2,2-dichloro-1,1,1-trifluoroethane

Basic toxicokinetics

Administrative data

Endpoint:

basic toxicokinetics

Type of information:

experimental study

Adequacy of study:

supporting study

Reliability:

2 (reliable with restrictions)

Data source

Reference

Reference 1

Reference Type:

study report

Title:

Unnamed

Year:

1993

Reference 2

Reference Type:

publication

Title:

No information

Author:

Urban, G. et al.

Year:

1994

Bibliographic source:

Chem. Res. Toxicol., 7(2):170-176 (BIOSIS/94/16152)

Reference 3

Reference Type:

publication

Title:

No information

Author:

Godin, C. S. et al.

Year:

1993

Bibliographic source:

Drug Metab. Dispos., 21(3):551-553

Reference 4

Reference Type:

publication

Title:

Gas uptake pharmacokinetics of 2,2- dichloro-1,1,1-trifluoroethane (HCFC-123)

Author:

Loizou GD, Urban G, Dekant W, Anders MW.

Year:

1994

Bibliographic source:

Drug Metab. Dispos., 22(4):511-517 (NIOSH/00222612)

Materials and methods

Objective of study:

metabolism

Test guideline

Qualifier:

no guideline available

GLP compliance:

not specified

Test material

Test material information

Constituent 1

Reference substance name:

2,2-dichloro-1,1,1-trifluoroethane

EC Number:

206-190-3

EC Name:

2,2-dichloro-1,1,1-trifluoroethane

Cas Number:

306-83-2

Molecular formula:

C2HCl2F3

IUPAC Name:

2,2-dichloro-1,1,1-trifluoroethane

Constituent 2

Reference substance name:

Ethane,2,2-dichloro-1,1,1-trifluoro-

IUPAC Name:

Ethane,2,2-dichloro-1,1,1-trifluoro-

Details on test material:

- Name of test material (as cited in study report): HCFC-123

Radiolabelling:

yes

Remarks:

14-C-HCFC 123

Test animals

Species:

other: Rat and guinea pig

Strain:

other: Sprague Dawley rats and Hartley guinea pigs

Sex:

male/female

Administration / exposure

Route of administration:

inhalation: gas

Vehicle:

unchanged (no vehicle)

Duration and frequency of treatment / exposure:

6 hours

Doses / concentrations

Remarks:

Doses / Concentrations:
2000 ppm (metabolic study); 500 and 5000 ppm in toxicokinetic study

Control animals:

not specified

Results and discussion

Toxicokinetic / pharmacokinetic studies

Details on absorption:

Uptake studies carried out with 14C-HCFC 123 in rats indicated that a single saturable component was involved in both sexes without significant differences between males and females in in vivo metabolic constants. An uptake of about 56-60% of the applied radioactivity was observed in rats, whereas about 95% uptake was recorded in guinea pigs.

Details on distribution in tissues:

Low radioactivity % were recorded in the analysed organs (liver, kidney, lung, brain, pancreas, testes and spleen). A low but measurable covalent binding to proteins was observed in liver, followed by the lung and the kidney.

Details on excretion:

The excretion of the major metabolite trifluoroacetic acid appeared to be suject to a saturable mechanism. After 48 hours, excretion accounted for about 20-30% of the applied radioactivity in rats and guinea pigs. As no complete mass balance was undertaken, the loss of the remaining radiolabelled substance was unknown, but presumably absorbed.

Metabolite characterisation studies

Metabolites identified:

yes

Details on metabolites:

The in vitro metabolism of HCFC-123 was examined in rat and human liver microsomes. The major metabolite in both species was trifluoroacetic acid. Chlorodifluoroacetic acid and inorganic fluoride were also identified as products of the enzymatic oxidation of HCFC-123. Microsomes from rats treated with ethanol and pyridine, inducers of P450 2E1, metabolized HFC-123 at higher rates. The microsomes also exhibit high rates of p-nitrophenol oxidation, a substrate mainly metabolized by P450 2E1. Trifluoroacetic acid formation was significantly reduced by the P450 2E1 inhibitor diethylthiocarbamate; p-nitrophenol also inhibited HCFC-123 oxidation in rat and human microsomes.

In vivo: trifluoroacetic acid was identified as the major metabolites excreted in urine by rats and guinea pigs. Minor metabolites were N-trifluoroacetyl-2- aminoethanol and N-acetyl-S-(2,2-dichloro-1,1-difluoroethyl)-L-cysteine.

The metabolic pathway of HCFC 123 was proposed (see figure 1)