Barium: Rationale for a new oral reference dose

The U.S. Environmental Protection Agency (EPA) has an established oral refe rence dose (RfD) value for Ba of 0.07 mg Ba/kg/d based on a 1984 investigat ion that reported hypertension. In this study, the toxicological data for B a has been reevaluated and a revised oral RfD is proposed. The toxicokineti c, acute, and chronic toxicity, carcinogenicity, and reproductive animal st udies as well as epidemiological and occupational health human studies for Ba exposure were reviewed for applicability to an oral RfD. The available h uman studies have some utility but suffer from either a small population si ze, a short exposure regimen, or difficulties in identifying definitive Ba exposure in the study population. As a result, the available long-term anim al studies were found to be more appropriate for the RfD derivation. A dose -response assess ment of no-observed-adverse-effect level (NOAEL) and lowes t-observed-adverse-effect level (LOAEL) values determined that kidney effec ts are the most sensitive endpoint for adverse health effects related to ch ronic soluble Ba ingestion in mammals. The most complete animal studies wer e conducted by the National Toxicology Program (NTP, 1994) and the lowest s pecies NOAELs were 75 mg Ba/kg/d in male mice and 60 mg Ba/kg/d for male ra ts. The male rats were identified to be the most sensitive population teste d and their NOAEL value was selected for extrapolation to an oral RfD. Appl ication of overall uncertainty factors to the lowest NOAEL value from a chr onic animal study of either 90 (based on an approach proposed by Dourson, 1 994) or the generally accepted 100 results in an oral RfD of 0.66 mg Ba/kg/ d or 0.6 mg Ba/kg/d, respectively. It is proposed to use the more conservat ive value of 0.6 mg Ba/kg/d. This reassessment results in nearly an order o f magnitude increase in the U.S. EPA oral RfD for Ba.