Comment from Center for Food Safety

Ortho(o)-phthalates are commonly studied plasticizers that have applications across numerous industries such as construction, automotive and consumer goods, including select uses in food packaging and other food contact materials. In this review, we surveyed the published literature on eight o-phthalates that currently have authorized food contact uses in the United States (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)) to comparatively assess their physicochemical, toxicokinetic and toxicodynamic properties in order to determine whether they should be considered chemically and/or pharmacologically related (CPR) for the purposes of a cumulative risk assessment (CRA). This review discusses current approaches used by other regulatory authoritative bodies for CRA and independently examines the available scientific literature on these select o-phthalates to assess trends in toxicity outcomes from oral exposures, mode(s) of action (MOA), physicochemical properties, and toxicokinetic profiles. 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 these o-phthalates and determine Ortho(o)-phthalates are commonly studied plasticizers that have applications across numerous industries such as construction, automotive and consumer goods, including select uses in food packaging and other food contact materials. In this review, we surveyed the published literature on eight o-phthalates that currently have authorized food contact uses in the United States (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)) to comparatively assess their physicochemical, toxicokinetic and toxicodynamic properties in order to determine whether they should be considered chemically and/or pharmacologically related (CPR) for the purposes of a cumulative risk assessment (CRA). This review discusses current approaches used by other regulatory authoritative bodies for CRA and independently examines the available scientific literature on these select o-phthalates to assess trends in toxicity outcomes from oral exposures, mode(s) of action (MOA), physicochemical properties, and toxicokinetic profiles. 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 these o-phthalates and determine Our results support grouping DEHP, DCHP, DIOP and DINP as CPR substances . \scientifically supportable inclusion or exclusion criteria for CPR classification of the evaluated o-phthalates. Our results support grouping DEHP, DCHP, DIOP and DINP as CPR substances Ortho(o)-phthalates are commonly studied plasticizers that have applications across numerous industries such as construction, automotive and consumer goods, including select uses in food packaging and other food contact materials. In this review, we surveyed the published literature on eight o-phthalates that currently have authorized food contact uses in the United States (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)) to comparatively assess their physicochemical, toxicokinetic and toxicodynamic properties in order to determine whether they should be considered chemically and/or pharmacologically related (CPR) for the purposes of a cumulative risk assessment (CRA). This review discusses current approaches used by other regulatory authoritative bodies for CRA and independently examines the available scientific literature on these select o-phthalates to assess trends in toxicity outcomes from oral exposures, mode(s) of action (MOA), physicochemical properties, and toxicokinetic profiles. Discussions include the use of weight of evidence and new approach methodologies (NAMs) based on The Center for Food Safety has been urging the FDA for more than 10 years to better regulate orthophthalates, We are glad to see The Center for Food Safety has urged FDA to regulate orthothphalates for 10 yrs. FDA is now starting to use predictive modeling to fill in the data gaps for some of these o-phthalates and determine scientifically supportable inclusion or exclusion criteria. We commend the FDA conclusion that the results support grouping DEHP, DCHP, DIOP and DINP as CPR substances. for the purposes of a future CRA. for the purposes of a future CRA.