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NE-SRA June 19, 2007

Why are Kids Different? Underlying Biological and Physiological Characteristics. NE-SRA June 19, 2007. Sandy Baird , Ph.D. MassDEP Office of Research and Standards. Topics to Cover. Susceptibility Lifestage approach Ontogeny of organ systems 

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NE-SRA June 19, 2007

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  1. Why are Kids Different? Underlying Biological and Physiological Characteristics NE-SRA June 19, 2007 Sandy Baird, Ph.D. MassDEP Office of Research and Standards

  2. Topics to Cover • Susceptibility • Lifestage approach • Ontogeny of organ systems  • Physiology underlying increased susceptibility • Exposure • Effects

  3. Evolution of Kids Risk – A Quick Review • 1993 Pesticides in the Diets of Infants and Children (NAS) • 1996 Food Quality Protection Act (FQPA) • 1997 Executive Order 13045 • 1997 Office of Children’s Health established • 2005 Supplemental Guidance for Early-life Exposures to Carcinogens • 2005 Guidance on Selecting Age Groups for Monitoring and Assessing Childhood Exposures to Environmental Contaminants • 2006 Framework for Assessing Health Risks of Environmental Exposures to Children

  4. Exposure/Dose Physiology Behavior Location Health Effects Incidence Severity Reversibility Type Latency Why the interest in kids risk?Evidence of increased susceptibility

  5. Susceptibility Increased likelihood of an adverse effect or exposure, often discussed in terms of relationship to a factor, that can be used to describe a human subpopulation, e.g., lifestage, demographic feature, or genetic characteristic (USEPA 2006) USEPA 2006 A Framework for Assessing Health Risks of EnvironmentalExposures to Children

  6. Vulnerability Physical, chemical, biological and cultural factorsaffecting communities and subpopulations Susceptibility Exposure Preparedness Recovery

  7. Dose-Response Exposure Assessment Exposure Characteristics Toxicokinetics Toxicodynamics Toxophore Tissue Interaction Exposure Tissue Dose Altered Structure/ Function • Observable • Response • Cellular • Tissue • Organ • Whole • organism Absorption Distribution Metabolism Excretion Elements of aChemical Exposure-Dose-Response Pathway Dose-Response Exposure Assessment Susceptibility Adapted from USEPA 1994, USEPA 2002

  8. Lifestage Approach2006 Children’s Framework Temporal Stages of Life have distinct characteristics • Anatomical • Physiological • Behavioral • Functional USEPA 2006 A Framework for Assessing Health Risks of EnvironmentalExposures to Children

  9. Lifestage Approach Considers • Mode of Action of Substance • Critical Windows of Sensitivity • Immediate and Later-life Effects USEPA 2006 A Framework for Assessing Health Risks of EnvironmentalExposures to Children

  10. Dose-Response Exposure Assessment Exposure Characteristics Toxicokinetics Toxicodynamics Conceptus Toxophore Tissue Interaction Toxophore Tissue Interaction Toxophore Tissue Interaction Exposure Exposure Exposure Tissue Dose Tissue Dose Tissue Dose Altered Structure/ Function Altered Structure/ Function Altered Structure/ Function Observable Response Observable Response Observable Response Absorption Distribution Metabolism Excretion Absorption Distribution Metabolism Excretion Absorption Distribution Metabolism Excretion Birth to<3 months Postmenopausalwomen Lifestage Dose-Response

  11. Definition of a Child2006 Children’s Framework Preconception Fetus Neonate Infant Preschool Child Adolescent11-<16 Adult16-<21 Conception BirthDay 0 1 month 1 year 6 years Puberty10-15 yo Sexually Mature Adult16-21 yo Child Developmental Exposure Period USEPA 2006 A Framework for Assessing Health Risks of EnvironmentalExposures to Children

  12. Birth < 1 month 1 to <3 months 3 to < 6 months 6 to < 12 months 12 to < 24 months 2 to < 6 years 6 to < 11 years 11 to < 16 years 16 to < 21 years Recommended Age GroupsBased on behavioral and physiological exposure characteristics < 1 year > 1 year USEPA 2005 Guidance on Selecting Age Groups for Monitoring and Assessing Childhood Exposure to Environmental Contaminants

  13. Increased Exposure Rate • Physiology • Inhalation – Ventilation Rate, alveolar surface area, lung architecture • Ingestion – water consumption, breast milk • Dermal - surface area • Body water content • Behavior • Crawling, eating limited food items, activities • Location • Floors, schools, playgrounds

  14. Male Age-Specific Ventilation Rates m3/day 20 m3/day Ratio of child-specific and adultdefault ventilation rates 4.4-5.2x 3.0-3.9x 1-2x Age (years) Draft Child EFH, Lordo et al 2006 m3/kg-day Child Default=10 m3/day/20kg=0.5 m3/kg-day Adult Default=20 m3/70 kg=0.28 m3/kg-day 0 -<2 yo >2 to <6 yo >6 - <21 yo

  15. Layton (1993) and Lordo et al. (2006)Ventilation Rate (m3/day) by Age in Males 20 m3/day 15 Ventilation Rate (m3/day) 9.3 7.3 Layton 1993 Age (years) Table 7-17 – Draft Child Specific Exposure Factors HandbookData: Lordo et al. 2006

  16. Layton (1993) and Lordo et al. (2006)Ventilation Rate Adjusted for BW (m3/kg-day) by Age in Males Layton 1993 Ventilation Rate (m3/kg-day) 0.521 0.404 0.283 Adult Default=20 m3/70 kg=0.286 m3/kg-day Age (years) Table 7-17 – Draft Child Specific Exposure Factors HandbookData: Lordo et al. 2006

  17. Layton vs. Lordo Ventilation RatesRatio male child by age to default adult (m3/kg-day)

  18. Increased Adverse Effects • Effects that occur result from the interaction of the agent with the specific processes that are occurring in a tissue or organ system during the time of exposure. • Effects may be observable immediately or may not be evident until later, after additional development or exposures occur.

  19. Timelines for Development Age (years)

  20. Developing Brain as a Target of ToxicityRodierEHP, 1995 Migration Proliferation • Very complex system • Dozens of different types of neurons • Specific functions • Specific timing • Pre- and Postnatal development • No blood-brain barrier in utero and in early-life Cell Death Synaptogenesis Transmitters and receptors Trimming of connections

  21. Development of the Respiratory System • Extrathoracic Region: • Nose, nasal passages, larynx, pharynx, mouth • Tracheobronchiole Region: • Trachea, bronchi, bronchioles, terminal bronchioles (<25,000) • Alveolar-Interstitial Region: • Respiratory bronchioles, alveolar ducts, sacs with alveoli (<300 million), interstitial connective tissue • 40 different cell types • More than 80% of the alveoli in the adult arise postnatally. • Dietert et al. EHP 2000 Trachea Primary Bronchi Alveoli

  22. Lung Development Timeline Humans Dietert et al. 2000

  23. Immune Development Timeline Humans Dietert et al. 2000

  24. Increased Adverse Effects • Incidence – vinyl chloride • Irreversible – ozone, neurotoxicants • Type – lead, mercury, DES • Latency – DES, vinyl chloride • Severity – lead, mercury

  25. Thank You!

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