2,4,6-tri-tert-butylphenol

Endpoint summary

Description of key information

Absorption is rapid and extensive.  Clearance from plasma is rapid.  Most of this compound after disappearing from the blood moves into adipose tissue.  The blood elimination half-lives were 18.2 minutes for the α-phase and 11.8 hours for the slower β-phase.  A metabolite (but no parent) was detected in the faeces. The faecal metabolite had a molecular weight of 261 and was considered to be 2,4,6-tri-tbutylphenoxy radical. The phenoxy radical was also detected in the bile of rats.

Key value for chemical safety assessment

Bioaccumulation potential:

high bioaccumulation potential

Absorption rate - oral (%):

100

Absorption rate - dermal (%):

25

Absorption rate - inhalation (%):

100

Additional information

In the study performed by Takahashi O & Hiraga K (1983) single oral doses (up to 260 mg/kg bw) were well absorbed in the Sprague Dawley rat. Peak blood levels of the test material were reached in 15 to 60 minutes. The blood elimination half-lives were 18.2 minutes for the α-phase and 11.8 hours for the slower β-phase. Maximum tissue concentrations were reached after 2 to 3 hours in the liver, 2 to 6 hours in the kidneys, 1.5 to 2.5 hours in the spleen and >24 hours in epididymal adipose tissues.

Most of this compound after disappearing from the blood moved into adipose tissue. It was not metabolised to less lipophilic compounds. Therefore excretion of the material from plasma is rapid (t ½ alpha), but the material that gets into fat is more slowly released from fat back into plasma (t ½ beta). The rather short β-phase halfe-life though is not indicative of bioaccumulation of the substance in rats.

The test material and its metabolites were not excreted in the urine. A metabolite (but no parent) was detected in the faeces. The faecal metabolite had a molecular weight of 261 and was considered to be 2,4,6-tri-tbutylphenoxy radical. The phenoxy radical was also detected in the bile of rats.

On the basis of the absence of parent in the faeces and the extremely rapid clearance from the blood, absorption across the GIT is considered to be 100%.

In the absence of an quantitative information, inhalation absorption is set at 100 % for risk assessment purposes.

Oral data would indicate rapid diffusion of the substance across the gut hence its physical chemical properties (MW 262, water solubility 0.512 mg/L at 25 °C, Kow 6) do not hinder absorption in this regard. Hence adoption of the conservative default dermal absorption value of 25 %, based on EFSA guidance on dermal absorption (2012), is considered appropriate for risk assessment purposes.