Genotoxicity and subchronic toxicity studies of supercritical carbon dioxide and acetone extracts of rosemary
| Autor: | Dayna Lozon, Kirt R. Phipps, Nigel Baldwin |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
Male
food.ingredient Antioxidant medicine.medical_treatment 010501 environmental sciences Toxicology medicine.disease_cause 030226 pharmacology & pharmacy 01 natural sciences Carnosol Ames test Acetone 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine food medicine Animals Food science Enzyme inducer 0105 earth and related environmental sciences No-Observed-Adverse-Effect Level biology Chemistry Mutagenicity Tests Plant Extracts Food additive Toxicity Tests Subchronic Carnosic acid General Medicine CYP2E1 Carbon Dioxide Rosmarinus Diet Rats Liver biology.protein Solvents Female Chemical and Drug Induced Liver Injury Genotoxicity |
| Zdroj: | Regulatory toxicology and pharmacology : RTP. 119 |
| ISSN: | 1096-0295 |
| Popis: | Toxicology studies conducted with oil-soluble rosemary extracts to support authorization as a food additive (antioxidant) in the EU include an Ames test using a supercritical carbon dioxide extract (D74), a full 90-day study using D74 and an acetone extract (F62), and an investigative 90-day study with a 28-day recovery period (using D74 only). D74 was non-mutagenic in the Ames test. In the full 90-day study, where rats (20/sex/group) were either provided control diet or diets containing D74 (300, 600, or 2400 mg/kg) or F62 (3800 mg/kg), liver enlargement and hepatocellular hypertrophy were observed. To determine a mode of action and assess the reversibility of the hepatic effects, an investigative 90-day study was conducted using female rats (10/group receiving control diet or diet containing 2400 mg/kg D74). Liver enlargement was fully reversible after 28 days and microsomal enzyme analysis revealed reversible induction of cytochrome P450 enzymes (CYP2A1, CYP2A2, CYP2C11, CYP2E1, and CYP4A), demonstrating that the hepatic effects were adaptive and of no toxicological concern. Therefore, the highest dietary concentrations were established as the NOAELs. The investigative 90-day study NOAEL (providing 64 mg/kg bw/day carnosol and carnosic acid [the primary antioxidant components]) was used to establish a temporary ADI for rosemary extracts. |
| Databáze: | OpenAIRE |
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