exposomes for children's studies: importance of life stage
TRANSCRIPT
Elaine M. Faustman, Ph.D. DABT
Professor and Director
Institute for Risk Analysis and Risk Communication
Department of Environmental and Occupational Health Sciences
Exposomes for Children's Studies: Importance of Life Stage Considerations
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Exposome and Systems Biology
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Lifecourse Specificity
Inhalation
Oral
Dermal
Exposure
Absorption
Distribution
Metabolism
Elimination
Toxicokinetics
Adolescent
Child
Newborn
Conceptus
Organ, Tissues
Cellular
Organelle
Molecular
Toxicodynamics
Normal Parameters
Developmental Disorder
• Lethality
• Growth Retardation
• Malformation
• Altered Function
Outcome
Incorporating Population Level Sustainability Factors, Polymorphism and Variability Data
Rodents PopulationsHumans
In vitro In vivo In vitro In vivo
Biochemical
Molecular
Cellular
Tissue
Organ
Biochemical
Molecular
Cellular
Tissue
Organ
Organism
Biochemical
Molecular
Cellular
Tissue
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Biochemical
Molecular
Cellular
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Population
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Rodents PopulationsHumans
In vitro In vivo In vitro In vivo
Biochemical
Molecular
Cellular
Tissue
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Biochemical
Molecular
Cellular
Tissue
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Organism
Biochemical
Molecular
Cellular
Tissue
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Biochemical
Molecular
Cellular
TissueTissue
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Molecular
Cellular
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TissueTissue
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Incorporating
Population
Level
Polymorphism
Data
0.0 0.5 1.0 1.5 2.0 2.5 3.0
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Multimodal
Distribution
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Population
Pre-natal
Post-natal Infant
AdolescentLIFESTAGE
RISK ASSESSMENT
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Faustman, 2016
Initial Appearance Of Organs During Gestation In Humans Can Define Windows Of Sensitivity
4Hill, 2010
Definitions of Exposome by Disciplines
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Adapted from NCS, 2011; Hubal et al 2014
Questionnaire/
Diary/
Observation
Biological
Measurements
“True”
Exposure
(or Dose)
Communit
y
Household
Individual
Scale Life Stage
Environmental
Measurements
Cumulative Exposure Approaches for Assessing Exposome within Children’s Cohort Studies
NCS, 2011
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“Environment” Broadly Defined in NCS
• Physical environment:
– housing, neighborhoods and communities, climate, radiation…
• Chemical exposures:
– air, water, soil, food, dust, industrial products, pharmaceuticals…
• Biological environment:
– womb, infection, nutrition; inflammatory and metabolic response…
• Genetics:
– influence of genetics on disease; relationships between genes and the environment
• Psychosocial:
– influence of family, socio-economics, community, culture, stress…
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CHC Cohort – Yakima Valley
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Longitudinal Children’s Health Center Study Design
Integrated Framework Tool
1999
2002
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Dimethyl DAPs in Farmworker and Non-Farmworker Adults
Values represent geometric means and 95% confidence intervals
Guerrette et al. (2012)11
Metab
olite C
on
cen
tration
(n
g/ml)
Values represent geometric means and 95% confidence intervals
Guerrette et al. (2012)
Dimethyl DAPs in Farmworker and Non-Farmworker Children
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Child DMTP
Metabolite concentrations in urine (ug/L)
sa
mp
le q
uan
tile
s
1 10 100 1000
0.0
0.2
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1.0
yr1, ctl, no pome n=29yr1, ctl, pome n=78yr1, int, no pome n=28yr1, int, pome n=69yr4, ctl, no pome n=30yr4, ctl, pome n=86yr4, int, no pome n=30yr4, int, pome n=58
Distribution of Child DMTP from year 1 to year 4 of CHC study: Impacts of year to year variability
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Example Exposome for Farmworker and Non-Farmworker House Dust Across 2 Different Years,
Same Season
AZM
Ph
osm
et
Mal
ath
ion
CP
Dia
zin
on
Car
bar
yl
Pro
po
xur
Bo
scal
idA
ceta
mip
rid
Imid
aclo
pri
d
Per
met
hri
n
Sum
ith
rin
Tetr
amet
hri
n
Cyp
hen
oth
rin
Imip
roth
rin
Sbio
alle
thri
n
AZM
Ph
osm
etM
alat
hio
n
CP
Dia
zin
on
Car
bar
yl
Pro
po
xur
Bo
scal
idA
ceta
mip
rid
Imid
aclo
pri
d
Per
met
hri
n
Sum
ith
rin
Tetr
amet
hri
n
Cyp
hen
oth
rin
Imip
roth
rin
Sbio
alle
thri
n
Class
Use
Class OP NM Carbarmate Ag Ag & General GeneralNeonicotinoid Pyrethroid Use
2005 Thinning Season House Dust 2011 Thinning Season House Dust
Farm
wo
rker
sN
on
-Far
mw
ork
ers
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K. Olden et al,
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Plascak et al. 2016 Submitted
Jesse Plascak, Marissa N Smith, Elaine Faustman, Beti Thompson
Latino residential segregation, discrimination, neighborhood disorder and hair cortisol concentration among
Latinas. 2016. Submitted
Integrating Chemical and Non-Chemical Exposures
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• Km is the rate constant for free cortisol metabolism
• Ks is the rate constant for free cortisol transfer to saliva
• Ku is the rate constant for free cortisol transfer to urine,
• Kh is the rate constant for free cortisol transfer to hair
• CBG bound cortisol is bound to corticosteroid binding globulin (CBG) in the blood
Biokinetic Models/Needed for Integration of Biomarkers
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Smith et al 2013 JESEE
Conceptual Model for Pathways linking neighborhood factors, social stress and health
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Plascak et al. 2016 Submitted
Conceptual Model for Pathways linking neighborhood factors, social stress and health
19Plascak et al. 2016 Submitted
Model estimated percent changes in hair cortisol concentrations by Latino residential
segregation, discrimination and social organization, For Healthy Kids! Stress Study (N=25)1
Figures A-G represent separate models including each discrimination or neighborhood disorder
measure.
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Framework of modifying factors for exposure associated with geography and culture.
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Source: Children’s Health, Nation’s Health, IOM report, 2004
Life Course Based Model of Children’s Health and its Influences
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Lessons Learned for Children’s Exposome
1. Unique features and needs for children’s exposomeLifestage assessments matter!
2. Models are needed that link kinetic and dynamic features in order to understand the potential for exposure at specific sensitive lifestages, the form of the exposures in complex environments, and duration and magnitude of exposures related to disease outcomes that may happen at the same lifestage or much later in life.
3. Temporal specific exposures are useful for designing and evaluating interventions
4. Temporal considerations for children’s exposome are essential for predicting and identifying impacts during childhood development
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Acknowledgements
The NIEHS, EPA funded Center for Children's Environmental Health Risks Research (RD-83170901, ES-09601)
National Institute of Child Health and Human Development, National Institutes of Health, Department of Health and Human Services, under Contract No. HHSN267200700023C
The National Institute Of Environmental Health Sciences under the Award Number 5P01ES009601
US Environmental Protection Agency Biomarkers grant (RD-83273301) and contract (2W-2296-NATA)
EPA funded Predictive Toxicology Center (USEPA STAR grant RD-83573801)
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Extra Slides
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After a series of presentations made in second and third grade classrooms, students were invited to enter a coloring contest. Winning entries were included in a calendar. In this drawing the woman tells the man to wash his own clothes, because she’s going to a dance…and she reminds him to leave his boots outside.
Photo: Gloria Coronado
Community Intervention
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