definition of “safe” varies according to the applicable legal provision. For example, for contaminants, the statutory definitions of safety are proscribed in section 402(a)(1). Food is considered adulterated if an added contaminant is in the food in a quantity “...which may render it [the food] injurious to health”, or, if the substance is an inherent natural constituent of the food (i.e. “not an added substance”) and is in the food in a quantity that would “ordinarily render it [the food] injurious to health”. As another example, the phrase “reasonable certainty that no harm will result” is used in section 408 (a)(4) regarding the safety of tolerances for a pesticide chemical residue in or on a food.
For a safety assessment, the term “safety” has connotations involving both the degree of certainty and an assumption of “negligible risk.” The prototype chemical safety assessment is the Acceptable Daily Intake (ADI) method which was first articulated by Fitzhugh and Lehman (1954) for use in considering the significance of available animal data. This approach or variations of it are used throughout the world (WHO, 1987). The ADI for a chemical is calculated from the No Observed Adverse Effect Level (NOAEL) and Uncertainty Factor (UF) using the following equation:
ADI = NOAEL / UF.
The same basic methodology can be used to derive other regulatory standards such as Tolerable Daily Intake (TDI), Reference Dose (RfD), and Minimal Risk Level (MRL). These values are derived from controlled animal studies, human clinical studies, or epidemiological studies that provide the exposure level for which there is no apparent adverse effect or which identify the lowest observable adverse effect level (i.e., NOAEL, LOAEL). These adverse effect levels are also considered in conjunction with one or more uncertainty factor(s). Uncertainty factors are applied to account for inter-species and inter-individual differences and other uncertainties in the data (WHO, 2004).
There have been consistent efforts to improve this process to make better use of scientific knowledge. These efforts have focused on both replacing the NOAEL approach and refining the development of uncertainty factors. One example is the development of the benchmark dose (BMD) concept (Crump, 1984; Kimmel and Gaylor, 1988). The BMD concept involves fitting a dose-response model to all the available data and to determine the statistical lower bound of the BMD (i.e., the BMDL). The major advantage of the approach is that the BMDL is not constrained to one of the experimental doses from a controlled study, as is the case with the NOAEL (Crump, 1994). The U.S. Environmental Protection Agency (EPA) uses the BMD method in health risk assessments (Filipsson et al., 2003).
3. Risk Assessment-Based Approach. A risk assessment is a systematic, scientific examination of known or potential adverse heath effects resulting from human exposure to a hazard. The generally accepted paradigm separates risk assessment into four components: hazard identification, exposure assessment, hazard characterization (dose- response), and risk characterization. This framework allows for organization of information, definition of uncertainties, and identification of data gaps. Risk assessments can describe the likelihood of adverse health effects either quantitatively or qualitatively
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