Reference ranges for key biomarkers of chemical exposure within the UK population.

Human biomonitoring (HBM) is a widely accepted tool to aid assessment of chemical uptake in risk assessment. However, our understanding of the biological relevance of the results of HBM can be restricted, due in some part to the limited information on background environmental exposures and biomarker concentrations in the general population. The study described here specifically addresses the question of what constitutes normal background levels in the UK population of a number of biomarkers (the chemical itself or one of its stable metabolites) for a variety of environmental chemicals that are frequently encountered because of their widespread use. The environmental chemicals selected for this study were benzene, chlorinated hydrocarbons, dithiocarbamates, cadmium, mercury, naphthalene, diethylhexyl phthalate, synthetic pyrethroids and xylene. Volunteers (n=436) were randomly sought by a postal survey based on the UK Electoral Register. Participants were asked to complete a questionnaire and provide a urine sample. The overall response rate was 7.5%, with volunteers being recruited from all areas of the UK including, England, Scotland, Wales and Northern Ireland. Study participants were adults and comprised 45% male and 55% females. We have conducted a simple, postal-based, cost-effective study and generated similar reference values to very large surveys such as NHANES. This demonstrates that large investigations may not be necessary to get a reasonable idea of environmental exposures, especially in initial 'screening-type' investigations to identify particular exposures of concern or to demonstrate that exposures are reassuring low and that no further survey data needs to be gathered.

Background levels of key biomarkers of chemical exposure within the UK general population--pilot study.

The use of biomarkers is now an accepted measure of chemical uptake (possibly exposure) in risk assessment. However, information on background exposures and biomarker concentrations of many environmental chemicals in the general UK population is limited. This study aims to determine reference ranges for eleven biomarkers of chemical exposure, measurable in urine, within the general adult UK population. The study will involve 400 volunteers throughout the UK and is currently underway. Described here is a pilot study, carried out during August and September 2005 to test the study methodology. The initial results of the postal survey and urinary concentrations for cadmium (UCd) and mercury (UHg) are reported. A total of 78 individuals were recruited by post from the UK Electoral Register, to take part in the pilot study. Participants were asked to complete a questionnaire and provide a urine sample. The overall response rate was 16%, of which 60.3% were female and 39.7% male. Those living in suburban areas accounted for 60% of respondents, current smokers 12.8% and vegetarians 1.3%. Levels of UCd were higher in females compared to males and smoking status influenced levels; smokers displayed higher levels of UCd than individuals who had previously smoked or who had never smoked. The mean, median and range of UHg was 1.12, 0.55 (

Substrate characterisation of a recombinant sulfotransferase SULT1 and mRNA expression in chub (Leuciscus cephalus) tissues.

We have studied the role and regulation of sulfonation of xenobiotics and endogenous substrates in Leuciscus cephalus, an abundant and environmentally relevant freshwater fish. A sulfotransferase 1 (SULT1) cDNA and promoter region was cloned from chub liver and the cDNA expressed in Escherichia coli. The translated protein displayed 51% and 50% amino acid identity to mSULT1D1, hSULT1A1, respectively. We identified two conserved co-substrate binding motifs for 3'-phosphoadenosine 5'-phosphosulfate: RKGxxGDWKxxFT and YPKSGTxW. The recombinant SULT displayed a strong preference towards the isoflavones genistein (K(m)=1.7 microM) and daidzein (K(m)=4.4 microM) and lesser activity towards the endogenous substrate dopamine. Based on sequence identity and substrate preferences, the SULT was classified as SULT1,3. SULT1,3 mRNA expression was highest in the liver and kidney with low levels expressed in brain, gonad, and gill. Mature males displayed higher hepatic SULT1,3 mRNA expression compared to females. Analysis of the promoter region revealed several putative half palindromic estrogen response elements (ERE).