4-tert-butyltoluene

Endpoint summary

Additional information

The elimination of [methyl-¹⁴C]p-tert-butyltoluene (purity not given) after intragastric and inhalational administration (doses of 100 mg/kg) was studied in male Wistar rats and in male Dunkin Hartley guinea pigs (Ingebritson and Walde, 1982; Walde and Scheline, 1983).

 

The chemical was well absorbed through the gastro-intestinal and respiratory tract, was quickly distributed, and was eliminated within a few days.

In rats, 73% of a single oral dose (100 mg/kg) was recovered in the urine and feces within 3 days. After 10 days, 83% of the administered dose was recovered; the ratio of urinary/fecal radioactivity was ca. 3.5 : 1. Elimination was biphasic with the slower elimination phase beginning on day 6 after dosing.

At day 3 after dosing, urinary excretion of radioactivity was 45% and 25% after oral and inhalational exposure, respectively, in rats and 42% and 41% after oral and inhalational administration, respectively, in guinea pigs.

 

In a metabolism study (Roche 1982), p-tert-butyltoluene (purity not given) was administered orally to rats at dose levels of 0, 25, and 100 mg/kg bw. Urine was collected within 24 h after dosing, worked up and analyzed by GC and GC/MS.

p-Tert-butylbenzoic acid (TBBA) was detected in a dose-related way in the urine samples of all treated rats. However, the corresponding p-tert-butyl hippuric acid (TBHA; i.e. the glycine conjugate of TBBA) could not be detected. GC/MS revealed additional peaks which were tentatively assigned to the trimethylsilyl derivatives of p-tert-hydroxybutylbenzoic acid and p-tert-carboxybutylbenzoic acid. These results suggested that p-tert-butyltoluene was metabolized by rats to a considerable degree to TBBA, which was eliminated in the urine (probably as glucuronide). Minor amounts of TBBA were further oxidized at the tertiary butyl group and then excreted in the urine. The oxidation reaction was likely to be a result of microsomal enzymes in the liver.

The following metabolic pathway was proposed: tert-butyl toluene is oxidized to p-tert-butyl benzoic acid and, in parts, further oxidized to p-tert-hydroxybutyl benzoic acid. The two latter compounds and are excreted in the urine, probably as glucuronides.

This metabolism study in the rat is classified acceptable and satisfies the guideline requirement for a metabolism study in rats. 

On the occasion of various 5 day oral toxicity studies of TBT, mice, guinea pigs and dogs were administered 100 mg/kg bw/d TBT for 5 days, and urine was collected for 24 h after the last administration and analyzed for the different metabolites, i.e. TBBA and TBHA by GC analysis. TBBA was determined as metabolite in urine samples of treated dogs and at very low amounts in guinea pigs. However, TBHA was found to be at higher levels in urine samples of treated mice and guinea pigs compared to TBBA, whereas TBHA levels were lower in the urine of dogs than TBBA levels