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Description of key information

No ADME studies are available for FAT 40045 Z. Therefore, the toxicokinetic assessment of FAT 40045 Z is predicted based on its physico-chemical properties and available toxicological study data. The OECD QSAR application toolbox v3.2 was also utilized to make a qualitative prediction of metabolites formed in the liver and skin.
The absorption, distribution, metabolism and excretion of FAT 40045 Z have been predicted in the absence of toxicokinetic studies.

Key value for chemical safety assessment

Bioaccumulation potential:
low bioaccumulation potential

Additional information

No ADME studies are available for FAT 40045/Z. Therefore, the toxicokinetic assessment of FAT 40045/Z is predicted based on its physico-chemical properties and available toxicological study data. The OECD QSAR application toolbox v3.2 was also utilized to make a qualitative prediction of metabolites formed in the liver and skin.

The absorption, distribution, metabolism and excretion of FAT 40045/Z have been predicted in the absence of toxicokinetic studies.

FAT 40045/Z (and/or blue-coloured metabolites formed in GI tract) is clearly absorbed based on ubiquitous nature of blue colouration in tissues and organs in repeated dose study.

FAT 40045/Z is expected to have a low to very low deposition into alveoli, due to particle size and therefore uptake via the inhalation route is expected to be low to very low.

FAT 40045/Z (and/or its blue-coloured metabolites) is clearly absorbed via the dermal route at the highest concentration applied in a LLNA test, as indicated by blue-coloured urine at the highest dose. Although this is not a dermal absorption study, it indicates that absorption via the dermal route is possible.

FAT 40045/Z (and/or its blue-coloured metabolites) is clearly distributed throughout the body based on results of repeated dose study. Due to the log Pow value, bioaccumulation is also predicted.

The OECD toolbox predicted chlorine (from skin metabolism) and two organic metabolites (liver metabolism) with very similar structures to the parent. Visual assessment of the parent also indicates the possibility of a chloro-diamino triazine metabolite, although toolbox does not predict this.

Excretion of parent (and/or metabolites) is via biliary duct and GI tract for oral route, but for dermal route it would appear that excretion (possibly of a blue metabolite, not formed by oral route) is also possible. This excretion via urine for the dermal route would not have been predicted and is an unexpected finding with no obvious explanation.

Although there is clear evidence that FAT 40045/Z is being systemically absorbed, there was no noticeable toxicity seen in the repeated dose oral toxicity study and the local lymph node assay.