The Toxicity Profile of Hydrolyzed Aqueous Olive Pulp Extract

The toxicity profile of HIDROX™ (Hydrolyzed Aqueous Olive Pulp Extract; OPE) was characterized in a series of toxicology studies. A limit dosage of 2000 mg kg produced no toxicity in mice (acute oral NOAEL: 2000 mg kg). In rats, an acute oral NOAEL of 2000 mg kg was established, based on reductions...

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Published in:Drug and chemical toxicology (New York, N.Y. 1978) N.Y. 1978), 2004-01, Vol.27 (4), p.309-330
Main Authors: Christian, Mildred S., Sharper, Valerie A., Hoberman, Alan M., Seng, John E., Fu, LiJie, Covell, Donna, Diener, Robert M., Bitler, Catherine M., Crea, Roberto
Format: Article
Language:English
Subjects:
Abnormalities, Drug-Induced
Administration, Oral
Animals
Biological and medical sciences
Dose-Response Relationship, Drug
Female
Fetus - drug effects
Food toxicology
HIDROX
Hydrolysis
Male
Medical sciences
Mice
Mutagenicity Tests
No-Observed-Adverse-Effect Level
Olea
Olive pulp extract
Plant Extracts - toxicity
Pregnancy
Rats
Rats, Sprague-Dawley
Reproduction - drug effects
Toxicity profile
Toxicology
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Summary:The toxicity profile of HIDROX™ (Hydrolyzed Aqueous Olive Pulp Extract; OPE) was characterized in a series of toxicology studies. A limit dosage of 2000 mg kg produced no toxicity in mice (acute oral NOAEL: 2000 mg kg). In rats, an acute oral NOAEL of 2000 mg kg was established, based on reductions in weight gains in both sexes at 5000 mg kg. Reduced gains in female rats at 1500 and 2000 mg kg were not significantly different from control values. Daily oral dosages of 1000, 1500 and 2000 mg kg day for 90 days produced small decreases in body weight gains at 2000 mg kg day in the male rats and in all groups of female rats. Feed consumption was comparable to controls. There were no adverse clinical, hematologic, biochemical, organ weight or gross necropsy effects. Focal, minimal or mild hyperplasia of the mucosal squamous epithelium of the limiting ridge of the forestomach occurred in some rats at 2000 mg kg day; this change was attributed to local irritation by repeated intubation of large volumes of viscous, granular dosing suspension. A NOAEL of 2000 mg kg day was established for the 90-day study, based on the lack of significant adverse effects. Toxicokinetic data indicated that hydroxytyrosol (HT, the major component of OPE) was rapidly absorbed. Mean concentrations were measurable through 1 to 4 hours (tlast) at 1000 and 1500 mg kg day and through 8 hours at 2000 mg kg day. Dosages of OPE ranging from 500 to 2000 mg kg day did not adversely affect any of the mating, fertility, delivery or litter parameters investigated in an oral rat dosage-range reproduction study. Adverse effects were also absent in a rat developmental toxicity study in which pregnant dams were treated with 1000, 1500 or 2000 mg kg day on days 6 through 20 of gestation. Plasma levels for pregnant and lactating rats were comparable to non-pregnant rats; minimal levels crossed the placenta. Quantifiable levels were not identified in maternal milk or plasma from nursing pups. A bacterial reverse mutation and a CHO chromosome aberration assay revealed evidence of mutagenic activity at high dosages with S9 metabolic activation. However, three rat micronucleus evaluations performed after single and repeated (28-day) dosages of up to 2000 mg kg day and dosages of 5000 mg kg day for 29 days resulted in negative findings; therefore, OPE was not considered to be mutagenic in this in vivo assay.
ISSN:0148-0545
1525-6014
DOI:10.1081/DCT-200039714