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Administrative data

Link to relevant study record(s)

Description of key information

The test substance is rapidly metabolised in vitro in mammalian and trout hepatocytes, as well as in vivo in rats.  Predicted BCF for the test substance indicates that it would not bioaccumulate in fish.

Key value for chemical safety assessment

Bioaccumulation potential:
low bioaccumulation potential

Additional information

In an in vivo biopersistence and pharmacokinetic study, rats were given 300 mg/kg orally in a single dose. Blood plasma, liver, and fat were collected at various time points from 0 to 168 hours, and were analysed for presence of the test substance. The test substance was detected in very small amounts in plasma (< 40.0 ng/mL at the 1-, 2- and 4-hour post-dosing time points), liver (< 20.0 ng/mL at the 6-, 12-, and 24-hour post-dosing time points), and fat (< 20.0 to 99.9 ng/g at the 6-, 12-, 24-, 48-, 72-, and 96-hour post-dosing time points).

Metabolism of the test substance was examined in male and female rat hepatocytes and male mouse hepatocytes compared to heat inactivated controls. The half-life in male and female rat hepatocytes was reported as <3 minutes, as an actual rate was not attainable due to the fact that there was <5% of the parent compound remaining 5 minutes after incubation and no parent compound remaining after 15 minutes of incubation. Significant metabolism was also observed in male mice hepatocytes, but half- life and clearance rates could not be calculated due to the shape of the data curve. The steep portion of the curve between 0 and 3 minutes indicated rapid metabolism (5 µM to 1.1 µM). In the in vitro rat and mouse hepatocyte study, the largest metabolite was 6:2 uFTOH-GH. Additional major metabolites in rat hepatocytes included 6:2 GTOH-Gluc, 6:2 diOH-diGluc, 6:2 FTOH (by GC/MS), 6:2 FMA-GS (male hepatocytes only), 6:2 FTOH-Sulf (female hepatocytes only), and 6:2 UAL-GS (isomer II DNPH deriv.) (female hepatocytes only). Additional major metabolites in mouse hepatocytes included 6:2 UA-GS, 6:2 uFTOH-N-acetyl-GS, 5:2 OH-Gluc, 6:2 FTOH-Gluc, and 5-2 Ketone (DNPH deriv.).

Metabolism of the test substance was also examined in freshly isolated trout hepatocytes. Time-dependent disappearance of the test substance was observed. The steep portion of the curve between 0 and 30 minutes indicates rapid metabolism, with 83% loss of the parent compound. The curve shape in the live incubations was biphasic, with a rapid elimination phase in the first 30 minutes (alpha phase) and a slower rate between 30 and 90 minutes (beta phase). The calculated trout hepatic clearance for the test substance was 112.7 mL/h/kg. Based on the findings of this study, the predicted BCF for the test substance is 268, indicating that it would not bioaccumulate in fish.