1. Risk Assessment

2. Types Of Risk Assessment
Human Health Risk Assessment - The characterization of the probability of potentially adverse health effects from human exposures to environmental hazards.
Ecological Risk Assessment – A process that estimates the likelihood of undesirable ecological effects occurring as a result of human activities.

3. Problems With Risk Assessments
A basic problem with both human and ecological risk assessments is the sparseness and uncertainty of the scientific data. Also -
Variability within dose-response curves
Extrapolation of animal data to humans
Extrapolation from high-dose to low-dose effects

4. Four Steps To A Risk Assessment Document
Hazard Identification
Dose-Response Assessment
Exposure Assessment
Risk Characterization

5. Hazard Identification
Hazard identification involves gathering and evaluating toxicity data on the types of health injury or disease that may be produced by a chemical and the conditions of exposure under which injury or disease is produced.
The subset of chemicals selected for the study is termed “chemicals of potential concern”.

6. Hazard Identification – Data
Data from acute, subchronic, and chronic dose-response studies are used.
a H.R.A. would have a priority ranking of studies that would involve humans and other mammals.
an E.R.A. would use different species in different tropic levels; the test species selected are generally representative of naturally occurring species with practical considerations such as ease of culture, sensitivity, availability, and existing databases also involved.

7. Dose-Response Assessment
The dose-response assessment involves describing the quantitative relationship between the amount of exposure to a chemical and the extent of toxic injury or disease.
The description is different for non-carcinogenic versus carcinogenic effects.

8. Non-Carcinogenic Effects
Allowable Daily Intake - The US Food and Drug Administration, the World Health Organization, and the Consumer Product Safety Commission use the Allowable Daily Intake (ADI) to calculate permissible chronic exposure levels.
The ADI is determined by applying safety factors to the highest dose in chronic human or animal studies that has been demonstrated not to cause toxicity.

9. Non-Carcinogenic Effects - Continued
Reference Dose - The US Environmental Protection Agency has slightly modified the ADI. For the EPA, the acceptable safety level is known as the Reference Dose (RfD)
an estimate of a daily exposure level for human populations, including sensitive subpopulations, that is likely to be without an appreciable risk of deleterious health effects during a lifetime

10. Non-Carcinogenic Effects - Continued
The position of the EPA is that humans are as sensitive as the most sensitive test species unless other data are available.
RfD = NOAEL or LOAEL
UF1 x UF2 … x Ufx

11. Non-Carcinogenic Effects - Continued
Safety/Uncertainty Factors
x10 Human Variability
x10 Extrapolation from animals to humans
x10 Use of less than chronic data
x10 Use of LOAEL instead of NOAEL
x10 Incomplete database
x0.1 to 10 MF Modifying Factors

12. Non-Carcinogenic Effects - Continued
Minimum Risk Levels (MRLs), used by ATSDR, are similar to the EPA's Reference Dose (RfD) and Reference Concentration (RfC).
An MRL is an estimate of the daily human exposure to a hazardous substance that is likely to be without appreciable risk of adverse noncancer health effects over a specified duration of exposure.

13. Non-Carcinogenic Effects Continued
For a H.R.A. any toxic effect can be used for the NOAEL or LOAEL so long as it is the most sensitive toxic effect and it is considered likely to occur in humans.
For an E.R.A. chief measurement endpoints are mortality, growth and development, and reproduction. In E.R.A.s one must sometimes extrapolate effects from a surrogate species to the species of interest, or from acute data to chronic data.

14. Carcinogenic Effects
Mathematical models are used to extrapolate from the high doses used in animal experiments to the low doses to which humans are normally exposed in a chronic setting.

15. Carcinogenic Effects - Continued

16. Carcinogenic Effects - Continued

17. Carcinogenic Effects - Continued
The key risk assessment parameter derived from the carcinogen risk assessment process is the “slope factor”. The slope factor is a toxicity value that quantitatively defines the relationship between dose and response.
= a plausible upper bound estimate of the probability that an individual will develop cancer if exposure is to a chemical for a lifetime of 70 years.

18. Carcinogenic Effects - Continued
Slope Factor = a plausible upper-bound estimate of the probability of a response per unit intake of chemical over a lifetime
Risk per unit dose
Units of Risk (mg/kg-day)-1
Symbol for Slope Factor = q1*

19. Cancer Assessment Categories

20. Exposure Assessment
Exposure assessment involves describing the nature and size of various populations exposed to a chemical agent, and the magnitude and duration of their exposures.
Without exposure there can be no toxicity.

21. Steps In Exposure Assessment
Characterization of exposure setting
Identification of exposure pathways
Quantification of exposure

22. Characterize The Exposure Setting
What are the situations which could lead to exposure?
What would lead to high exposure, medium exposure, and low exposure?
Describe the situations for the various exposure scenarios.
Who are the people / animals exposed?

23. Identification of Exposure Pathways
Contaminated groundwater – ingestion (drinking water), dermal contact (bathing), and inhalation of volatile organic compounds (showering)
Surface water and sediments – incidental ingestion and dermal absorption of contaminants (people in bodies of water)
Contaminated food – ingestion of contaminated fish tissue, vegetables and fruit grown in contaminated soil or covered with contaminated dust, meat, and dairy products

24. Identification of Exposure Pathways
Surface soils – ingestion and dermal absorption of contaminants by children playing in dirt
Fugitive dust and VOC emissions – inhalation by nearby residents or onsite workers
Subsurface soil and air-borne contaminants – future land-use conditions during construction activities
Contaminated breast milk – nursing infants whose mothers were exposed to highly toxic lipophilic contaminants

25. Exposure Pathways - Continued
All potential exposure pathways are considered with an analysis of
the contaminants released
the fate and transport of the contaminants
the population exposed to the contaminants

26. Quantification of Exposure
General statement
[ ] Of Chemical x Intake x Retention Factor x Length of Exposure
For Noncarcinogens
Maximum Daily Dose (MDD)
For Carcinogens
Lifetime Average Daily Dose (LADD)

27. Lifetime Average Daily Dose
= [ ] Of The Chemical x Contact Rate x Contact Fraction x Exposure Duration ________________________________
Body Weight x Lifetime

28. LADD Calculation Example

29. LADD Calculation Example - Continued

30. Important Note to Calculation of LADD
Be aware of the units used for consumption of the chemical (How often the chemical is obtained).
You may need to back calculate the number to mg/kg/day averaged over 70 years (a lifetime)
If the units are already in mg/kg/day, then no back calculation is needed, if units are mg/kg/month, then you only need to calculate back from months to days.

31. Risk Characterization
Exposure Assessments and Toxicity Assessments are integrated to give a probability of a negative effect.
Risk characterization is conducted for individual chemicals and then summed for mixtures of chemicals – Additivity is assummed.

32. Risk Characterization - Continued
For Noncarcinogenic chemicals –
The Maximum Daily Dose is compared to the RfD. If MDD is < RfD, then no problem- except when dealing with multiple chemicals.
For ecological issues –
Estimated Environmental [ ]/Toxic Endpoint [ ] = Quotient, Quotients approaching or exceeding 1.0 represent increasing risk

33. Risk Characterization - Continued
For Carcinogenic Chemicals –
You determine the “upper confidence Limit on Risk”
UCL Risk = Slope Factor x LADD
Units for Slope Factor are (mg/kg/day)-1
Units for LADD are mg/kg/day
Therefore units cancel and you get a unit-less number
This unit-less number represents the increase in the number of cancer cases per year due to chemical

34. Risk Characterization - Continued
Virtually Safe Dose –
This was initially defined (1961) as 1 extra cancer death per 100 million people exposed
Found unenforceable by FDA in 1977
Currently the EPA uses 1 extra cancer death per 1 million people exposed.
California uses 1 extra death per 100,000 people exposed (Proposition 65)