title: Safety assessment of a natural tomato oleoresin containing high amounts of Z-isomers of lycopene prepared with supercritical carbon dioxide.
abstract: BACKGROUND
  Z-isomers of lycopene, which are abundantly present in processed tomato products, are more bioavailable than (all-E)-lycopene found predominantly in raw tomatoes. Despite extensive studies on the bioavailability and biological activities of Z-isomers of lycopene, detailed studies on their safety and toxicology are limited.
  
  
  RESULTS
  The geno-, acute and subacute toxicities of tomato oleoresin that contained high amounts of lycopene Z-isomers (10.9% lycopene with 66.3% Z-isomer content) and had been prepared with supercritical carbon dioxide were investigated. The oleoresin was non-mutagenic in the Ames test with and without metabolic activation (S9 mix). The medial lethal dose (LD50) of the oleoresin in rats, as determined by a single-dose oral test, was more than 5000 mg kg body weight-1(bw) [361 mg (Z)-lycopene kg bw-1]. In the 4-week repeated-dose oral toxicity test, rats were administered oleoresin at 4500 mg kg-1day-1[325 mg (Z)-lycopene kg bw-1day-1]. There were no clinically significant changes with respect to vital signs, physical examination outcomes and laboratory test values during the test period.
  
  
  CONCLUSIONS
  Based on our findings and as supported by its long history of consumption, tomato oleoresin that contains high amounts of Z-isomers of lycopene prepared with supercritical carbon dioxide can be considered as safe for human consumption. © 2016 Society of Chemical Industry.
authors.affiliation: Research & Development Division, Kagome Company, Limited, Nishitomiyama, Nasushiobara, 329-2762, Japan.
authors.forename: Masaki
authors.initials: M
authors.lastname: Honda
authors.affiliation: Research & Development Division, Kagome Company, Limited, Nishitomiyama, Nasushiobara, 329-2762, Japan.
authors.forename: Takuma
authors.initials: T
authors.lastname: Higashiura
authors.affiliation: Research & Development Division, Kagome Company, Limited, Nishitomiyama, Nasushiobara, 329-2762, Japan.
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Fukaya
mesh_terms: D000818:Animals; D002245:Carbon Dioxide / Q000737:chemistry; D002338:Carotenoids / Q000009:adverse effects* / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism; D025924:Chromatography, Supercritical Fluid; D019587:Dietary Supplements / Q000009:adverse effects*; D005260:Female; D005503:Food Additives / Q000009:adverse effects* / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism; D005511:Food Handling; D005638:Fruit / Q000737:chemistry*; D007928:Lethal Dose 50; D000077276:Lycopene; D018551:Solanum lycopersicum / Q000737:chemistry*; D008297:Male; D008862:Microsomes, Liver / Q000201:enzymology / Q000378:metabolism; D009152:Mutagenicity Tests; D010936:Plant Extracts / Q000009:adverse effects* / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013237:Stereoisomerism; D023382:Toxicity Tests, Acute; D059551:Toxicity Tests, Subacute
chemical_list: D005503:Food Additives; D010936:Plant Extracts; C018620:oleoresins; D002245:Carbon Dioxide; D002338:Carotenoids; D000077276:Lycopene
keywords: 4-week repeated-dose oral toxicity test; Z-isomers of lycopene; acute oral toxicity test; bacterial reverse mutation assay; supercritical carbon dioxide; tomato