Biotransformation of 2,3,3,3-tetrafluoropropene (HFO-1234yf)

Journal Article · Mon Dec 01 04:00:00 EST 2008 · Toxicology and Applied Pharmacology

DOI:https://doi.org/10.1016/j.taap.2008.08.018· OSTI ID:21180499

Schuster, Paul; Bertermann, Ruediger ^[1]; Snow, Timothy A; Xing, Han ^[2]; Rusch, George M ^[3]; Jepson, Gary W ^[2]; Dekant, Wolfgang ^[1]

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1. Institut fuer Toxikologie, Universitaet Wuerzburg, Versbacher Str. 9, 97078 Wuerzburg (Germany)
2. DuPont Haskell Global Centers for Health and Environmental Sciences, Newark, DE 19714 (United States)
3. 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, Journal Name: Toxicology and Applied Pharmacology Journal Issue: 2 Vol. 233; ISSN TXAPA9; ISSN 0041-008X
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
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