Studies have been conducted on the biotransformation of a structural isomer, HCFO 1233zd(E) - (1-Propene, 1-chloro-3,3,3-trifluoro-, (1E)-) (Schmidt et al., 2013). Male Sprague-Dawley rats and female albino New Zealand rabbits were exposed by inhalation to levels of 2,000, 5,000, and 10,000 ppm for 6 hours. Urine was collected for 48 hours after the end of the exposure period and urinary metabolites were identified by19F-NMR, LC-MS/MS and GC/MS.
The major metabolites identified in rat urine were 3,3,3-trifluorolactic acid (32%) and N-acetyl-S-(3,3,3-trifluoro-trans-propenyl)-L-cysteine (40%). Other metabolites included S-(3,3,3-trifluoro-trans-propenyl)-mercaptolactic acid; trifluoroacetic acid; 3,3,3-trifuoro-1,2-dihydroxypropane; and 3,3,3-trifluoropropionic acid. In rabbit urine,N-acetyl-S-(3,3,3-trifluoro-trans-propenyl)-L-cysteine (46% of the total) was identified. Other metabolites included S-(3,3,3-trifluoro-trans-propenyl)-mercaptolactic acid; trifluoroacetic acid; 3,3,3-trifluoro-1,2-dihydroxypropane, S-(3,3,3-trifluoro-trans-propenyl)-L-cysteine and 3,3,3-trifluoro-1-propanol. These metabolites suggest that HCFO 1233zd(E) is metabolised via glutathione conjugation and by oxidative metabolism by cytochrome P-450 In vitro studies were also carried out in the presence of liver microsomes from rats, rabbits and humans in the presence or absence of glutathione and/or a NADPH regenerating system. S-(3,3,3-trifluoro-trans-propenyl)-glutathione was the major metabolite in the liver microsomes when glutathione was present.
The quantified amounts of the metabolites excreted with urine in both mice and rabbits, suggest only a low extent and rate of biotransformation of HCFO 1233zd(E) (~ 0.01% of dose received in rabbits, and ~0.002% of dose received in rats); the major metabolites were excreted rapidly after the end of the exposures (t1/2< 6 h).