There are also fundamental issues concerning the use of ADIs or RfDs for setting tolerance limits or MRLs. These pre-accepted safe daily intakes are only as accurate or meaningful as the toxicity data used which are ever lacking. These intake limits may not have incorporated an adequate safety factor for infants and children (including pregnant and nursing women), who are known to be more vulnerable to most chemical exposures. Another concern is that the toxicologic endpoints used in the MRL or tolerance derivation are different in severity among (groups of) POCs. It is also important to note that the ADIs or RfDs used had rarely, if not never at all, addressed the potential for synergism or additivity of toxicity.