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Based on the available toxicokinetics information no quantitative conclusions can be drawn with respect to absorption, metabolism and excretion as no mass balance was determined in the in vivo studies. However, the available in vitro study it can be concluded that the level of biotransformation of the substances is likely to be very low. This was confirmed by the in vivo inhalation studies where less than 1%  of the received dose was recovered from urine in the form of metabolites, thus also indicating that biotransformation of the substance is low. Furthermore, the majority of the absorbed HFO-1234ze compound is likely to have been exhaled as parent compound due to its low boiling point. 

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Additional information

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 (1)H-coupled and (1)H-decoupled (19)F-NMR and by LC/MS-MS or GC/MS. Metabolites were identified by (19)F-NMR chemical shifts, signal multiplicity, (1)H-(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 (19)F-NMR signals in urines. No (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 (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(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. The lack of significant oxidation and glutathione conjugation may explain the lack of hepato or nephrotoxicity with HFO-1234ze. 

Based on the presented data, no quantitative conclusions can be drawn with respect to absorption, distribution, metabolism and excretion, as no mass balance was determined in any of the in vivo studies. However, since less than 1% of the administered dose was recovered from urine in the form of metabolites, biotransformation appears to be quite low and most of the absorbed HFO-1234ze will have been exhaled as parent compound. HFO-1234ze total body burden of exposure via the skin (acting as a barrier) is expected to be much lower than via inhalation.