Qualitative Risk Assessment

Chapter-9 Date: 31 October, 2012

What is risk?
A controversial but inherent property of everyday life
Examples of some commonplace risks in the United States Risk Cancer from cigarette smoking (one pack per day) Death in a motor vehicle accident Homicide Home accident deaths Cancer from exposure to radon in homes Death from hepatitis A Exposure to the pesticide aflatoxin in peanut butter Diarrhea from rotavirus Exposure to typical EPA maximum chemical contaminant levels Lifetime risk of mortality 1:4 2:100 1:100 1:100 3:1000 3:1000 6:10,000 1:10,000 1:10,0001:10,000,000

Why do we need risk assessment?

Standards for levels of toxic chemicals or pathogenic microorganisms in water or food Analyses of contaminated sites to determine the need for action and the extent of cleanup Constructing what-if scenarios to compare treatment alternatives and to set priorities for corrective action. Evaluating existing vs. new technologies Articulating community public health concerns Developing consistent public health expectations among different localities

Microbial vs. chemical risk assessment

There are some inherent differences between microbial and chemical risk assessments. Usually disease due to chemical exposure is cumulative over a long period of exposure. In contrast, for microbes, disease may occur following exposure to a single pathogen and will depend on the virulence of the pathogen and the susceptibility of the host. Therefore, one must estimate a risk of infection based on different factors. (For example, the risk of infection by Pseudomonas aeruginosa is very small in general but is large in a burn unit where burn patients are very susceptible to this opportunistic pathogen. Thus, much more stringent (and expensive) disinfection precautions are taken in the burn unit)

Voluntary vs. involuntary risk

Voluntary risk (e.g., driving a car) is always more acceptable than involuntary risk (e.g., consuming hamburger contaminated with E. coli).

It is generally agreed that a lifetime involuntary risk on the order of 1:1,000,000 is small enough to be acceptable or is a tolerable risk.

Risk Assessment
Definition: The process of estimating both the probability that an event will occur and the probable magnitude of its adverse effects over a specified time period. Both chemical and microbial risk assessments can be performed. Each consists of four basic steps: 1) 2) 3) 4) Hazard identification - identify the chemical (e.g, lead) or microbial (e.g, Polio virus) contaminant Exposure assessment Dose-response assessment Risk characterization

Step 2 - Exposure assessment The process of measuring or estimating the intensity, frequency and duration of human exposures to a chemical or microbe Exposure pathway the path from a source to the receptor air water Exposure route intake pathway inhalation ingestion absorption through skin Exposure response is mediated by concentration of chemical/microbe exposure rate (magnitude, frequency, duration) receptor characteristics (body weight, genetics, immunity)

Event trees simplify modeling the infectivity of a pathogen. The following is an example of an event tree used to estimate the human exposure to Salmonella as a result of biosolids applied to a lettuce crop.
Raw sewage 2.9 x 107 CFU/ton

Raw sewage sludge

Anaerobic digestion

2.4 x 107 CFU/ton

2.4 x 105 CFU/ton

Dilution after incorporation into soil

Decay in the soil after 5 months

2.4 x 103 CFU/ton

2.4 x 10-2 CFU/ton

Amount transferred to lettuce

Assume 4500 g lettuce consumed/year: Salmonella ingested/person/year

4.8 x 10-4 CFU/ton

2.1 x 10-6 Salmonella ingested/year

Step 3 - Dose-response assessment Quantitating adverse effects from exposure based on the degree of exposure The goal of a dose-response assessment is to obtain a mathematical relationship between the amount of a toxicant/microbe involved in an exposure to the risk of an adverse outcome. To determine the capacity of an agent to cause harm, we need to quantify toxicity or infectivity. Dose mg chemical/body weight # microbes/exposure Possible responses no response temporary response permanent response chronic functional impairment death

Step 4 - Risk characterization Estimating the potential impact of a contaminants based on the severity of its effects and the amount of exposure. If one looks at the four steps of risk assessment, there is uncertainty associated with each step of the assessment. The various sources of uncertainty include: extrapolation from high to low doses extrapolation from animal to human responses extrapolation from one route of exposure to another limitations of analytical methods estimates of exposure In addition, one must consider vulnerable populations that may be impacted differently than the general population by the outcome of a risk analysis.

Uncertainty can be assessed using

sensitivity analysis the uncertain quantities of each parameter are varied to find out how changes affect the final risk estimate. Monte Carlo simulation assumes that all parameters are random or uncertain. The computer chooses random variations of the parameters and generates risk estimates. The final phase of risk assessment is to integrate exposure and dose-response assessments to yield probabilities of effects. Risk analysis can be quite accurate but most risk analysis is associated with a great deal of uncertainty.

Example: Infectious hepatitis and viral gastroenteritis are caused by consumption of raw or, in some cases, cooked clams and oysters. The concentration of echovirus 12 was found to be 8 plaque-forming units (PFU) per 100 g in oysters collected from coastal New England waters. What are the risks of becoming infected and ill from echovirus 12 if the oysters are consumed? Assume that a person usually consumes 60 g of oyster meat in a single serving:

It has been found that a modified exponential model works well for microbial risk assessment:

P = 1 (1 + N/)-

where: P is the probability of infection, N is the number of organisms ingested, and and are parameters characterizing the host-virus interaction from the dose-response curve. For this example, = 0.374, = 186.69, these parameters were estimated from ingestion studies for echovirus 12. Recall there are 8 PFU/100 g oyster and 60 g are consumed: N = 4.8 PFU consumed Using this model for this example: P = 1 (1 + 4.8/186.69)-0.374 = 9.4 x 10-3

If the percentage of infections that result in risk of clinical illness is 50%, then the risk of clinical illness is: Risk of clinical illness = (9.4 x 10-3)(0.50) = 4.7 x 10-3
If a person consumes oyster 10 times a year with 4.8 PFU per serving, then one can calculate the risk of infection in 1 year: Annual risk = PA = 1 (1 9.4 x 10-3)365 = 9.7 x 10-1

Example 2 Comparison of outbreak data to model predictions for assessment of risks associated with exposure to Salmonella

Food Water Pancretin Ice cream

Dose CFU 17 200 102

Amount consumed 1 liter 7 doses 1 portion

Attack rate (%) 12 100 52

Predicted P (%) 12 77 54

Cheese
Cheese Ham

100500
105 106

28 g
100 g 50100 g

2836
100 100

5398
>99.99 >99.99

Risk assessment provides an effective framework for determining the relative urgency of problems and the allocation of resources to reduce risks. Risk assessment is used routinely to make decisions by: FDA (Food and Drug Administration) OSHA (Occupational Safety and Health Administration) EPA (Environmental Protection Agency) These agencies use risk assessment in a variety of situations: Setting standards for chemical or pathogens in water/food

Assessing risk from GEMS (genetically engineered microbes) Conducting baseline analysis of contaminated sites to determine need for cleanup Cost/benefit analysis Development of cleanup goals Constructing what if scenarios Evaluation of existing and new technologies for pollution prevention and control Articulation of public health concerns