A reference dose is the United States Environmental Protection Agency's (EPA) maximum acceptable oral dose of a toxic substance, "below which no adverse noncancer health effects should result from a lifetime of exposure". Reference doses have been most commonly determined for pesticides. The EPA defines an oral reference dose (abbreviated RfD) as:
[A]n 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.
Definition The EPA defines a reference dose (abbreviated RfD) as the maximum acceptable oral dose of a toxic substance, below which no adverse non cancerous health effects should result from a lifetime of exposure. It is 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.
Regulatory status RfDs are not enforceable standards, unlike National Ambient Air Quality Standards. RfDs are risk assessment benchmarks, and the EPA tries to set other regulations, so that people are not exposed to chemicals in amounts that exceed RfDs. According to the EPA from 2008, "[a]n aggregate daily exposure to a [chemical] at or below the RfD (expressed as 100 percent or less of the RfD) is generally considered acceptable by EPA." States can set their own RfDs. For example, the EPA set an acute RfD for children of 0.0015 mg/kg/day for the organochlorine 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.
Types Reference doses are chemical-specific, i.e. the EPA determines a unique reference dose for every substance it evaluates. Often separate acute (0-1 month)and chronic RfDs (more than one month) 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. RfDs apply only to non-cancer effects. When evaluating carcinogenic effects, the EPA uses the Q1* method.
Safe Drinking Water Act Under the Safe Drinking Water Act, EPA is required to first develop a maximum contaminant level goal (MCLG) for an individual chemical, before development of a regulatory standard. The MCLG is the highest level of a contaminant in drinking water where there is no known or anticipated health effect. EPA calculates a "Drinking Water Equivalent Level" (DWEL) by multiplying the RfD by body weight, divided by daily water consumption. The DWEL is then multiplied by the percentage of total drinking water exposure for the general population. The agency uses the MCLG to develop a "maximum contaminant level", which is an enforceable standard applicable to public water systems.
Determination 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 susceptible 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 substantially more sensitive to the effects of substances than others. Additional uncertainty factors may also be applied. In general:
R f D ( m g / k g / d a y ) = N O E L ( m g / k g / d a y ) U F i n t e r ⋅ U F i n t r a ⋅ U F o t h e r {\displaystyle \mathrm {RfD} \mathrm {(mg/kg/day)} ={\mathrm {NOEL} \mathrm {(mg/kg/day)} \over \mathrm {UF} _{\mathrm {inter} }\cdot \mathrm {UF} _{\mathrm {intra} }\cdot \mathrm {UF} _{\mathrm {other} }}}
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