Toxicological and pharmacokinetic properties of sucralose-6-acetate and its parent sucralose: in vitro screening assays
Susan S Schiffman 1,
Elizabeth H Scholl 2,
Terrence S Furey 3,
H Troy Nagle 1 4
Affiliations expand
Abstract
The purpose of this study was to determine the
toxicological and pharmacokinetic properties of sucralose-6-acetate, a structural analog of the artificial sweetener sucralose. Sucralose-6-acetate is an intermediate and impurity in the manufacture of sucralose, and recent commercial sucralose samples were found to contain up to 0.67% sucralose-6-acetate. Studies in a rodent model found that sucralose-6-acetate is also present in fecal samples with levels up to 10% relative to sucralose which suggest that sucralose is also acetylated in the intestines. A MultiFlow® assay, a high-throughput genotoxicity screening tool, and a micronucleus (MN) test that detects cytogenetic damage both indicated that sucralose-6-acetate is genotoxic. The mechanism of action was classified as clastogenic (produces DNA strand breaks) using the MultiFlow® assay. The amount of sucralose-6-acetate in a single daily sucralose-sweetened drink might far exceed the threshold of toxicological concern for genotoxicity (TTCgenotox) of 0.15 µg/person/day.
The RepliGut® System was employed to expose human intestinal epithelium to sucralose-6-acetate and sucralose, and an RNA-seq analysis was performed to determine gene expression induced by these exposures. Sucralose-6-acetate significantly increased the expression of genes associated with inflammation, oxidative stress, and cancer with greatest expression for the metallothionein 1 G gene (MT1G). Measurements of transepithelial electrical resistance (TEER) and permeability in human transverse colon epithelium indicated that sucralose-6-acetate and sucralose both impaired intestinal barrier integrity. Sucralose-6-acetate also inhibited two members of the cytochrome P450 family (CYP1A2 and CYP2C19). Overall, the toxicological and pharmacokinetic findings for sucralose-6-acetate raise significant health concerns regarding the safety and regulatory status of sucralose itself.
So NOT tested in an actual COMPLETE HUMAN GI tract. The test model used:
"The RepliGut® model is a unique, human stem cell-derived platform that recreates the intestinal epithelium in a continuous layer of stem and differentiated cells. RepliGut® system can be purchased as a kit, or our team of experts can provide the services you require."
So tested in an environment that is significantly different than the human gi tract. Off the top of my head: no bacterial cultures, no yeasts, no digestive juices/enzymes, no water and I'm sure other things I am missing.
Now this could make a HUGE difference, or it could not make any, OR it could be even worse in a human gut. We really should do more studies on this exact scenario. I would also like to see if the manufacturing process could be "purified" a little more to remove the compound in the starting product as the study ONLY showed it being converted in rats and not humans as of yet.