Development of an occupational exposure limit for n-propylbromide using benchmark dose methods

This paper presents the development of an occupational exposure level (OEL) for n-propylbromide (nPB) using benchmark dose methods. nPB is a non-ozone depleting solvent, proposed under the Significant New Alternatives Policy (SNAP) for use as a precision vapor degreaser. OELs have generally been developed on the basis of a NOAEL or LOAEL and application of uncertainty factors; this paper represents a departure from historic methods. Six recently completed toxicological studies were critically reviewed to identify (1) toxicologically significant endpoints, (2) dose–response information on these endpoints, and (3) uncertainties and limitations associated with the studies. Dose–response data were compiled and entered into the USEPA’s benchmark dose software for calculation of a benchmark dose (BMD) and a benchmark dose low (BMDL). Once values were estimated for all relevant studies, they were then incorporated into a weight-of-evidence approach to develop a single BMD and BMDL representative of nPB. This approach is similar to that recently taken by USEPA to develop their own recommended OEL for nPB. USEPA’s approach is compared and contrasted with ours, particularly in relation to the application of uncertainty factors (UFs) to generate a final OEL. There are no published criteria for application of UFs in developing an OEL. Although USEPA recommends utilizing a UF of 9, based on intraspecies variability and pharmacokinetic differences between rats and humans, to meet the goal of protecting healthy adult in a workplace setting, no uncertainty factor was deemed necessary for nPB in this paper. Therefore, the BMDL was recommended as the OEL.