Dehp

SOT’s 52nd Annual Meeting San Antonio, Texas March 10th –14th 2013

IS INDOOR EXPOSURE TO DEHP A HEALTH RISK?

D.A. SarigiannisS.P. KarakitsiosA. Gotti

1Aristotle University of Thessaloniki, Department of Chemical Engineering, Environmental Engineering Laboratory, Thessaloniki, 54124, Greece; 2Centre for Research and Technology Hellas (CE.R.T.H.), Thessaloniki, 57001,Greece


DEHP is used as plasticizer in PVC plastics, including personal care products, packaging materials, toys, building materials,….

As DEHP is not chemically bound to PVC it can leach, migrate or evaporate into indoor air, dust, foodstuff, other materials,… Consequently, DEHP is ubiquitous in our environment

Rationale

systemic health effects local health effects (inhalation)

Threshold value systemic ref Health effect –

local effects ? Threshold value local

effect ref

DEHP

Reproductive effects 50 µg/kg bw/day

(20 µg/kg bw/day)*(25 µg/kg bw/day)**

(CSTEE, 1998;ECB, 2008;EFSA,

2005a)

inhalation; increased asthma risk in children

? (Bornehag et al., 2004))Developmental

effects


GI tract – portal vein

Liver

Heart

Brain

Muscles

Skin

Kidneys

Adipose

Bones

Breast

Uterus - gonads

Lungs


Liver

Heart

Brain

Muscles

Skin

Kidneys

Adipose

Bones

Breast

Uterus - gonads

LungsArterial blood

Venous blood

Arterial blood

Venous blood

Indoor processesoDispersionoSorptionoDepositionoChemical reactionsoResuspensionoDilution/ventilation

Outdoor contribution

SOURCESPollutant

Oral exposure

Dermal exposure

Inhalation exposure

Source conditions: e.g.oEmission strengthoTime patternoChemical/physical properties of pollutant

Housing conditions: e.g.oDimensions and layoutoVentilation characteristicsoSources location

Individual conditions: e.g.oTime activity patterns in houseoSource use pattern

Methodological concept of the approach


Concentrations

__ _ _ _ _

__ _

_ __ _

_

chem gaschem gas ind out chem gas chem gas out

chem PMchem gas p chem gas

p PM

chem dust dustd chem gas chem PM

dust

dCV E Q C C V

dt

Ck C V r C V

K C

C mr C C V

K

_ __

__ _

chem PM chem PMp chem gas

p PM

chem PMind out PM PM out

PM

dC CV r C V

dt K C

CQ C C V

C

_ _ __ _

_

chem dust chem dust dustd chem gas chem PM

dust

dC C mV r C C V

dt K

Gas phase mass equilibrium

Particles phase mass equilibrium

Dust phase mass equilibrium

Echem_gas : chemical emission rate

Qint_out : Indoor/outdoor air exchange rate

K : chemical decay coefficient

KP : gas/particles partition coefficient

Kdust : gas/dust partitioning coefficient

rP, rd : partitioning kinetics

V : location volume

CPM : PM concentration indoors

CPM_out : PM concentration outdoors

CDEHP_gas : chemical concentration in gas phase

CDEHP_PM : chemical concentration in PM phase

CDEHP_dusts : chemical concentration in dust phase

m_dust : mass of dust in the location


1 1 2 2A A A Askin

skin V skin skin b

dCV k C k C k C k C

dt

1 1 2 2A A A Askin

skin V skin skin b

dCV k C k C k C k C

dt

/P in C BLV

C P b

Q C Q CC

Q Q P

1ex DS in DS alvC F C F C

_ _ _ _ exp ( ) dust soil hand to mouth object to mouthOral osure non dietary M M M M

Uptake from exposure routesD

erm

alIn

hala

tion

Ora

l

T n nn

C f C

0

1

2

3

4

5

6

7

8

9

0

0.2

0.4

0.6

0.8

1

1.2Ambient air

Home

Workplace

Exposure

Benzene metabolites

Time

Ben

zen

e co

nce

ntr

ati

on

(μ

g/m

3)

Ben

zen

e m

eta

bo

lites

co

nce

ntr

ati

on

(μ

g/l)

stomlumenstom stomach stomlumen lumen

dQ t= RateIng F + Ka C t

dt

The potential dose represents the dose that is in contact with the biologicalbarriers of the human body (e.g., digestive tract, lungs and skin), while the absorbed dose is the quantity of the compound that effectively passes across them and reaches the systemic blood circulation and internal organs.

home home home work work work other other other E f C i f C i f C i


Internal exposure (PBPK) modeling

( ) lim Priji i j ij ij ij ij ij

dCV Q CA CV Metab E Absorp Binding

dt


Liver

Heart

Brain

Muscles

Skin

Kidneys

Adipose

Bones

Breast

Uterus - gonads

Lungs


Liver

Heart

Brain

Muscles

Skin

Kidneys

Adipose

Bones

Breast

Uterus - gonads

LungsArterial blood Venous blood Arterial blood Venous blood


Liver

Heart

Brain

Muscles

Skin

Kidneys

Adipose

Bones

Breast

Uterus - gonads

Lungs


Liver

Heart

Brain

Muscles

Skin

Kidneys

Adipose

Bones

Breast

Uterus - gonads

LungsArterial blood Venous blood Arterial blood Venous blood

DEHP MEHP 5-OH MEHP 5- oxo - MEHP


Exposure pathways considered: Exposure through inhalation:

- gas phase- particles phase

Exposure through skin:- Rubbing of dust (0.01 g/day)

Exposure through ingestion- Dust ingestion through hand to mouth behavior

Infants Toddlers Children

Female Teens Male Teens

Female Adults

Male Adults

House dust ingestion (g/day) 0.05 0.05 0.01 0.001 0.001 0.001 0.001

DEHP is emitted from electronic equipment and vinyl flooring. Lets assume a typical scenario of a common residential dwelling (size of 270 m2 and air exchange rate equal to 0.5) characterized by total DEHP gaseous emissions of 200 μg/h (vinyl flooring and other plastic equipment)

The vinyl floor case


DEHP concentration in different media

1 26 51 76 1011261511762012262512763013263513764014264514760

1

2

3

4

5

6

0

500

1000

1500

2000

2500

3000

3500

4000

gasparticlesdust

Time (h)

Gas

/par

tcle

s ph

ase

conc

entr

atio

n (μ

g/m

3)

Dus

t pha

se c

once

ntra

tion

(μg/

g du

st)

Concentration in EU indoor locations

Gas + particles (μg/m3) Dust (μg/g_dust) Study

0.13 626 Weschler et al, 2008

3214 Clausen et al. 2003

970 Butte et al., 2008

604 Abb et al., 2009

540 Langer et al. 2010


DEHP internal exposure

1 27 53 79 1051311571832092352612873133393653914174434690.0

1.0

2.0

3.0

4.0

5.0

0

0.01

0.02

0.03

0.04

0.05

0.06

0.07

Adipose tissueVenous bloodMilk

Time (h)

Adi

pose

tiss

ue c

once

ntra

tion

(μg/

L)

Ven

ous

- mot

hers

milk

con

cent

ratio

n (μ

g/L)


1 23 45 67 89 1111331551771992212432652873093313533753974194414630

0.1

0.2

0.3

0.4

0.5

0.6

0.7

0.8

0.9

MEHPDEHP5-OH-MEHP 5-oxo-MEHP

Time (h)

Ven

ous

bloo

d co

ncen

trat

ion

(μg/

L)DEHP and major metabolites internal exposure


Major metabolites urine concentrations

1 23 45 67 89 1111331551771992212432652873093313533753974194414630

1

2

3

4

5

6

7

8

5-OH-MEHP MEHP 5-oxo-MEHP

Time (h)

Uri

ne c

once

ntra

tion

(μg/

gCr)


Inhalation Oral Skin0.0

0.2

0.4

0.6

0.8

1.0

1.2

1.4Adults

Kids

Route

Upt

ake

(μg/

kg_b

w/d

)DEHP daily uptake per route


Conclusions

• Linking Emissions, Concentrations, Exposure and Internal dose within a “continuous” mathematical frame allows us to couple environmental and biological processes efficiently

• Capturing jointly toxicokinetics, toxicodynamics and exposure dynamics allowed us to incorporate mechanistic knowledge in exposure assessment and thus improve the validity and relevance of the risk characterization outcome

• It also allowed the identification of exposure scenarios that could pose health risk

• Integrated external and internal exposure assessment for DEHP highlights the fact that the current health risk from human exposure to DEHP indoors is very low.

• Sum of urinary DEHP metabolites one order of magnitude lower than the BE (660 ug/g creatinine)

• Daily uptake is higher for children than for adults. • Oral and skin uptake are important routes for children, but negligible for adults.


Thank you for your kind attention

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