Juvenile toxicity study of Gossence™ (galactooligosaccharides) in Sprague Dawley rats

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Gossence™ (galactooligosaccharide; GOS) is a prebiotics and used as one of the major constituents in infant milk formulas that act as a functional food. Gossence is manufactured by Tata Chemicals Ltd, India, through a patented process of biotransformation of lactose. A toxicology study in juvenile rats was carried out to assess the safety profile of Gossence intended for pediatric population. The objective of this study is to assess the potential systemic toxicity of Gossence when administered through gavage at dose levels of 1000, 2000, or 5000/3000 mg/kg/day (equivalent to 1347, 2694, and 6735/4041 mg/kg/day of GOS, respectively) to juvenile Sprague Dawley rats from postnatal day (PND) 4 to PND 52 (i.e. total 49 days of dosing period). A separate group of animals were treated with vehicle (purified Milli Q water) for a similar duration. The following parameters were evaluated during the study period: morbidity/mortality check, clinical signs, body weights, body weight changes, food consumption, functional observational battery, motor activity, postnatal developmental observations, hematology, clinical chemistry, urinalysis, organ weight, gross pathology, and histopathology. During dosing phase, the high-dose group, 5000 mg/kg/day, was reduced to 3000 mg/kg/day (equivalent to 4041 mg/kg/day dose of GOS) from day 16 (PND 19) onward, due to clinical signs of watery feces and yellow color stains at urogenital region and mortality in two animals on day 15 (PND 18) of the study. Time-weighted average dose for 5000 mg/kg/day was equivalent to 3600 mg/kg/day. No further deaths or clinical signs were noticed in animals at 3000 mg/kg/day from day 18 (PND 21) of dosing phase to until terminal euthanization. At the terminal euthanization, there were no test item-related gross changes observed in all surviving rats except for, an increased cecum size in some of the rats at 5000/3000 mg/kg/day, which correlated with the increased weights of cecum with contents during organ weight recording, but this had no correlating light microscopic changes during histological examination. The cecal enlargement was completely recovered following the 14-day recovery period. The no-observedadverse-effect level is 3000 mg/kg/day for Gossence, which is equivalent to 4041 mg/kg/day of GOS in both sexes.