title: The acute, genetic, developmental and inhalation toxicology of trans-1,3,3,3-tetrafluoropropene (HFO-1234ze).
abstract: HFO-1234ze is being developed as a refrigerant, propellant, and foam-blowing agent because it has a very low global warming potential (less than 10), as contrasted to the hydrofluorocarbons with values of over 500. Several toxicology studies were conducted to develop a toxicology profile for this material. There was no lethality in mice and rats receiving single 4-hour exposures up to 103,300 or 207,000 ppm, respectively. Exposures up to 120,000 ppm did not induce cardiac sensitization to adrenalin. Rats were exposed to HFO-1234ze at levels of 5,000, 20,000, and 50,000 ppm 6 hours/day 5 days/week for 2 weeks. Predominate findings of increased liver and kidney weights and histopathological changes in the liver and heart suggested that these organs were the targets for HFO-1234ze toxicity. In a 4-week study at 1000, 5000, 10,000, and 15,000 ppm, the only organ showing treatment-related effects was the heart. In a 90-day study with exposures of 1500, 5000, and 15,000 ppm 6 hours/day 5 days/week, again, the heart was the only target organ. The findings consisted of focal and multifocal mononuclear cell infiltrates in the heart. There was no evidence of fibrosis, and, when compared to the 2- and 4-week studies, there did not appear to be an increase in severity with length of exposure. HFO-1234ze was inactive in a mouse and rat micronucleus assay, an Ames assay, and an unscheduled DNA synthesis assay and was not clastogenic in human lymphocytes. It was also not a developmental toxin in either the rat or rabbit, even at exposure levels up to15,000 ppm.
authors.affiliation: Honeywell International, Morristown, New Jersey 07962-1139, USA. george.rusch@honeywell.com
authors.forename: George M
authors.initials: GM
authors.lastname: Rusch
authors.forename: Ann
authors.initials: A
authors.lastname: Tveit
authors.forename: Hans
authors.initials: H
authors.lastname: Muijser
authors.forename: Mariska-M
authors.initials: MM
authors.lastname: Tegelenbosch-Schouten
authors.forename: Gary M
authors.initials: GM
authors.lastname: Hoffman
mesh_terms: D000280:Administration, Inhalation; D000335:Aerosol Propellants / Q000008:administration & dosage / Q000633:toxicity*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D005260:Female; D005466:Fluorocarbons / Q000008:administration & dosage / Q000633:toxicity*; D057232:Global Warming; D006321:Heart / Q000187:drug effects; D006801:Humans; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000473:pathology; D008214:Lymphocytes / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D009929:Organ Size / Q000187:drug effects; D011817:Rabbits; D051381:Rats; D017207:Rats, Sprague-Dawley; D013045:Species Specificity; D013997:Time Factors; D018675:Toxicity Tests / Q000379:methods*
chemical_list: C581936:1,3,3,3-tetrafluoropropene; D000335:Aerosol Propellants; D005466:Fluorocarbons