Biotransformation of trans-1,1,1,3-tetrafluoropropene (HFO-1234ze)

Journal Article · Tue Sep 15 04:00:00 EDT 2009 · Toxicology and Applied Pharmacology

DOI:https://doi.org/10.1016/j.taap.2009.06.018· OSTI ID:21272646

Schuster, Paul ^[1]; Bertermann, Ruediger ^[2]; Rusch, George M ^[3]; Dekant, Wolfgang ^[1]

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1. Institut fuer Toxikologie, Universitaet Wuerzburg, Versbacher Str. 9, 97078 Wuerzburg (Germany)
2. Institut fuer Anorganische Chemie, Universitaet Wuerzburg, Am Hubland, 97074 Wuerzburg (Germany)
3. Honeywell, P.O. Box 1057, Morristown, NJ 07962-1057 (United States)

trans-1,1,1,3-Tetrafluoropropene (HFO-1234ze) is a non-ozone-depleting fluorocarbon replacement with a low global warming potential and is developed as foam blowing agent. The biotransformation of HFO-1234ze was investigated after inhalation exposure. Male Sprague-Dawley rats were exposed to air containing 2000; 10,000; or 50,000 ppm (n = 5/concentration) HFO-1234ze. Male B6C3F1 mice were only exposed to 50,000 ppm HFO-1234ze. All inhalation exposures were conducted for 6 h in a dynamic exposure chamber. After the end of the exposures, animals were individually housed in metabolic cages and urines were collected at 6 or 12 h intervals for 48 h. For metabolite identification, urine samples were analyzed by {sup 1}H-coupled and {sup 1}H-decoupled {sup 19}F-NMR and by LC/MS-MS or GC/MS. Metabolites were identified by {sup 19}F-NMR chemical shifts, signal multiplicity, {sup 1}H-{sup 19}F coupling constants and by comparison with synthetic reference compounds. In urine samples of rats exposed to 50,000 ppm HFO-1234ze, the predominant metabolite was S-(3,3,3-trifluoro-trans-propenyl)-mercaptolactic acid and accounted for 66% of all integrated {sup 19}F-NMR signals in urines. No {sup 19}F-NMR signals were found in spectra of rat urine samples collected after inhalation exposure to 2000 or 10,000 ppm HFO-1234ze likely due to insufficient sensitivity. S-(3,3,3-Trifluoro-trans-propenyl)-L-cysteine, N-acetyl-S-(3,3,3-trifluoro-trans-propenyl)-L-cysteine and 3,3,3-trifluoropropionic acid were also present as metabolites in urine samples of rats and mice. A presumed amino acid conjugate of 3,3,3-trifluoropropionic acid was the major metabolite of HFO-1234ze in urine samples of mice exposed to 50,000 ppm and related to 18% of total integrated {sup 19}F-NMR signals. Quantification of three metabolites in urines of rats and mice was performed, using LC/MS-MS and GC/MS. The quantified amounts of the metabolites excreted with urine in both mice and rats, suggest only a low extent (< 1% of dose received) of biotransformation of HFO-1234ze and 95% of all metabolites were excreted within 18 h after the end of the exposures (t{sub 1/2} app. 6 h). The obtained results suggest that HFO-1234ze is likely subjected to an addition-elimination reaction with glutathione and to a CYP 450 mediated epoxidation at low rates.

• OSTI ID: 21272646
• Journal Information: Toxicology and Applied Pharmacology, Journal Name: Toxicology and Applied Pharmacology Journal Issue: 3 Vol. 239; ISSN TXAPA9; ISSN 0041-008X
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
CHEMICAL SHIFT
COUPLING CONSTANTS
CYSTEINE
FLUORINE 19
FOAMS
GAS CHROMATOGRAPHY
GLUTATHIONE
HYDROGEN 1
INHALATION
MASS SPECTROSCOPY
METABOLITES
MICE
NUCLEAR MAGNETIC RESONANCE
ORGANIC FLUORINE COMPOUNDS
RATS
URINE