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

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

L

i

v

e

r

H

e

a

r

t

B

r

a

i

n

M

u

s

c

l

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k

i

n

K

i

d

n

e

y

sA

d

i

p

o

s

eB

o

n

e

s

B

r

e

a

s

tUterus - gonads

L

u

n

g

s

GI tract – portal vein

L

i

v

e

r

H

e

a

r

t

B

r

a

i

n

M

u

s

c

l

e

sS

k

i

n

K

i

d

n

e

y

sA

d

i

p

o

s

eB

o

n

e

s

B

r

e

a

s

tUterus - gonads

L

u

n

g

s

metabol

ite

formati

on

A

r

t

e

r

i

a

l

b

l

o

o

d

V

e

n

o

u

s

b

l

o

o

d

A

r

t

e

r

i

a

l

b

l

o

o

d

V

e

n

o

u

s

b

l

o

o

d

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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