title: Review of genotoxicity and rat carcinogenicity investigations with astaxanthin.
abstract: Synthetic astaxanthin has been extensively tested for safety. Genotoxicity studies including Ames and in vitro Micronucleus Tests show absence of genotoxic potential. Although a long-term mouse study showed no carcinogenicity potential, the rat carcinogenicity study with dietary dosages of 0 (control), 0 (placebo beadlet), 40, 200 and 1000 mg astaxanthin/kg bw/day showed an increased incidence of benign, hepatocellular adenoma in females only, at 200 mg/kg bw/day and above. There was no clear evidence of toxicity during the in-life phase. Discoloration of feces was observed and a reduction in body weight gain in all groups receiving beadlets, probably reflecting a nutritional influence. Blood sampling confirmed systemic exposure and some minor clinical chemistry differences in females at 200 and 1000 mg/kg bw/day. There was no effect on adjusted liver weight. Histopathological examination showed hepatic changes indicative of slight hepatotoxicity and hepatocyte regeneration in females at 200 and 1000 mg/kg bw/day, in addition to the adenoma. Taking into account this pathological background in the female rat, and a wide variety of other supporting information, it is concluded that the hepatocellular adenoma in female rats was secondary to hepatotoxicity and regeneration, and is most probably a species-specific phenomenon of doubtful human relevance.
authors.affiliation: NIC-RD/HN Toxicology and Kinetics, DSM Nutritional Products Ltd., Wurmisweg 576, 4303 Kaiseraugst, Switzerland. Electronic address: james-a.edwards@dsm.com.
authors.forename: James A
authors.initials: JA
authors.lastname: Edwards
authors.affiliation: NIC-RD/HN Toxicology and Kinetics, DSM Nutritional Products Ltd., Wurmisweg 576, 4303 Kaiseraugst, Switzerland. Electronic address: phillip.bellion@dsm.com.
authors.forename: Phillip
authors.initials: P
authors.lastname: Bellion
authors.affiliation: NIC-RD/HN Toxicology and Kinetics, DSM Nutritional Products Ltd., Wurmisweg 576, 4303 Kaiseraugst, Switzerland. Electronic address: paul.beilstein@dsm.com.
authors.forename: Paul
authors.initials: P
authors.lastname: Beilstein
authors.affiliation: NIC-RD/HN Toxicology and Kinetics, DSM Nutritional Products Ltd., Wurmisweg 576, 4303 Kaiseraugst, Switzerland. Electronic address: robert.ruembeli@dsm.com.
authors.forename: Robert
authors.initials: R
authors.lastname: Rümbeli
authors.affiliation: Analytical Research Centre, DSM Nutritional Products Ltd., Wurmisweg 576, 4303 Kaiseraugst, Switzerland. Electronic address: joseph.schierle@dsm.com.
authors.forename: Joseph
authors.initials: J
authors.lastname: Schierle
mesh_terms: D018248:Adenoma, Liver Cell / Q000139:chemically induced; D000818:Animals; D015197:Carcinogenicity Tests; D005260:Female; D008297:Male; D051379:Mice; D009152:Mutagenicity Tests; D051381:Rats; D012737:Sex Factors; D013045:Species Specificity; D024341:Xanthophylls / Q000633:toxicity
chemical_list: D024341:Xanthophylls; C005948:astaxanthine
keywords: Ames test; Astaxanthin; Carcinogenicity; Clastogenicity; Genotoxicity; Hepatocellular adenoma; Hepatotoxicity; Micronucleus test; Mutagenicity; Rat