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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#r EPA Glossary REGULATORY STATUS Unlike Insecticide Endosulfan , based on neurological effects observed in test animals. The EPA then looked at dietary exposure to endosulfan, and found that for the most exposed 0.1% of children age 1-6, their daily consumption of the endosulfan exceeded this RfD. To remedy this, the EPA revoked the use of endosulfan on the crops that contributed the most to exposure of children: certain beans, peas, spinach, and grapes. Reregistration Eliligibility Decision for Endosulfan TYPES OF RFDS
DETERMINATION RfDs are usually derived from 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 NOAEL. 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 " No Observable Adverse Effect Level " or 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. If studies using Human Subject s are used to determine a RfD, then the interspecies uncertainty factor can be reduced to 1, but generally the 10-fold intraspecies uncertainty factor is retained. Such studies are rare. AN EXAMPLE As an example, consider the following determination of the RfD for the insecticide Chlorpyrifos , adapted from the EPA's Interim Reregistration Eligibility Decision for chlorpyrifos. Interim Reregistration Eligibility Decision for Chlorpyrifos
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