The purpose of this Toxicological Review is to provide scientific support and rationale for the hazard and dose-response assessment in IRIS pertaining to chronic exposure to 2,2',4,4',5-pentabromodiphenyl ether. It is not intended to be a comprehensive treatise on the chemical or toxicological nature of 2,2',4,4',5-pentabromodiphenyl ether (BDE-99). The majority of the available toxicological information on the pentabromodiphenyl ether homolog group (CAS No. 32534-81-9) relates to the pentabromodiphenyl congener BDE-99 (CASRN 60348-60-9). Toxicological information related to other congeners in the pentabromodiphenyl ether homolog group is also discussed. However, this health assessment does not deal with commercial mixtures of brominated diphenyl ether homologs containing pentabromodiphenyl ether as one of the constituents of commercial formulations. In addition to BDE-99, IRIS health assessments have also been prepared for three other polybrominated diphenyl ether congeners: tetraBDE-47, hexaBDE-153, and decaBDE-209. These four congeners are those for which toxicological studies suitable for dose-response assessments were available and are the ones most commonly found in the environment and human biological media. The intent of Section 6, Major Conclusions in the Characterization of Hazard and Dose Response, is to present the major conclusions reached in the derivation of the reference dose, reference concentration and cancer assessment, where applicable, and to characterize the overall confidence in the quantitative and qualitative aspects of hazard and dose response by addressing the quality of data and related uncertainties. The discussion is intended to convey the limitations of the assessment and to aid and guide the risk assessor in the ensuing steps of the risk assessment process.