Zhang, Nan. Analytical, in vitro and in vivo metabolic studies of short chain cyclic polyester oligomers (lactones) from polyurethane laminating adhesives. Retrieved from https://doi.org/doi:10.7282/T3TT4SKG
DescriptionPolyurethane (PU) laminating adhesive for food packaging is often formulated with polyester polyol to impart soft chain segments for the material’s flexibility. Polyester polyol synthesis results in undesirable, low molecular weight cyclic oligomer by-products which are commonly observed in Food and Drug Administration (FDA) migration studies. Currently, only a few cyclic polyester migrants were identified and published, many other possible structures are still to be characterized. There is also a lack of information regarding the prevalence and toxicology of these migrants. From the migration study data reports of 518 industrial laminates, we were able to identify 23 new short chain cyclic polyesters and 4 linear chain esters from PU adhesives. A tabulated summary on the frequency of occurrence for all cyclic polyester migrants that we have identified so far reveals that diethylene glycol adipate cyclic diester (DEG-AA), diethylene glycol isophthalate cyclic diester (DEG-IPA), neopentyl glycol adipate cyclic diester (NPG-AA) and di-neopentyl glycol adipate cyclic diester (NPG-AA 2+2) to be the migrants for our initial metabolism studies. We hypothesize that the mammalian non-specific esterase would hydrolyze these cyclic oligomers into their corresponding monoester and monomer precursors. Our metabolism studies focused on the hydrolysis of cyclic oligomers with porcine liver esterase (PLE). We used a combination of GC-MS and GC-FID with trimethylsilyl derivatization methods for analysis. We also investigated the hydrolysis of cyclic oligomers with human liver S9 fraction, a complex enzyme system which is often used in the Ames test to assess a substance’s mutagenic potential. Finally, we collaborated with other labs to analyze for the in vivo metabolites of NPG-AA 2+2 from mouse plasma. The results show stepwise enzymatic conversion of cyclic oligomers to their open ring monoesters followed by the complete hydrolysis to monomers. Different types of cyclic polyester migrants showed different resistance to enzyme hydrolysis under the same test conditions. Experimental parameters such as substrate levels, incubation time, enzyme concentration and surfactant addition were found to influence the degree of hydrolysis. Also, NPG-AA 2+2 was found to rapidly and completely break down in mice. All of the information is useful for future safety assessment investigations.