Morpholine, 4-[(triethoxysilyl)methyl]-

Endpoint summary

Additional information

(N-Morpholinomethyl)triethoxysilane is hydrolytically unstable and it reacts spontaneously with air humidity and with water under formation of (N-Morpholinomethyl)silantriol and ethanol. It can be assumed that in biological systems similar reactions occur. The hydrolysis will be cata-lyzed at lower pHs like in the stomach. Thus it can be assumed that resorption of at least the resulting ethanol will occur. To get further information on the bioavailabilty of the silan moiety, as needed for the interprtation of the in vivo micronucleus test, an animal experiment with radio-labelled (N-Morpholinomethyl)triethoxysilane (labelled at the morpholino ring) was carried out. Twelve male and twelve female NMRI mice were treated once orally with 14C-Silan 449029 VP at a nominal dose of 2000 mg/kg. The animals were sacrificed after one (three males and three females), after four (three males and three females) and after twentyfour hours (six males and six females). The concentrations of total radioactive residues were determined by Liquid Scintilla-tion Counting (LSC) in blood, plasma, femur, stomach, large intestine, small intestine, GI tract contents, liver and kidney. 24 hours after treatment total radioactivity was additionally deter-mined in faeces and urine.

One hour after application the mean total radioactive residue concentrations in male and female mice were found to be between 70.0 – 74.6μgeq/g in blood, 72.7 – 78.2μgeq/g in plasma, 42.4 – 48.9μgeq/g in femur, 5512.9 – 9183.3.μgeq/g in stomach, 2867.6 – 3180.5μgeq/g in small in-testine, 1221.5 – 1328.9μgeq/g in large intestine, 8480.0 – 23815.0μgeq/g in GI tract contents, 177.0 – 179.2μgeq/g in liver and 332.8 – 481.3μgeq/g in kidney.

Compared to 1 hour after application mean radioactive residue concentrations in male and fe-male mice were similar or higher 4 hours after application in, in small intestine, in large intestine and in combined GI tract contents reflecting the proceeding passage through the GI tract. In con-trast, in blood, in plasma, in kidney and in liver a decrease in mean radioactive residue concen-tration was observed. In femur, similar or slightly lower mean radioactive residue concentrations were observed.

24 hours after application only minor mean radioactive residue concentrations were left in stom-ach, small intestine, large intestine and combined GI tract contents compared to the 1 and 4 hours sampling time points. The same was true for blood, and femur.

At the end of the 24 hours time period, 24.9% and 17.4% of the applied dose was detected in urine, 3.4% and 9.8% of the applied dose in cage wash of male and female mice, respectively. Based on these data the systemic absorption (bioavailability) for Silan 449029 VP was at least 28.3% in male mice and 27.2% in female mice. During the same period, a total of 63.8% and 64.2% of the applied dose was excreted via faeces in male and female mice, respectively.

Overall, significant mean levels of the test item were found in blood and plasma as early as 1 hour after application. This indicates that after oral administration the test item was rapidly absorbed in significant amounts.