Biomonitoring equivalents for deltamethrin

Measured concentrations of chemicals in blood or urine in biomonitoring studies provide an integrated reflection of exposures to chemicals via multiple routes and pathways. The potential significance of the measured concentrations of chemicals in the context of existing toxicology data and risk assessments can be assessed if chemical-specific quantitative screening criteria are available. This work presents the derivation of Biomonitoring Equivalents (BEs) for deltamethrin, a synthetic Type II pyrethroid. BEs are estimates of biomarker concentrations that are consistent with risk assessment-based exposure guidance values such as reference doses or acceptable daily intakes. BE values were derived for deltamethrin based on two biomarkers: deltamethrin in plasma and 3-(2,2-dibromovinyl)-2,2-dimethylcyclopropane carboxylic acid (DBCA), a specific metabolite, in urine. BE values for deltamethrin in plasma were based on extrapolation from measured deltamethrin concentrations in plasma in rats under conditions consistent with the Point of Departure in the critical study underlying the USEPA RfD. BE values for DBCA in urine were derived based on pharmacokinetic data from a study in human volunteers on the urinary excretion of deltamethrin and metabolites. BE values for deltamethrin in plasma corresponding to the USEPA RfD for adults and children are 20 and 2μg/L, respectively. BE values for DBCA in urine corresponding to the adult and child-specific RfDs are 50 and 7μg/L, respectively. The urinary BE value corresponding to the ADI established by the European Commission and the Joint Meeting on Pesticide Residues is 60μg/L (as DBCA in urine). These values can be used to screen biomonitoring data in the context of current risk assessments for detlamethrin.     

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.     

Biomonitoring equivalents for 2,2',4,4',5-pentabromodiphenylether (PBDE-99)

Biomonitoring Equivalents (BEs) are defined as the concentration or range of concentrations of a chemical or its metabolite in a biological medium (blood, urine, or other medium) that is consistent with an existing health-based exposure guideline such as a reference dose (RfD) or tolerable daily intake (TDI). BE values can be used as a screening tool for the evaluation of population-based biomonitoring data in the context of existing risk assessments. This study reviews health based risk assessments and exposure guidance values for 2,2',4,4',5-pentabromodiphenylether (PBDE-99) from Health Canada and the United States Environmental Protection Agency (US EPA). Toxicokinetic data from laboratory animals and humans are reviewed. A BE value corresponding to the US EPA RfD is derived here for PBDE-99 based on the assumption of chronic steady-state exposure, distribution into body lipids, and a previously-estimated first-order half-life of elimination of 1040days. The steady-state lipid-adjusted BE(RfD) is 520ng/g lipid. Sources of uncertainty relating to the underlying toxicokinetic and toxicologic database for PBDE-99 and the simultaneous exposure to multiple PBDE congeners are discussed. The BE(RfD) value may be used as a screening tool for evaluation of population biomonitoring data for PBDE-99 in the context of the existing US EPA risk assessment and can assist in prioritization of the potential need for additional risk assessment efforts for PBDE-99 relative to other chemicals.     

Quantitative interpretation of human biomonitoring data

Biomonitoring, the measurement of chemicals in human tissues and fluids, is becoming commonplace, and biomonitoring data has proved to be an important resource for identifying the presence of chemicals, both natural and synthetic, in human populations. However, the concentrations of the chemicals detected in human samples are generally very low, typically in the parts per billion (ppb) or parts per trillion (ppt) range, and the degree of risk posed by these chemicals depends on whether the exposure levels approach those known to cause toxicity in test animals or people. Unfortunately, it is often difficult to relate a measured concentration of a chemical in a human tissue or fluid to the administered doses used in animal toxicity studies. As the number of chemicals identified in human tissues increases, so does the challenge for providing a risk context for the observed concentrations. Moreover, the challenges associated with interpretation of biomonitoring data on different classes of chemicals can be quite different. This review focuses on the use of pharmacokinetic modeling, and in particular, physiologically based pharmacokinetic (PBPK) modeling, to support the interpretation of human biomonitoring data from the perspective of exposure reconstruction and risk characterization. A general approach, referred to as reverse dosimetry, is described for estimating the distribution of exposure levels in the environment that could give rise to measured biomarker concentrations in a population. These exposure distributions can be compared to regulatory exposure guidance values or no-effect levels in toxicity studies to put potential risks in context.     

Derivation of Biomonitoring Equivalents for cyfluthrin

Recent efforts worldwide have resulted in a growing database of measured concentrations of chemicals in blood and urine samples taken from the general population. However, few tools exist to assist in the interpretation of the measured values in a health risk context. Biomonitoring Equivalents (BEs) are defined as the concentration or range of concentrations of a chemical or its metabolite in a biological medium (blood, urine, or other medium) that is consistent with an existing health-based exposure guideline, and are derived by integrating available data on pharmacokinetics with existing chemical risk assessments. This study reviews available health-based exposure guidance values for cyfluthrin from Health Canada, the United States Environmental Protection Agency (USEPA), and the World Health Organization/Food and Agriculture Organization. BE values corresponding to the oral reference dose (RfD), or acceptable daily intake (ADI) estimates from these agencies were derived based on data on excretion fractions of the urinary metabolite 4-fluoro-3-phenoxybenzoic acid (FPBA), which is a metabolite specific to cyfluthrin. These values may be used as screening tools for evaluation of biomonitoring data for cyfluthrin as the metabolite FPBA in the context of existing risk assessments and for prioritization of the potential need for additional risk assessment efforts for cyfluthrin relative to other chemicals.     

Biomonitoring equivalents for DDT/DDE

Biomonitoring Equivalents (BEs) are defined as the concentration or range of concentrations of a chemical or its metabolite in a biological medium (blood, urine, or other medium) that is consistent with an existing health-based exposure guideline such as a reference dose (RfD) or tolerable daily intake (TDI). BE values can be used as a screening tool for the evaluation of population-based biomonitoring data in the context of existing risk assessments. This study reviews available health based risk assessments and exposure guidance values for DDT (1,1,1-trichloro-2,2-bis(p-chlorophenyl)ethane, CAS #50-29-3) and related metabolites and degradation products DDE (1,1-dichloro-2,2-bis(p-chlorophenyl)ethane, CAS #72-55-90) and DDD (1,1-dichloro-2,2-bis(p-chloro-phenyl)ethane) based on both non-cancer and cancer risk assessments from the Food and Agriculture Organization/World Health Organization (FAO/WHO), the United States Environmental Protection Agency (US EPA), and other organizations. Laboratory data on distribution and toxicokinetics of DDT and metabolites and estimates of human elimination half-lives were used to estimate BE values (lipid-adjusted blood, serum, or plasma concentrations) corresponding to the various non-cancer exposure guidance values and cancer risk-specific doses. The BE values based on non-cancer risk assessments range from 5000 to 40,000ng/g lipid for the sum of DDT, DDE, and DDD. The BE values corresponding to a 1E-05 cancer risk level for DDT and DDE based on the US EPA assessment are 300 and 500ng/g lipid, respectively. Sources of uncertainty relating to both the basis for the BE values and their use in evaluation of biomonitoring data are discussed. The BE values derived here can be used as a screening tools for evaluation of population biomonitoring data for DDT and related compounds in the context of the existing risk assessment and can assist in prioritization of the potential need for additional risk assessment efforts for DDT relative to other chemicals.     

Derivation of Biomonitoring Equivalents for di(2-ethylhexyl)phthalate (CAS No. 117-81-7)

Recent efforts worldwide have resulted in a growing database of measured concentrations of chemicals in blood and urine samples taken from the general population. However, few tools exist to assist in the interpretation of the measured values in a health risk context. Biomonitoring Equivalents (BEs) are defined as the concentration or range of concentrations of an environmental chemical or its metabolite in a biological medium (blood, urine, or other medium) that is consistent with an existing health-based exposure guideline, and are derived by integrating available data on pharmacokinetics with existing chemical risk assessments. This study reviews available health-based exposure guidance values for di(2-ethylhexyl)phthalate (DEHP) from Health Canada, the United States Environmental Protection Agency (U.S. EPA), the Agency for Toxic Substances and Disease Registry (ATSDR), the European Chemicals Bureau (ECB), and the European Food Safety Authority (EFSA). BE values corresponding to the oral reference dose (RfD), minimal risk level (MRL) or tolerable daily intake (TDI) estimates from these agencies were derived based on data on excretion fractions of key urinary metabolites. BE values based on the sum of three, four, and five of the most predominant and commonly-measured metabolites of DEHP are presented. These values may be used as screening tools for evaluation of biomonitoring data for DEHP metabolites in the context of existing risk assessments and for prioritization of the potential need for additional risk assessment efforts for DEHP relative to other chemicals.     

Biomonitoring Equivalents for triclosan

Recent efforts worldwide have resulted in a growing database of measured concentrations of chemicals in blood and urine samples taken from the general population. However, few tools exist to assist in the interpretation of the measured values in a health risk context. Biomonitoring Equivalents (BEs) are defined as the concentration or range of concentrations of a chemical or its metabolite(s) in a biological medium (blood, urine, or other medium) consistent with an existing health-based exposure guideline, and are derived by integrating available data on pharmacokinetics with existing chemical risk assessments. This study reviews available health-based exposure guidance values for triclosan based on recent evaluations from the United States Environmental Protection Agency (US EPA), the European Commission’s Scientific Committee on Consumer Products (EC SCCP) and the Australian National Industrial Chemicals Notification and Assessment Scheme (NICNAS). BE values corresponding to the reference dose (RfD) or margin of safety (MOS) targets from these agencies were derived based on kinetic data (urinary excretion and plasma clearance) from human studies and measured blood concentration data in animal studies. Estimated BE values for urinary total triclosan (free plus conjugates) corresponding to the US EPA RfD and the EC-identified margin of safety target from the NOAEL are 6.4 and 2.6 mg/L, respectively (corresponding to 8.3 and 3.3 mg/g creatinine, respectively). Plasma BE values corresponding to the US EPA, EC, and Australian NICNAS values are 0.3, 0.9, and 0.4 mg/L, respectively. These values may be used as screening tools for evaluation of population biomonitoring data for triclosan in a risk assessment context.     

Derivation of Biomonitoring Equivalents for di-n-butyl phthalate (DBP), benzylbutyl phthalate (BzBP), and diethyl phthalate (DEP)

Recent efforts worldwide have resulted in a growing database of measured concentrations of chemicals in blood and urine samples taken from the general population. However, few tools exist to assist in the interpretation of the measured values in a health risk context. Biomonitoring Equivalents (BEs) are defined as the concentration or range of concentrations of a chemical or its metabolite in a biological medium (blood, urine, or other medium) that is consistent with an existing health-based exposure guideline, and are derived by integrating available data on pharmacokinetics with existing chemical risk assessments. This study reviews available health-based exposure guidance values for di-n-butyl phthalate (DBP), benzylbutyl phthalate (BzBP), and diethyl phthalate (DEP) from Health Canada, the United States Environmental Protection Agency (U.S. EPA), the Agency for Toxic Substances and Disease Registry (ATSDR), and the European Food Safety Authority (EFSA). BE values corresponding to the oral reference dose (RfD), minimal risk level (MRL) or tolerable daily intake (TDI) estimates from these agencies were derived for each compound based on data on excretion fractions of key urinary metabolites. These values may be used as screening tools for evaluation of biomonitoring data for metabolites of these three phthalate compounds in the context of existing risk assessments and for prioritization of the potential need for additional risk assessment efforts for each of these compounds relative to other chemicals.     

Biomonitoring: is body burden relevant to public health?

Biomonitoring is the study of the presence and concentration of chemicals in humans usually by the measurement of blood, urine or breath (exhaled air). Properly conducted, these data provide a picture of the amount of a chemical or agent actually absorbed into the body for a specific period of time. This review provides a history of biomonitoring, as well as the limitations and potential benefits of these studies. Examples of the proper and possibly improper use of biomonitoring and the impact made on our society are provided. Reasons for having comprehensive national biomonitoring programs are summarized, along with the societal benefits and risks. A brief discussion of the history of the NHANES program and select results from the 2005 Report are presented. By 2010, it has been predicted that the Centers for Disease Control (CDC) will be monitoring nearly 1000 chemicals in persons from all regions of the nation. The measurement of chemicals and biomarkers has revolutionized the field of exposure assessment. Overall, we recommend an approach of careful interpretation, understanding that the data obtained are useful for establishing baseline information about exposure, rather than equating detection with risk. We present suggestions for contextualizing biomonitoring results in order to provide the public with the tools to distinguish genuine health risks from trivial ones.     

Biomonitoring equivalents for di-isononyl phthalate (DINP)

Biomonitoring Equivalents (BEs) are defined as the concentration or range of concentrations of a chemical or its metabolite in a biological medium (blood, urine, or other medium) that is consistent with an existing health-based exposure guideline such as a reference dose (RfD) or tolerable daily intake (TDI). BE values can be used as a screening tool for the evaluation of population-based biomonitoring data in the context of existing risk assessments. This study reviews available health based risk assessments and exposure guidance values for di-isononyl phthalate (DINP) from Health Canada, the United States Consumer Product Safety Commission (US CPSC), and the European Food Safety Authority (EFSA). Controlled dosing data reporting the urinary excretion fractions of major DINP metabolites following administration of labeled DINP are reviewed, and BE values corresponding to the available exposure guidance values are derived assuming chronic, steady-state intake and excretion at those exposure values. The BE values range from 1500 to 3600μg/L (1900-4600μg/g creatinine) based on the sum of three oxidative metabolites. Sources of uncertainty relating to both the basis for the BE values and their use in evaluation of biomonitoring data, including the transience of the biomarkers relative to exposure frequency, are discussed. The BE values derived here can be used as screening tools for evaluation of population biomonitoring data for DINP in the context of existing risk assessments and can assist in prioritization of the potential need for additional risk assessment efforts for DINP relative to other chemicals.     

Chemical-specific screening criteria for interpretation of biomonitoring data for volatile organic compounds (VOCs) – Application of steady-state PBPK model solutions

The National Health and Nutrition Examination Survey (NHANES) generates population-representative biomonitoring data for many chemicals including volatile organic compounds (VOCs) in blood. However, no health or risk-based screening values are available to evaluate these data from a health safety perspective or to use in prioritizing among chemicals for possible risk management actions. We gathered existing risk assessment-based chronic exposure reference values such as reference doses (RfDs), reference concentrations (RfCs), tolerable daily intakes (TDIs), cancer slope factors, etc. and key pharmacokinetic model parameters for 47 VOCs. Using steady-state solutions to a generic physiologically-based pharmacokinetic (PBPK) model structure, we estimated chemical-specific steady-state venous blood concentrations across chemicals associated with unit oral and inhalation exposure rates and with chronic exposure at the identified exposure reference values. The geometric means of the slopes relating modeled steady-state blood concentrations to steady-state exposure to a unit oral dose or unit inhalation concentration among 38 compounds with available pharmacokinetic parameters were 12.0 μg/L per mg/kg-d (geometric standard deviation [GSD] of 3.2) and 3.2 μg/L per mg/m³ (GSD = 1.7), respectively. Chemical-specific blood concentration screening values based on non-cancer reference values for both oral and inhalation exposure range from 0.0005 to 100 μg/L; blood concentrations associated with cancer risk-specific doses at the 1 E−05 risk level ranged from 5 E−06 to 6 E−02 μg/L. The distribution of modeled steady-state blood concentrations associated with unit exposure levels across VOCs may provide a basis for estimating blood concentration screening values for VOCs that lack chemical-specific pharmacokinetic data. The screening blood concentrations presented here provide a tool for risk assessment-based evaluation of population biomonitoring data for VOCs and are most appropriately applied to central tendency estimates for such datasets.     

Biomonitoring Equivalents for benzene

Biomonitoring Equivalents (BEs) are defined as the concentration or range of concentrations of a chemical or its metabolite in a biological medium (blood, urine, or other medium) that is consistent with an existing health-based exposure guideline such as a reference dose (RfD) or tolerable daily intake (TDI). BE values can be used as a screening tool for the evaluation of population-based biomonitoring data in the context of existing risk assessments. This study reviews available health based risk assessments and exposure guidance values for benzene from the United States Environmental Protection Agency (US EPA), Texas Commission on Environmental Quality (TCEQ), California's Office of Environmental Health Hazard Assessment (OEHHA) and the Agency for Toxic Substances and Disease Registry (ATSDR) to derive BE values for benzene in blood and urine. No BE values were derived for any of the numerous benzene metabolites or hemoglobin and albumin adducts. Using existing physiologically based pharmacokinetic (PBPK) models, government risk assessment values were translated into corresponding benzene levels in blood assuming chronic steady-state exposures. BEs for benzene in urine were derived using measured correlations between benzene in urine with benzene in blood. The BE values for benzene in blood range from 0.04 to 1.29 μg/L, depending upon the underlying non-cancer risk assessment used in deriving the BE. Sources of uncertainty relating to both the basis for the BE values and their use in evaluation of biomonitoring data, including the transience of the biomarkers relative to exposure frequency, are discussed. The BE values derived here can be used as screening tools for evaluation of population biomonitoring data for benzene in the context of the existing risk assessment and can assist in prioritization of the potential need for additional risk assessment efforts for benzene relative to other chemicals.     

Biomonitoring Equivalents for selenium

Selenium is an essential nutrient for human health with a narrow range between essentiality and toxicity. Selenium is incorporated into several proteins that perform important functions in the body. With insufficient selenium intake, the most notable effect is Keshan disease, an endemic cardiomyopathy in children. Conversely, excessive selenium intake can result in selenosis, manifested as brittle nails and hair and gastro-intestinal disorders. As such, guidance values have been established to protect against both insufficient and excessive selenium exposures. Dietary Reference Intakes (DRIs) have been established as standard reference values for nutritional adequacy in North America. To protect against selenosis resulting from exposure to excessive amounts of selenium, several government and non-governmental agencies have established a range of guidance values. Exposure to selenium is primarily through the diet, but monitoring selenium intake is difficult. Biomonitoring is a useful means of assessing and monitoring selenium status for both insufficient and excessive exposures. However, to be able to interpret selenium biomonitoring data, levels associated with both DRIs and toxicity guidance values are required. Biomonitoring Equivalents (BEs) were developed for selenium in whole blood, plasma and urine. The BEs associated with assuring adequate selenium intake (Estimated Average Requirements – EAR) are 100, 80 and 10 μg/L in whole blood, plasma and urine, respectively. The BEs associated with protection against selenosis range from 400 to 480 μg/L in whole blood, 180–230 μg/L in plasma, and 90–110 μg/L in urine. These BE values can be used by both regulatory agencies and public health officials to interpret selenium biomonitoring data in a health risk context.     

Collection and use of exposure data from human milk biomonitoring in the United States

Human milk is a unique biological matrix that can be used to estimate exposures in both the mother and the breastfed infant. In addition, the presence of environmental chemicals in human milk may act as a sentinel for exposures to a broader population. Several factors play a role in determining the quantity of chemicals transferred to milk and, subsequently, to the breastfeeding infant, including maternal, infant, and chemical characteristics. Exposure to certain environmental chemicals during critical periods can disrupt normal infant development, yet few data exist to quantify the hazards posed by environmental chemicals in human milk. Chemicals measured in human milk may also provide insights to agents suspect in altering breast development and breast-related disease risk. Carefully designed exposure assessment and toxicokinetic studies are needed to elucidate mechanisms and establish relationships between human milk and other biologic matrices. Data from human milk biomonitoring studies can be used to inform and validate models that integrate information about chemical properties, human metabolism, and biomarker concentrations. Additional research is needed to determine the degree to which environmental chemicals enter, are present in, and are excreted from human milk, their impact on the host (mother), and the extent of their bioavailability to breastfeeding infants. This article describes how the collection and use of exposure data from human milk biomonitoring in the United States can be designed to inform future research and policy.     

Biomonitoring Equivalents for inorganic arsenic

This paper presents Biomonitoring Equivalents (BEs) for inorganic arsenic. Biomonitoring Equivalents (BEs) are defined as the concentration or range of concentrations of a chemical or its metabolite in a biological medium (blood, urine, or other medium) that is consistent with an existing health-based exposure guideline, and are derived by integrating available data on pharmacokinetics with existing chemical risk assessments. This study reviews available health-based exposure guidance values for arsenic based on recent evaluations from the United States Environmental Protection Agency (US EPA), US Agency for Toxic Substances and Disease Registry (ATSDR) and Health Canada (HC). BE values corresponding to the Reference Dose (RfD) or risk-specific doses for cancer endpoints from these agencies were derived based on kinetic data (urinary excretion) from controlled dosing studies in humans. The BE values presented here provide estimates of the sum of inorganic arsenic-derived urinary biomarkers (inorganic arsenic, monomethylated arsenic, and dimethylated arsenic). The BE associated with the United States Environmental Protection Agency’s Reference Dose and the Agency for Toxic Substances and Disease Registry’s Minimal Risk Level is 6.4 μg arsenic/L urine. The BEs associated with the various cancer risk assessments are significantly lower. These BE values may be used as screening tools for evaluation of biomonitoring data for inorganic arsenic in a public health risk context.     

Cadmium exposure and tobacco consumption: Biomarkers and risk assessment

To investigate whether cadmium has an independent role in diseases associated with tobacco consumption, epidemiology data were reviewed, biomonitoring data were analyzed, and probabilistic risk assessment (PRA) was performed. Results from previous epidemiology studies have indicated that there are adverse health effects potentially in common between cadmium exposure and tobacco consumption. Analysis of publically available biomonitoring data showed that blood (B–Cd) and urine (U–Cd) cadmium were higher in cigarette smokers compared with smokeless tobacco (SLT) consumers, and B–Cd and U–Cd in SLT consumers were not significantly different than in non-consumers of tobacco. Comparison with previously established biomonitoring equivalent (BE) values indicated that B–Cd and U–Cd in the majority of these cigarette smokers and SLT consumers did not exceed the blood and urine BEs. Results of the PRA showed that the mean hazard estimate was below a generally accepted regulatory threshold for SLT consumers, but not for cigarette smokers. In total, this evaluation indicated that cadmium exposures in tobacco consumers differed by product category consumed; cadmium in tobacco may not be associated with tobacco consumption related diseases; if cadmium in tobacco contributes to tobacco consumption related diseases, differences in hazard and/or risk may exist by product category.     

Di-alkyl phosphate biomonitoring data: assessing cumulative exposure to organophosphate pesticides

The 1996 Food Quality Protection Act (FQPA) requires the evaluation of both aggregate and cumulative health risks from pesticides (FFDCA 408(b)(2)(D)(v) and (vi).) Organophosphate (OP) pesticides are the first class of chemicals to undergo FQPA mandated aggregate and cumulative assessments. In this report, summary data on biomonitoring for urinary levels of six alkyl phosphate (AP) metabolites of OPs, as reported in the initial, March 2001, U.S. Centers for Disease Control and Prevention's (CDC) "National Report on Human Exposure to Environmental Chemicals," are compared to EPA modeled estimates of OP exposure reported in Registration Eligibility Decision documents (REDs), Interim REDs and to currently reported cumulative exposure estimates in the EPA's Cumulative Risk Assessment of the Organophosphate Pesticides. This comparison indicates that EPA's aggregate exposure estimates (dietary, drinking water, and non-dietary residential exposures) for many individual OPs were greater than the cumulative estimate for all OPs combined based on the CDC AP biomonitoring data. The results also suggest that EPA's screening level assessments of OPs, while being qualitative indicators of the relative importance of various exposure sources, are not good quantitative indicators of actual exposures. However, the mean biomonitoring estimate of cumulative OP exposure appears to exceed the EPA's subsequent preliminary estimate of cumulative OP exposure by as much as the REDs appear to overestimate the biomonitoring results. While the conservatism, tendency to overestimate exposure, in the individual REDs is readily acknowledged, the conservatism and limitations of applying currently available CDC AP biomonitoring data to evaluate human exposure to OPs are not as readily apparent. We postulate that oral absorption of non-anti cholinergic, pre-hydrolyzed OPs, sources of APs other than pesticides, and the conservative result of summing exposure from each AP at the geometric mean contribute to non-quantified overestimates of absorbed dosage from the CDC biomonitoring data reported in March 2001. CDC AP biomonitoring data may serve a useful purpose in providing an upper bound estimate of absorbed dosage for "ground truthing" aggregate exposure estimated from first tier models used in REDs, but at best may provide only a credible "target" for the complex cumulative exposure assessment models currently under development. The reliability of quantitative estimates of OP exposure levels will improve as cumulative risk exposure models are validated over time and under use conditions prevalent at the time the AP biomonitoring samples are collected. Analyses contained herein should be revisited and compared to the CDC Second National Report on Human Exposure to Environmental Chemicals ( http://www.cdc.gov/exposurereport), released to the public on January 31, 2003, and the final EPA OP Cumulative Risk Assessment.     

Biomonitoring equivalents: a screening approach for interpreting biomonitoring results from a public health risk perspective

Advances in both sensitivity and specificity of analytical chemistry have made it possible to quantify substances in human biological specimens, such as blood, urine, and breast milk, in specimen volumes that are practical for collection from individuals. Research laboratories led by the Centers for Disease Control and Prevention (CDC) in its series National Report on Human Exposure to Environmental Chemicals [Centers for Disease Control and Prevention (CDC), 2005. Third National Report on Human Exposure to Environmental Chemicals. NCEH Pub. No. 05-0570.] are dedicating substantial resources to designing and conducting human biomonitoring studies and compiling biomonitoring data for the general population. However, the ability to quantitatively interpret the results of human biomonitoring in the context of a health risk assessment currently lags behind the analytical chemist's ability to make such measurements. The traditional paradigm for human health risk assessment of environmental chemicals involves comparing estimated daily doses to health-based criteria for acceptable, safe, or tolerable daily intakes (for example, reference doses [RfDs], tolerable daily intakes [TDIs], or minimal risk levels [MRLs]) to assess whether estimated doses exceed such health screening levels. However, biomonitoring efforts result in measured chemical concentrations in biological specimens (the result of absorption, distribution, metabolism and excretion of administered doses) rather than estimated intake doses. Quantitative benchmarks of acceptable or safe concentrations in biological specimens (analogous to RfDs, TDIs, or MRLs) needed to interpret these levels exist for very few chemicals of environmental interest. This paper discusses issues inherent in converting existing health screening benchmarks based on intake doses to screening levels for evaluating biomonitoring data, and presents methods and approaches that can be used to derive such screening levels (termed "Biomonitoring Equivalents," or BEs) for a range of chemicals and biological media.