title: Hydroxytyrosol: lack of clastogenicity in a bone marrow chromosome aberration study in rats.
abstract: BACKGROUND
  Hydroxytyrosol is naturally found in olives, olive oil and wine, and is consumed as part of a normal diet. The substance may have utility as a preservative in a wide variety of foods due to its antioxidant, antimicrobial and amphipathic properties. The potential for hydroxytyrosol to cause chromosome aberrations in vitro had been tested previously, with positive results at high concentrations. An OECD Guideline 475 study (mammalian bone marrow chromosome aberration test) was conducted in rats with the oral limit dose of 2000 mg/kg bw to determine whether hydroxytyrosol is a clastogen in vivo.
  
  
  RESULTS
  The oral limit dose of 2000 mg/kg hydroxytyrosol was well tolerated by most rats; however, some rats exhibited clinical signs that abated within 24 hours. Treatment with hydroxytyrosol did not significantly enhance the number of aberrant cells or the mitotic index 24 or 48 hours post-dose. The positive control (cyclophosphamide) induced the expected increase in chromosomal aberrations and a decrease in the mitotic index, confirming the validity of the assay.
  
  
  CONCLUSIONS
  An oral limit dose of 2000 mg/kg hydroxytyrosol does not induce chromosome aberrations in bone marrow cells of the rat. Accordingly, hydroxytyrosol is not a clastogen in vivo.
authors.forename: Laurie C
authors.initials: LC
authors.lastname: Dolan
authors.forename: Hana
authors.initials: H
authors.lastname: Hofman-Hüther
authors.affiliation: Wacker Chemie AG, Johannes-Hess-Str, 24, Burghausen 84489, Germany. Nicole.Amann@wacker.com.
authors.forename: Nicole
authors.initials: N
authors.lastname: Amann
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects; D001854:Bone Marrow Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D002869:Chromosome Aberrations / Q000187:drug effects; D003520:Cyclophosphamide / Q000633:toxicity; D005260:Female; D008297:Male; D008940:Mitotic Index; D009152:Mutagenicity Tests; D009153:Mutagens / Q000633:toxicity; D010626:Phenylethyl Alcohol / Q000031:analogs & derivatives* / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar
chemical_list: D000975:Antioxidants; D009153:Mutagens; C005975:3,4-dihydroxyphenylethanol; D003520:Cyclophosphamide; D010626:Phenylethyl Alcohol