Biotransformation of 2,3,3,3-tetrafluoropropene (HFO-1234yf)
- Institut fuer Toxikologie, Universitaet Wuerzburg, Versbacher Str. 9, 97078 Wuerzburg (Germany)
- DuPont Haskell Global Centers for Health and Environmental Sciences, Newark, DE 19714 (United States)
- Honeywell, P.O. Box 1057, Morristown, NJ 07962-1057 (United States)
2,3,3,3-Tetrafluoropropene (HFO-1234yf) is a non-ozone-depleting fluorocarbon replacement with a low global warming potential which has been developed as refrigerant. The biotransformation of HFO-1234yf was investigated after inhalation exposure. Male Sprague-Dawley rats were exposed to air containing 2000, 10,000, or 50,000 ppm HFO-1234yf for 6 h and male B6C3F1 mice were exposed to 50,000 ppm HFO-1234yf for 3.5 h in a dynamic exposure chamber (n = 5/concentration). After the end of the exposure, animals were individually housed in metabolic cages and urines were collected at 6 or 12-hour intervals for 48 h. For metabolite identification, urine samples were analyzed by {sup 1}H-coupled and 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 all urine samples, the predominant metabolites were two diastereomers of N-acetyl-S-(3,3,3-trifluoro-2-hydroxy-propyl)-L-cysteine. In {sup 19}F-NMR, the signal intensity of these metabolites represented more than 85% (50,000 ppm) of total {sup 19}F related signals in the urine samples. Trifluoroacetic acid, 3,3,3-trifluorolactic acid, 3,3,3-trifluoro-1-hydroxyacetone, 3,3,3-trifluoroacetone and 3,3,3-trifluoro-1,2-dihydroxypropane were present as minor metabolites. Quantification of N-acetyl-S-(3,3,3-trifluoro-2-hydroxy-propyl)-L-cysteine by LC/MS-MS showed that most of this metabolite (90%) was excreted within 18 h after the end of exposure (t{sub 1/2} app. 6 h). In rats, the recovery of N-acetyl-S-(3,3,3-trifluoro-2-hydroxy-propyl)-L-cysteine excreted within 48 h in urine was determined as 0.30 {+-} 0.03, 0.63 {+-} 0.16, and 2.43 {+-} 0.86 {mu}mol at 2000, 10,000 and 50,000 ppm, respectively suggesting only a low extent (<< 1% of dose received) of biotransformation of HFO-1234yf. In mice, the recovery of this metabolite was 1.774 {+-} 0.4 {mu}mol. Metabolites identified after in vitro incubations of HFO-1234yf in liver microsomes from rat, rabbit, and human support the metabolic pathways of HFO-1234yf revealed in vivo. The obtained results suggest that HFO-1234yf is subjected to a typical biotransformation reaction for haloolefins, likely by a cytochrome P450 2E1-catalyzed formation of 2,3,3,3-tetrafluoroepoxypropane at low rates, followed by glutathione conjugation or hydrolytic ring opening.
- OSTI ID:
- 21180499
- Journal Information:
- Toxicology and Applied Pharmacology, Vol. 233, Issue 2; Other Information: DOI: 10.1016/j.taap.2008.08.018; PII: S0041-008X(08)00369-4; Copyright (c) 2008 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA); ISSN 0041-008X
- Country of Publication:
- United States
- Language:
- English
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BIOLOGICAL PATHWAYS
CHEMICAL SHIFT
COUPLING CONSTANTS
CYSTEINE
EXPOSURE CHAMBERS
FLUORINE 19
GAS CHROMATOGRAPHY
GLUTATHIONE
GREENHOUSE EFFECT
HYDROGEN 1
IN VITRO
IN VIVO
INCUBATION
INHALATION
LIVER
MASS SPECTROSCOPY
METABOLITES
MICE
MICROSOMES
MULTIPLICITY
NUCLEAR MAGNETIC RESONANCE
OZONE
RABBITS
RATS
REFRIGERANTS
URINE