Registration Dossier

Administrative data

Link to relevant study record(s)

Description of key information

No bioaccumulation potential indicated by different literature studies. 

Key value for chemical safety assessment

Additional information

Kamil (1953)

The toxicokinetic behaviour of the test item was examined. A single exposure was given to rabbits to determine the metabolism of the test item. After a single gavage of 441 mg/kg bw the test item to rabbits 57.5 % was urinary excreted within 2 days p.a. The substance as a conjugate with glucuronic acid was identified in urine.

Amberg (1999)

The toxicokinetic behaviour of the test substance was examined by using 3 male rats. The test item was administered orally. Rats were treated with 250 mg/kg [13C] test item. Urine was collected for 48h. Urinary metabolites were identified by GC/MS and 13C NMR. As a result the following results were determined:Metabolites excreted in the urine: Major metabolites: tert-amyl alcohol glucuronide and 2-methyl-2,3-butanediol and its glucuronide, Minor metabolites: free tert-amyl alcohol, 2-hydroxy-2-methylbutric acid, 3-hydroxy-3-methylbutyric acid. Enzymes identified were Cytochrom p450-monooxygenase and Glucuronyltransferase.

Thierfelder (1885)

The toxicokinetic behaviour of the test item was determined. The excretion potential of the test item was examined on rabbits and dogs. The route of administration was oral. The following metabolites were excreted into the urine: Small amounts of conjugated glucuronic acid were found in the urine. Dogs excreted no glucuronic acid conjugate following test item administration.

Collins (1999)

The toxicokinetic behaviour of the test item was examined on rats. In the liver, the test item is metabolized by two different mechanisms, P450 oxidation and glucuronide conjugation. The metabolites resulting from these reactions are 2, 3 -dihydroxy-2 -methyl-butane and the glucuronide of test item.

Pohl (1908)

The toxicokinetic behaviour of the test item was examined. The excretion potential of the test item was examined on two dogs and one rabbit. The route of administration was intravenous and subcutan. Doses of 7.3 mg/kg bw (i.v.), 10.7 mg/kg bw (s.c.) and 14.6 mg/kg bw (i.v.) were applied. As a result 65% was excreted by expired air after 5 hours and 45 min. in dogs after i.v. administration. 51.6% was excreted by expired air after 9 hours and 42 min. in dogs after s.c. administration. 22% was excreted by expired air after 3 hours and 30 min. in rabbits after i.v. administration.

Haggard (1945)

The excretion potential of the test item was determined. The test item was administered intraperitoneal to rats at a dose of 1000 mg/kg bw. Four equally devided doses at 15-minute intervals were given. Elemination via the expired air was 26.4 % and 8.9 % which was excreted in the urine within 50 hours p.a. After administration the maximum concentration in blood determined at the frist measurement at 1 hour after the first quarter application amounted to 1.23 mg/ml. At this blood concentration level the ratio of distribution between blood and tissue was 1 : 0.8. The subsequent elimination via the expired air was 26.4 % of the administered dose and 8.9 % were excreted in the urine within 50 hours p.a. The remaining 64.7 % of the injected amount of test item failed to appear but metabolism was slow since more than 50 hours were required for disapearance of the substance from blood.

Nolan (1979)

The toxicokinetik potential of the test item was examined. The test item was administered by inhalation to rats, dogs and mice over a period of 6 hours. The test item was administered at doses of 150, 500 and 1500 ppm single exposure and 50 and 1000 ppm repeated exposure. The plasma clearance was determined: Clearance: t1/2 = 100 min when rats were exposed to 150 ppm (first order kinetic), 500 and 1500 ppm exposure: saturation kinetics; Repeated exposure with 50 ppm (first order kinetic) : t1/2 = 47 min (rat), t1/2 = 69 min (dog). The concentrations of the test item in plasma of Fischer 344 rats immediately following 6 hour exposure to 150, 500, 1500 ppm were 10, 75 and 350 µg/mL, respectively. The clearance of test substance from the plasma of rats exposed to 150 ppm was apparently first order (t1/2 = 100 minutes) but exhibited saturation kinetics following 500 and 1500 ppm single exposures. Upon repeated exposure to 50 ppm, test item was cleared by rats (t1/2 = 47 minutes) and by Beagle dogs (t1/2 = 69 minutes) in an apparent first order manner. End exposure plasma concentrations after repeated exposure to 1000 ppm were approx. 110 µg/mL in rats and CD-1 mice and 480 µg/mL in dogs.