Safety evaluation of pectin-derived acidic oligosaccharides (pAOS): genotoxicity and sub-chronic studies.
Pectin-derived acidic oligosaccharides (pAOS) are non-digestible carbohydrates to be used in infant formulae and medical nutrition. To support its safety, the genotoxic potential of pAOS was evaluated. pAOS was not mutagenic in the Ames test. Positive results were obtained in the chromosome aberration test only at highly cytotoxic concentrations. The effects obtained in the mouse lymphoma test were equivocal; pAOS was not mutagenic in vivo. A sub-chronic dietary study, preceded by 4-week parental and in utero exposure phase, investigated general safety. Administration of pAOS did not affect parental health nor pup characteristics. No effects specific for acidic oligosaccharides were observed in the subsequent sub-chronic study. Slight diffuse hyperplasia of epithelial layer of the urinary bladder was noted to result from concurrently elevated urinary sodium, due to high sodium in pAOS, and elevated urinary pH. This phenomenon was confirmed in a mechanistic (sub-chronic) study. In contrast, in rats fed pAOS in combination with NH(4)Cl, an acidifying agent, the induced low urinary pH completely prevented the development of urothelial hyperplasia. Hyperplasia induced by this mechanism in rats is considered not relevant to man. Based on the current knowledge we consider pAOS safe for human consumption under its intended use.
Garthoff
Jossie A
JA
Danone Research, Centre for Specialised Nutrition, Department Product Safety, Wageningen, The Netherlands. jossie.garthoff@danone.com
Heemskerk
Suzanne
S
Hempenius
Rixta A
RA
Lina
Ben A R
BA
Krul
Cyrille A M
CA
Koeman
Jan H
JH
Speijers
Gerrit J A
GJ
D000284:Administration, Oral; D000818:Animals; D000831:Animals, Newborn; D001835:Body Weight / Q000187:drug effects; D016466:CHO Cells; D045744:Cell Line, Tumor; D002869:Chromosome Aberrations / Q000139:chemically induced; D003257:Consumer Product Safety; D006224:Cricetinae; D003412:Cricetulus; D004305:Dose-Response Relationship, Drug; D004926:Escherichia coli / Q000187:drug effects / Q000235:genetics; D005260:Female; D041943:Infant Formula / Q000737:chemistry / Q000592:standards*; D007774:Lactation; D008297:Male; D018811:Maternal Exposure / Q000009:adverse effects; D051379:Mice; D008940:Mitotic Index; D009152:Mutagenicity Tests; D009844:Oligosaccharides / Q000737:chemistry / Q000302:isolation & purification / Q000633:toxicity*; D009929:Organ Size / Q000187:drug effects; D010368:Pectins / Q000737:chemistry*; D011247:Pregnancy; D051381:Rats; D017208:Rats, Wistar; D012486:Salmonella typhimurium / Q000187:drug effects / Q000235:genetics; D036401:Toxicity Tests, Chronic; D001743:Urinary Bladder / Q000187:drug effects / Q000473:pathology
D009844:Oligosaccharides; D010368:Pectins