Boron tolerable intake - Re-evaluation of toxicokinetics for data-derived uncertainty factors

Boron, which is ubiquitous in the environment, causes developmental and rep roductive effects in experimental animals. This observation has led to effo rts to establish a Tolerable Intake value for boron. Although risk assessor s agree on the use of fetal weight decreases observed in rats as an appropr iate critical effect, consensus on the adequacy of toxicokinetic data as a basis for replacement of default uncertainty factors remains to be reached. A critical analysis of the existing data on boron toxicokinetics was condu cted to clarify the appropriateness of replacing default uncertainty factor s (10-fold for interspecies differences and 10-fold for intraspecies differ ences) with data-derived values. The default uncertainty factor for variability in response from animals to humans of 10-fold (default values of 4-fold for kinetics and 2.5-fold for d ynamics) was recommended, since clearance of boron is 3- to 4-fold higher i n rats than in humans and data on dynamic differences-in order to modify th e default value-are unavailable. A data-derived adjustment of 6-fold (1.8 f or kinetics and 3.1 for dynamics) rather than the default uncertainty facto r of 10-fold was considered appropriate for intrahuman variability, based o n variability in glomerular filtration rate during pregnancy in humans and the lack of available data on dynamic differences. Additional studies to in vestigate the toxicokinetics of boron in rats would be useful to provide a stronger basis for replacement of default uncertainty factors for interspec ies variation.