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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.
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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 • 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*
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
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)