19. 5. 2015
1
MASARYK UNIVERSITY
Brno – Czech Republic RECETOX
HUMAN HEALTH RISK ASSESSMENTHUMAN HEALTH RISK ASSESSMENT
Pavel Čupr -Risk assessment methodology
(basic introduction of this approach, main equations,
exposure model, important WEB data sources)
Research group
Human Exposure Assessment and Risks
Human Health Risk Assessment
– exposure assessment tool for risk prediction
-Important tool for better interpretation
of contaminantion levels
in the environment (food, air, etc).
H h lth i k t i th t ti t thHuman health risk assessment is the process to estimate the
probability of adverse health effects in humans who may be exposed
to chemicals/stresors in contaminated environmental media (soil,
water, air, food), now or in the future (prospective and retrospective).
19. 5. 2015
2
Lecture: RISK ASSESSMENT METHODOLOGY
HAZARD / RISK
…explanation of important terminology and differences
HAZARD –
‘A Hazard is a potential source of
harm or adverse health effect on a
person or persons’.
RISK ASSESSMENT METHODOLOGY
p p
RISK ‘Risk
is the likelihood that a person
may be harmed or suffers adverse
health effects if exposed to a hazard‘.
…practical deffinition
19. 5. 2015
3
RISK ASSESSMENT METHODOLOGY
Risk Assessment Process
(U.S. EPA approach)
Hazard
Identification
Exposure
Assessment
Toxicity
Assessment
Risk Characterization
4 Main parts of
this methodology
19. 5. 2015
4
RISK ASSESSMENT METHODOLOGY
MAIN AIM = interpretation of exposure to chemicals!! - Important X or not
RESULTS:
CDI (input)
and
Probability
Of Cancer
and Noncancer
RISKs in
humanhuman
population
Human Health Risk Assessment AIM - The characterization of the
probability of potentially adverse health effects from human
exposures to environmental hazards / environmental STRESORS.
Advantage of this propabilistic approach =
RISK ASSESSMENT METHODOLOGY
http://nnlm.gov/ntc/guide_on_the_side/tutorial/risk-asssessment-protocol
19. 5. 2015
5
Step 1:Hazard Identification
• chemical concentrations of pollutants in
selected matrices (from evaluated sites)
The first step in the RA is the Hazard identification. The hazard
identification defines the problem (problem formulation), identifies the
components like:
selected matrices (from evaluated sites)
– obtained by sampling (air, drink. water,
food..etc)
• To identify available data about toxicity of
these identified chemicals
• To develop model of how chemical may
move through environment (to the next
AFCEE, 2002
move through environment (to the next
exposure media)
© Vermont DPS, 2000
Step 2: Exposure Assessment
!! Without exposure there can be no toxicity.
19. 5. 2015
6
Step 2: Exposure Assessment
- to quantify the exposure of the receptor (selected population) to
chemicals via a given pathway.
- to predict the daily intake of a contaminant by selected individual
pathways as total chronic daily intake CDI (mg/kg/day).p y y ( g g y)
- CDI can be calculated by using of contaminant concentrations in
environmental samples (water, food-diet, sediments, soils, air..) and human
behavior information (=exposure parameters = from exposure surveys,
questinares approches,…).
Alternatively, total exposure
(POPs,…) can be estimated by(POPs,…) can be estimated by
collecting human tissue
samples for chemical analysis
(i.e., blood and breast milk
samples) by using if
toxikokinetic modeling.
Exposure scenarios
Step 2: Exposure Assessment
19. 5. 2015
7
Step 2: Exposure Assessment
• Who is Exposed?
– Adult, Child, Special Populations
• How Are They Exposed?
– Ingestion, Inhalation, Skin Contact
• What is the Concentration of Chemical to Which They are
Exposed?
– ng.l-1,…
• How Often Are They Exposed?
– Days per year, Number of years
= Prediction of
Exposure Scenarios
and
Exposure factors
Putting it all together (general exposure equation)
– exposure parameters
C
daykgmgCDIDoseIntake )/( daykgmgCDIDoseIntake  )/(
• Intake Equation for Drinking Water Example
C= Chemical Concentration (Obtain from sampling)
CR= Contact Rate (…2 liters water/day)
EF= Exposure Frequency (350 days/year)
ED= Exposure Duration (30 years)ED= Exposure Duration (30 years)
BW=Body Weight (70 kg.)
AT= Averaging Time (10,950 days)
19. 5. 2015
8
Step 2: Exposure Assessment
19. 5. 2015
9
Which value for selected exposure
parameter we can use?
All exposure factors and parameters!!!!
http://cfpub.epa.gov/ncea/cfm/recordisplay.cfm?deid=20563
- All population statistics
Age groups
19. 5. 2015
10
Age groups
TWO different types of toxic chemicals
Step 3: Toxicity assessment / Dose-Response Curve relationship
Cancer
chemicals
Non-Cancer
chemicals
LOAEL
19. 5. 2015
11
Step 3: Toxicity assessment / Dose-Response Curve relationship
NoncancerNoncancer
risks
(noncancer
chemicals =
treshold type
of effects)
The toxicity assessment attempts
- to use Dose/response relationship for Reference Doses prediction
Dose – Chemical concentration per unit
body weight
Response – Level of
measured adverse effect
o u o / po a o p o os s p d o
- to quantify the sensitivity of the receptor to the chemical hazard (STRESOR).
Step 3: Toxicity assessment / Dose-Response Curve relationship
NoncancerNoncancer
risks
(noncancer
chemicals =
treshold type
of effects)
The RfD is determined by use of the following equation:
RfD = NOAEL / (UF x MF) (uncertainty factor modifying factor)
(http://www.epa.gov/iris/rfd.htm)
How to use all UF & MF factors for RfD prediction
RfD NOAEL / (UF x MF) (uncertainty factor, modifying factor).
In general, the RfD is an estimate of a daily exposure to the human population
(including sensitive subgroups) that is likely to be without an appreciable risk
of deleterious effects during a lifetime (…adverse effect).
The RfD is generally expressed in units of milligrams per kilogram of bodyweight per day
(mg/kg/day).
19. 5. 2015
12
Exposure equations - Exposure scenarios
http://www.epa.gov/oswer/riskassessment/ragsa/pdf/rags_ch6.3.pdf
DRINKING WATER INGESTION
CDI = CW x IR x EF x ED / (BW x AT)
CDI chronic daily intake (mg.kg-1
.day-1
)
CW concentration of chemical in water (mg.l-1
)( g )
IR ingestion rate of water (l.day-1
)
EF exposure frequency (den.year-1
)
ED exposure duration (years)
BW body weight (kg)
AT averaging time (days)
for non-carcinogenic: ED (years) x 365 days.year-1
for carcinogenic: 70 years x 365 days.years-1
WATER INGESTION – SWIMMING OR SHOWERING/BATHING
CDI = CW x CR x ET x EF x ED / (BW x AT)
CDI chronic daily intake (mg kg
-1
day
-1
)CDI chronic daily intake (mg.kg .day )
CW concentration of chemical in water (mg.l-1
)
CR ingestion rate of water (l.hod-1
)
ET exposure time (hours.day-1
)
EF exposure frequency (den.year-1
)
ED exposure duration (years)
BW body weight (kg)
AT averaging time (days)
for non-carcinogenic: ED (years) x 365 days.year-1
for carcinogenic: 70 years x 365 days.years-1
Exposure equations - Exposure scenarios
DERMAL CONTACT WITH WATER
ADD / LADD = CW x SA x Kp x ET x EF x ED x CF / (BW x AT)ADD / LADD CW x SA x Kp x ET x EF x ED x CF / (BW x AT)
ADD/LADD average daily dose (mg.kg
-1
.day
-1
)
CW concentration of chemical in water (mg.l-1
)
SA skin surface area available for contact (cm2
)
Kp permeability coefficient (cm.hour
-1
)
ET exposure time (hours.day
-1
)
EF exposure frequency (den.year
-1
)
ED exposure duration (years)
CF conversing factor (0,001 l.cm-3
)
BW body weight (kg)
AT averaging time (days)
for non-carcinogenic: ED (years) x 365 days year
-1
for non-carcinogenic: ED (years) x 365 days.year
for carcinogenic: 70 years x 365 days.years-1
19. 5. 2015
13
Exposure equations - Exposure scenarios
SOIL OR DUST INGESTION
CDI = CS x IR x CF x FI x EF x ED / (BW x AT)CDI CS x IR x CF x FI x EF x ED / (BW x AT)
CDI chronic daily intake (mg.kg-1
.day-1
)
CS concentration of chemical in soil (mg.kg-1
)
IR ingestion rate of soil (mg.day-1
)
CF conversing factor (10– 6
kg.mg-1
)
FI fraction ingested from source (0 – 1, unitless)
EF exposure frequency (den.year-1
)
ED exposure duration (years)
BW body weight (kg)
AT averaging time (days)
for non-carcinogenic: ED (years) x 365 days.year-1
for carcinogenic: 70 years x 365 days years-1
for carcinogenic: 70 years x 365 days.years
Exposure equations - Exposure scenarios
DERMAL CONTACT WITH SOIL
ADD / LADD = CS x CF x SA x AF x ABSd x EF x ED / (BW x AT)
ADD/LADD average daily dose (mg.kg-1
.day-1
)
CS concentration of chemical in soil (mg.kg-1
)
CF conversing factor (10– 6
kg.mg-1
)
SA skin surface area available for contact (cm2
or cm2
.event-1
)
AF soil to skin adherence factor (mg.cm-2
)
ABSd absorption factor (0 - 1, unitless)
EF exposure frequency (den.year-1
)
ED exposure duration (years)
BW body weight (kg)
AT averaging time (days)g g ( y )
for non-carcinogenic: ED (years) x 365 days.year-1
for carcinogenic: 70 years x 365 days.years-1
19. 5. 2015
14
Exposure equations - Exposure scenarios
CONTAMINATED AIR INHALATION
CDI = CA x IR x ET x EF x ED / (BW x AT)
CDI chronic daily intake (mg.kg-1
.day-1
)
CA concentration of chemical in air (mg.m-3
)
IR inhalation rate (m3
.hour-1
)
ET exposure time (hours.day-1
)
EF exposure frequency (den.year-1
)
ED exposure duration (years)
BW body weight (kg)
AT averaging time (days)
for non-carcinogenic: ED (years) x 365 days.year-1
for carcinogenic: 70 years x 365 days.years-1
RISK ASSESSMENT METHODOLOGY – noncancer risk
Internal dose
Exposure scenario models
[C] concentrations
RISK = CDI / RfD
Noncancer – ratio of CDI and RfD
Interpretation:
RISK > 1
RISK < 1 Acceptable risk
Significant risk
Step 4: Risk Characterization – to predict final RISK
Chemical 1
Chemical 2
Chemical 3
… Total RISK
(aditive sum of individual ChemicalChronic
Daily Intake
…. (aditive sum of individual Chemical-
risks)
Noncancer RISK ASSESSMENT
RfD – reflect the worst type of noncancer health
outcomes from these exposure
RfD is only for noncancer (threshold) chemicals!
…..
……
19. 5. 2015
15
Internal dose
Chronic Daily Intake
Exposure scenario models
[C] concentrations
Cancer
RISK = 1 - exp (-CDI * SF)
DESE – RESPONSE relationship
EXTRAPOLATION TO
P
RISK
Relevant to
Cancer risks
(cancer
chemicals)
RISK ASSESSMENT METHODOLOGY – cancer risk
RISK > 1.10-6 Significant
risk
Gama-HCH
7 PCBs
DDT
DDE
DDD Total RISK
(aditive sum of individual Chemical-risks) =
expressed as a probability of health effects
Chronic Daily Intake
SF – SLOPE FACTOR
DOSE
LOW DOSE
!!! Databases of these RISK INDEXES - WEB
(mg/kg/day)-1
expressed as a probability of health effects
RISK - probability of an individual developing
cancer over a lifetime as a result of exposure to
the potential carcinogen
Acceptable RISK = 1.10-6 (probability of
carcinogenesis for 1 person per million)
Cancer RISK - probabilistic approach
Beta-HCH
Alpha-HCH
RISK = 1 - exp (-CDI * SF)
RISK ASSESSMENT METHODOLOGY
Internal dose
Chronic Daily Intake
Exposure scenario models
[C] concentrations
RISK = CDI / Rfd
Cancer
Noncancer
Gama-HCH
7 PCBs
DDT
DDE
DDD Total RISK
(aditive sum of individual Chemical-
isks)
Chronic Daily Intake
risks)
= expressed as a probability of health
effects
Cancer and Noncancer
RISK ASSESSMENT
-U.S. EPA probabilistic approach
Beta-HCH
Alpha-HCH
physiologically based
pharmacokinetic (PBPK) model
19. 5. 2015
16
Nutritional
health
Food pesticide
levels
Soil/dust
levels
Water pollutant
levels
Air pollutant
levels !!Emphasize!!
Chemical stress is
only ONE of all stresors
and relevant
PREDICTORS for final
Human Health RISKs!!
Lifestyle
Overall
health
Predicted level of
toxicant in people
Metabolism
Accumulation
Excretion
Lung, intestine, and
skin absorption rates
Genetic
predisposition
Personal
habits
RISK ASSESSMENT METHODOLOGY
Detail description of Risk assessment method:
1) Quantitative Environmental Risk Analysis for Human Health – detail
description of Risk assessment method with many exercises - case studies.
(Robert A. Fjeld et al., 2007)
Robert A. Fjeld; Norman A. Eisenberg; Compton, K. L. Eds.) (2007): Quantitative Environmental
Risk Analysis for Human Health. Chapter 9 Exposure Assessment, chapter 10 Basic Human
Toxicology, chapter 11 Dose–Response and Risk Characterization, (pp 199-314). John Wiley &
Sons, Inc. Hoboken, New Jersey.
Download from IS.MUNI.CZ: (teaching materials):
https://is.muni.cz/auth/el/1431/jaro2015/C2003/um/55931844/Fjeld_2007.pdf
2) Risk Assessment Guidance for Superfund, (U.S. EPA)
Part A (1989) Part B (1991) Part C (1991) Part D (2001) Part E (2004) Part F (2009)
3) WHO toolkit:
DOWNLOAD
19. 5. 2015
17
RISK ASSESSMENT METHODOLOGY
Where we can get these informations
SOURCEs ? DATABASES?
http://www.epa.gov/reg3hwmd/risk/index.htm
Source of important toxicological data:
RfD, Slope Factor, …
IRIS
(CAS, chemicals..
http://www.epa.gov/iris309–00–2example:
19. 5. 2015
18
http://toxnet.nlm.nih.gov/
http://www.inchem.org/
19. 5. 2015
19
ECOTOX Databasehttp://cfpub.epa.gov/ecotox/
Calculator
http://epa-prgs.ornl.gov/cgi-bin/chemicals/csl_search
19. 5. 2015
20
SOFTWARE
Risk-Related Software
http://www.riskworld.com/risk-software/
Up-todate list
US EPA soft:
http://www.weblakes.com/products/iraph/protocol.html
Up-todate list
commercial
Spatial Analysis and Decision Assistance (SADA) Freeware
http://www.sadaproject.net/download.html
SOFTWARE
19. 5. 2015
21
Thank you for your attentionThank you for your attention
Pavel Čupr
cuprcupr@@recetox.muni.czrecetox.muni.cz
RECETOXRECETOX
41
office No. 309office No. 309