Biomarker targeting

As developed in Chapter 6, workplace biomarker targets also provide context and a frame of reference for communicating general-population biomonitoring results. However, this raises a number of communication issues, given that workplace biomarker criteria are not directly relevant to the general public, for the reasons described previously and because the standards may be established with a different level of health protection than would be suitable for the general public. 

Kamio M (2009) Towards identifying sex pheromones in blue crabs using biomarker targeting within the context of evolutionary chemical ecology. Ann NY Acad Sci 1170 456-461... 

As described below, we have used biomarker targeting to search for blue crab sex pheromones by seeking molecules that distinguish urine of pubertal females from urines of other females, premolt males, juveniles, and any other urine that does not have pheromonal bioactivity. 

Liquid Chromatography-Mass Spectrometry (LC-MS)-Based Biomarker Targeting... 

An advantage of NMR-based biomarker targeting is that it does not require any separation methods and thus we can use more complex mixtures. But this advantage brings with it a challenge it can be difficult to identify the compounds in the complex NMR spectrum. A limitation is that NMR, especially 1D-NMR, alone usually yields partial structures even for a pure compound. 2D-NMR gives more information and resolution for structure analysis, but its lower sensitivity is a disadvantage. Complete molecular identification often requires a combination of approaches. 

Due to a nascent understanding of the use and interpretation of biomarkers, implementation of biomarkers as tools of exposure in the general population is very limited. A biomarker of exposure is a xenobiotic substance or its metabolite(s), or the product of an interaction between a xenobiotic agent and some target molecule(s) or cell(s) that is measured within a compartment of an organism (NAS/NRC 1989). The preferred biomarkers of exposure are generally the substance itself or substance-specific metabolites in readily obtainable body fluid(s) or excreta. However, several factors can confound the use and... 

A biomarker of susceptibility is an indicator of an inherent or acquired limitation of an organism s ability to respond to the challenge of exposure to a specific xenobiotic substance. It can be an intrinsic genetic or other characteristic or a preexisting disease that results in an increase in absorbed dose, a decrease in the biologically effective dose, or a target tissue response. If biomarkers of susceptibility exist, they are discussed in Section 3.10 Populations That Are Unusually Susceptible. 

These so-called Pareto-based techniques do not force consolidation over multiple criteria in advance and aim to return a representation of the set of optimal compounds. They support discussion between team members who may have different views on the downstream impacts of different risk factors perhaps, for example, one team member may know that there is a reliable biomarker for one potential side-effect. This would then mean that assessing this risk need not consume much development time and cost, and the risk factor can have a reduced weighting within the target product profile being evolved by the team. 

Effect. No biomarkers of effect were identified that were specific to diisopropyl methylphosphonate. No specific target organs of diisopropyl methylphosphonate are known, and no toxic effects in humans can be positively linked to diisopropyl methylphosphonate exposure. 

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