A mixture of: triphenylthiophosphate and tertiary butylated phenyl derivatives

Endpoint summary

Description of key information

The substance is absorbed after ingestion and causes a strong, reversible enlargement of liver upon subacute gavage dosing.  Skin permeability is likely to be hindered by the very low water solubility and lower than oral absorption. However, no experimental data is available and the criteria for assuming a lower skin permeability (MW, log Pow) are not fulfilled.  The vapour pressure is too low to result in inhalation exposure.

Key value for chemical safety assessment

Bioaccumulation potential:

no bioaccumulation potential

Absorption rate - oral (%):

100

Absorption rate - dermal (%):

100

Absorption rate - inhalation (%):

100

Additional information

There were no studies available in which the toxicokinetic properties of the test substance were investigated. 

The test substance is a clear yellowish liquid with a molecular weight range of 342 - 510 g/mol. It is a UVCB substance, specifically a mixture of triphenylthiophosphate and tertiary butylated phenyl derivatives.

The test substance is of low volatility (7 x 10 -5kPa) at 20°C, (see IUCLID, chapter 4.6), very low water solubility, < 0.1 mg/L at 20°C (see IUCLID, chapter 4.8 water solubility) and the components have an n-octanol-water partition coefficient (log Pow) between 4.8 – 8.8 at 22 °C (see IUCLID, chapter 4.7 partition coefficient).

 

Absorption 

Due to its high fat solubility, low water solubility (Log P of 4,8,- 8,8), and relatively low molecular weight, it is likely there is a low to moderate potential for absorption both via ingestion and the skin. In the 28 day oral toxicity study, systemic effects of the test substance were observed (RCC, Research and Consulting Company, 1997). Dose-related increases in the absolute liver weights were recorded in both sexes in all groups (50, 100, 200 mg/kg). After the treatment-free recovery period, only the liver weights of females of the 200 mg/kg group were statistically significantly higher when compared with the controls.

The test substance has a low vapour pressure of 7 x 10e-5 Pa at 20°C (Geoffroy A, 1996, see IUCLID, chapter 4.6 vapour pressure); subsequently, the calculated vapour saturation threshold is ca. 0.0000141 mg/L. Therefore, exposure of the test substance via the inhalative route during activities at room temperature is not assumed.

 

Metabolism 

Considering its technical function as an antioxidant in lubricants, both enzymatic and non-enzymatic rapid oxidation of the thiophosphate to the phosphate is expected. In addition, phosphate esters are known to be susceptible to enzymatic hydrolysis. This may be slowed for the fraction with a tertiary butyl group in o-position to the ester bond, but in principle, all components of the test substance are expected to undergo hydrolysis. The resulting alkylated phenols should be readily conjugated by UDP-glucuronosyltransferases or sulfotransferases. The conjugates are sufficiently small and water soluble for renal elimination.

In a 28-day rat study, a dose-dependent strong increase in absolute and relative liver weight was observed. Only a few minor findings which attained statistical significance were recorded in the clinical biochemistry data. The liver enlargement is therefore assumed to represent metabolic adaptations. After the recovery period, the clinical biochemistry findings seen at the end of the treatment period indicated reversibility and/or were found to be similar to those of the controls with no statistical relevance. Noteworthy, was a slight increase in the total cholesterol, phospholipid and potassium levels in the males of the 200 mg/kg group (p<0.05 - p<0.01). After the treatment-free recovery period only the liver weights of females of the 200 mg/kg group were statistically significantly higher when compared to the controls. Hepatocellular hypertrophy, noted at the termination of the treatment period in the liver of the mid- and high-dose males and females, accompanied the liver enlargement. The absence of this finding in the recovery rats indicates reversal of this change after the 2-week recovery period. Experimental information about potential metabolites is not available.

Distribution

Due to the high lipophilicity of the test substance, distribution to the adipose tissue is possible. This would be counteracted by liver metabolism.

Excretion

Given that there is no information available about potential metabolites, it can be concluded from the reversibility of observed effects - in the subacute repeated dose study - that the metabolites of the test item can be excreted.

Overall, it is considered that accumulation of the substance in the body will only occur if the metabolic capacity of the body is overloaded.