6-phenyl-1,3,5-triazine-2,4-diyldiamine

Endpoint summary

Description of key information

Data from in vitro or in vivo studies, which were designed to identify the toxicokinetic properties of the substance, are not available. This means, that absorption, distribution, metabolism and excretion (ADME) can only be derived from available physical-chemical data. To estimate the toxicokinetic properties of the substance available physical-chemical data were considered.

Key value for chemical safety assessment

Absorption rate - oral (%):

100

Absorption rate - dermal (%):

75

Absorption rate - inhalation (%):

10

Additional information

Toxicokinetic Properties

To estimate the toxicokinetic properties of the substance the following information was considered (cited from IUCLID5 data file, section 4):

 

Parameter	Value used for CSR
Molecular weight	187.17 g/Mol
Melting point	228 °C
Boiling point	> 350 °C (at 1,013 hPa)
Density	1.425 g/cm^3(at 15 °C)
Vapor pressure	< 4.1 x 10^-5Pa (at 100 °C); 1.6 x 10^-5Pa (at 25 °C) estimated
Partition coefficient n-octanol/water (log Pow)	1.38 (at 25 °C)
Water solubility	320 mg/L (at 25 °C)
pH	6.5 (at 20 °C; 300 mg/L)
pKa	3.91 (at 25 °C)
Particle size	typically: 74 µm, range: 1-100 µm

Absorption:

Based on above data the substance may be absorbed through the skin in relevant amounts (molecular weight < 500 g/Mol, -1 < log P_ow< 4, see EUROPEAN COMMISSION HEALTH & CONSUMER PROTECTION DIRECTORATE-GENERAL:Guidance Document on Dermal AbsorptionSanco/222/2000 rev. 7 19 March 2004).

Taking in account the low water solubility and the only weak acidic pKa, a 100 % dermal absorption is unlikely

For exposure assessments a value of 75 % of absorption after dermal exposure may be appropriate.

The uptake after direct inhalation of the substance may be of low relevance due to the high mean diameter of particles, which significantly exceeds the maximum inhalable particle diameter of 10 µm. Uptake by inhalation after evaporation is unlikely, the substance is a solid at room temperature and has a very high boiling point together with a very low vapour pressure .

The absorption after oral ingestion cannot be calculated due to lack of data; by default an absorption of 100 % may be appropriate, until specific data will be available, although such a high absorption is rather unlikely.

Distribution:

The substance is neither highly lipophilic nor highly hydrophilic the fact of which makes an estimation on which body compartment would be preferred for distribution in the human body practically impossible such that a more detailed description is futile.

Metabolism and Excretion:

Taking into account the structural elements of the formula it follows that two (nucleophilic) amino-groups stand out, which are known for their typical reaction with sulfotransferases, acetyltransferases and for glucuronidation. The substance may also be subject to glutathione (GSH) conjugation.

All of these reaction will increase the relatively low water solubility of the substance and improve urinary excretion, which may be the most relevant way of excretion for this substance.

But even when the water solubility stays low, a renal excretion of the unchanged molecule is possible.

Metabolic conversions at the benzene moiety or the triazine ring are quite unlikely and may not be considered any further. This means, that the basic chemical structure will not undergo a metabolic transformation.

Another relevant pathway for excretion may be by feces, especially for the fraction, which has not been absorbed in the gastrointestinal tract after oral uptake.

Excretion by exhalation does not seem to be relevant.