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SECTIONF'I VE VoxfollyAssessmena 5.2 TOXICITY ASSESSMENT FOR HONCARCINOGENIC EFFECTS Substances that produce noncarc isogenic effects are generally thought to have a threshold dose below which there are no observable adverse health effects In developing a toxicity value for noncarcinogenic effects, the approach is to identify this threshold dose of No Observed Adverse Effect Level (NOAEL) through studies with experimental animals or from epidemiological studies A NOAEL is an experimentally (or epidemiologically) determined highest dose at which there was no statistically or biologically significant effect of concern, often called the "critical toxic effect " For certain substances, only a Lowest Observed Adverse Effect Level (LOAEL) has been determined This is the lowest dose of a substance that produces either a statistically or biologically significant indication of the critical toxic effect The NOAEL or the LOAEL may be used to calculate the RfD of a particular contaminant (EPA, 1988) RfDs are calculated by dividing the NOAEL(or LOAEL)by uncertainty factors, which generally range from 10 to 1,000 For example, uncertainties include vanations in the sensitivity of individuals within a population and the extrapolation of data from experimental animals to humans The RM is expressed in units of milligrams of contaminant per lulogram of body weight per day (mg/kg-day) for oral exposure The EPA has developed various types of RfDs depending on the exposure route (ingestion or inhalation), the critical effect, and the length of exposure beteg evaluated(chronic or subchronic) The EPA bases the Rf ) on the most sensitive animal species tested (i e, the species that experiences adverse effects at the lowest dose) rThe EPA defuses a chronic Rf ) as an estimate of a daily exposure level for the human population that is unlikely to result in deleterious effects during a lifetime (70 years, according to EPA guidance) A chronic Rf ) is used to evaluate the potential noncarcinogenic hazards associated with long-term contaminant exposures(7 years to a lifetime) 5.3 TOXICITY ASSESSMENT FOR CARCINOGENIC EFFECTS In estimating the risk posed by potential carcinogens, it is the common practice of the EPA and other regulatory agencies to assume that any exposure level is associated with a finite probability, however minute, of producing a carcinogenic response EPA assumes that a small number of molecular events can evoke changes in.a single cell that can lead to uncontrolled cellular proliferation This mechanism for carcinogenicity is referred to as "non-threshold" since there is theoretically no level of exposure for such a substance that does not pose a small probability of producing a carcinogenic response There is increasing evidence that this assumption is not correct for several chemicals That is, it does appear ® TAID97W73008NA%STOCKTOtAREPORT%SHOREP#1 D0C%&FEB-M730D9NAMA 5-2