Neurotoxicity studies on sucralose and its hydrolysis products with special reference to histopathologic and ultrastructural changes.

ABSTRACT

Comparative neuropathological studies of 1,6-dichloro-1, 6-dideoxy-beta-D-fructofuranosyl-4-chloro-4-deoxy-alpha-D-galactopyra noside (sucralose), an equimolar mixture of 1,6-dichloro-1, 6-dideoxyfructose (1,6-DCF) and 4-chloro-4-deoxygalactose (4-CG), the hydrolysis products of sucralose, and 6-chloro-6-deoxyglucose (6-CG) were conducted in male and female mice and male marmoset monkeys, focusing on morphological changes in the central nervous system. 6-Chloro-6-deoxyglucose, previously reported to produce neurotoxic effects, served as the positive control and was administered by gavage at a daily dose of 500mg/kg. Sucralose and the sucralose hydrolysis products (sucralose-HP) were similarly administered to mice and marmosets at doses of up to 1000mg/kg for 21 and 28 days, respectively. No changes were detected in the central nervous system by light or electron microscopy in either of the species that received sucralose or its hydrolysis products. 6-Chloro-6-deoxyglucose, in contrast, induced symmetrical lesions in the deep nuclei of the cerebellum, brain stem and spinal cord with definitive neurological signs of CNS involvement.