{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T20:27:13Z","timestamp":1786998433419,"version":"build-2736575974"},"reference-count":45,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2020,8,1]],"date-time":"2020-08-01T00:00:00Z","timestamp":1596240000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2020,8,1]],"date-time":"2020-08-01T00:00:00Z","timestamp":1596240000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"}],"funder":[{"DOI":"10.13039\/501100010203","name":"Agriculture Research System of China","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100010203","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004731","name":"Natural Science Foundation of Zhejiang Province","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004731","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Regulatory Toxicology and Pharmacology"],"published-print":{"date-parts":[[2020,8]]},"DOI":"10.1016\/j.yrtph.2020.104695","type":"journal-article","created":{"date-parts":[[2020,6,5]],"date-time":"2020-06-05T04:11:06Z","timestamp":1591330266000},"page":"104695","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":39,"special_numbering":"C","title":["Safety assessment of astaxanthin from Haematococcus pluvialis: Acute toxicity, genotoxicity, distribution and repeat-dose toxicity studies in gestation mice"],"prefix":"10.1016","volume":"115","author":[{"given":"Tingting","family":"Niu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiawei","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feng","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rongrong","family":"Xuan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juanjuan","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haimin","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"issue":"13","key":"10.1016\/j.yrtph.2020.104695_bib1","doi-asserted-by":"crossref","first-page":"1917","DOI":"10.1001\/jama.1988.03410130125037","article-title":"Low-density lipoprotein subclass patterns and risk of myocardial infarction","volume":"260","author":"Austin","year":"1988","journal-title":"J. Am. Med. Assoc."},{"issue":"8","key":"10.1016\/j.yrtph.2020.104695_bib2","doi-asserted-by":"crossref","DOI":"10.3390\/antiox8080259","article-title":"Do we utilize our knowledge of the skin protective effects of carotenoids enough?","volume":"8","author":"Balic","year":"2019","journal-title":"Antioxidants"},{"key":"10.1016\/j.yrtph.2020.104695_bib3","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1016\/j.fct.2015.04.017","article-title":"Safety assessment of [3S, 3'S]-astaxanthin--Subchronic toxicity study in rats","volume":"81","author":"Buesen","year":"2015","journal-title":"Food Chem. Toxicol."},{"issue":"4","key":"10.1016\/j.yrtph.2020.104695_bib4","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1007\/s13749-013-0051-5","article-title":"Synthetic astaxanthin is significantly inferior to algal-based astaxanthin as an antioxidant and may not be suitable as a human nutraceutical supplement","volume":"12","author":"Capelli","year":"2013","journal-title":"Nutrafoods"},{"issue":"9","key":"10.1016\/j.yrtph.2020.104695_bib5","doi-asserted-by":"crossref","first-page":"899","DOI":"10.1007\/s40618-016-0607-5","article-title":"Gestational diabetes mellitus: an updated overview","volume":"40","author":"Chiefari","year":"2017","journal-title":"J. Endocrinol. Invest."},{"issue":"4","key":"10.1016\/j.yrtph.2020.104695_bib6","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1007\/s11130-011-0258-9","article-title":"Positive effects of astaxanthin on lipid profiles and oxidative stress in overweight subjects","volume":"66","author":"Choi","year":"2011","journal-title":"Plant Foods Hum. Nutr."},{"issue":"2","key":"10.1016\/j.yrtph.2020.104695_bib7","doi-asserted-by":"crossref","first-page":"220","DOI":"10.1017\/S0007114510003454","article-title":"Pharmacokinetics and first-pass metabolism of astaxanthin in rats","volume":"105","author":"Choi","year":"2011","journal-title":"Br. J. Nutr."},{"issue":"12","key":"10.1016\/j.yrtph.2020.104695_bib8","doi-asserted-by":"crossref","first-page":"2600","DOI":"10.1080\/10408398.2015.1063477","article-title":"Marine carotenoids: bioactivities and potential benefits to human health","volume":"57","author":"Chuyen","year":"2017","journal-title":"Crit. Rev. Food Sci. Nutr."},{"key":"10.1016\/j.yrtph.2020.104695_bib9","doi-asserted-by":"crossref","first-page":"782137","DOI":"10.1155\/2013\/782137","article-title":"Dietary intake of carotenoids and their antioxidant and anti-inflammatory effects in cardiovascular care","volume":"2013","author":"Ciccone","year":"2013","journal-title":"Mediat. Inflamm."},{"issue":"1\u20133","key":"10.1016\/j.yrtph.2020.104695_bib10","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1016\/j.cca.2004.09.011","article-title":"Plasma appearance of unesterified astaxanthin geometrical E\/Z and optical R\/S isomers in men given single doses of a mixture of optical 3 and 3'R\/S isomers of astaxanthin fatty acyl diesters","volume":"139","author":"Coral-Hinostroza","year":"2004","journal-title":"Comp. Biochem. Physiol. C Toxicol. Pharmacol."},{"issue":"2","key":"10.1016\/j.yrtph.2020.104695_bib11","doi-asserted-by":"crossref","first-page":"e77","DOI":"10.1016\/j.wombi.2017.08.128","article-title":"Folic acid supplement use and the risk of gestational hypertension and preeclampsia","volume":"31","author":"De Ocampo","year":"2018","journal-title":"Women Birth"},{"key":"10.1016\/j.yrtph.2020.104695_bib12","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1016\/j.yrtph.2015.12.009","article-title":"Review of genotoxicity and rat carcinogenicity investigations with astaxanthin","volume":"75","author":"Edwards","year":"2016","journal-title":"Regul. Toxicol. Pharmacol."},{"issue":"14","key":"10.1016\/j.yrtph.2020.104695_bib13","doi-asserted-by":"crossref","DOI":"10.3390\/molecules24142640","article-title":"The neuroprotective effects of astaxanthin: therapeutic targets and clinical perspective","volume":"24","author":"Fakhri","year":"2019","journal-title":"Molecules"},{"issue":"1","key":"10.1016\/j.yrtph.2020.104695_bib15","doi-asserted-by":"crossref","first-page":"49","DOI":"10.3109\/00498259609046688","article-title":"Effects of canthaxanthin, astaxanthin, lycopene and lutein on liver xenobiotic-metabolizing enzymes in the rat","volume":"26","author":"Gradelet","year":"1996","journal-title":"Xenobiotica"},{"issue":"4","key":"10.1016\/j.yrtph.2020.104695_bib16","doi-asserted-by":"crossref","first-page":"15","DOI":"10.3793\/jaam.6.15","article-title":"Efficacy and safety of eight-week treatment with astaxanthin in individuals screened for increased oxidative stress burden","volume":"6","author":"Iwabayashi","year":"2009","journal-title":"Anti-Aging Medicine"},{"issue":"3","key":"10.1016\/j.yrtph.2020.104695_bib17","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1017\/S0007114599000434","article-title":"Effect of dietary supplementation with carotenoids on xenobiotic metabolizing enzymes in the liver, lung, kidney and small intestine of the rat","volume":"81","author":"Jewell","year":"1999","journal-title":"Br. J. Nutr"},{"issue":"6","key":"10.1016\/j.yrtph.2020.104695_bib18","doi-asserted-by":"crossref","first-page":"1041","DOI":"10.1590\/S1415-52732010000600010","article-title":"Astaxanthin: structural and functional aspects","volume":"23","author":"Juc\u00e1","year":"2010","journal-title":"Rev. Nutr."},{"key":"10.1016\/j.yrtph.2020.104695_bib19","doi-asserted-by":"crossref","first-page":"582","DOI":"10.1016\/j.toxrep.2014.08.008","article-title":"A sub-chronic toxicity evaluation of a natural astaxanthin-rich carotenoid extract of Paracoccus carotinifaciens in rats","volume":"1","author":"Katsumata","year":"2014","journal-title":"Toxicol Rep"},{"issue":"2","key":"10.1016\/j.yrtph.2020.104695_bib20","doi-asserted-by":"crossref","first-page":"211","DOI":"10.14310\/horm.2002.1582","article-title":"Pregnancy-Induced hypertension","volume":"14","author":"Kintiraki","year":"2015","journal-title":"Hormones (Basel)"},{"issue":"2","key":"10.1016\/j.yrtph.2020.104695_bib21","first-page":"161","article-title":"Evaluation of antioxidant, hypolipidemic, and antiatherogenic property of lycopene and astaxanthin in atherosclerosis-induced rats","volume":"9","author":"Kumar","year":"2017","journal-title":"Pharmacogn. Res."},{"issue":"24","key":"10.1016\/j.yrtph.2020.104695_bib22","doi-asserted-by":"crossref","first-page":"1955","DOI":"10.1001\/jama.279.24.1955","article-title":"Fasting insulin and apolipoprotein B levels and low-density lipoprotein particle size as risk factors for ischemic heart disease","volume":"279","author":"Lamarche","year":"1998","journal-title":"J. Am. Med. Assoc."},{"key":"10.1016\/j.yrtph.2020.104695_bib23","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1016\/j.biochi.2019.09.012","article-title":"Microalgal carotenoids and phytosterols regulate biochemical mechanisms involved in human health and disease prevention","volume":"167","author":"Le Goff","year":"2019","journal-title":"Biochimie"},{"issue":"1\u20132","key":"10.1016\/j.yrtph.2020.104695_bib24","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1007\/s11120-010-9583-3","article-title":"Secondary ketocarotenoid astaxanthin biosynthesis in algae: a multifunctional response to stress","volume":"106","author":"Lemoine","year":"2010","journal-title":"Photosynth. Res."},{"key":"10.1016\/j.yrtph.2020.104695_bib25","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1016\/j.yrtph.2017.05.003","article-title":"Safety assessment of astaxanthin derived from engineered Escherichia coli K-12 using a 13-week repeated dose oral toxicity study and a prenatal developmental toxicity study in rats","volume":"87","author":"Lin","year":"2017","journal-title":"Regul. Toxicol. Pharmacol."},{"issue":"2","key":"10.1016\/j.yrtph.2020.104695_bib26","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1016\/j.ogc.2017.02.002","article-title":"Gestational diabetes: diagnosis, classification, and clinical care","volume":"44","author":"Mack","year":"2017","journal-title":"Obstet. Gynecol. Clin. N. Am."},{"issue":"4","key":"10.1016\/j.yrtph.2020.104695_bib27","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1016\/S0928-0987(03)00135-0","article-title":"Oral bioavailability of the antioxidant astaxanthin in humans is enhanced by incorporation of lipid based formulations","volume":"19","author":"Mercke Odeberg","year":"2003","journal-title":"Eur. J. Pharmaceut. Sci."},{"issue":"6","key":"10.1016\/j.yrtph.2020.104695_bib28","doi-asserted-by":"crossref","first-page":"1551","DOI":"10.1021\/acs.jafc.7b05493","article-title":"Astaxanthin induces the Nrf2\/HO-1 antioxidant pathway in human umbilical vein endothelial cells by generating trace amounts of ROS","volume":"66","author":"Niu","year":"2018","journal-title":"J. Agric. Food Chem."},{"key":"10.1016\/j.yrtph.2020.104695_bib29","first-page":"1","article-title":"Opinion of the scientific panel on additives and products or substances used in animal feed on the request from the European commission on the safety of use of colouring agents in animal nutrition PART I. General principles and astaxanthin","volume":"291","year":"2005","journal-title":"The EFSA Journal"},{"issue":"10","key":"10.1016\/j.yrtph.2020.104695_bib30","doi-asserted-by":"crossref","first-page":"482","DOI":"10.1016\/S0955-2863(00)00104-2","article-title":"Plasma appearance and distribution of astaxanthin E\/Z and R\/S isomers in plasma lipoproteins of men after single dose administration of astaxanthin","volume":"11","author":"\u00d8sterlie","year":"2000","journal-title":"J. Nutr. Biochem."},{"key":"10.1016\/j.yrtph.2020.104695_bib31","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1186\/1743-7075-7-52","article-title":"Astaxanthin uptake in domestic dogs and cats","volume":"7","author":"Park","year":"2010","journal-title":"Nutr. Metab."},{"issue":"1","key":"10.1016\/j.yrtph.2020.104695_bib32","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/0165-1161(75)90058-8","article-title":"The micronucleus test","volume":"31","author":"Schmid","year":"1975","journal-title":"Mutat. Res."},{"key":"10.1016\/j.yrtph.2020.104695_bib33","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1016\/j.fct.2016.02.001","article-title":"A developmental toxicity study of 3S, 3'S-Astaxanthin in New Zealand white rabbits","volume":"90","author":"Schneider","year":"2016","journal-title":"Food Chem. Toxicol."},{"issue":"3","key":"10.1016\/j.yrtph.2020.104695_bib34","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1016\/j.cca.2003.12.006","article-title":"Plasma appearance and tissue accumulation of non-esterified, free astaxanthin in C57BL\/6 mice after oral dosing of a disodium disuccinate diester of astaxanthin (Heptax)","volume":"137","author":"Showalter","year":"2004","journal-title":"Comp. Biochem. Physiol. C Toxicol. Pharmacol."},{"key":"10.1016\/j.yrtph.2020.104695_bib35","first-page":"1","article-title":"Protective effects of astaxanthin on skin: recent scientific evidence, possible mechanisms, and potential indications","volume":"1","author":"Singh","year":"2019","journal-title":"J. Cosmet. Dermatol."},{"issue":"9","key":"10.1016\/j.yrtph.2020.104695_bib36","doi-asserted-by":"crossref","first-page":"3030","DOI":"10.1016\/j.fct.2008.05.038","article-title":"Safety assessment of astaxanthin-rich microalgae biomass: acute and subchronic toxicity studies in rats","volume":"46","author":"Stewart","year":"2008","journal-title":"Food Chem. Toxicol."},{"issue":"3","key":"10.1016\/j.yrtph.2020.104695_bib37","doi-asserted-by":"crossref","first-page":"373","DOI":"10.2131\/jts.39.373","article-title":"Genotoxicity and subacute toxicity studies of a new astaxanthin-containing Phaffia rhodozyma extract","volume":"39","author":"Tago","year":"2014","journal-title":"J. Toxicol. Sci."},{"key":"10.1016\/j.yrtph.2020.104695_bib38","first-page":"867","article-title":"Toxicological studies of astaxanthin from haematococcus pluvialis-Ames test, oral single dose and 90-days subchronic toxicity studies in rats","volume":"20","author":"Takahashi","year":"2005","journal-title":"J. Clin. Therap. Med."},{"issue":"3","key":"10.1016\/j.yrtph.2020.104695_bib39","doi-asserted-by":"crossref","first-page":"398","DOI":"10.1016\/j.cbi.2009.03.017","article-title":"Intervention of astaxanthin against cyclophosphamide-induced oxidative stress and DNA damage: a study in mice","volume":"180","author":"Tripathi","year":"2009","journal-title":"Chem. Biol. Interact."},{"issue":"3","key":"10.1016\/j.yrtph.2020.104695_bib40","doi-asserted-by":"crossref","first-page":"819","DOI":"10.1016\/j.yrtph.2015.10.013","article-title":"Subchronic (13-week) toxicity and prenatal developmental toxicity studies of dietary astaxanthin in rats","volume":"73","author":"Vega","year":"2015","journal-title":"Regul. Toxicol. Pharmacol."},{"issue":"1","key":"10.1016\/j.yrtph.2020.104695_bib41","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1039\/C6FO01721E","article-title":"Astaxanthin in cardiovascular health and disease: mechanisms of action, therapeutic merits, and knowledge gaps","volume":"8","author":"Visioli","year":"2017","journal-title":"Food Funct"},{"key":"10.1016\/j.yrtph.2020.104695_bib42","series-title":"Study of Astaxanthin Esters on Improving Chronic Inflammation Effects and Mechanism of Insulin Resistance Mice","author":"Wang","year":"2015"},{"issue":"9","key":"10.1016\/j.yrtph.2020.104695_bib43","doi-asserted-by":"crossref","first-page":"5750","DOI":"10.3390\/md13095750","article-title":"Astaxanthin as a potential neuroprotective agent for neurological diseases","volume":"13","author":"Wu","year":"2015","journal-title":"Mar. Drugs"},{"issue":"3","key":"10.1016\/j.yrtph.2020.104695_bib44","doi-asserted-by":"crossref","first-page":"2697","DOI":"10.3892\/mmr.2016.5569","article-title":"Astaxanthin blocks preeclampsia progression by suppressing oxidative stress and inflammation","volume":"14","author":"Xuan","year":"2016","journal-title":"Mol. Med. Rep."},{"issue":"7","key":"10.1016\/j.yrtph.2020.104695_bib45","doi-asserted-by":"crossref","first-page":"4310","DOI":"10.3390\/md13074310","article-title":"Multiple mechanisms of anti-cancer effects exerted by astaxanthin","volume":"13","author":"Zhang","year":"2015","journal-title":"Mar. Drugs"},{"issue":"3","key":"10.1016\/j.yrtph.2020.104695_bib46","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1039\/c3fo60607d","article-title":"Microalgal carotenoids: beneficial effects and potential in human health","volume":"5","author":"Zhang","year":"2014","journal-title":"Food Funct"}],"container-title":["Regulatory Toxicology and Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0273230020301215?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0273230020301215?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,10,3]],"date-time":"2025-10-03T12:30:08Z","timestamp":1759494608000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0273230020301215"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,8]]},"references-count":45,"alternative-id":["S0273230020301215"],"URL":"https:\/\/doi.org\/10.1016\/j.yrtph.2020.104695","relation":{},"ISSN":["0273-2300"],"issn-type":[{"value":"0273-2300","type":"print"}],"subject":[],"published":{"date-parts":[[2020,8]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Safety assessment of astaxanthin from Haematococcus pluvialis: Acute toxicity, genotoxicity, distribution and repeat-dose toxicity studies in gestation mice","name":"articletitle","label":"Article Title"},{"value":"Regulatory Toxicology and Pharmacology","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.yrtph.2020.104695","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2020 Elsevier Inc. All rights reserved.","name":"copyright","label":"Copyright"}],"article-number":"104695"}}