{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T12:44:47Z","timestamp":1791809087969,"version":"4.3.4"},"reference-count":64,"publisher":"SAGE Publications","license":[{"start":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T00:00:00Z","timestamp":1789689600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T00:00:00Z","timestamp":1789689600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Int J Toxicol"],"abstract":"<jats:p>\n                    The preclinical safety of human-equivalent lactoferrin alpha (heqLF\u03b1; effera\n                    <jats:sup>\u00ae<\/jats:sup>\n                    ), produced by\n                    <jats:italic toggle=\"yes\">Komagataella phaffii<\/jats:italic>\n                    , was evaluated to support its use as a food ingredient in infant formula and products for young children. Genotoxicity was assessed using a bacterial reverse mutation (Ames) assay in five strains of\n                    <jats:italic toggle=\"yes\">Salmonella typhimurium<\/jats:italic>\n                    and\n                    <jats:italic toggle=\"yes\">Escherichia coli,<\/jats:italic>\n                    and an in vitro micronucleus assay in TK6 cells. Both studies followed OECD guidelines and were conducted up to the recommended limit concentrations (5000\u00a0\u00b5g\/plate and 2000\u00a0\u00b5g\/mL, respectively). A 14-day non-GLP juvenile dose range-finding study and a 13-week GLP juvenile rat toxicity study with a 4-week recovery phase were conducted under ICH S11 guidance. Neonatal Sprague-Dawley rats received heqLF\u03b1 at 0, 1500, 3000, or 5000\u00a0mg\/kg body weight\/day by twice-daily oral gavage from postnatal day 7 to 98. Bovine lactoferrin (bLF) and whey protein at 5000\u00a0mg\/kg body weight\/day served as reference controls. heqLF\u03b1 was non-mutagenic and non-clastogenic in both genotoxicity assays. In the 13-week juvenile rat study, no heqLF\u03b1-related mortality, clinical signs, developmental, neurobehavioral, or immune toxicity effects were observed. Minor, non-adverse renal findings consistent with high protein intake were observed and largely reversed during recovery. Clinical pathology parameters fully resolved during recovery. Toxicokinetic evaluation showed no systemic accumulation. Based on the absence of toxicologically relevant adverse findings, heqLF\u03b1 is well tolerated at doses up to 5000\u00a0mg\/kg body weight\/day, establishing a no observed adverse effect level (NOAEL) of 5000\u00a0mg\/kg\/day, the highest dose tested, and supporting its safety across intended populations from birth to adulthood.\n                  <\/jats:p>","DOI":"10.1177\/10915818261483229","type":"journal-article","created":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T22:27:16Z","timestamp":1789770436000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":0,"title":["Preclinical Safety Evaluation of Human Lactoferrin Alpha (Effera\n                    <sup>\u00ae<\/sup>\n                    )"],"prefix":"10.1177","author":[{"given":"Ross","family":"Peterson","sequence":"first","affiliation":[{"name":"Helaina, Research&Development\/Regulatory&Scientific Affairs, Helaina Inc."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nigel","family":"Baldwin","sequence":"additional","affiliation":[{"name":"Consultant, Baldwin Advisory Services Ltd."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anthony J.","family":"Clark","sequence":"additional","affiliation":[{"name":"Helaina, Research&Development\/Regulatory&Scientific Affairs, Helaina Inc."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Norbert E.","family":"Kaminski","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, Institute for Integrative Toxicology, The Center for Research on Ingredient Safety, Michigan State University"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lance","family":"Blevins","sequence":"additional","affiliation":[{"name":"Institute for Integrative Toxicology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alan","family":"Hoberman","sequence":"additional","affiliation":[{"name":"Argus International Consultant, Discovery & Safety Assessment, Charles River Laboratories"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rajasekhar","family":"Pala","sequence":"additional","affiliation":[{"name":"Discovery & Safety Assessment"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elise","family":"Lewis","sequence":"additional","affiliation":[{"name":"Discovery & Safety Assessment"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Vaden-Harris","sequence":"additional","affiliation":[{"name":"Discovery & Safety Assessment"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3377-5921","authenticated-orcid":false,"given":"Carrie-Anne","family":"Malinczak","sequence":"additional","affiliation":[{"name":"Helaina, Research&Development\/Regulatory&Scientific Affairs, Helaina Inc."},{"name":"Helaina, Research & Development, Certara"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2026,9,18]]},"reference":[{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10534-018-0092-8"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1099\/00222615-48-6-541"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1159\/000490298"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.nut.2015.08.010"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.3390\/nu13010003"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(15)01024-7"},{"key":"e_1_3_4_8_2","volume-title":"GRN No. 464. 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