1,3,5-Triazine-2,4-diamine, N2-[(1R,2S)-2,3-dihydro-2,6-dimethyl-1H-inden-1-yl]-6-(1-fluoroethyl)-

Additional toxicological data

Administrative data

Endpoint:

additional toxicological information

Type of information:

experimental study

Adequacy of study:

other information

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP guideline study. Not relevant under REACH.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2009

Report date:

2009

Materials and methods

Type of study / information:

Metabolism of radiolabelled test substance in the lactating goat.

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

other: EPA.OPPTS 860.1300, Nature of the Residue - Livestock

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

other: PMRA Ref.: DACO 6.2, Livestock

Deviations:

no

Test guideline 3

Qualifier:

according to guideline

Guideline:

other: OECD Guideline for the Testing of Chemicals - Metabolism in Livestock (8 January 2007)

Deviations:

no

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

N-[(1R,2S)-2,6-dimethyl-2,3-dihydro-1H-inden-1-yl]-6-[(1R)-1-fluoroethyl]-1,3,5-triazine-2,4-diamine

EC Number:

619-749-5

Cas Number:

730979-19-8

Molecular formula:

C16H20FN5

IUPAC Name:

N-[(1R,2S)-2,6-dimethyl-2,3-dihydro-1H-inden-1-yl]-6-[(1R)-1-fluoroethyl]-1,3,5-triazine-2,4-diamine

Results and discussion

Any other information on results incl. tables

The TRR (expressed in AE 1170437 equivalents) in the milk samples ranged from 0.011 ppm in the day-1 morning, day-3 morning, and day-5 morning milk to 0.048 ppm in the day-2 evening milk. The TRR found in the tissue samples was 0.368, 0.006, 0.007, 0.013, 0.015, and 0.153 ppm in liver, loin muscle, round muscle, perirenal fat, omental fat, and kidney, respectively. The residues extrapolated to 1 -times the anticipated maximum dietary burden would be <0.001 ppm in all tissues and milk.

The majority of the residues (85% to 100% of the TRR) in the milk and tissues were extractable, and only 2% to 15% of the TRR (< 0.001 to 0.023 ppm) of the residues in milk and tissues were unextractable.

The major residues found in the milk and tissues were parent AE 1170437 (2% to 20% of the TRR; 0.003 to 0.011 ppm), AE 1170437-4-hydroxy-hydroxymethyl (2% to 16% of the TRR; <0.001 to 0.020 ppm), AE 1170437-dihydroxy (11% to 14% of the TRR; 0.016 to 0.020 ppm), AE 1170437-3-ketohydroxymethyl (2% to 13% of the TRR; <0.001 to 0.017 ppm), AE 1170437-3-ketohydroxymethyl GA (2% to 28% of the TRR; 0.002 to 0.105 ppm), AE 1170437-3-hydroxyindane GA (12% to 19% of the TRR; 0.002 to 0.017 ppm), 3-hydroxyindane (12% to 18% of the TRR; 0.018 to 0.021 ppm), and AE 1170437-carboxylic acid (6% to 26% of the TRR; 0.008 to 0.089 ppm). The minor residues found in the milk and tissues were AE 1170437-4-hydroxy acid (2% to 7% of the TRR; <0.001 to 0.006 ppm) and AE 1170437-3-keto-4-hydroxy (3% to 5% of the TRR; 0.004 to 0.007 ppm).

Metabolic degradation of AE 1170437 is rapid and extensive, with between 2% and 20% of the TRR being observed in the milk and tissues as unmetabolized parent (AE 1170437). Oxidation products including AE 1170437-4-hydroxy-hydroxymethyl, AE 1170437- dihydroxy, AE 1170437-3-ketohydroxymethyl, 3-hydroxyindane, and AE 1170437-carboxylic acid were observed in milk and tissue samples, indicating that oxidation is the main route of metabolism for the parent compound. Glucuronic acid conjugates AE 1170437-3- hydroxyindane GA and AE 1170437-3-ketohydroxymethyl GA were also observed.