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Toxicological information

Basic toxicokinetics

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Administrative data

Endpoint:
basic toxicokinetics in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1994
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: modern study from a well known, experienced laboratory.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1994
Report Date:
1994

Materials and methods

Objective of study:
metabolism
Test guideline
Qualifier:
no guideline available
Principles of method if other than guideline:
Groups of 3 male rats were exposed to HFC-143a by inhalation at starting concentrations of 88 to 4800 ppm in a closed recirculating chamber for 4-5 hours. Chamber concentrations were measured by GC every 10 minutes. The rate of loss of HFC-143a from the chamber and the measured blood, liver, fat and muscle : air partition coefficients were used with a PBPK model to estimate the kinetic constants for metabolism in the intact rat. In addition a group of 4 male rats were exposed to 40,000 ppm in a 13 l chamber for 4 hrs. Urine and faeces were analyzed for metabolites.
GLP compliance:
not specified

Test material

Reference
Name:
Unnamed
Type:
Constituent
Radiolabelling:
no

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male
Details on test animals and environmental conditions:
Rats housed individually in wire mesh cages over absorbant cage board and given Purina rodent chow 5002 and tap water ad libitum except during exposures. There was no access to food and water during exposures.

Administration / exposure

Route of administration:
inhalation: gas
Vehicle:
unchanged (no vehicle)
Details on exposure:
Groups of 3 rats were exposed to nominal levels of 100 to 4800 ppm (measured concentrations: 4600, 1860, 340, and 88 ppm) in a closed recirculating 13 liter chamber and one group of 4 rats was exposed to a 40000 ppm level. Carbon dioxide was removed with a soda lime trap and oxygen was added to maintain levels at approximately 21%. Oxygen levels were monitored using a Model 3300 Oxygen Analyzer.
Duration and frequency of treatment / exposure:
single 4-5 hr exposure
Doses / concentrations
Remarks:
Doses / Concentrations:
Initial exposure levels were approximately: 4600, 1860, 900, 340 and 88 ppm (measured concentrations) for the 13 l recirculating chamber. One 40000ppm exposure was conducted to determine the metabolites.
No. of animals per sex per dose:
3 males
Control animals:
no
Positive control:
no
Details on study design:
The highest level was selected as approximately 1/2 of the lower flammability level. This was based on safety considerations. The lower levels were designed to allow for the determination of consumption of the test material by the test animals.
Details on dosing and sampling:
The test atmospheres were generated by injecting a known volume of gas into the system.
Statistics:
Vmax and Km were calculated

Results and discussion

Toxicokinetic / pharmacokinetic studies

Details on distribution in tissues:
Partition coefficients: Blood : air 0.66; Liver : air 1.13; Muscle : air 0.99; Fat : air 1.04 [Saline : air <0.01]
Details on excretion:
The PBPK model indicates that nearly all HFC-143a is cleared from the blood within 2 hours following a 6 hr exposure.

Metabolite characterisation studies

Metabolites identified:
yes
Details on metabolites:
One set of 4 rats was exposed to 40000 ppm of HFC-143a for 4 hours. and then held in metabolism cages for 16 hours. Urine and faeces were collected. Following treatment with beta-glucuronidase, the urine was analyzed by F-19 NMR for HFC-143a metabolites. The major metabolite was trifluoroethanol. Trifluoroacetic acid, the glucuronide conjugate of TFE, the hydrate of trifluoroacetaldehyde and the urea conjugate of trifluoroacetaldehyde were also identified.

Any other information on results incl. tables

Rate of metabolism was determined from the decline curves of HFC-143a in the exposure chambers. Vmax = 4.15 +/- 0.1 mg/hr-kg and Km = 4.37 +/- 0.18 mg/l

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information): no bioaccumulation potential based on study results
HFC-143a is poorly adsorbed into the blood from air, as shown by the low blood air partition coefficient. The compound is also poorly soluble in tissues. The PBPK model indicates that nearly all is cleared from the blood within 2 hours after the end of a 6 hour exposure. It is metabolized primarily to trifluoroethanol at a low rate and excreted either unchanged or as the glucuronide conjugate.
Executive summary:

HFC-143a is poorly adsorbed into the blood from air, as shown by the low blood air partition coefficient. The compound is also poorly soluble in tissues. The PBPK model indicates that nearly all is cleared from the blood within 2 hours after the end of a 6 hour exposure. It is metabolized primarily to trifluoroethanol at a low rate and excreted either unchanged or as the glucuronide conjugate. The low uptake and rapid clearance demonstrate that it will not bioaccumulate.