Using Biomonitoring Equivalents to interpret human biomonitoring data in a public health risk context

Increasingly sensitive analytical tools allow measurement of trace concentrations of chemicals in human biological media in persons from the general population. Such data are being generated by biomonitoring programs conducted by the US Centers for Disease Control and other researchers. However, few screening tools are available for interpretation of such data in a health risk assessment context. This review describes the concept and implementation of Biomonitoring Equivalents (BEs), estimates of the concentration of a chemical or metabolite in a biological medium that is consistent with an existing exposure guidance value such as a tolerable daily intake or reference dose. The BE approach integrates available pharmacokinetic data to convert an existing exposure guidance value into an equivalent concentration in a biological medium. Key concepts regarding the derivation and communication of BE values resulting from an expert workshop held in 2007 are summarized. BE derivations for four case study chemicals (toluene, 2,4‐dichlorophenoxyacetic acid, cadmium and acrylamide) are presented, and the interpretation of biomonitoring data for these chemicals is presented using the BE values. These case studies demonstrate that a range of pharmacokinetic data and approaches can be used to derive BE values; fully developed physiologically based pharmacokinetic models, while useful, are not required. The resulting screening level evaluation can be used to classify these compounds into relative categories of low, medium and high priority for risk assessment follow‐up. Future challenges related to the derivation and use of BE values as tools in risk management are discussed. Copyright © 2008 John Wiley & Sons, Ltd.

[1]  R. Lauwerys,et al.  Industrial chemical exposure : guidelines for biological monitoring , 1993 .

[2]  Sean M Hays,et al.  Biomonitoring Equivalents (BE) dossier for cadmium (Cd) (CAS No. 7440-43-9). , 2008, Regulatory toxicology and pharmacology : RTP.

[3]  Gunnar F. Nordberg,et al.  Routes of Exposure, Dose, and Metabolism of Metals , 2007 .

[4]  M E Andersen,et al.  Tissue dosimetry, pharmacokinetic modeling, and interspecies scaling factors. , 1995, Risk analysis : an official publication of the Society for Risk Analysis.

[5]  R Tardif,et al.  Physiologically-based pharmacokinetic modeling of a mixture of toluene and xylene in humans. , 1995, Risk analysis : an official publication of the Society for Risk Analysis.

[6]  V Fiserova-Bergerova Application of toxicokinetic models to establish biological exposure indicators. , 1990, The Annals of occupational hygiene.

[7]  K Krishnan,et al.  Modeling interchild differences in pharmacokinetics on the basis of subject-specific data on physiology and hepatic CYP2E1 levels: a case study with toluene. , 2006, Toxicology and applied pharmacology.

[8]  M. Kujawa Environmental Health Criteria 1. Mercury. 131 Seiten, 7 Abb., 6 Tab. World Health Organization, Geneva 1976, Preis: 14,- sfrs. , 1978 .

[9]  Panos G Georgopoulos,et al.  Reconstructing population exposures to environmental chemicals from biomarkers: Challenges and opportunities , 2009, Journal of Exposure Science and Environmental Epidemiology.

[10]  T. Fennell,et al.  Metabolism and hemoglobin adduct formation of acrylamide in humans. , 2005, Toxicological sciences : an official journal of the Society of Toxicology.

[11]  J. van Asperen,et al.  Application of physiologically based toxicokinetic modelling to study the impact of the exposure scenario on the toxicokinetics and the behavioural effects of toluene in rats. , 2003, Toxicology letters.

[12]  Dana B Barr,et al.  Estimating pesticide dose from urinary pesticide concentration data by creatinine correction in the Third National Health and Nutrition Examination Survey (NHANES-III) , 2004, Journal of Exposure Analysis and Environmental Epidemiology.

[13]  D. Haggerty,et al.  What do we mean by a , 2001 .

[14]  Adam Gross,et al.  Urinary cadmium as indicator of renal cadmium in humans: an autopsy study , 1998, Human & experimental toxicology.

[15]  B. E. Watt,et al.  Mechanisms of Toxicity, Clinical Features, and Management of Acute Chlorophenoxy Herbicide Poisoning: A Review , 2000, Journal of toxicology. Clinical toxicology.

[16]  R Tardif,et al.  Physiologically based modeling of the toxicokinetic interaction between toluene and m-xylene in the rat. , 1993, Toxicology and applied pharmacology.

[17]  L. Costa,et al.  Formation of hemoglobin adducts of acrylamide and its epoxide metabolite glycidamide in the rat. , 1991, Toxicology and applied pharmacology.

[18]  J. Dorne,et al.  The refinement of uncertainty/safety factors in risk assessment by the incorporation of data on toxicokinetic variability in humans. , 2005, Toxicological sciences : an official journal of the Society of Toxicology.

[19]  M. Churchwell,et al.  DNA adducts derived from administration of acrylamide and glycidamide to mice and rats. , 2005, Mutation research.

[20]  Vera Fiserova-Bergerova Development of Biological Exposure Indices (BEIs) and their Implementation , 1987 .

[21]  H. Clewell,et al.  Acrylamide: Review of Toxicity Data and Dose-Response Analyses for Cancer and Noncancer Effects , 2006, Critical reviews in toxicology.

[22]  Arun Sharma,et al.  Evaluation of certain food additives and contaminants. , 2000, World Health Organization technical report series.

[23]  Harvey J Clewell,et al.  Reverse dosimetry: interpreting trihalomethanes biomonitoring data using physiologically based pharmacokinetic modeling , 2007, Journal of Exposure Science and Environmental Epidemiology.

[24]  David J. Williams,et al.  Cadmium Levels in the Lung, Liver, Kidney Cortex, and Urine Samples from Australians without Occupational Exposure to Metals , 2002, Archives of environmental health.

[25]  James M. Hassett,et al.  URINARY CADMIUM ELIMINATION AS A BIOMARKER OF EXPOSURE FOR EVALUATING A CADMIUM DIETARY EXPOSURE - BIOKINETICS MODEL , 2001, Journal of toxicology and environmental health. Part A.

[26]  Charles Timchalk,et al.  Comparative inter-species pharmacokinetics of phenoxyacetic acid herbicides and related organic acids. evidence that the dog is not a relevant species for evaluation of human health risk. , 2004, Toxicology.

[27]  Hugh A Barton,et al.  The Acquisition and Application of Absorption, Distribution, Metabolism, and Excretion (ADME) Data in Agricultural Chemical Safety Assessments , 2006, Critical reviews in toxicology.

[28]  Melvin E. Andersen,et al.  What do we Mean by Dose , 1995 .

[29]  L L Needham,et al.  Exposure assessment: serum levels of TCDD in Seveso, Italy. , 1999, Environmental research.

[30]  G. Nordberg,et al.  A kinetic model of cadmium metabolism in the human being. , 1978, Environmental research.

[31]  G. Blau,et al.  The fate of 2,4-dichlorophenoxyacetic acid (2,4-D) following oral administration to man. , 1977, Toxicology.

[32]  Rodney Snyder,et al.  Role of CYP2E1 in the epoxidation of acrylamide to glycidamide and formation of DNA and hemoglobin adducts. , 2005, Toxicological sciences : an official journal of the Society of Toxicology.

[33]  L Edler,et al.  Risk assessment of substances that are both genotoxic and carcinogenic report of an International Conference organized by EFSA and WHO with support of ILSI Europe. , 2006, Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association.

[34]  Conrad Brunk,et al.  Guidelines for the communication of Biomonitoring Equivalents: report from the Biomonitoring Equivalents Expert Workshop. , 2008, Regulatory toxicology and pharmacology : RTP.

[35]  R A Becker,et al.  Biomonitoring equivalents: a screening approach for interpreting biomonitoring results from a public health risk perspective. , 2007, Regulatory toxicology and pharmacology : RTP.

[36]  Sean M Hays,et al.  Biomonitoring Equivalents (BE) dossier for 2,4-dichlorophenoxyacetic acid (2,4-D) (CAS No. 94-75-7). , 2008, Regulatory toxicology and pharmacology : RTP.

[37]  Conrad Brunk,et al.  Guidelines for the derivation of Biomonitoring Equivalents: report from the Biomonitoring Equivalents Expert Workshop. , 2008, Regulatory toxicology and pharmacology : RTP.

[38]  R. Lauwerys,et al.  Industrial Chemical Exposure: Guidelines for Biological Monitoring, Third Edition , 1983 .

[39]  Lutz Edler,et al.  Risk assessment of substances that are both genotoxic and carcinogenic: Report of an International Conference organized by EFSA and WHO with support of ILSI Europe , 2006 .

[40]  B. N. Gupta,et al.  Absorption and excretion of 2,4-dichlorophenoxyacetic acid in man. , 1974, Xenobiotica; the fate of foreign compounds in biological systems.

[41]  B. van Ravenzwaay,et al.  Comparative metabolism of 2,4-dichlorophenoxyacetic acid (2,4-D) in rat and dog , 2003, Xenobiotica; the fate of foreign compounds in biological systems.

[42]  Canada.,et al.  Canadian Environmental Protection Act and commentary , 2005 .

[43]  John F. Young,et al.  Relationships between biomarkers of exposure and toxicokinetics in Fischer 344 rats and B6C3F1 mice administered single doses of acrylamide and glycidamide and multiple doses of acrylamide. , 2006, Toxicology and applied pharmacology.

[44]  James S Bus,et al.  Strategies to assess systemic exposure of chemicals in subchronic/chronic diet and drinking water studies. , 2006, Toxicology and applied pharmacology.

[45]  Ken Sexton,et al.  Human Biomonitoring of Environmental Chemicals , 2004 .

[46]  G Würtzen,et al.  Threshold of toxicological concern for chemical substances present in the diet: a practical tool for assessing the need for toxicity testing. , 2000, Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association.

[47]  M. Okino,et al.  Use of a pharmacokinetic model to assess chlorpyrifos exposure and dose in children, based on urinary biomarker measurements. , 2001, Toxicological sciences : an official journal of the Society of Toxicology.

[48]  C H Pierce,et al.  Interindividual differences in 2H8-toluene toxicokinetics assessed by semiempirical physiologically based model. , 1996, Toxicology and applied pharmacology.

[49]  L. Bankir,et al.  Sex difference in urine concentration across differing ages, sodium intake, and level of kidney disease. , 2007, American journal of physiology. Regulatory, integrative and comparative physiology.

[50]  Hugh A. Barton,et al.  Biomonitoring Equivalents (BE) dossier for toluene (CAS No. 108-88-3). , 2008, Regulatory toxicology and pharmacology : RTP.

[51]  Vernon A Benignus,et al.  Quantitative comparisons of the acute neurotoxicity of toluene in rats and humans. , 2007, Toxicological sciences : an official journal of the Society of Toxicology.

[52]  Vernon A Benignus,et al.  A dosimetric analysis of the acute behavioral effects of inhaled toluene in rats. , 2007, Toxicological sciences : an official journal of the Society of Toxicology.

[53]  S M Hays,et al.  Introduction to the Biomonitoring Equivalents Pilot Project: development of guidelines for the derivation and communication of Biomonitoring Equivalents. , 2008, Regulatory toxicology and pharmacology : RTP.

[54]  Harvey J Clewell,et al.  Development of a Screening Approach to Interpret Human Biomonitoring Data on Volatile Organic Compounds: Reverse Dosimetry on Biomonitoring Data for Trichloroethylene , 2007, Risk analysis : an official publication of the Society for Risk Analysis.

[55]  D. Knopp,et al.  Biological monitoring of 2,4-dichlorophenoxyacetic acid-exposed workers in agriculture and forestry , 1991, International archives of occupational and environmental health.

[56]  Gurumurthy Ramachandran,et al.  Children’s Exposure to Volatile Organic Compounds as Determined by Longitudinal Measurements in Blood , 2004, Environmental health perspectives.

[57]  Sean M Hays,et al.  Biomonitoring Equivalents (BE) dossier for acrylamide (AA) (CAS No. 79-06-1). , 2008, Regulatory toxicology and pharmacology : RTP.

[58]  Pierre O. Droz,et al.  Simulation of Toluene in Venous Blood with a Physiologically Based Pharmacokinetic Model: Its Application to Biological Exposure Index Development , 1996 .

[59]  L. Ehrenberg,et al.  Evaluation of genetic risks of alkylating agents. II. Haemoglobin as a dose monitor. , 1976, Mutation research.

[60]  P Apostoli,et al.  Biological monitoring of cadmium exposure--an Italian experience. , 1993, Scandinavian journal of work, environment & health.

[61]  John F. Young,et al.  Toxicokinetics of acrylamide and glycidamide in Fischer 344 rats. , 2005, Toxicology and applied pharmacology.

[62]  D. Knopp,et al.  Assessment of exposure to 2,4-dichlorophenoxyacetic acid in the chemical industry: results of a five year biological monitoring study. , 1994, Occupational and environmental medicine.

[63]  Chlorinated Paraffins,et al.  Canadian Environmental Protection Act Priority Substances List Assessment Report , 1995 .

[64]  Jerry L. Campbell,et al.  Quantitative interpretation of human biomonitoring data. , 2008, Toxicology and applied pharmacology.