Biomarkers, for chemicals

Schoeters, E., Verheyen, G.R., Nelissen, I., Van Rompay A.R., Flooyberghs, J., Van Den Heuvel, R.L., Witters, H Schoeters, G.E., Van Tendeloo, V.F. and Berneman, Z.N. (2007) Microarray analyses in dendritic cells reveal potential biomarkers for chemical-induced skin sensitization. Molecular Immunology, 44, 3222-3233. 

Stegeman, J.J., M. Brouwer, R.T. DiGiulio, L. Forlin, B.M. Fowler, B.M. Sanders and P. Van Veld. Molecular responses to environmental contamination enzyme and protein systems as indicators of contaminant exposure and effect. In Biomarkers for Chemical Contaminants, edited by R.J. Huggett, Boca Raton, FL, CRC Press, pp. 237-339, 1992. 

For more information on biomarkers for renal and hepatic effects of chemicals, see ATSDR/CDC Subcommittee Report on Biomarkers of Organ Damage and Dysfunction (1990) and for information on biomarkers for neurological effects, see OTA (1990). 

The more difficult thing is to develop models that can, with reasonable confidence, be used to predict ecological effects. A detailed discussion of ecological approaches to risk assessment lies outside the scope of the present text. For further information, readers are referred to Suter (1993) Landis, Moore, and Norton (1998) and Peakall and Fairbrother (1998). One important question, already touched upon in this account, is to what extent biomarker assays can contribute to the risk assessment of environmental chemicals. The possible use of biomarkers for the assessment of chronic pollution and in regulatory toxicology is discussed by Handy, Galloway, and Depledge (2003). 

No information is available on whether biomarkers for exposure or effect of -hexane validated in adults (exhaled -hexane, 2,5-hexanedion in urine) also are valid for children. Interactions of -hexane with other chemicals have not been reported in children, but have occurred in adults (Altenkirch et al. 1977). Since interactions in adults are dependent on toxickinetic parameters, predicting interactions in children requires greater understanding of the metabolism of -hexane in children. 

Because cholinesterase inhibition is a very sensitive biomarker for other chemicals, it is not always conclusive evidence of disulfoton exposure. However, depression of cholinesterase activity can alert a physician to the possibility of more serious neurological effects. Erythrocyte acetylcholinesterase activity more accurately reflects the degree of synaptic cholinesterase inhibition in nervous tissue, while serum cholinesterase activity may be associated with other sites (Goldfrank et al. 1990). In addition, a recent study showed that after rats received oral doses of disulfoton for 14 days, acetylcholinesterase levels in circulating lymphocytes correlated better with brain acetylcholinesterase activity than did erythrocyte cell cholinesterase activities during exposure (Fitzgerald and Costa 1993). However, recovery of the activity in lymphocytes was faster than the recovery of activity in the brain, which correlated better with the activity in erythrocytes. Animal studies have also demonstrated that brain acetylcholinesterase depression is a sensitive indicator of neurological effects (Carpy et al. 1975 Costa et al. 1984 Schwab and Murphy 1981 Schwab et al. 1981, 1983) however, the measurement of brain acetylcholinesterase in humans is too invasive to be practical. 

In occupational settings, the concentrations of chemicals are often monitored in the working environment to monitor compliance with occupational exposure limits as required by various national laws. Moreover, medical surveys of workers are often performed including analyses of biomarkers for exposure and/or effects. In addition, workers also generally have the possibility to report signs and symptoms of nuisances related to their working environment. Such data, which in some cases are available in the open literamre, are relevant for use in a hazard assessment. 

To ensure lot-to-lot consistency, standardization of extracts often relies on constituents as biomarkers for plant identity and potency. SJW Hypericum perforatum), a perennial shrub traditionally used as a mood enhancer and mild antidepressant, has been tested in dozens of clinical trials, with mixed results for efficacy. Some of its purported bioactive constituents include naphthodianthrones, including hypericin flavonoids phloroglucinols, including hyperforin and essential oils. For many years, hypericin was presumed to be the active component. As a result most extracts were standardized based on hypericin concentration. Recent data, however, support other components such as hyperforin and the flavanoids, that may also contribute to the therapeutic efficacy of the SJW extracts (33-35). Because these secondary components were previously unaccounted for in the standardization of the former clinical test articles, and because these constituents are chemically unrelated to and their content within the plant varies independently of hypericin, it has been argued that the potency of these constituents in any particular batch was unlikely to be similar to that of other batches. This variability between batches could explain the observed differences in the clinical trial results (36). 

The first report included an analysis of 27 chemicals for 1999 the second, released in 2002, included an analysis of 116 chemicals for 1999-2000, including the 27 from the first report (CDC 2003). The third report, released in July 2005, includes 148 chemicals for 2001-2002 (CDC 2005). The analytes measured in the third report are listed in Table 2-1. The third report includes newly established biomarkers (phthalates), lower limits of detection (of dioxins, furans, and PCBs), and reference ranges for chemicals not previously monitored (pyrethroid insecticides, phthalates, additional dioxins, PCBs, and other pesticides and herbicides). 

For chemicals with half-lives of months or years—such as dioxins, polychlorinated biphenyls (PCBs), polybrominated biphenyl ethers, and first-generation halogenated insecticides—biomarkers can detect exposures months or even years after they have occurred. Such lipophilic chemicals are usually measured in blood, and the principal exposure source is usually diet. After ingestion, they are readily absorbed into the blood supply blood concentration then decreases rapidly as the blood supply equilibrates with... 

It is important to note that short half-life chemicals do have the potential to be useful biomarkers for establishing the reference range if exposure is fairly frequent at about the same concentrations. In this case, rapid clearance can be balanced by frequent exposure to yield a stable blood or urinary concentration. Biomonitoring examples with cotinine and phthal-ates, as described in Chapter 4, illustrate this point. 

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