Aggarwal et al., Nature, 2012   
2016 Impact Factor: Ranked (total number of cites)
BIOMARKERS AND RISK ASSESSMENT: CONCEPTS AND PRINCIPLES At the Sixth Meeting of the IPCS Programme Advisory Committee (31 October to 3 November 1989) it was recommended that the IPCS give priority to work on biomarkers, as outlined at an IPCS Planning Meeting (25-28 October 1989).
Haemoglobin has the unique biological property of having a life span equivalent to that of the erythrocyte, which in humans is approximately 120 days, and therefore adduct levels reflect exposures over several months.
The examples in Table 1 are given as general information.
Although the modes of action of non-genotoxic carcinogens are poorly understood, several have been proposed, including immunosuppression, hormonal effects, promotion, inorganic carcinogenesis, co-carcinogenic effects and solid-state carcinogenesis (Weisburger & Williams, 1981).
A compilation of NTP rodent data, designed to test the concordance between short-term tests and in vivo carcinogenicity assays, showed that more than 30% of rodent carcinogens do not test positively for genotoxicity (Ashby & Tennant, 1991).
al., 1978; Hancock et al., 1984; Lamm et al., 1989).
These models can then be used to extrapolate between different exposure situations for the predicted levels of markers (Ramsay & Andersen, 1984; Droz et al., 1989).
An example is the use of haemoglobin adducts to predict the amount of DNA adducts at a critical site, e.g., after exposure to ethylene oxide (Passingham et al., 1988).
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3.1.1 General laboratory considerations Measurement of biomarkers may range from molecular events to functional outcomes such as behaviour or pulmonary function; the same consideration should be applied to all biomarkers.
Environ Mol Mutagen, 18: 245-248.
This will include data from in vitro, mammalian and human studies, with assessment of the validity of data and the study protocols; (3) selection of biomarker(s) specific to the outcome of interest with careful consideration of the biomarker to identify what is being quantified, to assess the sensitivity and specificity of the marker in relation to exposure, and the significance with respect to health outcome or pathological change over time; (4) consideration of specimens potentially available for analysis, with emphasis on protecting the integrity of the specimen between collection and analysis, and a preference for non-invasive techniques; (5) review of the analytical procedures available for quantification of biomarkers and their limitations with respect to detection limit, sensitivity, precision and accuracy; (6) establishment of an appropriate analytical protocol with provision for quality assurance and quality control; (7) evaluation of intra- and inter-individual variation for a non-exposed population; (8) analysis of the data base to establish dose-effect and dose-response relationships and their variation, with special emphasis on susceptible individuals; (9) calculation or prediction of risk to human health either for the general population or a sub-group; and (10) review of ethical and social considerations.
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3.1.2 Quality assurance and control Critical to the successful and effective application of biomarkers is a well-documented quality assurance and control programme.
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To select the most appropriate biomarker requires several steps: (1) the identification and definition of the end-point of interest; (2) the assembly of the data base to document the relationship between the chemical exposure, the possible biomarkers and the end-point.
Am Rev Respir Dis, 139: 370-372.
Desirable characteristics of biomarkers include that: (1) the marker (measurement) (a) reflects the interaction (qualitative or quantitative) of the host biological system with the chemical of interest, (b) has known and appropriate specificity and sensitivity to the interaction, (c) is reproducible qualitatively and quantitatively with respect to time (short- and long-term); (2) the analytical measurement has defined and appropriate accuracy and precision; (3) the marker is common to individuals within a population or subgroup and is of defined variability within the normal, non-exposed population or group of interest; and (4) the marker is common between species.
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