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Administrative data

Link to relevant study record(s)

Description of key information

An assessment of the toxicokinetic behaviour of the substance to the extent that could be derived from the relevant available information was conducted as defined in Annex VII, Section 8.8 of the REACH Regulation. Using only the available data, general conclusions can be drawn regarding the toxicokinetics of hexahydro-1,3,5-trimethyl-S-triazine. It is clear that systemic effects are elicited after repeated oral administration and the fact that the substance was shown to be a sensitizer indicates that dermal adsorption can occur. However in the absence of ADME data no reliable quantitative conclusions can be drawn and therefore adsorption is considered to be 100% for all routes for risk assessment purposes

Key value for chemical safety assessment

Bioaccumulation potential:
low bioaccumulation potential
Absorption rate - oral (%):
100
Absorption rate - dermal (%):
100
Absorption rate - inhalation (%):
100

Additional information

TOXICOKINETIC ASSESSMENT

The partition coefficient (log Pow) of hexahydro-1,3,5-trimethyl-S-triazine is 0.76, meaning that the substance is essentially equally soluble in water and octanol. This property of the substance is favourable for absorption. In addition, the low molecular weight (MW= 129.2) and the high water solubility (>300 g/L) of hexahydro-1,3,5-trimethyl-S-triazine are favourable for uptake from the gastro-intestinal (G.I.) tract. The pKa for hexahydro-1,3,5-trimethyl-S-triazine is predicted to be approximately 9.0, meaning that at physiological pH, the majority of the molecule is likely to be ionized. Under certain conditions, ionized molecules tend to be less well absorbed in the G.I. tract than non-ionized species, as ionization limits passive transport through lipid membranes. However ionization may have little impact on the uptake of highly water soluble, low molecular weight molecules such as hexahydro-1,3,5-trimethyl-S-triazine, where uptake may occur via bulk water uptake through aqueous pores. In the absence of any quantitative studies regarding adsorption, distribution, metabolism and excretion (ADME) and the observation that repeated oral administration resulted in systemic effects, absorption from the G.I. tract is assumed to be significant, and for risk assessment purposes the oral absorption is set at 100%.

 

Once absorbed in the blood and plasma, hexahydro-1,3,5-trimethyl-S-triazine is expected to be widely distributed in the body, again as tissue uptake is thought to be favourable for low molecular weight water soluble molecules. Hexahydro-1,3,5-trimethyl-S-triazine is likely to be metabolized to some extent, possibly at first pass of the liver, however without specific ADME data this is not possible to determine with confidence. 

 

Excretion via the urine is favoured for low molecular weight (<300) molecules with high water solubility and which are ionised at the pH of urine; this is the likely excretion route of hexahydro-1,3,5-trimethyl-S-triazine.

 

The boiling point (149˚C) and vapour pressure (279-340 Pa) of hexahydro-1,3,5-trimethyl-S-triazine indicate that it is unlikely to reach the nasopharyngeal region or the tracheobronchial region. If hexahydro-1,3,5-trimethyl-S-triazine reaches the tracheobrochial region, absorption through aqueous pores may take place; additionally due to the slight lipophilic character of hexahydro-1,3,5-trimethyl-S-triazine, adsorption through the alveolar and capillary membranes is favoured. The high water solubility of hexahydro-1,3,5-trimethyl-S-triazine (>300 g/L) is favourable for dissolution of the substance in the mucus lining of the respiratory tract. If hexahydro-1,3,5-trimethyl-S-triazine is inhaled, significant absorption of the substance is considered likely. In the absence of qualitative ADME studies, pulmonary absorption is set at 100% for risk assessment purposes.

 

Hexahydro-1,3,5-trimethyl-S-triazine, being a highly soluble liquid (>300 g/L), has the potential to partition from the strateum corneum into the epidermis. According to the REACH Guidance (Chapter R.7C) if water solubility is high and log Pow less than 0, the substance may be too hyrdrophilic to cross the lipid rich environment of the stratum corneum; log Pow values between 1 and 4 favour dermal absorption, particularly if solubility is high. As a Tier I screen, it is proposed in the above REACH guidance that for chemicals with a molecular weight >500 and log Pow of <-1 or >4, that 10% absorption be assumed and that for chemicals outside this range, 100% absorption occurs. Based on the corrosive properties of hexahydro-1,3,5-trimethyl-S-triazine (which may enhance absorption) it is proposed that 100% adsorption is used for risk assessments.

 

Using only the available data, general conclusions can be drawn regarding the toxicokinetics of hexahydro-1,3,5-trimethyl-S-triazine. It is clear that systemic effects are elicited after repeated oral administration and the fact that the substance was shown to be a sensitizer indicates that dermal adsorption can occur. However in the absence of ADME data no reliable quantitative conclusions can be drawn and therefore adsorption is considered to be 100% for all routes for risk assessment purposes. 

Reference: SMGJ Pelgrom (2010) Toxicokinetic assessment of hexahydro-1,3,5 -trimethyl-1,3,5 -triazine, NOTOX B.V. Report Number 491811.

Owner Companies:

Nalco Limited

P.O. Box 11

Winnington Avenue, Northwich,

CHESHIRE CW8 4DX.

United Kingdom

 

Synthite Limited

Alyn Works, Denbigh Road, Mold,

FLINTSHIRE CH7 1BT.

United Kingdom

 

Taminco N.V.

Panterschipstraat 207

9000 GENT

Belgium