Biomarkers exposure

Urinary thiosulfate levels as an exposure biomarker have been examined in rabbits (Kage et al. 1992). Urinary thiosulfate levels were detected in rabbit urine 24 hours after exposure to nonfatal concentrations of 100-200 ppm of hydrogen sulfide. Thiosulfate levels could be detected in the blood for up to 2 hours following exposure, whereas blood sulfide was not detectable. Measurements of thiosulfate levels in the blood, lung, or brain were found following fatal exposures to 500-1,000 ppm of hydrogen sulfide in experimental animals. 

Biomarkers are broadly defined as indicators signaling events in biologic systems or samples. They have been classified as biomarkers of exposure, biomarkers of effect, and biomarkers of susceptibility (NAS/NRC 1989). 

For applications in the diagnostics and biomarker area, 8-oxo-7,8-dihydro-2,-deoxyguanosine (8-oxoGuo) was measured as an oxidation stress biomarker in urine samples from smokers and non-smokers (Hu et al. 2006). When 100, uL of samples (10 times dilution) were used, a detection limit of 5.7 pg/mL (2.0 fmol) was achieved. The cycle time was 10 min per sample. The application was used for clinical scale. A similar approach was used for the detection of N7-methylguanine, another carcinogen exposure biomarker in human urine (Chao et al. 2005). 

Calafat AM, Wong L-Y, Silva MJ, Samandar E, Preau JL Jr, Jia LT, Needham LL (2011) Selecting adequate exposure biomarkers of diisononyl and diisodecyl phthalates data from the 2005-2006 National Health and Nutrition Examination survey. Environ Health Perspect 119 50-55... 

The most important question for biomonitoring efforts to address is whether exposure to a chemical causes health effects. Few data are available on most of the chemicals measured in population studies, such as NHANES, to address that question (Metcalf and Orloff 2004). For example, the Government Accountability Office (GAO 2005) reports that EPA has limited data on the health and environmental risks posed by chemicals now used in commerce. A survey of risk-assessment practitioners on the extent to which biomarkers are used in risk assessment concluded that the absence of chemical-specific data (for example, toxicologic and epidemiologic data) was the primary limitation in using exposure biomarkers in risk assessment (Maier et al. 2004). 

Chapter 7 presents the committee s recommendations on approaches that should be utilized to obtain data on exposure-biomarker relationships within ongoing large-scale biomonitoring studies. 

Which of the myriad uncertainties in biomonitoring are of most concern or most difficult to understand For example, are laypeople more interested in reduction of uncertainties about biomarker-effects relations or exposure-biomarker relations ... 

Exposure. No biomarkers of exposure were identified for white phosphorus smoke. In addition, no information on the metabolism of white phosphorus smoke were located. Studies designed to assess the metabolism of white phosphorus smoke would be useful in identifying biomarkers of exposure. Biomarkers of exposure are useful in facilitating future medical surveillance that can lead to early detection and possible treatment. 

Biomarker of exposure Biomarker of effect Biomarker of susceptibility... 

Van den Heuvel JP, Clark GC, Thompson CL, et al. 1993. CYP1A1 mRNA levels as a human exposure biomarker use of quantitative polymerase chain reaction to measure CYP1A1 expression in human peripheral blood lymphocytes. Carcinogenesis 14 2003-2006. 

Biomarkers do not measure exposure directly, but are an indicator of absorbed dose. A biomarker of exposure is defined as a xenobiotic substance or its metabolite(s) or the product of an interaction between a xenobiotic agent and some target molecules(s) or cell(s) that is measured within a compartment of an organism and can be related to exposure. Urine, blood, nail, saliva, hair, and faeces are common media collected for biomarker measurements. Maternal biomarkers of exposure can also be measured in amniotic fluid and breast milk. These matrices can also provide a measure of exposure for children, both prenatally and postnatally. Biomarkers in first teeth have also been used to assess early childhood exposure, whereas biomarkers in meconium and cord blood have been used to assess in utero exposures. Biomarkers of genetic damage (e.g. DNA adducts) have been extensively used to assess exposure to genotoxic agents (Neri et al., 2006). 

An important question in this area relates to the widespread use of exposure biomarker responses for monitoring effluents and receiving waters for endocrine disrupter activity. In oviparous species, vitellogenin is the major example of such a... 

Hogue CJ, Brewster MA. 1991. The potential of exposure biomarkers in epidemiologic studies of reproductive health. Environ Health Perspect 90 261-269. 

Another important issue related to exposure biomarkers is whether analysis of PCBs in serum and adipose tissue provide comparable information on body burden. Stellman et al. (1998) measured 14 PCB congeners in adipose tissue and serum from 293 women with nonoccupational exposure. The relative patterns of the 14 PCB congeners were similar to those reported in other human studies. Significant positive serum to adipose correlation coefficients were obtained for PCBs 74, 99,118,138, 146,153, 156, 167, 170, 180, 183, and 187, while PCBs 172 and 178 did not reach statistical significance. Thus, this study supports the conclusion that either serum or adipose tissue PCB levels may serve as useful biomarkers of body burden and/or exposure. 

Farmer, P. B. (2004b). Exposure biomarkers for the study of toxicological impact on carcinogenic processes. lARC Sci Publ, 71—90. 

Grandjean, P., E. Budtz-Jorgensen, R.F. White, P. Weihe, F. Defies, and N. Keiding. 1999. Methylmercury exposure biomarkers as indicators of neurotoxicity in children aged 7 years. Am. J. Epidemiol. 150(3) 301-305. 

Methylmercury exposure biomarkers as indicators of neurotoxicity in children aged 7 years. Am. J. Epidemiol 150(3) 301-305. 

Study Site Size of Cohort Identified and Enrolled Exposure Biomarker MeHg or Total Hg Concentration Age at Assessment Number of Children Assessed End Points Reference... 

Bao 1981 Campbell et al. 1985 Cox et al. 1992 Djuric 1967 Helasova 1969 Lieben 1974 McKee et al. 1943 NIOSH 1989 Pellizzari et al. 1982 Teisinger and Soucek 1949 WHO 1979). However, because of the rapid metabolism and elimination of carbon disulfide, these fluid and breath levels do not correlate well with environmental levels, except for the urinary marker, 2-thiothiazolidine-4-carboxylic acid. In addition, the interaction of carbon disulfide with other potential confounders may affect the reliability of urinary metabolites as biomarkers of exposure. Biomarkers may therefore be of limited utility in the quantitative assessment of human exposure to carbon disulfide at hazardous waste sites however, biomarkers may be useful in qualitatively establishing that possible exposure has occurred. 

Poirier, M.C. (1997) DNA adducts as exposure biomarkers and indicators of cancer risk. Environ. Health Perspect.,... 

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