Diisopentyl ether

Endpoint summary

Additional information

No data are available that describe the toxicokinetics of diisopentyl ether, therefore relevant substance properties and data from toxicity studies indicating systemic bioavailability were taken together to assess the general toxicokinetics of the substance.

 

Physical-chemical properties

Diisopentyl ether is a clear colourless liquid with a molecular weight of 158.3 g/mol. The octanol/water partition coefficient (Log Pow) is 5.1, the water solubility is 27.5 mg/L at 20°C.

Data from acute and repeated dose toxicity studies

Acute oral and inhalation toxicity studies

The available acute oral toxicity (dose levels: 2000 mg/kg bw) did not reveal any effects which indicate systemic availability of the substance (Phycher, 2011). However, in an acute inhalation study (single exposure of 4 hours to 2 and 7 mg/L) mortality was observed in the high dose group. At 7 mg/L, one male was found dead and the remaining two males were sacrificed for humane reasons on Day 1 post-exposure. Two females were found dead on Day 2 and one female survived the observation period of 14 days. At 2 mg/L, no mortality occurred. Macroscopic post mortem examination of the animals that were found dead or sacrificed for ethical reasons during the study revealed abnormalities at the lungs (dark red discolouration). No abnormalities were found at macroscopic examination of the surviving animals.

Subacute (28 days) oral toxicity study

A combined 28-day repeated dose toxicity study with the reproduction/developmental toxicity screening test was conducted with diisopentyl ether in rats by oral gavage (De Raaf-Beekhuijzen, 2012). Four groups of ten male and ten female Wistar Han rats were exposed by oral gavage to the test substance at 0, 100, 300 and 1000 mg/kg. Males were exposed for 29 days, i.e. 2 weeks prior to mating, during mating, and up to termination. Females were exposed for 41-47 days, i.e. during 2 weeks prior to mating, during mating, during post-coitum, and during at least 4 days of lactation. No treatment-related clinical abnormalities, differences in food consumption and body weight, and changes in haematology or clinical chemistry parameters were observed.

Macroscopic examination at necropsy did not show any treatment-related gross pathology. Treatment-related microscopic findings were noted in the 1000 mg/kg treated rats in the thyroid (males), thymus (females) and liver (both sexes), and in the kidneys (males) of the 100 mg/kg, 300 and 1000 mg/kg treated rats.

 

Absorption figures used for the DNEL derivation

In the absence of substance specific quantitative data on absorption, 100% absorption is assumed for the inhalation and 50% for the oral route. Both the results of the acute and sub-acute study indicate absorption of the test substance.

Based on the absence of dermal absorption data, it is assumed that the dermal bioavailability is equal to oral bioavailability (worst case scenario).