Registration Dossier

Administrative data

basic toxicokinetics, other
Type of information:
Adequacy of study:
weight of evidence
2 (reliable with restrictions)

Data source

Materials and methods

Results and discussion

Applicant's summary and conclusion

No direct toxicokinetic data exist. Evidence of oral absorption comes from the repeated dose study in rats. Poor dermal absorption and absorption thorugh lungs are also inferred from in vivo studies in animals. As it is not irritating to the skin, the absorption through dermal route is expected to be poor.
Executive summary:

There is no direct experimental data on toxicokinetics. The following description is based on the physicochemical properties and some indirect evidence from in vivo data.

The water solubility of the substance is high and therefore it is expected to be absorbed from the gastrointestinal tract. However in the respiratory tract, hydrophilic substances are effectively removed from the air in to the mucus in the upper respiratory tract.

Pentamethyl-trioxepane is hydrolytically stable (half-life > 1 year at 25 °C) in aqueous solutions buffered at pH 7 and pH 9. The half-life of pentamethyl-trioxepane is 172 hours in aqueous solutions buffered at pH 4 at 25 °C.

In a repeat dose study in rats, when orally administered by gavage, there were systemic treatment-related microscopic effects in different organs such as liver, kidneys, spleen, and gall bladder. Thus, the substance is able to be absorbed in sufficient quantities and get distributed into various organs, transported into the cells and bring about biological effects. One high dose animal died at 450 mg/kg bw/d.

After absorption and distribution, the substance is presumed to be eliminated via normal enzymatic degradation and detoxification mechanisms, including conjugation by various organs, especially liver, and eliminated through the kidneys and digestive track.

However, the dermal absorption appears to be low as revealed by its lack of biological effects such as skin irritation in rabbits. The LD50 for acute toxicity by dermal route is very high (> 2000 mg/kg) confirming poor dermal absorption. In mice, a minimal dermal absoption was evident based on the LLNA test results. While some reativity occured, it was not significantly high enough to be classified as a skin sensitizer. Based on very few systemic signs, and the lack of death in an acute inhalation study (high LD50; not classified), the pulmonary absorption potential appears to be minimal.

No invitro toxicokinetic data are available.