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Consistently linked with exposure at relevant levels of exposure with confounding and background exposures assesseda Effect Consistently linked with increased risk with confounding and effect modifying factors assessed Susceptibility Can distinguish subgroups at risk given specific exposure a Biomarkers of exposure may also be validated by establishing a constant link to an adverse health effect or to the concentration of the chemical in the target organ.
This applies to any form of exposure. It is due to intervening host factors that vary between individuals such as breathing rate and capacity, activation, detoxification, elimination, DNA repair, etc. Thus a high correlation between exposure and the marker may not always be observed and an exposure-response relationship may vary between people.
It is therefore important to identify and adjust for factors that can influence an exposure-response relationship. For example, to validate hydroxy-ethyl haemoglobin adducts as exposure biomarkers for ethylene oxide at low dose, investigators adjusted for age, smoking, and education in a linear regression model Schulte et al.
Additionally it may be useful to consider effect modifying factors, such as metabolic polymorphisms Bois et al. There are some exceptions to the validation strategy that focuses on the demonstration of a correspondence between a biomarker of exposure and external exposure.
Alternative ways to validate biomarkers include the assessment of their relationship with the concentration in the critical organ e.
Indeed, a good biomarker of exposure should be useful to predict adverse effects, rather than exposure levels. This may be especially the case when accurate and valid measurements of the "true" exposure are difficult or impossible to obtain use of protective devices, multiple pathways of uptake, etc.
It is possible to apply qualitative tests to determine whether external exposure or an exposure biomarker would be a better predictor for disease Steenland et al. One test involves determining if the biomarker is more highly correlated or associated with the disease than external exposure.
A second test is whether, given the same level of exposure, those with higher levels of the biomarkers are more likely to develop the disease. When absorption mainly occurs through the dermal route or when individual protective devices are used, biomarkers of exposure can provide reliable measurements of internal dose, which are useful to assess dose-response relationships.
On the basis of the parameters of the logistic regression, the calculated benchmark dose corresponds to 0. In evaluating the role of metabolic polymorphisms, the presence of a range of doses in which the modifying effect of metabolic enzymes could be seen, is a major issue.
A pertinent example comes from a study on the urinary excretion of 1-hydroxypyrene in traffic police officers Merlo et al.
Once validated, these markers can serve as surrogates for disease, albeit with some probability functions since generally not all people with a given biomarker will develop the disease, but the groups with the high levels generally will be at greatest risk.
A good example comes from a recent prospective study on the association between cytogenetic biomarkers and cancer risk Hagmar et al. This study, which followed five European cohorts has shown that subjects in the group with the highest frequency of chromosomal aberrations experienced an overall cancer risk more than double with respect to the lowest frequency group.
In the same study, no association was observed between sister chromatid exchange SCE frequency and cancer risk, whereas inconclusive results were found for the micronucleus assay.Nordic Pulp & Paper Research Journal Vol 29 no (1) 69 Difference between bamboo- and wood-derived cellulose nanofibers prepared by .
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Nordic Pulp and Paper Research Journal (NORD PULP PAP RES J) RG Journal Impact: * *This value is calculated using ResearchGate data and is based on average citation counts from work published.