Page 1
Environmental
Engineering
Laboratory
Dep. of Chemical Engineering
School of Engineering
Aristotle Univ. of Thessaloniki
128th Annual Conference International Society for Environmental Epidemiology 31 Aug - 4 Sept 2016 Rome, Italy
Assessing health impacts of hazardous waste:
the exposome paradigm
D.A. SarigiannisEnvironmental Engineering Laboratory
Department of Chemical Engineering
Aristotle University of Thessaloniki
Page 2
Environmental
Engineering
Laboratory
Dep. of Chemical Engineering
School of Engineering
Aristotle Univ. of Thessaloniki
228th Annual Conference International Society for Environmental Epidemiology 31 Aug - 4 Sept 2016 Rome, Italy
Exposure
modelling
Systems Effects /
Individual exposome
Community
Effects / Cohorts
GI tract – portal vein
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v
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r
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k
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y
sA
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tUterus - gonads
L
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n
g
s
GI tract – portal vein
L
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v
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r
H
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t
B
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a
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B
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tUterus - gonads
L
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g
s
metabol
ite
formati
on
A
r
t
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i
a
l
b
l
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o
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V
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V
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b
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o
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Cellular/tissue
effects
Molecular
initiating events
Transcriptomics
Ubiquitous
personal sensors
Environmental
sensors
Environmental
modeling / data
management
Remote
sensing
Environmental
analysis
Human
biosampling
Agent based
modelling
Metabolomics
Fluxomics
(dynamic flux
balance analysis)
Pathway analysisBioinformatics /
systems biology
EWAS
Epigenetics
Genetic polymorphisms
Connectivity-based workflow for exposome studies
Page 3
Environmental
Engineering
Laboratory
Dep. of Chemical Engineering
School of Engineering
Aristotle Univ. of Thessaloniki
328th Annual Conference International Society for Environmental Epidemiology 31 Aug - 4 Sept 2016 Rome, Italy
The external exposome
Page 4
Environmental
Engineering
Laboratory
Dep. of Chemical Engineering
School of Engineering
Aristotle Univ. of Thessaloniki
428th Annual Conference International Society for Environmental Epidemiology 31 Aug - 4 Sept 2016 Rome, Italy
External Exposome workflow
Measured data
Exposure
at individual
level
Exposure for
population groups
Sensors
Modelled data
Questionnaires
Outdoor
Indoor
Food
Soil
Water
Drinking water
≠ env.SES
TAMD
ABMProbabilistic framework
(MCMC)
Uncertainty
Data
Fusion
Decision theory
Kalman filters
Error reduction
ANN
Page 5
Environmental
Engineering
Laboratory
Dep. of Chemical Engineering
School of Engineering
Aristotle Univ. of Thessaloniki
528th Annual Conference International Society for Environmental Epidemiology 31 Aug - 4 Sept 2016 Rome, Italy
Dylos (PM)
Netatmo
(temperature, humidity, air
pressure, CO2 and noise)
Occasionally:
NO2 , O3
Fitbit Flex
Smartphone apps
Paper Log &
Questionnaires
Dust fall
Vacuum
Sample
Pilot
Campaign
Page 6
Environmental
Engineering
Laboratory
Dep. of Chemical Engineering
School of Engineering
Aristotle Univ. of Thessaloniki
628th Annual Conference International Society for Environmental Epidemiology 31 Aug - 4 Sept 2016 Rome, Italy
Personal Exposure
Assessment
Buildings,
Land Use
Road Network
Population
Data
Air Quality
Data
Personal
Exposure
Agent Based Modelling
Human Agent
Trajectories
INPUT SIMULATION OUTPUT
Sleeping
Indoor activities
In transit
Working
Relaxing
Sports
ACTIVITIES LAND USE
ABM simulation preview
Thessaloniki, Greece
Page 7
Environmental
Engineering
Laboratory
Dep. of Chemical Engineering
School of Engineering
Aristotle Univ. of Thessaloniki
728th Annual Conference International Society for Environmental Epidemiology 31 Aug - 4 Sept 2016 Rome, Italy
Waste types and pollutants
Municipal
waste
Agricultural
waste
e-waste
Hospital waste
Industrial waste
PCDDs and
PCDFs
Heavy metals
(Cd, As, Pb, Hg,
Cr)
VOCs
PAHs
H2S
Biogas
Pesticides
Phthalates
PCBs
CFCs
PHAHs
- Other metals
and rare earth
elements
Pharmaceutical
Page 8
Environmental
Engineering
Laboratory
Dep. of Chemical Engineering
School of Engineering
Aristotle Univ. of Thessaloniki
828th Annual Conference International Society for Environmental Epidemiology 31 Aug - 4 Sept 2016 Rome, Italy
Environmental mobility and exposure pathways
Aniline
Fluoride
organotin compounds
Arsenic
Mecoprop
Pentachlorophenol
Biphenyl
methyl chlorophenoxy acetic acid
Phenols
Cyanide
methyl tertiary butyl ether
Phosphorus
di(2-ethyl hexyl)phthalate
Naphthalene
Polycyclic aromatic hydrocarbons
Dichloromethane
Nitrogen
Toluene
Ethylbenzene
Nonylphenol
xylenes
Leachate substances
associated with health risks
Page 9
Environmental
Engineering
Laboratory
Dep. of Chemical Engineering
School of Engineering
Aristotle Univ. of Thessaloniki
928th Annual Conference International Society for Environmental Epidemiology 31 Aug - 4 Sept 2016 Rome, Italy
Continent
Region Local
Detailed micro-environmental concentrations taking
into account interactions among different media (gas,
particles and dust)
Microenvironment
Consumer products
Detailed exposure modelling taking into account
multiple pathways and routes of exposure
Multiple scale interactions of environmental modelling
Page 10
Environmental
Engineering
Laboratory
Dep. of Chemical Engineering
School of Engineering
Aristotle Univ. of Thessaloniki
1028th Annual Conference International Society for Environmental Epidemiology 31 Aug - 4 Sept 2016 Rome, Italy
The internal exposome
Page 11
Environmental
Engineering
Laboratory
Dep. of Chemical Engineering
School of Engineering
Aristotle Univ. of Thessaloniki
1128th Annual Conference International Society for Environmental Epidemiology 31 Aug - 4 Sept 2016 Rome, Italy
Exposure biology workflowRendering high dimension biology operational
Untargeted metabolite profiling
LC-MS/MS, MS/MS-ToF, NMR
Whole genome mRNA
expression
mRNA Microarrays
Molecular
pathways
Metabolic pathways
PoT
hypothesis
Targeted
proteomics
Targeted metabolomics
Targeted DNA
Methylation analysis
Phenotypic/endotypic
anchoring
Targeted (bio)chemical
analysis
Functional
assays
Page 12
Environmental
Engineering
Laboratory
Dep. of Chemical Engineering
School of Engineering
Aristotle Univ. of Thessaloniki
1228th Annual Conference International Society for Environmental Epidemiology 31 Aug - 4 Sept 2016 Rome, Italy
LC-MS/MS
GC-MS/MS
Microarrays Biological
Pathways
MassHunter Qual/Quant
ChemStation AMDIS
Feature Extraction GeneSpring Platform
Alignment to Reference GenomeNGS
Exposure biology workflow
Page 13
Environmental
Engineering
Laboratory
Dep. of Chemical Engineering
School of Engineering
Aristotle Univ. of Thessaloniki
1328th Annual Conference International Society for Environmental Epidemiology 31 Aug - 4 Sept 2016 Rome, Italy
Methodological transition facilitated by exposome
Congenital anomalies → RR 1.01 - 1.08 for various defects (2 km from landfills)
Cancer risk → RR 1.035 for all cancer types (3 km from incinerators)
• Which compounds are associated to each endpoint?
• How we can refine exposure to these compounds related to waste disposition?
Improved exposure modelling
Assimilation of biomonitoring data
• How to improve health associations and identify causalities
Identification of molecular markers of exposure and effect
Page 14
Environmental
Engineering
Laboratory
Dep. of Chemical Engineering
School of Engineering
Aristotle Univ. of Thessaloniki
1428th Annual Conference International Society for Environmental Epidemiology 31 Aug - 4 Sept 2016 Rome, Italy
Waste management in Athens
Page 15
Environmental
Engineering
Laboratory
Dep. of Chemical Engineering
School of Engineering
Aristotle Univ. of Thessaloniki
1528th Annual Conference International Society for Environmental Epidemiology 31 Aug - 4 Sept 2016 Rome, Italy
Acute exposure to waste hazardsCancerogenicity
Background levels
0
4
8
12
16
20
24
8 6 7 8 9 6 11 8 9 10 7 6 9 11 9 273841552941324225394231293942255836474930364924342936483839443842274449344148534953483934
Children AdultsCo
nc.
(pg
/g l
ipid
_T
EQ
)
Individuals age (years)
1
10
100
1,000
10,000
Rural areas City centre Industrial area Landfield fires Aspropyrgos fire
Co
nce
ntr
atio
n (
fg/m
3)
PCDDs and PCDFs (TEQ)5%-95%
Median
1.E-08
1.E-07
1.E-06
Background risk Post-accidental risk /adults
Post-accidental risk /neonates
Post-accidental risk /breast fed
Can
cer
risk
Risk5%-95%
Median
Page 16
Environmental
Engineering
Laboratory
Dep. of Chemical Engineering
School of Engineering
Aristotle Univ. of Thessaloniki
1628th Annual Conference International Society for Environmental Epidemiology 31 Aug - 4 Sept 2016 Rome, Italy
Metabolomics and
pathway analysis
Increased levels of unsaturated vs saturated fatty acids, compared to
controls → cholesterol homeostasis perturbation → AhR deregulation
Page 17
Environmental
Engineering
Laboratory
Dep. of Chemical Engineering
School of Engineering
Aristotle Univ. of Thessaloniki
1728th Annual Conference International Society for Environmental Epidemiology 31 Aug - 4 Sept 2016 Rome, Italy
Chronic exposure to waste hazards
Neurodevelopmental toxicity
Page 18
Environmental
Engineering
Laboratory
Dep. of Chemical Engineering
School of Engineering
Aristotle Univ. of Thessaloniki
1828th Annual Conference International Society for Environmental Epidemiology 31 Aug - 4 Sept 2016 Rome, Italy
Explore causality in EWAS
Page 19
Environmental
Engineering
Laboratory
Dep. of Chemical Engineering
School of Engineering
Aristotle Univ. of Thessaloniki
1928th Annual Conference International Society for Environmental Epidemiology 31 Aug - 4 Sept 2016 Rome, Italy
Conclusions
• Exposome science can overhaul the current
environmental health risk assessment paradigm. This
requires combination of high dimensional biology and
system science aiming at integration using big data
analytics and bioinformatics
• The connectivity approach to the exposome
elucidates toxicity pathways and assigns causal
associations between environmental stressors and
health
• Precise prevention towards environmental risks by
identifying the susceptible or vulnerable individuals or
age-groups
Page 20
Environmental
Engineering
Laboratory
Dep. of Chemical Engineering
School of Engineering
Aristotle Univ. of Thessaloniki
2028th Annual Conference International Society for Environmental Epidemiology 31 Aug - 4 Sept 2016 Rome, Italy
Bertold Brecht’s Life of Galileo:
“The main objective of science is not to open
the door to infinite wisdom but to roll back the
boundaries of infinite error”
www.enve-lab.eu
A connectivity perspective to environmental health