Leveraging Epidemiology to Improve Risk Assessment

The field of environmental public health is at an important crossroad. Our current biomonitoring efforts document widespread exposure to a host of chemicals for which toxicity information is lacking. At the same time, advances in the fields of genomics, proteomics, metabolomics, genetics and epigenetics are yielding volumes of data at a rapid pace. Our ability to detect chemicals in biological and environmental media has far outpaced our ability to interpret their health relevance, and as a result, the environmental risk paradigm, in its current state, is antiquated and ill-equipped to make the best use of these new data. In light of new scientific developments and the pressing need to characterize the public health burdens of chemicals, it is imperative to reinvigorate the use of environmental epidemiology in chemical risk assessment. Two case studies of chemical assessments from the Environmental Protection Agency Integrated Risk Information System database are presented to illustrate opportunities where epidemiologic data could have been used in place of experimental animal data in dose-response assessment, or where different approaches, techniques, or studies could have been employed to better utilize existing epidemiologic evidence. Based on the case studies and what can be learned from recent scientific advances and improved approaches to utilizing human data for dose-response estimation, recommendations are provided for the disciplines of epidemiology and risk assessment for enhancing the role of epidemiologic data in hazard identification and dose-response assessment.

[1]  Ord,et al.  Supplemental Guidance for Assessing Susceptibility from Early-Life Exposure to Carcinogens , 2013 .

[2]  Ord,et al.  A Review of the Reference Dose and Reference Concentration Processes , 2013 .

[3]  Jonathan I Levy,et al.  Science and Decisions: Advancing Risk Assessment , 2010, Risk analysis : an official publication of the Society for Risk Analysis.

[4]  R. Kruse,et al.  Prenatal phthalate exposure and reduced masculine play in boys. , 2010, International journal of andrology.

[5]  L. Giudice,et al.  Interpreting science in the policy context , 2010 .

[6]  M. Harada,et al.  Long-term exposure to methylmercury and its effects on hypertension in Minamata. , 2010, Environmental research.

[7]  N. Rothman,et al.  Application of OMICS technologies in occupational and environmental health research; current status and projections , 2009, Occupational and Environmental Medicine.

[8]  P. Poirier,et al.  Environmental Mercury Exposure and Blood Pressure Among Nunavik Inuit Adults , 2009, Hypertension.

[9]  D. Bellinger Interpreting epidemiologic studies of developmental neurotoxicity: conceptual and analytic issues. , 2009, Neurotoxicology and teratology.

[10]  K. He Fish, long-chain omega-3 polyunsaturated fatty acids and prevention of cardiovascular disease--eat fish or take fish oil supplement? , 2009, Progress in cardiovascular diseases.

[11]  Thomas Hartung,et al.  Chemical regulators have overreached , 2009, Nature.

[12]  D. Eilstein,et al.  Human biomonitoring programmes and activities in the European Union , 2009, Journal of Epidemiology & Community Health.

[13]  S. Isukapalli,et al.  Using National and Local Extant Data to Characterize Environmental Exposures in the National Children’s Study: Queens County, New York , 2009, Environmental health perspectives.

[14]  D. Carpenter,et al.  Ethical Issues in Measuring Biomarkers in Children’s Environmental Health , 2009, Environmental health perspectives.

[15]  N. Simunovic,et al.  Methodological issues in systematic reviews and meta-analyses of observational studies in orthopaedic research. , 2009, The Journal of bone and joint surgery. American volume.

[16]  Thomas Hartung A Toxicology for the 21st Century—Mapping the Road Ahead , 2009, Toxicological sciences : an official journal of the Society of Toxicology.

[17]  Melvin E Andersen,et al.  Toxicity Testing in the 21st Century: Implications for Human Health Risk Assessment , 2009, Risk analysis : an official publication of the Society for Risk Analysis.

[18]  E. Budtz-Jørgensen,et al.  Methylmercury Exposure and Adverse Cardiovascular Effects in Faroese Whaling Men , 2008, Environmental health perspectives.

[19]  Ronald H. White,et al.  State-of-the-Science Workshop Report: Issues and Approaches in Low-Dose–Response Extrapolation for Environmental Health Risk Assessment , 2008, Environmental health perspectives.

[20]  G. Ginsberg,et al.  Quantitative Approach for Incorporating Methylmercury Risks and Omega-3 Fatty Acid Benefits in Developing Species-Specific Fish Consumption Advice , 2008, Environmental health perspectives.

[21]  K. Mahaffey,et al.  Adult Women’s Blood Mercury Concentrations Vary Regionally in the United States: Association with Patterns of Fish Consumption (NHANES 1999–2004) , 2008, Environmental health perspectives.

[22]  G. Cooper,et al.  Use of epidemiologic data in Integrated Risk Information System (IRIS) assessments. , 2008, Toxicology and applied pharmacology.

[23]  Shanna H Swan,et al.  Environmental phthalate exposure in relation to reproductive outcomes and other health endpoints in humans. , 2008, Environmental research.

[24]  D. Rice,et al.  Overview of modifiers of methylmercury neurotoxicity: chemicals, nutrients, and the social environment. , 2008, Neurotoxicology.

[25]  J. Vlaanderen,et al.  Guidelines to Evaluate Human Observational Studies for Quantitative Risk Assessment , 2008, Environmental health perspectives.

[26]  Amy D. Kyle,et al.  Meeting Report: Moving Upstream—Evaluating Adverse Upstream End Points for Improved Risk Assessment and Decision-Making , 2008, Environmental health perspectives.

[27]  S. Ceccatelli,et al.  Human developmental neurotoxicity of methylmercury: impact of variables and risk modifiers. , 2008, Regulatory toxicology and pharmacology : RTP.

[28]  K. Mahaffey,et al.  Methylmercury and omega-3 fatty acids: co-occurrence of dietary sources with emphasis on fish and shellfish. , 2008, Environmental research.

[29]  G. Guyatt,et al.  GRADE: an emerging consensus on rating quality of evidence and strength of recommendations , 2008, BMJ : British Medical Journal.

[30]  Antonia M. Calafat,et al.  Prenatal Phenol and Phthalate Exposures and Birth Outcomes , 2008, Environmental health perspectives.

[31]  R. Jirtle,et al.  Environmental epigenomics in human health and disease , 2008, Environmental and molecular mutagenesis.

[32]  Patrick O. McGowan,et al.  The social environment and the epigenome , 2008, Environmental and molecular mutagenesis.

[33]  K. Taber,et al.  Mercury exposure: effects across the lifespan. , 2008, The Journal of neuropsychiatry and clinical neurosciences.

[34]  M. Marty Technical Support Document for Cancer Potency Factors: , 2008 .

[35]  P. Davidson,et al.  Is susceptibility to prenatal methylmercury exposure from fish consumption non-homogeneous? Tree-structured analysis for the Seychelles Child Development Study. , 2007, Neurotoxicology.

[36]  A. Calafat,et al.  Polyfluoroalkyl Chemicals in the U.S. Population: Data from the National Health and Nutrition Examination Survey (NHANES) 2003–2004 and Comparisons with NHANES 1999–2000 , 2007, Environmental health perspectives.

[37]  L. Thorpe,et al.  A Biomonitoring Study of Lead, Cadmium, and Mercury in the Blood of New York City Adults , 2007, Environmental health perspectives.

[38]  Chris Gennings,et al.  The simultaneous analysis of discrete and continuous outcomes in a dose-response study: using desirability functions. , 2007, Regulatory toxicology and pharmacology : RTP.

[39]  Dana B Barr,et al.  Uses and issues of biomonitoring. , 2007, International journal of hygiene and environmental health.

[40]  R. Jirtle,et al.  Environmental epigenomics and disease susceptibility , 2007, Nature Reviews Genetics.

[41]  J. Llobet,et al.  Benefits and risks of fish consumption Part II. RIBEPEIX, a computer program to optimize the balance between the intake of omega-3 fatty acids and chemical contaminants. , 2007, Toxicology.

[42]  K. Murata,et al.  Total mercury levels in hair, toenail, and urine among women free from occupational exposure and their relations to renal tubular function. , 2007, Environmental research.

[43]  T. Tuomainen,et al.  Mercury as a risk factor for cardiovascular diseases. , 2007, The Journal of nutritional biochemistry.

[44]  D. Engstrom,et al.  The Madison Declaration on Mercury Pollution , 2007, Ambio.

[45]  Thomas E. McKone,et al.  Using Biomarkers to Inform Cumulative Risk Assessment , 2007, Environmental health perspectives.

[46]  Tracey J. Woodruff,et al.  Dose–Response Relationship of Prenatal Mercury Exposure and IQ: An Integrative Analysis of Epidemiologic Data , 2007, Environmental health perspectives.

[47]  Esben Budtz-Jørgensen,et al.  Separation of Risks and Benefits of Seafood Intake , 2006, Environmental health perspectives.

[48]  Tracey J. Woodruff,et al.  Estimating Risk from Ambient Concentrations of Acrolein across the United States , 2006, Environmental health perspectives.

[49]  M. Karagas,et al.  Toenail mercury and dietary fish consumption , 2007, Journal of Exposure Science and Environmental Epidemiology.

[50]  A. Calafat,et al.  Altered Semen Quality in Relation to Urinary Concentrations of Phthalate Monoester and Oxidative Metabolites , 2006, Epidemiology.

[51]  Dariush Mozaffarian,et al.  Fish intake, contaminants, and human health: evaluating the risks and the benefits. , 2006, JAMA.

[52]  Nancy G Doerrer,et al.  Strategic biomonitoring initiatives: moving the science forward. , 2006, Toxicological sciences : an official journal of the Society of Toxicology.

[53]  Simon Wilson,et al.  Global anthropogenic mercury emission inventory for 2000 , 2006 .

[54]  L. Birnbaum,et al.  Polybrominated Diphenyl Ethers: A Case Study for Using Biomonitoring Data to Address Risk Assessment Questions , 2006, Environmental health perspectives.

[55]  D. Barr,et al.  Use of Biomonitoring Data to Evaluate Methyl Eugenol Exposure , 2006, Environmental health perspectives.

[56]  R. Albertini,et al.  The Use of Biomonitoring Data in Exposure and Human Health Risk Assessments , 2006, Environmental health perspectives.

[57]  G. Swaen A framework for using epidemiological data for risk assessment , 2006, Human & experimental toxicology.

[58]  Tracey J. Woodruff,et al.  Estimated Daily Phthalate Exposures in a Population of Mothers of Male Infants Exhibiting Reduced Anogenital Distance , 2006, Environmental health perspectives.

[59]  A. Calafat,et al.  Human exposure assessment to environmental chemicals using biomonitoring. , 2006, International journal of andrology.

[60]  Roger D. Peng,et al.  The Exposure–Response Curve for Ozone and Risk of Mortality and the Adequacy of Current Ozone Regulations , 2006, Environmental health perspectives.

[61]  T. Clarkson,et al.  The Toxicology of Mercury and Its Chemical Compounds , 2006, Critical reviews in toxicology.

[62]  D. Gee Late Lessons from Early Warnings: Toward Realism and Precaution with Endocrine-Disrupting Substances , 2005, Environmental health perspectives.

[63]  J. Hightower,et al.  Blood Mercury Reporting in NHANES: Identifying Asian, Pacific Islander, Native American, and Multiracial Groups , 2005, Environmental health perspectives.

[64]  Jorma Toppari,et al.  Human Breast Milk Contamination with Phthalates and Alterations of Endogenous Reproductive Hormones in Infants Three Months of Age , 2005, Environmental health perspectives.

[65]  P. Grandjean Non-precautionary aspects of toxicology. , 2005, Toxicology and applied pharmacology.

[66]  Michelle L. Bell,et al.  A Meta-Analysis of Time-Series Studies of Ozone and Mortality With Comparison to the National Morbidity, Mortality, and Air Pollution Study , 2005, Epidemiology.

[67]  Richard N Hill,et al.  Risk Assessment For Benefits Analysis: Framework for Analysis of A Thyroid-Disrupting Chemical , 2005, Journal of toxicology and environmental health. Part A.

[68]  P. Foster,et al.  Critical window of male reproductive tract development in rats following gestational exposure to di-n-butyl phthalate. , 2005, Birth defects research. Part B, Developmental and reproductive toxicology.

[69]  R. Kruse,et al.  Decrease in Anogenital Distance among Male Infants with Prenatal Phthalate Exposure , 2005, Environmental health perspectives.

[70]  H. Clewell,et al.  Quantitative Estimates of Risk for Noncancer Endpoints , 2005, Risk analysis : an official publication of the Society for Risk Analysis.

[71]  Simon Watkins,et al.  Personalized Exposure Assessment: Promising Approaches for Human Environmental Health Research , 2005, Environmental health perspectives.

[72]  Daniel Krewski,et al.  Residential Radon and Risk of Lung Cancer: A Combined Analysis of 7 North American Case-Control Studies , 2005, Epidemiology.

[73]  Alan H. Stern,et al.  A Revised Probabilistic Estimate of the Maternal Methyl Mercury Intake Dose Corresponding to a Measured Cord Blood Mercury Concentration , 2004, Environmental health perspectives.

[74]  Samuel P. Caudill,et al.  Urinary Creatinine Concentrations in the U.S. Population: Implications for Urinary Biologic Monitoring Measurements , 2004, Environmental health perspectives.

[75]  R Doll,et al.  Radon in homes and risk of lung cancer: collaborative analysis of individual data from 13 European case-control studies , 2004, BMJ : British Medical Journal.

[76]  M. Longnecker,et al.  Environmental Health: a Global Access Science Source Anogenital Distance in Human Male and Female Newborns: a Descriptive, Cross-sectional Study , 2004 .

[77]  P. Foster,et al.  Dose-dependent alterations in gene expression and testosterone synthesis in the fetal testes of male rats exposed to di (n-butyl) phthalate. , 2004, Toxicological sciences : an official journal of the Society of Toxicology.

[78]  Michael J Daniels,et al.  The National Morbidity, Mortality, and Air Pollution Study. Part III: PM10 concentration-response curves and thresholds for the 20 largest US cities. , 2004, Research report.

[79]  K. Mahaffey,et al.  Blood organic mercury and dietary mercury intake: National Health and Nutrition Examination Survey, 1999 and 2000. , 2004, Environmental health perspectives.

[80]  J. Brock,et al.  The relationship between environmental exposure to phthalates and computer-aided sperm analysis motion parameters. , 2004, Journal of andrology.

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

[82]  A. Stern,et al.  An assessment of the cord blood:maternal blood methylmercury ratio: implications for risk assessment. , 2003, Environmental health perspectives.

[83]  T. Woodruff,et al.  Assessment of potential risk levels associated with U.S. Environmental Protection Agency reference values. , 2003, Environmental health perspectives.

[84]  P. Foster,et al.  Pathogenesis of Male Reproductive Tract Lesions from Gestation Through Adulthood Following in Utero Exposure to Di(n-butyl) Phthalate , 2003, Toxicologic pathology.

[85]  Robert F. Herrick,et al.  Phthalate Exposure and Human Semen Parameters , 2003, Epidemiology.

[86]  Max Costa,et al.  Epigenetics and the Environment , 2003, Annals of the New York Academy of Sciences.

[87]  Akira Yasutake,et al.  Current hair mercury levels in Japanese: survey in five districts. , 2003, The Tohoku journal of experimental medicine.

[88]  David C Christiani,et al.  The relationship between environmental exposures to phthalates and DNA damage in human sperm using the neutral comet assay. , 2002, Environmental health perspectives.

[89]  E. Rimm,et al.  Mercury and the risk of coronary heart disease in men. , 2002, The New England journal of medicine.

[90]  Frans J Kok,et al.  Mercury, fish oils, and the risk of myocardial infarction. , 2002, The New England journal of medicine.

[91]  Robert Goble,et al.  A STRAW MAN PROPOSAL FOR A QUANTITATIVE DEFINITION OF THE RfD , 2002, Drug and chemical toxicology.

[92]  N. Skakkebaek,et al.  Testicular dysgenesis syndrome: an increasingly common developmental disorder with environmental aspects , 2001, Human reproduction.

[93]  K R Abrams,et al.  Bayesian methods in meta-analysis and evidence synthesis. , 2001, Statistical methods in medical research.

[94]  M. Berglund,et al.  Longitudinal study of methylmercury and inorganic mercury in blood and urine of pregnant and lactating women, as well as in umbilical cord blood. , 2000, Environmental research.

[95]  P. Foster,et al.  Effects of di-n-butyl phthalate (DBP) on male reproductive development in the rat: implications for human risk assessment. , 2000, Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association.

[96]  E Budtz-Jørgensen,et al.  Prenatal methylmercury exposure as a cardiovascular risk factor at seven years of age. , 1999, Epidemiology.

[97]  J M Samet,et al.  Epidemiology and risk assessment. , 1998, American journal of epidemiology.

[98]  C Cox,et al.  Effects of prenatal and postnatal methylmercury exposure from fish consumption on neurodevelopment: outcomes at 66 months of age in the Seychelles Child Development Study. , 1998, JAMA.

[99]  Environmental epidemiology in public health , 1998, The Lancet.

[100]  Roberta F. White,et al.  Cognitive deficit in 7-year-old children with prenatal exposure to methylmercury. , 1997, Neurotoxicology and teratology.

[101]  X. D. Wu,et al.  Maternal-fetal transfer of metallic mercury via the placenta and milk. , 1997, Annals of clinical and laboratory science.

[102]  D. Cook,et al.  Systematic Reviews: Synthesis of Best Evidence for Clinical Decisions , 1997, Annals of Internal Medicine.

[103]  A. Choi,et al.  Effects of prenatal methylmercury exposure from a high fish diet on developmental milestones in the Seychelles Child Development Study. , 1997, Neurotoxicology.

[104]  D Hattis,et al.  Human interindividual variability in susceptibility to toxic effects: from annoying detail to a central determinant of risk. , 1996, Toxicology.

[105]  F P Perera,et al.  Molecular epidemiology: insights into cancer susceptibility, risk assessment, and prevention. , 1996, Journal of the National Cancer Institute.

[106]  D. Cory-Slechta Bridging human and experimental animal studies of lead neurotoxicity: moving beyond IQ. , 1995, Neurotoxicology and teratology.

[107]  I Hertz-Picciotto,et al.  Epidemiology and quantitative risk assessment: a bridge from science to policy. , 1995, American journal of public health.

[108]  R J Kavlock,et al.  Benchmark Dose Workshop: criteria for use of a benchmark dose to estimate a reference dose. , 1995, Regulatory toxicology and pharmacology : RTP.

[109]  J. Salonen,et al.  Intake of mercury from fish, lipid peroxidation, and the risk of myocardial infarction and coronary, cardiovascular, and any death in eastern Finnish men. , 1995, Circulation.

[110]  A. Whittemore,et al.  Use of biological markers in risk assessment. , 1994, Risk analysis : an official publication of the Society for Risk Analysis.

[111]  J. Gerberding,et al.  Preventing lead poisoning in young children. , 1992, Kansas medicine : the journal of the Kansas Medical Society.

[112]  J. Hansen,et al.  Prenatal exposure to methyl mercury among Greenlandic polar Inuits. , 1990, Archives of environmental health.

[113]  D. Hattis The Use of Biological Markers in Risk Assessment , 1988 .

[114]  A. Smith,et al.  Epidemiologic input to environmental risk assessment. , 1988, Archives of environmental health.

[115]  F. Perera,et al.  The potential usefulness of biological markers in risk assessment. , 1987, Environmental health perspectives.

[116]  C. Cox,et al.  Fetal methylmercury poisoning. Relationship between concentration in single strands of maternal hair and child effects. , 1987, Archives of neurology.

[117]  R. Hertzberg,et al.  A new method for determining allowable daily intakes. , 1986, Fundamental and applied toxicology : official journal of the Society of Toxicology.

[118]  J. Verhey,et al.  Risk assessment in the federal government , 1983 .

[119]  C C SMITH Toxicity of butyl stearate, dibutyl sebacate, dibutyl phthalate, and methoxyethyl oleate. , 1953, A.M.A. archives of industrial hygiene and occupational medicine.