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The uncertainty factor is derived on a case-by-case basis, depending principally on the quality of the database. Generally, a factor of 1 to 10 is used to account for intraspecies variation and interspecies variation6. An additional factor of 1 to 100 is used to account for inadequacies of the database which include but are not necessarily limited to, lack of adequate data on developmental, chronic or reproductive toxicity, use of a LO(A)EL versus a NO(A)EL and inadequacies of the critical study. An additional uncertainty factor ranging between 1 and 5 may be incorporated where there is sufficient information to indicate a potential for interaction with other chemical substances commonly present in the general environment. If the chemical substance is essential or beneficial for human health, the dietary requirement is also taken into consideration in derivation of the Tolerable Daily Intake or Concentration. Exceptionally, in deriving a TDI or TDC for severe effects (e.g., teratogenicity), an additional uncertainty factor of 1 to 10 may be incorporated. Numerical values of the uncertainty factor normally range from 1 to 10,000. Uncertainty factors greater than 10,000 are not applied since the limitations of such a database are sufficient to preclude development of a reliable TDI or TDC. In some cases, where the uncertainty factor is less than 10,000 but there are limitations in the protocol of the critical study, a "tentative TDI" or "tentative TDC" may be established.
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