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The use of Haber's law in standard setting and risk assessment
1National Center for Toxicological Research, US Food and Drug Administration, 3900 NCTR Road, 72079, Jefferson, AR 72079, USA. dgaylor@nctr.fda.gov
Abstract:
Haber's Law simply states that the incidence and/or severity of a toxic effect depends on the total exposure, i.e. exposure concentration (c) rate times the duration time (t) of exposure (c x t). This rule, within constraints, is often used in setting exposure guidelines for toxic substances. Establishing reference doses (acceptable daily intakes) for long-term exposures when only the results of short-term studies are available requires the use of an uncertainty (safety) factor. The value of this uncertainty factor often approximates a value comparable to Haber's Law for extrapolation from short-term to long-term exposure durations. As a default procedure, cancer risk estimates are generally based on the average lifetime daily dose which is derived from the total cumulative exposure, i.e. Haber's (c x t). This has been shown both theoretically and empirically to be valid within a factor of 20 for carcinogenesis. This provides some credence for the use of an additional safety factor of 10, in some instances, for exposures of children to carcinogens. Finally, a generalization of Haber's Law, exposure concentration raised to a power times exposure duration, is discussed.
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