Toxicology: Risk Assessment
Risk Assessment Step 1 Problem Formation
The step is to: -identify the environmental health problem - the risk context and stressors - the population concerned about the effects - set out the RA goal and plan
Benchmark dose (BMD)
a dose that produces a change in the response rate (BMR) of an effect compared to the control/background exposure group
Benchmark dose-lower bound (BMDL)
a lower confidence limit on the dose at the BMD
Margin of exposure (MOE)
a measure of the ratio between the calculated NOAEL or BMD and the measured population exposure. A larger number (i.e., >100) typically indicates that the population exposure is lower than the level of concern
Hazard index (HI)
a measure of the ratio between the measured population exposure and the calculated RfD. A smaller number (i.e., <1) typically indicates that the population exposure is lower than the level of concern.
Benchmark response (BMR)
a selected percentage increase in response from effects measured in the background exposure group, used as a point of departure from the observed data
what are the five things a risk management evaluation process examines?
acceptable level of risk existing legislation economic costs and benefits admin costs stakeholder perceptions
Minimal Risk Levels
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
Reference dose (RfD) or reference concentration (RfC)
an estimate of the daily oral (or inhaled) exposure (with uncertainty spanning perhaps an order of magnitude) to the human population (including sensitive subgroups) that is likely to be without an appreciable risk of deleterious effects during a lifetime.
risk communication
an interactive process of exchanging information and opinions among individuals, groups and institutions. involves multiple messages about the nature of risk NOTE: stakeholder involvement greately facilitates effective risk communication
Unit cancer risk (UCR) or cancer slope factor (CSF)
an upper bound, approximating a 95% confidence limit on the increased cancer risk from lifetime exposure
Risk assessment (overall definition of what it is)
analyzing information to determine whether an environmental hazard might cause harm to exposed persons stepwise/setp-by-step process of organizing information on a hazard or agent of concern Ultimate goal is to inform decisions about risk management and reduction
typically risk is characterized by:
average population highly exposed individuals
we typically have _______ exposures to ________ levels of chemicals in the environment
chronic; low
Exposure assessment methods
direct measures by sampling air, water, soil survey people about their actual experiences statistical modeling
Baseline risk: disease risk affected by many factors:
environment genetics behavior lifestyle socio-economics race psychosocial life stage these factors combine to form the baseline risk of a population
RIsk Assessment Step 4 Exposure assessment
estimate chemical intake in a population
Risk Assessment Step 2 Hazard Identification
examining evidence for adverse health effects of agent exposure, and to evaluate the quality, nature and strength of the scientific evidence
hazard quotient - equation
hazard quotient = dose / RfD both dose and RfD need to be in mg/kg/day Hazard quotient > 1: individuals are exposed to higher levels of the substance than is acceptable, the risk of adverse health effects increase
Risk Assessment Step 5 Risk characterization
judgment on risk level of a particular adverse health effect related to exposure to a particular chemical in a particular population, including characterizing uncertainty
Risk Assessment Step 3 Dose-response assessment
looks at the relationship between the dose of a chemical received and the resulting incidence/severity of an adverse effect
Reference Dose (RfD)
the acceptable safety level for chronic non-carcinogenic and developmental effects (EPA)
Acceptable Daily Intake (ADI)
the amount of a chemical to which a person can be exposed each day for a long time (usually lifetime) without suffering harmful effects (FDA)
Internal Dose
the amount of a substance absorbed in the body
Dose
the amount of a substance administered
Target organ dose (biologically effective dose)
the amount that reaches the site(s) at which the adverse effects occur
No observed adverse effect level (NOAEL)
the highest dose, among doses tested in a study, that demonstrates no significant difference from effects measured in control animals.
exposure
the levels of a substance in the environment, but "outside" the organism
Population cancer risk
the lifetime average daily dose (LADD) multiplied by the cancer slope factor
Lowest observed adverse effect level (LOAEL)
the lowest dose, among doses tested in a study, that demonstrates a statistically or biologically significant difference from effects measured in control animals.
Risk
the probability that some adverse effect will occur combination of two aspects: -the probability that an adverse event will occur -the consequences of the adverse event
Risk management
the process of.... identifying evaluating prioritizing choosing ...among policy options. It is the decision-making step. It is based on risk assessment scientific findings, but non-science factors play important role such as economic costs and benefits
Hazard Quotient - definition
the ratio of an exposure over a period of time to the RfD for the substance
point of departure (POD)
the starting point for extrapolating to lower doses; it can be the lower bound on the dose for an estimated incidence or change in response level from a dose-response model (BMD), or aNOAEL or LOAEL.
Modifying factors
use to provide an additional safety element to compensate for the quality of the published studies
Five steps of risk assessment
1. Problem formation 2. Hazard identification 3. Dose-response assessment 4. Exposure asssessment 5. Risk characterization
what assumptions have to be made to conduct an exposure assessment for an average adult
20 m^3 air per day 2 liters water per day 70 kg these are the mean inhalation volume, mean water use, and average weight of an adult male
Risk assessment formulas for ADI and RfD ADI = ____ + _________ RfD = ________ + _________
ADI = NOAEL / cumulative safety factors RfD = NOAEL or LOAEL / cumulative safety factors
Uncertainty Factors: definition and types Factor (FH) Factor (FA) Factor (FL) Fator (FS) Factor (FD)
Allow for inter-species (animal-human) and intra-species (human-human) variability as well as for experimental inadequancies (short/long term duration or low n) Factor (FH)- human variability factor (10×) Factor (FA) - animal data extrapolation to humans (10×) Factor (FL) - LOAEL use in place of the NOAEL (10×) Fator (FS) - subchronic data (10×) Factor (FD) - a modifying factor (0.1 - 10×)
Dose expression
Average daily dose (ADD) Lifetime average daily dose (LADD)
Example of risk assessment and how to calculate reference dose RfD Example: a chemical for rats NOAEL = 15.5 mg/kg/day (chronic study) LOAEL = 62.7 mg/kg/day (subchronic study)
Example: a chemical for rats, NOAEL = 15.5 mg/kg/day (chronic study) RfD = NOAEL ÷ (FA × FH × FD) = 15.5 mg/kg/day (10 × 10 × 10) =0.015 mg/kg/day LOAEL = 62.7 mg/kg/day (subchronic study) RfD = NOAEL ÷ (FA × FL× FS × FH) = 62.7 mg/kg/day (10 × 10 × 10 × 10) =0.0063 mg/kg/day = 6.3 μg/kg/day