Exposure and Cancer Risk

Dep. of Chemical Engineering School of Engineering Aristotle Univ. of Thessaloniki

Chemical and Radiological Risk in the Indoor Environment (CheRRIE) Exposure and risk assessment of chemical compounds

Prof. Dimosthenis A. Sarigiannis, PhD Director of Environmental Engineering Laboratory (EnvE-Lab) Department of Chemical Engineering, Aristotle University of Thessaloniki - 54124, Greece

CheRRIE Progress meeting February 27, 2015 Thessaloniki, GR 1

Dep. of Chemical Engineering School of Engineering Health impact assessment Aristotle Univ. of Thessaloniki

Interaction at the level of metabolism (inhibition)

Xylene Toluene Ethylbenzene Benzene Liver (metabolism) Leukemia Probabilitydensity

Acetaldehyde Formaldehyde Nasopharyngeal Cancer Cumulative risk

Larynx Cancer

CheRRIE Progress meeting February 27, 2015 Thessaloniki, GR 2

1 Dep. of Chemical Engineering Methodology – exposure and School of Engineering Aristotle Univ. of Thessaloniki intake assessment Personal exposure is equal to the average concentration of a pollutant that a person is exposed to over a given period of time, e.g. 1 day, 1 month or 1 year. If over the given period of time, T, the person passes through n locations, spending a fraction fn of the period T in location n where the concentration of the pollutant under consideration is Cn, then the personal exposure for this period T, represented by the concentration CT

CT   fn Cn n

based on the time-weight contribution of the activities, the level of intensity and the corresponding inhalation rate, we derived adjustment factors for each location type. As a result, average exposure is given by the following formula, where inh is the inhalation adjustment factor for each type of microenvironment encountered in the calculations:

CT f n  C n  inh n

3 Daily intake I is estimated from the following formula, where inhr is the inhalation rate (m /h) for each type of microenvironment encountered in the calculations and tn is the time of residence in the specific microenvironment. Data about the activity patterns, inhalation rates (per age and gender) based on intensity and bodyweights (age and country dependent) are available and taken into account in the calculations:

tn C n  inh r I  n BW

CheRRIE Progress meeting February 27, 2015 Thessaloniki, GR 3

Dep. of Chemical Engineering Methodology – multistage cancer School of Engineering Aristotle Univ. of Thessaloniki model

CheRRIE Progress meeting February 27, 2015 Thessaloniki, GR 4

2 Dep. of Chemical Engineering Methodology – School of Engineering Aristotle Univ. of Thessaloniki internal dosimetry

CheRRIE Progress meeting February 27, 2015 Thessaloniki, GR 5

Dep. of Chemical Engineering Methodology – benzene PBPK School of Engineering Aristotle Univ. of Thessaloniki model

CheRRIE Progress meeting February 27, 2015 Thessaloniki, GR 6

3 Dep. of Chemical Engineering Methodology – BTEX metabolic School of Engineering Aristotle Univ. of Thessaloniki interaction

CheRRIE Progress meeting February 27, 2015 Thessaloniki, GR 7

Dep. of Chemical Engineering Toxic metabolites School of Engineering Aristotle Univ. of Thessaloniki in bone marrow concentration modulation

0.65 6 Benzene only BTEX Mixture A BTEX Mixture B Benzene exposure 0.60 5 0.55 ) 3 0.50 4 g/m μ

mol/L) 0.45 μ 3 0.40 Mixture A: Mixture B:

marrow ( marrow 0.35 • 20% Benzene • 10% Benzene 2 • 40% Toluene • 60% Toluene 0.30 • 10% Ethylbenzene • 10% Ethylbenzene • 30% Xylene • 20% Xylene 1 ( exposure Benzene 0.25 Toxic metabolites concentration in bone in concentration metabolites Toxic 0.20 0 1 5 9 13 17 21 25 29 33 37 41 45 49

Time (hours)

CheRRIE Progress meeting February 27, 2015 Thessaloniki, GR 8

4 Dep. of Chemical Engineering Biology based dose School of Engineering Aristotle Univ. of Thessaloniki response for benzene

1.0E-01

1.0E-02

1.0E-03

1.0E-04

1.0E-05 Cancer Cancer risk Crump 1.0E-06 Coupled PBBK/BBDR

1.0E-07 0.001 0.005 0.050 0.500 5.000

Benzene exposure (ppm)

CheRRIE Progress meeting February 27, 2015 Thessaloniki, GR 9

Dep. of Chemical Engineering Cancer risk estimation School of Engineering Aristotle Univ. of Thessaloniki for aldehydes Formaldehyde For formaldehyde, cancer (nasopharyngeal laryngeal cancer) risk R is calculated taking into account the:

- Formaldehyde distribution across the upper respiratory - The formation of DNA adducts (DPX) described by a non- linear response to exposure - The dose response function for the amount of DPX formatted in nasopharynx, based on the 2-stage clonal growth model 0.0239 y2  0.0245 y P1  e Where P is the nasopharyngeal cancer probability for a lifetime exposure (70 years) and y is the average lifetime internal dose of DPX Acetaldehyde For acetaldehyde, cancer (laryngeal cancer) risk R is calculated from the following relationship: R E  IUR where E is the exposure concentration in μg∙m-3 and IUR is the Inhalation Unit Risk, which is the upper-bound excess lifetime cancer risk estimated to result from continuous exposure to an agent at a concentration of 1 μg∙m-3 in air. For acetaldehyde, IUR is equal to 2.2·10-6

CheRRIE Progress meeting February 27, 2015 Thessaloniki, GR 10

5 Dep. of Chemical Engineering School of Engineering Intake (adults) Aristotle Univ. of Thessaloniki 6 Benzene intake Toluene intake Ethylbenzene intake Xylenes intake Formaldehyde intake Acetaldehyde intake 5

3 g/kg_bw) μ

1 Daily Daily intake (

0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 Kalamaria Kentro Ano ToumpaStauroupoli Polihni Evosmos AmpelokhpoiNeapoli Sykies TriandriaPylaia Peuka Panorama Thermi

CheRRIE Progress meeting February 27, 2015 Thessaloniki, GR 11

Dep. of Chemical Engineering School of Engineering Intake (children) Aristotle Univ. of Thessaloniki 14 Benzene intake Toluene intake Ethylbenzene intake Xylenes intake Formaldehyde intake Acetaldehyde intake 12

8 g/kg_bw)

μ 6

2 Daily Daily intake (

CheRRIE Progress meeting February 27, 2015 Thessaloniki, GR 12

6 Dep. of Chemical Engineering School of Engineering Cumulative risk Aristotle Univ. of Thessaloniki

Leukemia Nasopharyngeal cancer Laryngeal cancer 2.0E-05

1.6E-05

1.2E-05 Risk 8.0E-06

4.0E-06

0.0E+00 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 Kalamaria Kentro Ano ToumpaStauroupoli Polihni Evosmos AmpelokhpoiNeapoli Sykies TriandriaPylaia PeukaPanorama Thermi

CheRRIE Progress meeting February 27, 2015 Thessaloniki, GR 13

Dep. of Chemical Engineering School of Engineering Cumulative risk Aristotle Univ. of Thessaloniki

1.E-04 5%-95% Cancer risk Median Mean "Acceptable risk" 1.E-05 Risk

1.E-06

1.E-07 Leukemia Nasopharyngeal Laryngeal cancer Cumulative cancer cancer risk

CheRRIE Progress meeting February 27, 2015 Thessaloniki, GR 14

7 Dep. of Chemical Engineering Conclusions School of Engineering Aristotle Univ. of Thessaloniki

• Bodyweight normalized dose for children is about two times higher to respective one for the adults

• Estimated lifetime risk due to residential exposure in Thessaloniki for leukemia and nasopharyngeal cancer were below 10-6 (which is considered as acceptable risk), while laryngeal cancer was slightly above 10-6

• Cumulative risk was below 10-5, mainly increased by laryngeal cancer, which in turn is mainly defined by acetaldehyde. However, this is an artefact due to the calculation of laryngeal cancer risk (related to acetaldehyde exposure), which is estimated based on the IUR methodology

• Regarding the individual residential locations, higher risks are related to houses characterized by the combined presence of materials with high potency of VOCs (such as latex wall paints, gypsum decorates

CheRRIE Progress meeting February 27, 2015 Thessaloniki, GR 15

Dep. of Chemical Engineering School of Engineering Aristotle Univ. of Thessaloniki

Thank you for your kind attention

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A connectivity perspective to environment-health interactions

CheRRIE Progress meeting February 27, 2015 Thessaloniki, GR 16