2,2',2''-(hexahydro-1,3,5-triazine-1,3,5-triyl)triethanol

Endpoint summary

Key value for chemical safety assessment

Bioaccumulation potential:

no bioaccumulation potential

Additional information

The test substance rapidly hydrolyzed in aqueous solutions at pH values of 4 (simulated gastric conditions), 5, and 7 (BASF SE, 2010). Decomposition products were monoethanolamine (MEA) and formaldehyde. An aqueous solution of HHT at pH 9 showed immediately after preparation signals for a mixture of undecomposed HHT, MEA and formaldehyde. Methanol could not be detected under any experimental condition.

The following assessment on the toxicokinetic behavior is based on the physicochemical properties and the results from existing toxicological studies with the test substance.

 

Relevant phys-chem properties of the substance:

- Appearance: substance is liquid

- Vapour pressure: 0.00000005 hPa at 25 °C (calculated)

- Molecular weight: 219.2813 g/mol

- Partition coefficient (logPow): -2.0 at 24 °C

- Water solubility: > 1000 g/L at 20 °C

 

Interpretation of data from acute toxicity studies and repeated dose toxicity (RDT) studies:

There are data available on acute oral toxicity in rats (LD50 approx. 1000 mg/kg bw; BASF SE, 1997) and acute dermal toxicity in rats (LD50 > 4000 mg/kg bw; BASF SE, 1997). Furthermore, there are data available on oral RDT (subchronic exposure in drinking water), with a NOAEL (rat) = 64 mg/kg bw (BASF SE, 2002). After repeated oral application, no signs of systemic toxicity were observed, indicating limited absorption of the test substance by this exposure route.

After single dermal application no mortalities, clinical effects, specific target organ toxicity or any other changes were observed. This result is suggestive of a limited dermal absorption of the test substance. Supporting to the results from toxicological studies by oral administration, the properties of the test substance meet the physiological factors for GIT absorption (MW < 500 g/mol, good water solubility, relatively moderate logPow of -2.0). According to the Danish (Q)SAR Database (EPI Suite, DERMWIN v2.09), and supporting to the lack of systemic effects in toxicity studies with dermal application the dermal absorption of the test substance is estimated to be very low with an estimated Kp value of 4.32E-06 cm/hr.

In an acute inhalation toxicity study in rats with 4-hour head/nose liquid aerosol exposure HHT caused concentration-related severe clinical symptoms and mortality after 4-hour head/nose aerosol exposure at concentrations of 0.25, 0.5 and 1 mg/L. Histopathology performed at the high concentration revealed severe lesion at the entire respiratory tract. The death of several test animals was probably caused by a direct consequence of severe diffuse necrosis of laryngeal and nasal epithelium rather then by systemic toxicity effects. Supportingly, in a subacute inhalation study in Wistar rats with administration of the test substance as liquid aerosol for 28 days a a NOAEC could not be established for local irritation effects based on histopathology findings in larynx, trachea and lung (LOAEC = 3 mg/m³). For systemic effects the NOAEC was determined to be 30 mg/m³, the highest dose tested (Triazine Task Force, 2011).

The kidney effects observed in the subchronic oral RDT study in rats (BASF SE, 2002) may have been an adaptive response to disruption of cellular water balance arising from reduced water intake. Therefore, there is no sufficient evidence for distribution of the substance or its metabolites to this organ after oral absorption.

The assessment of the bioaccumulation potential of the substance is based on the measured 1-octanol/water partition coefficient (log Pow) of -2 (BASF AG, 2002). Regarding the logPow value, accumulation of the substance in organisms is not to be expected.