Safety assessment for octadecyl 3-(3,5-di-tert-butyl-4-hydroxyphenyl)-propionate (CAS Reg. No. 2082-79-3) from use in food contact applications.

Octadecyl 3-(3,5-di-tert-butyl-4-hydroxyphenyl)propionate (CAS Reg. No. 2082-79-3), currently marketed as Irganox 1076 (I-76), is a sterically hindered phenolic antioxidant used in a variety of organic substrates, including those used in the manufacture of food contact articles. In 2012, the US Food and Drug Administration (USFDA), Office of Food Additive Safety (OFAS), initiated a post-market re-evaluation of the food contact applications of I-76. This project aimed to ensure that current dietary exposures from the use of I-76 in food contact articles are accurately captured and the safety assessment considered all relevant and available toxicological information. To accomplish these aims, the USFDA reviewed the available toxicological studies and chemistry information on food contact applications of I-76. Based on this in-depth analysis, a NOAEL of 64 mg/kg-bw/d (female rats) from a chronic rat study and a cumulative estimated dietary intake (CEDI) of 4.5 mg/p/d, was used to calculate a margin of exposure (MOE) of ∼850. We concluded that the previous and current exposure levels provide an adequate margin of safety (MOS) and remain protective of human health for the regulated uses.

Contrasting copper-dioxygen chemistry arising from alike tridentate alkyltriamine copper(I) complexes.

Copper(I)-dioxygen interactions are of great interest due to their role in biological O2-processing as well as their importance in industrial oxidation processes. We describe here the study of systems which lead to new insights concerning the factors which govern Cu(II)-mu-eta2:eta2 (side-on) peroxo versus Cu(III)-bis-mu-oxo species formation. Drastic differences in O2-reactivity of Cu(I) complexes which differ only by a single -CH3 versus -H substituent on the central amine of the tridentate ligands employed are observed. [Cu(MeAN)]B(C6F5)4 (1) (MeAN = N,N,N',N',N'-pentamethyl-dipropylenetriamine) reacts with O2 at -80 degrees C to form almost exclusively the side-on peroxo complex [{CuII(MeAN)}2(O2)]2+ (3) in CH2Cl2, tetrahydrofuran, acetone, and diethyl ether solvents, as characterized by UV-vis and resonance Raman spectroscopies. In sharp contrast, [Cu(AN)]B(C6F5)4 (2) (AN = 3, 3'-iminobis(N,N-dimethyl-propylamine) can support either Cu2O2 structures in a strongly solvent-dependent manner. Extreme behavior is observed in CH2Cl2 solvent, where 1 reacts with O2 giving 3, while 2 forms exclusively the bis-mu-oxo species [{CuIII(AN)}2(O)2]2+ (4Oxo). Stopped-flow kinetics measurements also reveal significant variations in the oxygenation reactions of 1 versus 2, including the observations that 4Oxo forms much faster than does 3; the former decomposes quickly, while the latter is quite stable at 193 K. The solvent-dependence of the bis-mu-oxo versus side-on peroxo preference observed for 2 is opposite to that reported for other known copper(I) complexes; the factors which may be responsible for the unusual behavior of 1/O2 versus 2/O2 (possibly N-H hydrogen bonding in the AN chemistry) are suggested. The factors which affect bis-mu-oxo versus side-on peroxo formation continue to be of interest.