title: Toxicological evaluation of an olive extract, H35: Subchronic toxicity in the rat.
abstract: The safety of olive extract H35 containing 35% hydroxytyrosol (HT) was tested in a 90-day oral gavage study in Wistar rats. H35 was administered at 0, 345, 691 and 1381 mg/kg bw/day, equivalent to 0, 125, 250 and 500 mg HT/kg bw/day. Reductions in terminal body weight (9%), and a statistically significant reduction in body weight gain (17%, P < 0.05) at week 13 were observed in high dose males, as well as a statistically significant increase in relative weights of the liver, heart, and kidneys of high dose males and females. These changes were not accompanied by pathological or clinical observations and a trend towards reversal was observed in the recovery phase. H35 was well-tolerated and no toxicologically significant treatment-related changes were observed in condition and appearance of rats, neurobehavioral outcomes, motor activity assessments, functional observational battery (FOB), food intake, ophthalmoscopic examinations, hematology, clinical chemistry, urinalysis, necropsy findings, sperm parameters or estrus cycle. The lowest observed adverse effect level (LOAEL) was the 500 mg HT/kg bw/day based on statistically significant reductions in body weight gain and decreased body weight in males. The no observed adverse effect level (NOAEL) was 250 mg HT/kg bw/day, equivalent to 691 mg/kg bw/day of H35 extract.
authors.affiliation: Exponent, Inc., 1150 Connecticut Ave. NW, Suite 1100, Washington, DC 20036, USA. Electronic address: jheilman@exponent.com.
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Heilman
authors.affiliation: Exponent, Inc., 1150 Connecticut Ave. NW, Suite 1100, Washington, DC 20036, USA.
authors.forename: Njwen
authors.initials: N
authors.lastname: Anyangwe
authors.affiliation: Exponent, Inc., 1150 Connecticut Ave. NW, Suite 1100, Washington, DC 20036, USA.
authors.forename: Nga
authors.initials: N
authors.lastname: Tran
authors.affiliation: DSM Nutritional Products AG, NIC-RD/HN Product Safety, Wurmisweg 576, CH-4303 Kaiseraugst, Switzerland.
authors.forename: James
authors.initials: J
authors.lastname: Edwards
authors.affiliation: DSM Nutritional Products AG, NIC-RD/HN Product Safety, Wurmisweg 576, CH-4303 Kaiseraugst, Switzerland.
authors.forename: Paul
authors.initials: P
authors.lastname: Beilstein
authors.affiliation: Probelte Biotecnologia S.L., Pol. Ind. El Tiro, C/Antonio Belmonte Abellàn 3-7, 30100 Murcia, Spain.
authors.forename: José
authors.initials: J
authors.lastname: López
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000009:adverse effects*; D000975:Antioxidants / Q000008:administration & dosage / Q000009:adverse effects* / Q000737:chemistry; D001522:Behavior, Animal; D019587:Dietary Supplements / Q000009:adverse effects* / Q000032:analysis; D002149:Energy Intake; D005260:Female; D005638:Fruit / Q000737:chemistry*; D006321:Heart / Q000254:growth & development; D007668:Kidney / Q000254:growth & development; D008099:Liver / Q000254:growth & development; D008297:Male; D031658:Olea / Q000737:chemistry*; D009929:Organ Size; D010626:Phenylethyl Alcohol / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives / Q000032:analysis / Q000097:blood; D010936:Plant Extracts / Q000008:administration & dosage / Q000009:adverse effects* / Q000737:chemistry; D011897:Random Allocation; D017208:Rats, Wistar; D059550:Toxicity Tests, Subchronic; D015430:Weight Gain
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D000975:Antioxidants; D010936:Plant Extracts; C005975:3,4-dihydroxyphenylethanol; D010626:Phenylethyl Alcohol
keywords: H35; Hydroxytyrosol; Olive extract; Olive phenolics