Human Health Risk Assessment
Environment contamination is one of the factors that are concerned in human health adverse effects. During the last decades a number of negative effects related to environment contamination are confirmed.
There is increased incidence of many diseases in exposed population in case of contaminated environment. To these health problems belong affections of the respiratory system, cardiovascular system, chronic obstructive pulmonary disease, increase reproduction, but also occurrence of tumor diseases that can be concerned with exposure to carcinogenic compounds.
Contamination data of partial environmental matrix are used to retrospective health risk assessment with emphasis on carcinogenic and noncarcinogenic effects of assessed pollutants. Health risk assessment is methodological procedure that provides estimation and quantification of health risks probability using systematic evaluation of adverse environmental stressors. Advantage of this procedure is also prospective modeling of still nonexistent situations.
Health risk assessment is primarily based on real exposure dose prediction using pharmacokinetic models. This exposure is subsequently compared with maximum reference dose that do not cause any adverse health effect.
Health risk assessment is recommended to perform when relevant environmental contamination is suspected. In this cases risk assessment is conceived as decisive expert document for risk elimination process.
Health risk assessment procedure
Human health risk assessment is the process to estimate the nature and probability of adverse health effects in humans who may be exposed to chemicals in contaminated environmental media (soil, water, air, food), now or in the future.
There are six steps in the baseline risk assessment process:
- hazard identification
- evaluation of dose - response relationship
- exposure assessment
- risk characterization
- risk management
- risk communication
1. Hazard identification
Hazard identification identifies issues for which risk assessment is useful and establishes a context for the risk assessment by a process of identifying the concerns that the risk assessment needs to address. Issue Identification draws on all relevant lines of information.
Within hazard identification conceptual model of contamination is processed for assessed locality. Only for this model consequential health risk assessment is worked out.
Health risk identification includes:
- Determination of priority contaminants with regard to character, size and extent of contamination and with regard to identified recipients
- Toxicology description for priority contaminants
- Overview of additional risk factors for existing locality
- Summary of all risk recipients (with emphasis on sensitive population groups)
- Summarization of all transport pathways and overview of real exposure scenarios and their parameters
- Specification of exposure concentrations for existing exposure pathways, that means input concentrations for exposure scenarios quantification
2. Evaluation of dose - response relationship
Dose-Response Assessment is the process of quantitatively evaluating the toxicity of a given chemical agent as a function of human exposure to that chemical agent. The relationship between the dose of the contaminant administered or received and the incidence of adverse health effects in the exposed population forms the basis for the quantitative dose-response relationship. Based on mode of action, either non-linear or linear dose-response assessment is considered.
Non-linear dose-response assessment
Non-linear dose response assessment has its origins in the threshold hypothesis, which holds that a range of exposures from zero to some finite value can be tolerated by the organism with essentially no chance of expression of the toxic effect, and the threshold of toxicity is where the effects (or their precursors) begin to occur. It is often prudent to focus on the most sensitive members of the population; therefore, regulatory efforts are generally made to keep exposures below the population threshold, which is defined as the lowest of the thresholds of the individuals within a population. If the "mode of action" information (discussed above) suggests that the toxicity has a threshold, which is defined as the dose below which no deleterious effect is expected to occur, then type of assessment is referred to by the Agency as a "non-linear" dose-response assessment. The term "nonlinear" is used here in a narrower sense than its usual meaning in the field of mathematics; a nonlinear assessment uses a dose-response relationship whose slope is zero (i.e., no response) at (and perhaps above) a dose of zero.
A No-Observed-Adverse-Effect Level (NOAEL) is the highest exposure level at which no statistically or biologically significant increases are seen in the frequency or severity of adverse effect between the exposed population and its appropriate control population. In an experiment with several NOAELs, the regulatory focus is normally on the highest one, leading to the common usage of the term NOAEL as the highest experimentally determined dose without a statistically or biologically significant adverse effect. In cases in which a NOAEL has not been demonstrated experimentally, the term "lowest-observed-adverse-effect level (LOAEL)" is used, which this is the lowest dose tested.
The reference dose (RfD) is an oral or dermal dose derived from the NOAEL, LOAEL or BMDL by application of generally order-of-magnitude uncertainty factors (UFs).
These uncertainty factors take into account the variability and uncertainty within NOAEL or LOAEL determination:
UF1 (10-fold) variability within the human population;
UF2 (10-fold) possible differences between test animals and humans;
UF3 (10-fold) using data for subchronic instead of chronic studies;
UF4 (10-fold) using LOAEL values instead of NOAEL;
MF (1 - 10-fold) uncertainty flowing from professional judgment.
Thus, the RfD is determined by use of the following equation:
In general, the RfD is defined as an estimate (with uncertainty spanning perhaps an order of magnitude) of a daily oral exposure to the human population (including sensitive groups, such as asthmatics, or life stages, such as children or the elderly) that is likely to be without an appreciable risk of deleterious effects during a lifetime. The RfD is generally expressed in units of milligrams per kilogram of bodyweight per day: mg/kg/day. RfD values are determined in mg.kg-1.day-1 and are summarized in databases as IRIS, HEAST, ATSDR.
A similar term, know as reference concentration (RfC), is used to assess inhalation risks, where concentration refers to levels in the air (generally expressed in the units of milligrams agent per cubic meter of air: mg/m3). RfC for human exposure (weight of 70 kg and exposure rate of 20 m3.day-1):
RfDABS ( mg.kg-1.day-1 ) = RfDo ( mg.kg-1.day-1 ) x ABS GI
Dermal absorbed doses RfDABS are derived from oral reference doses RfDo according to following equation:
RfD ( mg.kg-1.day-1 ) = RfC ( mg.m-3) x 20 m3.day-1 x 70 kg-1
where ABSGI is fraction of contaminant absorbed in gastrointestinal tract.
Linear dose-response assessment
If the "mode of action" information (discussed above) suggests that the toxicity does not have a threshold, then this type of assessment is referred to by the Agency as a "linear" dose-response assessment. In the case of carcinogens, if "mode of action" information is insufficient, then linear extrapolation is typically used as the default approach for dose-response assessment. In this type of assessment, there is theoretically no level of exposure for such a chemical that does not pose a small, but finite, probability of generating a carcinogenic response. The extrapolation phase of this type of assessment does not use UFs; rather, a straight line is drawn from the point of departure for the observed data (typically the BMDL) to the origin (where there is zero dose and zero response). The slope of this straight line, called the slope factor or cancer slope factor, is use to estimate risk at exposure levels that fall along the line. When linear dose-response is used to assess cancer risk, EPA calculates excess lifetime cancer risk (i.e., probability that an individual will contract cancer over a lifetime) resulting from exposure to a contaminant by considering the degree to which individuals were exposed, as compared to the slope factor.
Thus,
Cancer Risk = Exposure x Slope Factor
Total cancer risk is calculated by adding the individual cancer risks for each pollutant in each pathway of concern (i.e., inhalation, ingestion, and dermal absorption), then summing the risk for all pathways. SF values are also summarized in databases as IRIS, HEAST, ATSDR.
A similar term, know as inhalation unit risk (IUR), is used to assess inhalation risks, where the exposure-response relationship refers to concentrations in the air.
For dermal exposure SFABS are derived from oral SFo values using ABSGI coefficient according to following equation:
SFABS( mg.kg-1.day-1 )-1 = SFo ( mg.kg-1.day-1 )-1 x ABS GI-1
3. Exposure assessment
Exposure assessment is the process of measuring or estimating the magnitude, frequency, and duration of human exposure to an agent in the environment, or estimating future exposures for an agent that has not yet been released.
An exposure assessment includes some discussion of the size, nature, and types of human populations exposed to the agent, as well as discussion of the uncertainties in the above information. Exposure can be measured directly, but more commonly is estimated indirectly through consideration of measured concentrations in the environment, consideration of models of chemical transport and fate in the environment, and estimates of human intake over time.
Exposure scenarios:
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) |
| IR | ingestion rate of water (l.day-1) |
| EF | exposure frequency (day.year-1) |
| ED | exposure duration (year) |
| BW | body weight (kg) |
| AT | averaging time (days) |
for non-carcinogenic: ED (year) x 365 days.year-1
for carcinogenic: 70 years x 365 days.yer-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) |
| CW | concentration of chemical in water (mg.l-1) |
| CR | ingestion rate of water (l.hour-1) |
| ET | exposure time (hour.day-1) |
| EF | exposure frequency (day.year-1) |
| ED | exposure duration (year) |
| BW | body weight (kg) |
| AT | averaging time (day) |
for non-carcinogenic: ED (year) x 365 days.year-1
for carcinogenic: 70 years x 365 days.years-1
DERMAL CONTACT WITH WATER
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 (hour.day-1) |
| EF | exposure frequencye (day.year-1) |
| ED | exposure duration (years) |
| CF | conversing factor (0,001 l.cm-3) |
| BW | body weight (kg) |
| AT | averaging time (day) |
for non-carcinogenic: ED (year) x 365 days.year-1
for carcinogenic: 70 years x 365 days.years-1
This equation is valid for most of inorganic and highly ionized organic chemicals. For remaining contaminants penetration delay, molecular weight and treatment time is considered. For exposure calculations following equations are used:
DAD = DAev x EV x EF x ED x SA / (BW x AT),
where DAev (mg.cm-2.event-1) is derived separately for short-term and long-term activity:
if (Tev ≤ Tst):
DAev = 2 FA x Kp x CW x CF x (6 x Tev / π)1/2
or if (Tev ≥ Tst):
DAev = FA x Kp x CW x CF x ((Tev /(1 + B)) + (2τ x (1 + 3 B + 3B2)/(1 + B)2))
| DAD | dermal absorbed dose (mg.kg-1.day-1) |
| DAev | absorbed dose per event (mg.cm-2.event-1) |
| EV | number of events (events.day-1) |
| EF | exposure frequency (day.year-1) |
| ED | exposure duration (year) |
| SA | skin surface area available for contact (cm2) |
| BW | body weight (kg) |
| AT | averaging time (days) |
| FA | absorbed fraction (0 - 1, unitless) |
| Kp | permeability coefficient (cm.hour-1) |
| CW | concentration of chemical in water (mg.l-1) |
| CF | conversing factor (0,001 l.cm-3) |
| Tev | event duration (hour.event-1) |
| Tst | time to reach steady state (hours); Tst = 2,4τ |
| B | lipophilic property lipophilic property (unitless) |
For B value determination is recommended following relationship:
B = Kp x MW1/2 / 2,6 where MW is molecular weight (g.mol-1)
SOIL OR DUST INGESTION
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 (day.year-1) |
| ED | exposure duration (years) |
| BW | body weight (kg) |
| AT | averaging time (day) |
for non-carcinogenic: ED (year) x 365 days.year-1
for carcinogenic: 70 years x 365 days.years-1
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.day-1 or cm2.event-1) | |
| AF | soil to skin adherence factor (mg.cm-2) |
| ABSd | absorption factor (0 - 1, unitless) |
| EF | exposure frequency (day.year-1) |
| ED | exposure duration (years) |
| BW | body weight (kg) |
| AT | averaging time (day) |
for non-carcinogenic: ED (year) x 365 days.year-1
for carcinogenic: 70 years x 365 days.years-1
Alternatively, following equations are possible to use if number of events per day is determined (in origin equation only 1 event per day is considered).
DAD = DAev x SA x EV x EF x ED / (BW x AT)
where: DAev = CS x CF x AF x ABSd
| DAD | dermal absorbed dose (mg.kg.den-1) |
| DAev | absorbed dose per event (mg.cm-2.event-1) |
| EV | event frequency (event.day-1) |
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-1) |
| IR | inhalation rate (m3.hour-1) |
| ET | exposure time (hour.day-1) |
| EF | exposure frequency (day.year-1) |
| ED | exposure duration (years) |
| BW | body weight (kg) |
| AT | averaging time (day) |
for non-carcinogenic: ED (year) x 365 days.year-1
for carcinogenic: 70 years x 365 days.years-1
VAPOUR INHALATION WITHIN CONTACT WITH CONTAMINATED WATER
- only for chemicals with Henry´s constant
Henry's constant 2 x 10-7 atm/m3/mol
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 (hour.day-1) |
| EF | exposure frequency (day.year-1) |
| ED | exposure duration (years) |
| BW | body weight (kg) |
| AT | averaging time (day) |
for non-carcinogenic: ED (year) x 365 days.year-1
for carcinogenic: 70 years x 365 days.years-1
FOOD INGESTION
CDI = C x IR x FI x EF x ED / (BW x AT)
| CDI | chronic daily intake (mg.kg-1.den-1) |
| C | concentration of chemical in food (mg.kg-1.day-1) |
| IR | ingestion rate of food (kg.event-1) |
| FI | fraction ingested from source (0 - 1, unitless) |
| EF | exposure frequency (event.year-1) |
| ED | exposure duration (year) |
| BW | body weight (kg) |
| AT | averaging time (day) |
for non-carcinogenic: ED (year) x 365 days.year-1
for carcinogenic: 70 years x 365 days.years-1
4. Risk characterization
Risk characterization is the final step in the risk assessment. In this step, the toxicity and exposure assessments are summarized and integrated into quantitative and qualitative expressions of risk.
The final risk characterization is rarely accurately quantitative because of the limitations of the data and this will be reflected in the uncertainty assessment.
Noncarcinogenic effects
The measure used to describe the potential for noncarcinogenic toxicity to occur in an individual is not expressed as the probability of an individual suffering an adverse effect. EPA does not at the present time use a probabilistic approach to estimating the potential for noncarcinogenic health effects.
The noncancer hazard quotient assumes that two there is a level of exposure (i.e., RfD) below which it is unlikely for even sensitive populations to experience adverse health effects. If the exposure (E) exceeds this threshold (i.e., if E/RfD exceeds unity), there may be concern for potential noncancer effects. As a rule, the greater value of E/RfD above unity, the greater level of concern.
Risk is represented by HQ (Hazard Quotient, unitless), calculated according to following equation:
HQ = E / RfD
| E | is absorbed daily dose ADD or chronic daily intake CDI (mg.kg-1.day-1) |
| RfD | is reference dose(mg.kg-1.day-1) |
For exposure to several substances is necessary to use aggregate risk calculation:
∑HQ = HQa + HQb + HQc + ... + HQn
When the hazard index exceeds unity, there may be concern for potential health effects. While any single chemical with an exposure level greater than the toxicity value will cause the hazard index to exceed unity, for multiple chemical exposures, the hazard index can also exceed unity even if no single chemical exposure exceeds its RfD. It is important to calculate the hazard index separately for chronic, subchronic, and shorter-term exposure periods. It is also important to remember to include RfDs for the noncancer effects of carcinogenic substances.
Carcinogenic effects
For carcinogens, risks are estimated as the incremental probability of an individual developing cancer over a lifetime as a result of exposure to the potential carcinogen (i.e., incremental or excess individual lifetime cancer risk - ELCR).
For chemicals A, B1, B2 category is possible to use following equation:
ELCR = CDI x SF resp. ELCR = LADD x SF,
| CDI | chronic daily intake(mg.kg-1.day-1) |
| SF | slope factor (mg.kg-1.day-1)-1
|
This calculation is valid for risk value < 0,01. For higher risk levels is recommended following equation:
ELCR = 1 - exp(-CDI x SF)
With regard to using 95% effect probability, ELCR represent upper bound of health risk whereas real risk should be lower.
Risk is considered appropriate if ELCR is:
- 1.10-6 (probability of carcinogenesis for 1 person per million) assessment of regional effects - usually over 100 endangered individuals
- 1.10-5 (probability of carcinogenesis for 1 person per 100.000) assessment of local effects - usually 10 - 100 endangered individuals
- 1.10-4 (probability of carcinogenesis for 1 person per 10.000) assessment of individuals up to 10 persons
Summarization of final risk
Final step of health risk procedure is presentation and characterization of all calculated risks, their following monitoring and possible elimination. Except risk quantification for particular exposure pathways verbal characterization is within risk assessment procedure also necessary. From these conclusions should result which contaminants and exposure pathways represent significant risk for individual risk recipient. Such risks have to be solved preferentially.
Limitation and uncertainty
All uncertainty connected with health risk assessment must be described together with recommendation of their reduction.
To basic uncertainties belong especially:
- uncertainties connected with exposure pathways determination
- uncertainties connected with derivation of exposure concentrations in case these concentrations is difficult to measure directly
- uncertainties related to dose-respond assessment (discussion about using RfD and SF values including uncertainty and modification factor)
- uncertainties connected to synergic effects assessment or possibly influences caused by combination of other risk factors.
References
U.S. EPA (2004): Risk Assessment Guidance for Superfund. Volume I: Human Health Evaluation Manual (Part E, Supplemental Guidance for Dermal Risk Assessment). Final.
U.S. EPA (1997):Exposure Factors Handbook, EPA/600/8-89/043
U.S. EPA (1999): Risk Assessment Guidance for Superfund. Volume I: Human Health Evaluation Manual (Part A, Baseline Risk Assessment). Interim Final.
U.S. EPA (1991):Risk Assessment Guidance for Superfund. Volume I: Human Health Evaluation Manual. Supplemental Guidance "Standard Default Exposure Factors". Interim Final.
U.S. EPA (1991):Risk Assessment Guidance for Superfund. Volume I: Human Health Evaluation Manual (Part B, Development of Risk-based Preliminary Remediation Goals). Interim.
U.S. EPA (1991):Risk Assessment Guidance for Superfund. Volume I: Human Health Evaluation Manual (Part C, Risk Evaluation of Remedial Alternatives). Interim.
U.S. EPA (1992): Guidelines for Exposure Assessment.
U.S. EPA (1996): Soil Screening Guidance: Technical Background Document, EPA/540/R95/128
U.S. EPA (1997):Superfund Today. Focus on Risk Assessment.
U.S. EPA (1998):Human Health Risk Exposure Model, RAIS
U.S. EPA (2001):Risk Assessment Guidance for Superfund. Volume I: Human Health Evaluation Manual (Part D, Standardized Planning, Reporting, and Review of Superfund Risk Assessment). Final.
U.S. EPA (2001):Risk Assessment Guidance for Superfund. Volume III - Part A, Process for Conducting Probabilistic Risk Assessment.
Links
Integrated Risk Information System (IRIS) http://www.epa.gov/iris/subst/
International Agency for Research on Cancer (IARC) http://www-cie.iarc.fr/monoeval/grlist.html
The Risk Assessment Information System http://risk.lsd.ornl.gov/
Voluntary Remediation Program (VRP) Risk Assessment Guidance Web site http://www.deq.state.va.us/vrprisk/
