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

Basic toxicokinetics

Administrative data

Endpoint:

basic toxicokinetics

Type of information:

other: expert statement

Adequacy of study:

key study

Study period:

April 2011

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: The statement is performend through an expert of toxicology referring to the available data.

Data source

Reference

Reference Type:

other: expert statement

Title:

Unnamed

Year:

2011

Materials and methods

Objective of study:

toxicokinetics

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

Expert statement

Test material

Test material information

Constituent 1

Reference substance name:

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

EC Number:

202-095-6

EC Name:

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

Cas Number:

91-76-9

Molecular formula:

C9H9N5

IUPAC Name:

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

Results and discussion

Main ADME results

Main ADME results 1

Type:

absorption

Results:

dermal 75 %; oral 100%; inhalative 10%

Main ADME results 2

Type:

distribution

Results:

no statement possible based on available data

Main ADME results 3

Type:

metabolism

Results:

the substance may be target of typical Phase II enzymes

Main ADME results 4

Type:

excretion

Results:

renal and fecal excretion seem possible, excretion by inhalation does not seem to be relevant

Any other information on results incl. tables

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: 125 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.

Applicant's summary and conclusion

Conclusions:

The presented assessment is reliable and adequate for 6-phenyl-1,3,5-triazine-2,4-diyldiamine, because the expert statement based on the available studies of the substance.