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