Lexikon
an estimate of a chemical substance, expressed on a bodyweight basis, to which a human population (including sensitive subgroups) can be exposed over a short period of time (24 hours or less), without an appreciable risk of deleterious effects during a lifetime.
Source, REACH
The US EPA defines a "lifelong" oral reference dose too, (abbreviated RfD) as: "an estimate, with uncertainty spanning perhaps an order of magnitude of a daily oral exposure to the human population (including sensitive subgroups) that is likely to be without an appreciable risk of deleterious effects during a lifetime.
reference dose is the maximum acceptable oral or dermal dose of a toxic substance. The EPA defines an oral reference dose (abbreviated RfD) as an estimate, with uncertainty spanning perhaps an order of magnitude, of a daily oral exposure to the human population (including sensitive subgroups) that is likely to be without an appreciable risk of deleterious effects during a lifetime. http://www.epa.gov/economics/children/basic_info/glossary.htm
Reference doses are chemical specific, i.e. the EPA determines a unique reference dose for every substance it evaluates. Often separate acute and chronic RfDs are determined for the same substance. Reference doses are specific to dietary exposure. When assessing inhalation exposure, EPA uses "Reference concentrations," (RfCs), instead of RfDs. Note that RfDs apply only to non-cancer effects. When evaluating carcinogenic effects, special risk assessment methodology is applied.
RfDs are usually derived from animal studies. Animals (typically rats) are dosed with varying amounts of the substance in question, and the largest dose at which no effects are observed is identified. This dose level is called the "No Observable effect Level," or NOEL. To account for the fact that humans may be more or less sensitive than the test animal, a 10-fold uncertainty factor is usually applied to the NOEL. This uncertainty factor is called the "interspecies uncertainty factor" or Ufinter. An additional 10-fold uncertainty factor, the "intraspecies uncertainty factor" or Ufintra, is usually applied to account for the fact that some humans may be substantually more sensitive to the effects of substances than others. Additional uncertainty factors may also be applied. In general:
Frequently, a NOAEL is used in place of a NOEL. If adverse effects are observed at all dose levels tested, then the smallest dose tested, the "Lowest Observed adverse effect Level" or LOAEL, is used to calculate the RfD. An additional uncertainty factor usually applied in these cases, since the NOAEL, by definition, would be lower than the LOAEL had it been observed.