthermore, mainly on parent compounds rather than their metabolites, on the effects of individual substances rather than mixtures on target organisms and on acute rather than chronic toxicity. In particular, metabolite analysis tended to be disregarded as their exposure is very difficult to assess due to a lack of consensus in the literature regarding excreted metabolite fractions moreover, analysis has shown that their relative contribution to the overall risk is typically low [99]. 

In the case of degradation products and metabolites, the situation is different. Generally, these compounds were not analysed because in most cases they are not regulated and no effective analytical methods exist for their determination. This means that a correct diagnosis of the environmental situation cannot be made and, as a consequence, no appropriate action can be taken. Therefore, in order to improve the risk assessment of a hazardous waste site for example, as many compounds as possible should be analysed at the beginning of the investigations (non-target analysis). 

Chemical Dosimetry bv TSP LC/MS. One of our long-term objectives in studying TSP LC/MS is the development of chemical dosimetry based on direct determination of polar metabolites in biological fluids. Most toxic substance exposure scenarios (i.e., near hazardous waste sites) involve complex and variable mixtures of substances. Biological monitoring, where human fluids, tissues and excreta are analyzed, measures actual exposure, whereas analysis of soil, air or water can only provide an estimate of potential exposure. Exposure data forms the basis of human health risk assessment, and ultimately defines cleanup requirements at contaminated sites. 

An ecotoxicological profile analysis is a procedure developed to evaluate the environmental impact of chemicals (commonly used for pesticides). The basis of the risk assessment is a list of properties of the investigated chemical. That list includes concentration used, pattern of application, biodegradability, type and properties of metabolites, environmental dispersion and accumulation. Related results from laboratory tests are weighted and classified following very specific rules. Finally, one relative index number is obtained which allows a simple comparison between ecological impacts of different chemicals (for details see Freitag and co-workers [29]). 

Fish bioaccmnulation and biomarkers in environmental risk assessment have been reviewed by Oost et al. [360]. Fish bioaccmnulation markers may be applied in order to elucidate the aquatic behavior of enviromnental contaminants and to assess exposme of aquatic organisms. The feasibility of PAH tissue concentrations in marine species as a monitoring parameter for PAH exposme depends on their uptake, biotransformation and excretion rates. Since it remains hard to accmately predict bioaccumulation in marine species, even with highly sophisticated models, analyses of tissue levels are required. The main problem is that PAHs do not tend to accumulate in fish tissues in quantities that reflect the exposme. The analysis of PAH metabolite levels in fish bile can be used to assess the actual PAH uptake, rather than the analysis of the non-hydroxylated PAHs content [328,361]. A number of sentinel fish species have been proposed to asses pollution by PAHs [325,326], as well as several mussels [322,323,326,352]. Several studies have also correlated the high levels of 1-OHPy and B(a)Py metabolites found in the bile of cat-shark with contamination sources such as boat traffic and combustion-based industries present in the sampling area [362]. 

Immunotoxicity. There are currently no data on the effects of 2-hexanone on the human immune system via any route of exposure. Animal data included an inhalation study in which there was a 40% decrease in peripheral white blood cells in rats exposed to 2-hexanone (Katz et al. 1980). In addition, 2,5-hexanedione, a metabolite of 2-hexanone, was shown to adversely affect lymphoid organs of the immune system in rats and to cause impairment of immunity in mice (Upreti and Shanker 1987). Immunological assessments, including analysis of peripheral blood components and effects on lymphoid tissue, conducted as part of intermediate-or chronic-duration studies and skin sensitization tests would be useful in developing a dose-response relationship and assessing the potential risk to chronically exposed persons in the vicinity of hazardous waste sites or to exposed workers. 

---