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HCFC 123 is readily absorbed by inhalation. Loizou et al. (1994) and Dekant (1994) described the uptake in rats by means of PBPK modeling. Both studies reported that a model with a single saturable component adequately described the uptake at lower concentrations, although it failed to describe the uptake in female rats exposed at >2000 ppm. Dekant (1994) found that 50 -60% and 95% of the administered HCFC 123 (6 h exposure to 4000 ppm) was absorbed by rats and guinea pigs, respectively.

Vinegar et al. (1994) found a biphasic uptake in rats exposed to 100, 1000, and 10000 ppm HCFC-123 for 4 hours, with a rapid initial uptake over 30 and 45 minutes, followed by a slower absorption phase. Uptake saturation was estimated at >2000 ppm.


Following absorption, HCFC 123 is rapidly distributed in the organism via the blood. Dekant (1994) examined the tissue and organ distribution following a 6 hour exposure to 4000 ppm radiolabeled HCFC 123 in rats. After 48 hours post exposure, low amount of radioactivity were detected. Relatively higher amounts of radioactivity were detected in the liver (5 -10 times higher than in other tissues). However, this difference was attributed also to the possible formation of protein adducts with trifluoroacetic acid, the major metabolite of HCFC 123. No accumulation in fat was observed.


HFCF 123 metabolism was studied both in vitro and in vivo. Dekant examined the metabolism in rat and human liver microsomes in vitro. In both species trifluoroacetic acid (TFA) was identified as the main formed metabolite, with chlorodifluoroacetic acid and inorganic fluoride detected as minor metabolites. Metabolisation rates were directly influenced by the specific induction or inhibition of the cytochrome P450 CYP2E1, indicating an involvement of this enzyme in the metabolic pathway. Luoizou et al (1994) and Dodd et al. (1993) examined the in vivo metabolism of HCFC 123 in rats. In both cases TFA was detected as the main metabolite, with a saturation concentration identified between 2000 and 3000 ppm. Dekant (1994) studied the metabolism in rats and guinea pigs. TFA was the major metabolite in both species, with about 20%-30% of the administered dose excreted as TFA in the urine.Othe rminor metabolites indicative of a reductive metabolic pathway via the possible formation of 1,1,-dichloro-2,2 -difluoroethene followed by conjugation to glutathione were also detected. The major role of P450 CYP2E1 observed in vitro was confirmed in in vivo experiments. The ability of HCFC 123 to form covalent TFA-protein adducts was studied in vitro and in vivo (Dekant, 1994; Harris et al, 1991 -1992; Ferrara et al., 1997; Zanovello et al., 2003 and Bortolato et al., 2003)


HCFC 123 can be excreted mainly unmetabolised via exhaled air and via the urine as TFA. The urinary excretion following hepatic elimination represents the rate limiting step in the biotransformation of HCFC 123. Buschmann (2001, reported in Section 7.8.1) and Cappon (2002) analysed the possible excretion via the milk in rats and monkeys, respectively. TFA was detected in rat milk and in the urine of litters nursed by treated dams in the Buschmann's study. Similarly, both TFA and HCFC 123 were detected in monkey milk, and TFA but not HCFC 123 was detected in the blood of both exposed mothers and neonates.