1,1,1,2,2,3,4,5,5,5-decafluoro-3-methoxy-4-(trifluoromethyl)pentane

Endpoint summary

Description of key information

The acute toxicity tests showed that the LD50 of the testsubstance is higher than 2000 mg/kg body weight, both after oral and after dermal administration. The NOAEL after oral administration for 28 days revealed a NOAEL of 150 mg/kg/day. Inhalation toxicity tests have been performed and the acute inhalation test resulted in an LC50 higher than 30000 ppm (60% of the saturated vapor pressure) and the NOAEL after 5 days inhalation was higher than 10000 ppm. Therefore, an extensive toxicokinetic assessment is considered of limited value. Below, a summary of the anticipated toxicokinetic behavior of the test substance is given.

Additional information

ABSORPTION

 

The water solubility of the test substance is extremely low (295 ug/l), caused by presence of apolar side groups in the molecule. In general, a compound needs to be dissolved before it can be taken up from the gastro-intestinal tract after oral administration (1). Thus, the extremely low water solubility can be considered a potentially rate-limiting factor for the absorption of the compound. However, in the presence of food and bile salts the systemic exposure might be a little higher. Overall, it is to be expected that the oral bioavailability, and thus the systemic exposure, of the test substance will be relatively low. Uptake via inhalation is anticipated to be low. Because of the low water solubility and the high vapour pressure (6.25 kPa) of the test substance, absorption across the lung/blood interface is expected to be negligible

 

Since it is generally accepted that substances with log Pow ranging from 0.1 to 6 penetrate the skin easily (2), it is to be expected that the test substance will penetrate the skin to some extent. However, unless the test substance is prevented from evaporating from the surface of the skin, it is expected the high volatility would preclude meaningful skin absorption. In conclusion, it is expected that absorption through normal industrial routes of exposure will be very low.

 

DISTRIBUTION

 

The test substance will show a high volume of distribution. Therefore, the very low amount of absorbed material will be reversibly distributed into peripheral tissue, especially fatty tissues. The plasma protein binding is expected to be high.

 

METABOLISM AND EXCRETION

 

Pulmonary excretion will occur via the lungs. It is anticipated that the larger part of the test substance will be excreted this way.

 

In the liver, metabolic oxidation will occur. Other segregated hydrofluoroethers are known to undergo oxidation and to be dehalogenated by cytochrome P450. (HFE-7100, HFE-7200: ELINCS 422-270-2 : 425-340-0, respectively).

 

Metabolites may be excreted via exhalation or via urine or bile. Limited cleavage of the ether bond is anticipated.

 

CONCLUSION

 

Based on the expected kinetic behavior in the body, as described above, the test substance will show low absorption through all routes of exposure. After absorption, excretion will mainly be via the lungs. Additionally, the test substance will be metabolized in the liver. Metabolites can be excreted via lungs, or bile or urine. Therefore, it is unlikely accumulation will occur in the body during prolonged exposure.

 

REFERENCES

 

1.    Martinez MN, Amidon GL. Mechanistic approach to understanding the factors affecting drug absorption: a review of fundamentals. J Clin Pharmacol 2002; 42: 620-43.

 

2.    T.G. Vermeire et al., Estimation of consumer exposure to chemicals: application of simple models. The Science of the Total Environment 1993; 136: 155-76.