Typically, EPA derives an RfD by starting with the highest dose at which no adverse effects can be observed (the No Observed Adverse Effect Level, or NOAEL). Learn more abou how the U.S. EPA sets RfD»

It is unprecedented to use the level at which no effect, even a mundane, biochemical effect, is observed (the No Observed Effect Level, or NOEL); however, this is the starting point that the NAS Committee used for perchlorate. The NAS Committee defined a NOEL as “the highest dose at which there are no statistically or biologically significant increases in the frequency or severity of any effect between the exposed populations and its appropriate control.” (See page 168 of the report, “Health Implications of Perchlorate Ingestion.”)

Where a NOAEL is used, uncertainty factors are customarily applied to the starting dose to account for scientific uncertainty and ensure the RfD protects public health. For example, to account for sensitive populations such as pregnant women, children, infants and fetuses, the EPA typically divides the NOAEL by an uncertainty factor of 3 or 10.

The NOEL dose that the NAS Committee selected as its starting point was 0.007 milligrams per kilogram per day and then divided this dose by a safety factor of 10 to account for sensitive populations. There is no  precedent for this level of conservatism. The NAS Committee identified the NOAEL for perchlorate as 0.4 milligrams per kilogram body weight per day, stating that, in adults, “sustained exposure” (i.e., several months or longer) to more than 0.4 milligrams per kilogram of perchlorate per day is likely required before any harm could occur.

Alternatively, if an uncertainty factor of 3 or 10 for sensitive populations was applied to the NOAEL the reference dose could have set at 1,400 to 4,655 ppb in drinking water.