The U.S. Food and Drug Administration (FDA) has published a literature review on the eight phthalates currently approved for food contact uses to determine whether they should be considered chemically and/or pharmacologically related (CRA) for the purpose of cumulative risk assessment.

The eight approved phthalates for food contact use in the U.S. are: diisononyl phthalate (DINP), diisodecyl phthalate (DIDP), di(2-ethylhexyl) phthalate (DEHP), dicyclohexyl phthalate (DCHP), butylphthalyl butyl glycolate (BPBG), diethyl phthalate (DEP), ethylphthalyl ethyl glycolate (EPEG), and diisooctyl phthalate (DIOP).

The review comparatively assessed the physicochemical, toxicokinetic, and toxicodynamic properties of the eight phthalates. It also discussed current approaches used by other regulatory authoritative bodies for CRA. Discussions include the use of weight of evidence and new approach methodologies (NAMs) based on predictive modeling to fill in the data gaps for some of the phthalates and determine scientifically supportable inclusion or exclusion criteria for CPR classification of the evaluated phthalates.

Overall, FDA’s findings support grouping DEHP, DCHP, DIOP, and DINP as CPR substances for the purposes of a future cumulative risk assessment. FDA will consider stakeholder input on the use of this grouping for a future cumulative risk assessment.