Phenol, dodecyl-, branched

Endpoint summary

Additional information

There were no toxicokinetic studies that directly addressed absorption, distribution, metabolism, or excretion of tetrapropenyl phenol. However, information is available from existing toxicology studies to infer potential toxicokinetic properties. Typical purity of this material as distributed in commerce is 50% alkyl phenol sulfide and 50% highly refined lubricant base oil. Thus, the absorption of the chemical may be influenced by the other component of the mixture and any toxicity observed may be the result of the lubricant base oil as well. 

Systemic availability of tetrapropenyl phenol depends on its ability to be absorbed across body surfaces. Factors that affect this process include water solubility, lipophilicity (characterized by the log of the partition coefficient, log K_ow), degree of ionization (the dissociation constant, pKa), and molecular size. The physical state of the compound is an oily liquid at 20ºC and 101.3 KPa. The compound is very lipophilic, with an estimated log K_ow of 7.14 and the estimated water solubility is 1.54 mg/L for the main component, which is considered slightly soluble (0.1-100 mg/L). 

Oral Exposure

Based on its high lipophilicity and low water solubility, the tetrapropenyl phenol is expected to be absorbed into and through the cell membrane, to be retained in the body, and to have a wide distribution.

Effects in subchronic toxicity studies confirm that tetrapropenyl phenol is distributed throughout the body after ingestion. In the key 28-day repeat dose study with rats, Harriman (2004) indicated effects were seen in the liver and reproductive organs of both males and females. A NOAEL was established at 60 mg/kg/day based on organ weight effects and microscopic findings in the liver at 60 mg/kg/day and higher that disappear after recovery, indicating elimination from the tissue. However, effects in other tissues continued to be seen after the recovery period at higher doses.

In an additional key 90-day study with rats, Vogin (1970) indicated similar testicular effects. Both of these studies indicate that the compound is absorbed and systemic toxicity occurs at relatively low doses, including changes in the liver, the primary organ expected to metabolize the compound. Whole body distribution is supported in the key study for reproductive toxicity with oral exposure (Edwards 2010) which found effects in both adults and neonates, indicating that tetrapropenyl phenol probably crosses the placental barrier; further studies would be required to separate reproductive effects from direct effects on the neonate and to better understand distribution of the substance in the pregnant dam and fetuses to confirm this. The liver is expected to be the primary organ to receive and metabolize the substance, making it more soluble by oxidation and conjugation and releasing the more polar compound into the bile for elimination via the gastrointestinal tract. 

Dermal Exposure

Tetrapropenyl phenol is predicted to penetrate the skin and circulate throughout the body based on its small molecular weight by formula (<500 g/mole) and its lipophilicity. This prediction is supported by data in rabbits from Randall and Robinson (1978) showing that at high acute doses, clinical signs included gross effects on lung, liver, spleen, kidney, gall bladder, and the GI tract. These organs were histologically normal by the end of the observation period, indicating that the compound was eliminated from the target tissues over time.

Inhalation Exposure

This substance only exists in liquid form and will not be found as an aerosol in its normal use pattern. Furthermore, information on the substance's vapour pressure suggests that the substance is unlikely to be inhaled. Thus exposures via inhalation that lead to absorption through the respiratory system are unlikely. 

In summary, the absorption, distribution, metabolism, and excretion of tetrapropenyl phenol has not been directly studied in vivo. However, toxicology studies show that tetrapropenyl phenol crosses the gastrointestinal tract and the dermal barrier, resulting in systemic distribution. While the compound appears to be eliminated from tissues, based on recovery from tissue effects seen in a subacute oral study (Harriman 2004) and in an acute dermal study (Randall and Robinson 1978), tissues from higher levels in the repeat dose oral study showed prolonged tissue effects which may be related to retention in the body consistent with lipophilic properties of the substance.