Registration Dossier

Administrative data

Link to relevant study record(s)

Description of key information

Since it is likely that the substance will be absorbed by inhalation and in the absence of substance-specific absorption data for the oral and dermal route, the default absorption values from the REACH guidance (Chapter 8, R.8.4.2) are used for DNEL derivation, namely: 100% for inhalation, 50% for oral and 50% for dermal absorption. Due to the rapid excretion of metabolites formed no bioaccumulation potential is to be expected.

Key value for chemical safety assessment

Bioaccumulation potential:
no bioaccumulation potential
Absorption rate - oral (%):
50
Absorption rate - dermal (%):
50
Absorption rate - inhalation (%):
100

Additional information

Introduction

The substance is a colorless, liquified gas with a boiling point of 19°C. The substance has a high vapour pressure of 1065 hPa, an octanol/water partition coefficient of 2.2 and the substance is highly soluble in water.

 

Absorption:

Oral and dermal: Substance-specific absorption data for the oral and dermal route are not available. However, the substance is a gas and therefore dermal and oral exposure is unlikely

 

Inhalation: The substance has a vapour pressure of 1065 hPa and therefore inhalation is the major route of exposure. Experiments in rats indicated absorption as systemic effects were observed in a 14-day inhalation study at 7500 and 20000 ppm and in a 90-day inhalation study at 10000 and 15000 ppm. Using physiologically based pharmacokinetic (PBPK) modeling techniques, occupational exposure simulation in an adult female human indicated rapid uptake and clearance from blood for the substance with the concentration falling to near zero before the start of a subsequent day's exposure. The blood/air (BA) partition coefficient also indicates absorption. The blood/air partition coefficient in the rat was at least twice as high as in humans. It can therefore be concluded that the substance is likely to be absorbed via the inhalation route.

 

Metabolism

Metabolism of the substance has been investigated in Sprague Dawley rats, New Zealand rabbits, and in human liver microsomes. S-(3,3,3-trifluoro-trans-propenyl)-glutathione was identified as predominant metabolite of the test substance in rat, rabbit and human liver microsomes in the presence of glutathione. Products of the oxidative biotransformation of the test substance were only minor metabolites when glutathione was present. In rats, both 3,3,3-trifluorolactic acid and N-acetyl-(3,3,3 -trifluoro-trans-propenyl)-L-cysteine were observed as major urinary metabolites. 3,3,3-trifluorolactic acid was not detected in the urine of rabbits exposed the test substance. Several minor metabolites formed by alternative reactions of S-(3,3,3-trifluoro-trans-propenyl)-glutathione were also excreted. Quantitation showed rapid excretion of both metabolites with urine t1/2 of less than 6 hours in both species. Based on metabolite recovery in urine and estimated doses of the test substance received by inhalation, the extent of biotransformation of the test substance was determined as approximately 0.01% of received dose in rabbits and approximately 0.002% in rats. The remaining material is likely exhaled due to its high volatility. The metabolite structures show that the test substance undergoes both oxidative biotransformation and glutathione conjugation at very low rates. The very low extent of biotransformation and the rapid excretion of metabolites formed are consistent with the very low potential for toxicity of the test substance in mammals.

 

Conclusion

The test substance is absorbed via the inhalation route. The extent of biotransformation is very low and metabolites formed are excreted rapidly. Untransformed test substance is likely exhaled due to the high volatility of the substance. As, moreover, the log P value of the substance is lower than 3, the substance is unlikely to accumulate with the repeated exposure patterns normally encountered in the workplace. In the absence of substance-specific absorption data for the oral and dermal route, the default absorption values from the REACH guidance (Chapter 8, R.8.4.2) are used for DNEL derivation, namely: 100% for inhalation, 50% for oral and 50% for dermal absorption