Risk Assessment

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.

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

Four Steps To A Risk Assessment Document

Hazard Identification Dose-Response Assessment Exposure Assessment Risk Characterization

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”.

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.

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.

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.

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

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

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

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.

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.

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.

Carcinogenic Effects - Continued

Carcinogenic Effects - Continued

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.

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*

Cancer Assessment Categories

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.

Steps In Exposure Assessment

Characterization of exposure setting

Identification of exposure pathways

Quantification of exposure

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?

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

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

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

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)

Lifetime Average Daily Dose

= [ ] Of The Chemical x Contact Rate x Contact Fraction x Exposure Duration ________________________________ Body Weight x Lifetime

LADD Calculation Example

LADD Calculation Example - Continued

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.

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.

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

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

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)