Using Biomarkers to Inform Cumulative Risk Assessment

Background Biomarkers are considered the method of choice for determining exposure to environmental contaminants and relating such exposures to health outcomes. However, the association between many biomarkers and outcome is not direct because of variability in sensitivity and susceptibility in the individual. Objectives We explore the relationship between environmental exposures and health outcomes as mitigated by differential susceptibility in individuals or populations and address the question “Can biomarkers enable us to understand and quantify better the population burden of disease and health effects attributable to environmental exposures?” Methods We use a case–study approach to develop the thesis that biomarkers offer a pathway to disaggregation of health effects into specific, if multiple, risk factors. We offer the point of view that a series or array of biomarkers, including biomarkers of exposure, biomarkers of susceptibility, and biomarkers of effect, used in concert offer the best means by which to effect this disaggregation. We commence our discussion by developing the characteristics of an ideal biomarker, then give some examples of commonly used biomarkers to show the strengths and weaknesses of current usage. We follow this by more detailed case-study assessment outlining the state-of-the-science in specific cases. We complete our work with recommendations regarding the future use of biomarkers and areas for continued development. Conclusions The case studies provide examples of when and how biomarkers can be used to infer the source and magnitude of exposure among a set of competing sources and pathways. The answer to this question is chemical specific and relates to how well the biomarker matches the characteristics of an “ideal” biomarker–in particular ease of collection and persistence. The use of biomarkers in combination provides a better opportunity to disaggregate both source and pathway contributions.

[1]  B. Schwartz,et al.  Thimerosal-Containing Vaccines and Autistic Spectrum Disorder: A Critical Review of Published Original Data , 2004, Pediatrics.

[2]  J. Emberlin.  Interaction between air pollutants and aeroallergens , 1995, Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology.

[3]  J. Hazelton,et al.  Consequences of endocrine disrupting chemicals on reproductive endocrine function in birds: establishing reliable end points of exposure. , 2005, Domestic animal endocrinology.

[4]  M. Chapman,et al.  Changing concepts of allergic disease: the attempt to keep up with real changes in lifestyles. , 1996, The Journal of allergy and clinical immunology.

[5]  G. Swanson,et al.  Human exposure to mercury: a critical assessment of the evidence of adverse health effects. , 1996, Journal of toxicology and environmental health.

[6]  E. Faustman,et al.  Human variability in mercury toxicokinetics and steady state biomarker ratios. , 2000, Environmental Research.

[7]  Z. A. Kuzyk,et al.  Biological Effects of Marine PCB Contamination on Black Guillemot Nestlings at Saglek, Labrador: Liver Biomarkers , 2003, Ecotoxicology.

[8]  D. Bellinger,et al.  The health effects of low level exposure to lead. , 1991, Annual review of public health.

[9]  Dana B. Barr,et al.  Biologic Monitoring of Exposure to Environmental Chemicals throughout the Life Stages: Requirements and Issues for Consideration for the National Children’s Study , 2005, Environmental health perspectives.

[10]  J. W. Roe,et al.  Patterns of respiratory illness in Sheffield junior schoolchildren. A follow-up study. , 1970, British journal of preventive & social medicine.

[11]  R. Jackson,et al.  Concentrations of dialkyl phosphate metabolites of organophosphorus pesticides in the U.S. population. , 2003, Environmental health perspectives.

[12]  E. Vesell,et al.  Metabolism of nicotine. , 1991, Drug metabolism reviews.

[13]  W. Morgan,et al.  Asthma and wheezing in the first six years of life. The Group Health Medical Associates. , 1995, The New England journal of medicine.

[14]  Alan L. Miller,et al.  The etiologies, pathophysiology, and alternative/complementary treatment of asthma. , 2001, Alternative medicine review : a journal of clinical therapeutic.

[15]  J. Roca,et al.  ANOTHER ASTHMA OUTBREAK IN BARCELONA: ROLE OF OXIDES OF NITROGEN , 1984, The Lancet.

[16]  Ken Sexton,et al.  If Cumulative Risk Assessment Is the Answer, What Is the Question? , 2007, Environmental health perspectives.

[17]  Halûk Özkaynak,et al.  Design and sampling methodology for a large study of preschool children's aggregate exposures to persistent organic pollutants in their everyday environments , 2004, Journal of Exposure Analysis and Environmental Epidemiology.

[18]  J. Lange.  Airborne exposure and soil levels associated with lead abatement of a steel tank , 2002, Toxicology and industrial health.

[19]  J. Giesy,et al.  The use of biomarkers in ecological risk assessment: recommendations from the Christchurch conference on Biomarkers in Ecotoxicology , 2001, Biomarkers : biochemical indicators of exposure, response, and susceptibility to chemicals.

[20]  G. Ross.  The public health implications of polychlorinated biphenyls (PCBs) in the environment. , 2004, Ecotoxicology and environmental safety.

[21]  J. T. Siedlecki.  Fundamentals of Industrial Hygiene , 1971 .

[22]  A. Murray,et al.  It is children with atopic dermatitis who develop asthma more frequently if the mother smokes. , 1990, The Journal of allergy and clinical immunology.

[23]  R. Dahl,et al.  Lung function and bronchial reactivity in asthmatics during exposure to volatile organic compounds. , 1991, The American review of respiratory disease.

[24]  Susan W Metcalf,et al.  Biomarkers of Exposure in Community Settings , 2004, Journal of toxicology and environmental health. Part A.

[25]  D. Spiegelman,et al.  Predictors of airborne endotoxin in the home. , 2001, Environmental health perspectives.

[26]  P. Schulte,et al.  Validation of biological markers for quantitative risk assessment. , 1991, Environmental health perspectives.

[27]  A. Lemly.  A teratogenic deformity index for evaluating impacts of selenium on fish populations. , 1997, Ecotoxicology and environmental safety.

[28]  Philip J. Landrigan,et al.  Biological markers in environmental health research , 1987 .

[29]  M. Klinnert,et al.  Metropolitan home living conditions associated with indoor endotoxin levels. , 2001, The Journal of allergy and clinical immunology.

[30]  J. Schwartz,et al.  Interrelations of lead levels in bone, venous blood, and umbilical cord blood with exogenous lead exposure through maternal plasma lead in peripartum women. , 2001, Environmental health perspectives.

[31]  K. Fent.  Ecotoxicological effects at contaminated sites. , 2004, Toxicology.

[32]  Andrew Ford,et al.  Models for management of wildlife populations: lessons from spectacled bears in zoos and grizzly bears in Yellowstone , 2004 .

[33]  M. Waalkes,et al.  Sequence of exposure to cadmium and arsenic determines the extent of toxic effects in male Fischer rats. , 1997, Toxicology.

[34]  L. Thompson,et al.  Geochemical analyses of a Himalayan snowpit profile: implications for atmospheric pollution and climate , 2000 .

[35]  U. Wahn,et al.  Natural course of sensitization to food and inhalant allergens during the first 6 years of life. , 1999, The Journal of allergy and clinical immunology.

[36]  R. Pool,et al.  Commission on Life Sciences , 2001 .

[37]  Linda S Sheldon,et al.  Exposures of preschool children to chlorpyrifos and its degradation product 3,5,6-trichloro-2-pyridinol in their everyday environments , 2005, Journal of Exposure Analysis and Environmental Epidemiology.

[38]  J. Links,et al.  The Longitudinal Association of Lead with Blood Pressure , 2003, Epidemiology.

[39]  J. Groopman,et al.  Role of metabolism and viruses in aflatoxin-induced liver cancer. , 2005, Toxicology and applied pharmacology.

[40]  D. Dockery,et al.  Concentration of indoor particulate matter as a determinant of respiratory health in children. , 1994, American journal of epidemiology.

[41]  Ken Sexton,et al.  Assessing Cumulative Health Risks from Exposure to Environmental Mixtures—Three Fundamental Questions , 2007, Environmental health perspectives.

[42]  H. Sachs.  Bone lead levels and delinquent behavior. , 1996, JAMA.

[43]  A. Saxon,et al.  Combined diesel exhaust particulate and ragweed allergen challenge markedly enhances human in vivo nasal ragweed-specific IgE and skews cytokine production to a T helper cell 2-type pattern. , 1997, Journal of immunology.

[44]  S. Adams.  Establishing Causality between Environmental Stressors and Effects on Aquatic Ecosystems , 2003 .

[45]  A. Saxon,et al.  Global increases in allergic respiratory disease: the possible role of diesel exhaust particles. , 1996, Annals of allergy, asthma & immunology : official publication of the American College of Allergy, Asthma, & Immunology.

[46]  Silverman Wa.  Non-treatment of defective newborn babies. , 1980, Lancet.

[47]  S G Selevan,et al.  Fetal growth and maternal exposure to particulate matter during pregnancy. , 1999, Environmental health perspectives.

[48]  David R. Williams,et al.  Vulnerability as a Function of Individual and Group Resources in Cumulative Risk Assessment , 2007, Environmental health perspectives.

[49]  Ayne,et al.  ASTHMA AND WHEEZING IN THE FIRST SIX YEARS OF LIFE , 1995 .

[50]  D. Dockery,et al.  Effects of ambient sulfur oxides and suspended particles on respiratory health of preadolescent children. , 1986, The American review of respiratory disease.

[51]  J. Nigg.  What causes ADHD , 2006 .

[52]  S. H. Arshad,et al.  Effect of environmental factors on the development of allergic disorders in infancy. , 1992, The Journal of allergy and clinical immunology.

[53]  L. Sheppard,et al.  An association between fine particles and asthma emergency department visits for children in Seattle. , 1999, Environmental health perspectives.

[54]  A. McMichael,et al.  Declining blood lead levels and changes in cognitive function during childhood: the Port Pirie Cohort Study. , 1998, JAMA.

[55]  R A Etzel,et al.  Effects of air pollution on the respiratory health of asthmatic children living in Mexico City. , 1996, American journal of respiratory and critical care medicine.

[56]  L. Needham,et al.  A longitudinal investigation of selected pesticide metabolites in urine , 1999, Journal of Exposure Analysis and Environmental Epidemiology.

[57]  D. Barr,et al.  Concentrations of selective metabolites of organophosphorus pesticides in the United States population. , 2005, Environmental research.

[58]  M. Klinnert,et al.  Relation between house-dust endotoxin exposure, type 1 T-cell development, and allergen sensitisation in infants at high risk of asthma , 2000, The Lancet.

[59]  P. Taylor,et al.  Major grass pollen allergen Lol p 1 binds to diesel exhaust particles: implications for asthma and air pollution , 1997, Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology.

[60]  J. Ring,et al.  Air pollution and allergy: experimental studies on modulation of allergen release from pollen by air pollutants. , 1997, International archives of allergy and immunology.

[61]  Renzhi Zhang,et al.  Differential sensitivity of two green algae, Scenedesmus quadricauda and Chlorella vulgaris, to 14 pesticide adjuvants. , 2004, Ecotoxicology and environmental safety.

[62]  D. Shen,et al.  Past adult lead exposure is linked to neurodegeneration measured by brain MRI , 2006, Neurology.

[63]  Richard L. Abbott,et al.  A Follow-up Study , 1990 .

[64]  M. Y. Liu,et al.  Effects of certain atmospheric pollutants (SO2, NO2 and CO) on the soluble amino acids, molecular weight and antigenicity of some airborne pollen grains. , 1986, Cytobios.

[65]  O Axelson,et al.  Symptoms of bronchial hyperreactivity and asthma in relation to environmental factors. , 1988, Archives of disease in childhood.

[66]  J. S. Woods.  Altered porphyrin metabolism as a biomarker of mercury exposure and toxicity. , 1996, Canadian journal of physiology and pharmacology.

[67]  U. Wahn,et al.  Childhood risk factors for atopy and the importance of early intervention. , 2001, The Journal of allergy and clinical immunology.

[68]  L. Costa,et al.  Measurement of paraoxonase (PON1) status as a potential biomarker of susceptibility to organophosphate toxicity. , 2005, Clinica chimica acta; international journal of clinical chemistry.

[69]  A. Wendroff.  The toxicology of mercury. , 2004, The New England journal of medicine.

[70]  Michael H Depledge,et al.  A Proposal for the Use of Biomarkers for the Assessment of Chronic Pollution and in Regulatory Toxicology , 2003, Ecotoxicology.

[71]  L. Costa.  Current issues in organophosphate toxicology. , 2006, Clinica chimica acta; international journal of clinical chemistry.

[72]  Julie Newman,et al.  Degradation of pesticides in nursery recycling pond waters. , 2006, Journal of agricultural and food chemistry.

[73]  Immunization Safety Review : Vaccines and Autism , 2004 .

[74]  W. L. Lockhart,et al.  Geographic variation of chlorinated hydrocarbons in burbot (Lota lota) from remote Lakes and Rivers in Canada , 1990, Archives of environmental contamination and toxicology.