{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T19:33:43Z","timestamp":1777923223233,"version":"3.51.4"},"reference-count":19,"publisher":"SAGE Publications","issue":"3","license":[{"start":{"date-parts":[[2019,3,1]],"date-time":"2019-03-01T00:00:00Z","timestamp":1551398400000},"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":["Toxicol Ind Health"],"published-print":{"date-parts":[[2019,3]]},"abstract":"<jats:p>\n                    Trans-1,1,1,4,4,4-hexafluoro-2-butene (HFO-133mzz-E) is an odorless gas that finds uses as a foam transfer agent, heat transfer fluid, and specialty gas. The acute 4-h LC\n                    <jats:sub>50<\/jats:sub>\n                    (in rats) for HFO-133mzz-E is &gt; 17,000 ppm; it was not an eye or dermal irritant in 3- and 13-week repeated-dose inhalation studies in rats at concentrations up to 1.5% (15,000 ppm). HFO-133mzz-E was not a cardiac sensitizer at 70,000 ppm in a standard epinephrine challenge study in Beagle dogs. In a 3-week, repeated-dose (non-GLP) inhalation range-finding study in male and female rats, HFO-133mzz-E concentrations of 7500 and 15,000 ppm were determined to be well-tolerated. In the follow-up, GLP-compliant, 28-day repeated-dose inhalation study (as per OECD 412), male and female rats were exposed to 0, 1000, 10,000, or 15,000\/20,000 ppm (20,000 ppm concentration was decreased to 15,000 ppm after week 1 because of deaths and body weight loss). The study no-observed-adverse-effect level (NOAEL) was established at 10,000 ppm based on reduced body weight gain and mortality observed at 15,000 ppm. In a 90-day GLP-compliant repeated-dose study (as per OECD 413), male and female rats were exposed to 0, 1000, 5000, 7500, or 15,000 ppm HFO-133mzz-E. Three male rats exposed to 15,000 ppm HFO-133mzz-E died during exposure; clinical signs such as restlessness, blepharospasm, and myoclonic jerks were also observed, during the first month of the study, at 15,000 ppm. There were no significant gross or histopathological organ\/tissue lesions attributable to HFO-133mzz-E exposure. The study NOAEL was established at 7500 ppm. In a GLP prenatal developmental study (OECD 414), groups of time-mated nulliparous female rats were exposed via inhalation to 0, 1000, 5000, 7500, or 15,000 ppm HFO-1336mzz-E beginning on gestation day (GD) 6 up to and including GD 19. Under the conditions of this study, the NOAEL for maternal and fetal effects was established at 7500 ppm. HFO-1336mzz-E was not genotoxic in either in vitro or in vivo assays. Based on the results of the 90-day inhalation study, 7500 ppm was determined to be the NOAEL and was selected as the point of departure for the derivation of the 8-h time-weighted average (TWA), health-based workplace environmental exposure level (WEEL) value. This subchronic inhalation NOAEL was adjusted to account for duration of exposure, interindividual variability, and intraindividual variability. The resulting 8-h TWA WEEL value of 400 ppm is fully expected to provide a significant margin of safety against the production of any potential adverse health effects in workers following long-term inhalation exposure to HFO-1336mzz-E.\n                  <\/jats:p>","DOI":"10.1177\/0748233719825529","type":"journal-article","created":{"date-parts":[[2019,3,13]],"date-time":"2019-03-13T00:54:46Z","timestamp":1552438486000},"page":"204-210","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":3,"title":["Trans-1,1,1,4,4,4-hexafluoro-2-butene (HFO-1336mzz-E) (2018)"],"prefix":"10.1177","volume":"35","member":"179","published-online":{"date-parts":[[2019,3,12]]},"reference":[{"key":"bibr1-0748233719825529","volume-title":"Water Solubility of Gases. Report No. 20150021.01","author":"Ahrens A","year":"2015"},{"key":"bibr2-0748233719825529","volume-title":"Acute cardiac sensitization study of KCD-9629 in Beagle dogs. Study No. WIL-189224. Report No. DuPont-17743-1522","author":"Atterson PR","year":"2010"},{"key":"bibr3-0748233719825529","volume-title":"CD-59 Foam Expansion Agent Safety Data Sheet. Version 4.1","author":"Chemours","year":"2016"},{"key":"bibr4-0748233719825529","volume-title":"H-29503. Bacterial reverse mutation assay using gas-phase exposure. No. DuPont-17743-501","author":"DuPont","year":"2010"},{"key":"bibr5-0748233719825529","volume-title":"H-29503. In Vitro mammalian Chromosome Aberration Test using gas-phase exposure. Report No. DuPont-17743-546","author":"DuPont","year":"2010"},{"key":"bibr6-0748233719825529","volume-title":"Flammability determination of HFO-1336mzz-E (trans-1,1,1,4,4,4-Hexafluoro-2-butene) using ASTM E-681-04 and ASHRAE Standard 34","author":"Fraser MR","year":"2013"},{"key":"bibr7-0748233719825529","volume-title":"Summary of HFO-1336mzz-E (trans-1,1,1,4,4,4-Hexafluoro-2-butene) boiling point determination (Report No. 1336-2E)","author":"Kao CP","year":"2007"},{"key":"bibr8-0748233719825529","volume-title":"Summary of HFO-1336mzz-E (trans-1,1,1,4,4,4-Hexafluoro-2-butene) density determination (Report No. 1336-3E)","author":"Kao CP","year":"2007"},{"key":"bibr9-0748233719825529","volume-title":"Summary of HFO-1336mzz-E (trans-1,1,1,4,4,4-Hexafluoro-2-butene) vapor pressure determination per OECD Test No. 104 (Report No. 1336-1E)","author":"Kao CP","year":"2007"},{"key":"bibr10-0748233719825529","volume-title":"H-28542: One-hour inhalation approximate lethal concentration (ALC) in male rats. Report No. DuPont-26135","author":"Kegelman TA","year":"2009"},{"key":"bibr11-0748233719825529","volume-title":"H-29966. Inhalation toxicity screening in rats. Project ID: DuPont-19179-700. E.I","author":"Kegelman TA","year":"2011"},{"key":"bibr12-0748233719825529","volume-title":"H-29966. Inhalation median lethal concentration (LC50) study in rats. Project ID No. DuPont-19179-721. E.I","author":"Kegelman TA","year":"2012"},{"key":"bibr13-0748233719825529","volume-title":"H-29503. Acute inhalation toxicity study in rats. Report No. DuPont-17743-721","author":"Li XY","year":"2010"},{"key":"bibr14-0748233719825529","volume-title":"A 3-week whole-body inhalation range-finding study of HFO-1336mzz-E in Wistar Hanover rats. Report No. WIL-287501","author":"Randazzo JM","year":"2016"},{"key":"bibr15-0748233719825529","volume-title":"H-30385: 28-Day inhalation toxicity study in the Wistar rat. Study Identification No. DuPont-19179-782","author":"Schuler D","year":"2013"},{"key":"bibr16-0748233719825529","volume-title":"H-31452: Determination of octanol\/water partition coefficient (Kow) by high performance liquid chromatography. DuPont-21115-386 RV1. E.I","author":"Sobocinski RL","year":"2015"},{"key":"bibr17-0748233719825529","volume-title":"H-31452: In vitro mammalian cell forward gene mutation (CHO\/HPRT) assay with duplicate cultures using gaseous exposure. Report No. DuPont-21115-516","author":"Stankowski LF","year":"2015"},{"key":"bibr18-0748233719825529","volume-title":"Inhalation prenatal developmental toxicity study with HFO-1336mzz-E in rats. Report No. V20685","author":"Theuns-van Vliet JG","year":"2016"},{"key":"bibr19-0748233719825529","volume-title":"Sub-chronic (13-week) inhalation toxicity study with HFO-1336mzz-E in rats. Report No. V20686","author":"van Triel JJ","year":"2016"}],"container-title":["Toxicology and Industrial Health"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/0748233719825529","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/full-xml\/10.1177\/0748233719825529","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/0748233719825529","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T20:41:52Z","timestamp":1777668112000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.1177\/0748233719825529"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,3]]},"references-count":19,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2019,3]]}},"alternative-id":["10.1177\/0748233719825529"],"URL":"https:\/\/doi.org\/10.1177\/0748233719825529","relation":{},"ISSN":["0748-2337","1477-0393"],"issn-type":[{"value":"0748-2337","type":"print"},{"value":"1477-0393","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,3]]}}}