1,2,4-Benzenetricarboxylic acid, mixed branched tridecyl and isodecyl esters

Endpoint summary

Additional information

There are no quantitative data on the toxicokinetics, metabolism, or distribution of the submission substance (i.e. CASRN 70225-05-7). Based on the physicochemical properties, it is expected that low amounts of CASRN 70225-05-7 are absorbed via oral, respiratory, and dermal routes of exposure. The inhalation and dermal availability is expected to be limited by poor water solubility (i.e. a log K_ow>10), and a relatively high molecular weight. The inhalation availability is furthermore reduced by the low vapour pressure of the substance (i.e. ~1.01 e-14mm Hg at 25°C).

 

The submission substance constitutes a relatively lipid-soluble substance which falls into the chemical class of “trimelletate esters”. Toxicokinetic data developed for the lower molecular weight trimelletate ester, TOTM, are considered to be representative, from a qualitative point of view, of the toxicokinetic behavior of the submission substance. This approach is consistent with the OECD SIDS and EPA HPV assessment on the chemical class “trimelletate esters” (OECD SIDS, 2002;ACC Phthalate Esters Panel HPV Testing Group,2006). 

 

The absorbability of radiolabelled TOTM was studied. TOTM mixed with corn oil was administered by gavage in a single dose of 100 mg/kg of body weight in 4 male SD rats. Rats were placed in glass metabolism cages and urine, feces and expired air were collected for 144 hrs(6 days), and at 144 hours, tissues and carcasses were collected for subsequent analysis. About 75% of the dose was excreted unchanged in the feces, 16% in the urine as metabolites and 1.9% was expired as¹⁴CO₂. Radioactivity was excreted in the feces as unchanged TOTM (85% of the fecal radioactivity), mono- and di(2- ethylhexyl) trimellitate (MOTM and DOTM, respectively), and as unidentified polar metabolites. Metabolites in the urine were identified as MOTM and metabolites of 2-ethylhexanol. Less than 0.6% of the dose remained in whole tissues. Elimination kinetics were estimated from breath and urinary excretion data. The absorption profile as reflected by excretion of ¹⁴CO₂was complex and appeared to involve two rate controlling processes. Elimination of ¹⁴CO₂was biphasic with half-lives of 4.3 and 31 hrs, and excretion of radioactivity in the urine was biphasic with half-lives of 3.4 hrs and 42 hrs. Based on remaining labeled ratio (less that 0.6% of dose) in whole tissues at 144 hours, it is considered that the accumulation of this chemical is negligible. These studies show that TOTM was hydrolyzed to a limited extent in the gastrointestinal tract and was largely excreted unchanged in the feces.

 

In a second study, the distribution of TOTM was studied in rats following intravenous administration of radiolabelled TOTM using an oil in water emulsion as the vehicle. TOTM given intravenously accumulated in the liver (72%), lungs and spleen in rats within 24h. Biliary excretion was the primary route of elimination.

 

Collective analysis of the results from the toxicokinetic experiments with TOTM indicates that the submission substance is not likely to be extensively absorbed; the predominant route of excretion is via the feces; and that this material undergoes metabolism and excretion, precluding any significant bioaccumulation in the tissues. These findings are consistent with the low order of toxicity exhibited by trimellitate esters.