{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,2]],"date-time":"2026-05-02T10:32:20Z","timestamp":1777717940993,"version":"3.51.4"},"reference-count":21,"publisher":"SAGE Publications","issue":"3","license":[{"start":{"date-parts":[[2019,4,14]],"date-time":"2019-04-14T00:00:00Z","timestamp":1555200000000},"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"],"published-print":{"date-parts":[[2019,5]]},"abstract":"<jats:p>This article presents a supplemental data analysis and evaluation of the findings from an oral (gavage) combined developmental and perinatal\/postnatal reproduction toxicity study of the ammonium salt of perfluorohexanoic acid (CASRN: 21615-47-4) in Crl: CD-1(ICR) mice. The original study has been cited as supporting a lowest-observed-adverse-effects level of 175 mg\/kg\/d and no-observed-adverse-effects level of 35 mg\/kg\/d for developmental effects from perfluorohexanoic acid (PFHxA, CASRN: 307-24-4) in mice. The statistical analysis reported in 2014 was accurate in terms of quantifying statistical significance within phase 2 of the study. However, given the low incidence of findings, the purpose of this article is to extend the analysis and interpretation of findings by pooling the control group information from both phases of the same study, comparing the study findings to the incidence rates for stillbirths and postpartum viability for this species and strain of mouse observed for similar studies conducted by the same laboratory, and evaluating data on the incidence and range of spontaneous eye abnormalities reported in the literature. Based on this supplemental evaluation, the original study supports a NOAEL of 175 mg\/kg\/d for PFHxA in mice, which is a factor of 5-fold higher than previously reported. Furthermore, to the extent that this study may be considered in the selection of a point of departure for PFHxA in mice, it is noted that 175 mg\/kg\/d for maternal exposure is an unbounded NOAEL for developmental effects, meaning that the study did not establish a dose at which developmental effects may occur.<\/jats:p>","DOI":"10.1177\/1091581819837904","type":"journal-article","created":{"date-parts":[[2019,4,15]],"date-time":"2019-04-15T01:54:21Z","timestamp":1555293261000},"page":"183-191","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":6,"title":["Addendum to Iwai and Hoberman (2014)\u2014Reassessment of Developmental Toxicity of PFHxA in Mice"],"prefix":"10.1177","volume":"38","author":[{"given":"Hiroyuki","family":"Iwai","sequence":"first","affiliation":[{"name":"Daikin Industries Ltd, Settsu, Osaka, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alan M.","family":"Hoberman","sequence":"additional","affiliation":[{"name":"Charles River Laboratories, Preclinical Services, Horsham, PA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Philip E.","family":"Goodrum","sequence":"additional","affiliation":[{"name":"Integral Consulting Inc, Fayetteville, NY, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Emma","family":"Mendelsohn","sequence":"additional","affiliation":[{"name":"Integral Consulting Inc, Fayetteville, NY, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Janet K.","family":"Anderson","sequence":"additional","affiliation":[{"name":"Integral Consulting Inc, Fayetteville, NY, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"179","published-online":{"date-parts":[[2019,4,14]]},"reference":[{"key":"bibr1-1091581819837904","doi-asserted-by":"publisher","DOI":"10.1177\/1091581814529449"},{"key":"bibr2-1091581819837904","doi-asserted-by":"publisher","DOI":"10.1016\/j.reprotox.2009.01.006"},{"key":"bibr3-1091581819837904","doi-asserted-by":"publisher","DOI":"10.1016\/j.tox.2009.07.011"},{"key":"bibr4-1091581819837904","unstructured":"Massachusetts Toxic Use Reduction Act Science Advisory Board. 2018. Updated Draft EHS Summary of Perfluorohexanoic acid for the MA TURA Science Advisory Board Meeting\u2014April 18, 2018.https:\/\/www.turi.org\/Calendar\/Wednesday_April_11_2018_-_Science_Advisory_Board_Meeting\/Draft_EHS_Summary_for_PFHxA_SAB_Meeting_04_11_18. Accessed August 27, 2018."},{"key":"bibr5-1091581819837904","unstructured":"National Industrial Chemicals Notification and Assessment Scheme (NICNAS). 2018. Human health tier II assessment for short-chain perfluorocarboxylic acids and their direct precursors. Australian Government: Sydney, Australia.https:\/\/www.nicnas.gov.au\/chemical-information\/imap-assessments\/imap-assessments\/tier-ii-environment-assessments\/short-chain-perfluorocarboxylic-acids-and-their-direct-precursors. Accessed June 18, 2018."},{"key":"bibr6-1091581819837904","unstructured":"Washington Department of Ecology. PFAS Chemical Action Plan. 2017. Draft chapter: Health. https:\/\/www.ezview.wa.gov\/?alias=1962&pageid=37105. Accessed June 18, 2018."},{"key":"bibr7-1091581819837904","doi-asserted-by":"publisher","DOI":"10.1038\/laban0710-205"},{"issue":"3","key":"bibr8-1091581819837904","first-page":"58","volume":"47","author":"Feinstein RE","year":"2008","journal-title":"J Am Assoc Lab Anim Sci"},{"issue":"6","key":"bibr9-1091581819837904","first-page":"80","volume":"45","author":"Krugner-Higby L","year":"2006","journal-title":"J Am Assoc Lab Anim Sci"},{"issue":"9","key":"bibr10-1091581819837904","first-page":"19","volume":"27","author":"Rollman C","year":"1998","journal-title":"Lab Anim"},{"key":"bibr11-1091581819837904","doi-asserted-by":"publisher","DOI":"10.1258\/002367786781062043"},{"key":"bibr12-1091581819837904","doi-asserted-by":"publisher","DOI":"10.1080\/10543400701216355"},{"key":"bibr13-1091581819837904","doi-asserted-by":"publisher","DOI":"10.1177\/0192623309336154"},{"key":"bibr14-1091581819837904","unstructured":"Charles River Laboratories. Reproductive toxicology historical control data in Crl: CD1(ICR) mice. 2018. Last Updated July 2018. Available from Elise Lewis, Ph.D. (elise.lewis@crl.com)."},{"issue":"3","key":"bibr15-1091581819837904","first-page":"248","volume":"36","author":"Van Winkle T","year":"1986","journal-title":"Lab Anim Sci"},{"key":"bibr16-1091581819837904","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-642-76640-4_3"},{"key":"bibr17-1091581819837904","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-319-78364-2_4"},{"key":"bibr18-1091581819837904","doi-asserted-by":"publisher","DOI":"10.1177\/0192623314548767"},{"key":"bibr19-1091581819837904","doi-asserted-by":"publisher","DOI":"10.1093\/toxsci\/kfj105"},{"key":"bibr20-1091581819837904","doi-asserted-by":"publisher","DOI":"10.1093\/toxsci\/kfn099"},{"key":"bibr21-1091581819837904","doi-asserted-by":"publisher","DOI":"10.3109\/01480545.2011.585162"}],"container-title":["International Journal of Toxicology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/1091581819837904","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/full-xml\/10.1177\/1091581819837904","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/1091581819837904","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T10:23:48Z","timestamp":1777458228000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.1177\/1091581819837904"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,4,14]]},"references-count":21,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2019,5]]}},"alternative-id":["10.1177\/1091581819837904"],"URL":"https:\/\/doi.org\/10.1177\/1091581819837904","relation":{},"ISSN":["1091-5818","1092-874X"],"issn-type":[{"value":"1091-5818","type":"print"},{"value":"1092-874X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,4,14]]}}}