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Administrative data

Link to relevant study record(s)

Description of key information

Based on the compound’s structure, associated physical-chemical characteristics, and evidence from in vivo studies, bioaccumulation is not likely to occur. After administration, the test item is expected to be well metabolised and to be distributed throughout the body fluids and rapidly excreted in conjugated and non-conjugated forms.

Key value for chemical safety assessment

Bioaccumulation potential:
no bioaccumulation potential

Additional information

The test item carries a chiral C-atom, allowing the appearance of a D- and L-form, being present in the product in approximately equal amounts. No influence on toxicokinetics due to isomerism is anticipated.

The substance has been shown to penetrate skin: following topical administration to rats, there is a rise in urinary metabolite concentration (as measured by bioassay).

Administered orally, the test item is absorbed from the gastrointestinal tract.Dose dependent increase in blood levels of the test item and its main metabolites have been shown in two rat studies after oral application.

When bioavailable after oral or dermal application the test item is metabolized. After oral administration of the test item to rats, dose dependent increases in plasma levels of the test item and its main metabolites have been shown. In rat plasma, a Tmax of 0.5 h has been found for the test item whereas the Tmax for the two main sequential metabolites was shifted towards the 1 h sampling point, an indication of the time lapse for metabolism. The second main metabolite is a physiologically occurring substance.

It is unlikely that the test item is metabolised to more reactive (toxic) products. This assumption is supported by results obtained in oral and dermal toxicity studies and three in vitro tests. In an Ames test, a chromosome aberration assay and a HPRT test no significant increase in toxicity was noted in the presence of a rodent microsomal S9-fraction, when compared to incubation without S9-fraction.Together, this data indicates that formation of reactive metabolites is rather unlikely.

The test item and its metabolism products are expected to easily distribute via systemic circulation and based on molecular weight and water solubility, will most likely be excreted via urine.

The compound’s relatively low LogPow-value and low BCF-value of 3.2 indicate that it is widely distributed in the body, but not likely to be bioaccumulative. This is supported by the measurements taken in a subchronic toxicity study showing non-cumulative plasma levels upon repeated daily administration. In another study efficient elimination was shown by decrease of the compound’s blood level to 10-17% of Cmaxsix hours after single dose administration.

In summary, based on the compound’s structure, associated physical-chemical characteristics, and evidence from in vivo studies, bioaccumulation is not likely to occur. After administration, the test item is expected to be well metabolised and to be distributed throughout the body fluids and rapidly excreted in conjugated and non-conjugated forms.