A proposed framework for the interpretation of biomonitoring data

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Abstract

Biomonitoring, the determination of chemical substances in human body fluids or tissues, is more and more frequently applied. At the same time detection limits are decreasing steadily. As a consequence, many data with potential relevance for public health are generated although they need not necessarily allow interpretation in term of health relevance. The European Centre of Ecotoxicology and Toxicology of Chemicals (ECETOC) formed a dedicated task force to build a framework for the interpretation of biomonitoring data. The framework that was developed evaluates biomonitoring data based on their analytical integrity, their ability to describe dose (toxicokinetics), their ability to relate to effects, and an overall evaluation and weight of evidence analysis. This framework was subsequently evaluated with a number of case studies and was shown to provide a rational basis to advance discussions on human biomonitoring allowing better use and application of this type of data in human health risk assessment.

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Establishing the background level of base oxidation in human lymphocyte DNA: results of an interlaboratory validation study.

Catherine M. Gedik, Andrew Collins, Lisa Giovannelli (2004)

Accurate measurement of low levels of 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodGuo) in DNA is hampered by the ease with which guanine is oxidized during preparation of DNA for analysis. ESCODD, a consortium of mainly European laboratories, has attempted to minimize this artifact and to provide standard, reliable protocols for sample preparation and analysis. ESCODD has now analyzed 8-oxodGuo in the DNA of lymphocytes isolated from venous blood from healthy young male volunteers in several European countries. Two approaches were used. Analysis of 8-oxodGuo by HPLC with electrochemical detection was performed on lymphocytes from 10 groups of volunteers, in eight countries. The alternative enzymic approach was based on digestion of DNA with formamidopyrimidine DNA glycosylase (FPG) to convert 8-oxo-7,8-dihydroguanine (8-oxoGua) to apurinic sites, subsequently measured as DNA breaks using the comet assay (7 groups of volunteers, in six countries). The median concentration of 8-oxodGuo in lymphocyte DNA, calculated from the mean values of each group of subjects as determined by HPLC, was 4.24 per 10(6) guanines. The median concentration of FPG-sensitive sites, measured with the comet assay, was 0.34 per 10(6) guanines. Identical samples of HeLa cells were supplied to all participants as a reference standard. The median values for 8-oxodGuo in HeLa cells were 2.78 per 10(6) guanines (by HPLC) and 0.50 per 10(6) guanines (by enzymic methods). The discrepancy between chromatographic and FPG-based approaches may reflect overestimation by HPLC (if spurious oxidation is still not completely controlled) or underestimation by the enzymic method. Meanwhile, it is clear that the true background level of base oxidation in DNA is orders of magnitude lower than has often been claimed in the past.

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Urinary aflatoxin biomarkers and risk of hepatocellular carcinoma.

G Qian, R. Paul Ross, Chia-Ming Yu … (1992)

Aflatoxins have long been suspected to be human hepatic carcinogens but no direct study was feasible until assays to measure individual aflatoxin exposure became available. We have used assays for urinary aflatoxin B1, its metabolites AFP1 and AFM1, and DNA-adducts (AFB1-N7-Gua) to assess the relation between aflatoxin exposure and liver cancer, as part of an ongoing prospective study of 18,244 middle-aged men in Shanghai, People's Republic of China. After 35,299 person-years of follow-up, 22 cases of liver cancer had been identified. For each case, 5 or 10 controls were randomly selected from cohort members without liver cancer on the date the disorder was diagnosed in the case and matched to within 1 year for age, within 1 month for sample collection, and for neighbourhood of residence. Subjects with liver cancer were more likely than were controls to have detectable concentrations of any of the aflatoxin metabolites (relative risk 2.4, 95% confidence interval 1.0-5.9). The highest relative risk was for aflatoxin P1 (6.2, 1.8-21.5). In an analysis adjusting for the effects of hepatitis B surface antigen seropositivity, level of education, cigarette smoking, and alcohol consumption, the relative risk for the presence of aflatoxin metabolites was 3.8 (1.2-12.2). There was a strong interaction between serological markers of chronic hepatitis B infection and aflatoxin exposure in liver-cancer risk. Reduction of aflatoxin exposure may be a useful intermediate goal in prevention of liver cancer, since the benefits of wide-scale hepatitis B vaccination will not be apparent for many years.

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Chlorophyllin intervention reduces aflatoxin-DNA adducts in individuals at high risk for liver cancer.

K J Helzlsouer, S Gange, Patricia A. Egner … (2001)

Residents of Qidong, People's Republic of China, are at high risk for development of hepatocellular carcinoma, in part from consumption of foods contaminated with aflatoxins. Chlorophyllin, a mixture of semisynthetic, water-soluble derivatives of chlorophyll that is used as a food colorant and over-the-counter medicine, has been shown to be an effective inhibitor of aflatoxin hepatocarcinogenesis in animal models by blocking carcinogen bioavailability. In a randomized, double-blind, placebo-controlled chemoprevention trial, we tested whether chlorophyllin could alter the disposition of aflatoxin. One hundred and eighty healthy adults from Qidong were randomly assigned to ingest 100 mg of chlorophyllin or a placebo three times a day for 4 months. The primary endpoint was modulation of levels of aflatoxin-N(7)-guanine adducts in urine samples collected 3 months into the intervention measured by using sequential immunoaffinity chromatography and liquid chromatography-electrospray mass spectrometry. This aflatoxin-DNA adduct excretion product serves as a biomarker of the biologically effective dose of aflatoxin, and elevated levels are associated with increased risk of liver cancer. Adherence to the study protocol was outstanding, and no adverse events were reported. Aflatoxin-N(7)-guanine could be detected in 105 of 169 available samples. Chlorophyllin consumption at each meal led to an overall 55% reduction (P = 0.036) in median urinary levels of this aflatoxin biomarker compared with those taking placebo. Thus, prophylactic interventions with chlorophyllin or supplementation of diets with foods rich in chlorophylls may represent practical means to prevent the development of hepatocellular carcinoma or other environmentally induced cancers.

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Conference

Journal ID (nlm-ta): Environ Health

Title: Environmental Health

Publisher: BioMed Central

ISSN (Electronic): 1476-069X

Publication date Collection: 2008

Publication date (Electronic): 5 June 2008

Volume: 7

Issue: Suppl 1

Page: S12

Affiliations

[1 ]Shell Health, Shell International bv, PO Box 162, 2501 AN The Hague, Netherlands

[2 ]Exxon Mobil Petroleum & Chemical, Hermeslaan 2, B-1831 Machelen, Belgium

Article

Publisher ID: 1476-069X-7-S1-S12

DOI: 10.1186/1476-069X-7-S1-S12

PMC ID: 2423449

PubMed ID: 18541066

SO-VID: 275aa046-46d5-4acd-82c2-fab677f1e016

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This is an open access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Conference name: Ethics and communication in human biomonitoring in Europe: results from preparation of pilot studies

Conference location: Copenhagen, Denmark

Conference date: 11–13 March 2007

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A proposed framework for the interpretation of biomonitoring data

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Most cited references 19

Establishing the background level of base oxidation in human lymphocyte DNA: results of an interlaboratory validation study.

Urinary aflatoxin biomarkers and risk of hepatocellular carcinoma.

Chlorophyllin intervention reduces aflatoxin-DNA adducts in individuals at high risk for liver cancer.

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