Reaction product of 1,3,5-Triazine-2,4,6-triamine, polymer with formaldehyde, methylated and C16-18 fatty alcohols

Bioaccumulation: aquatic / sediment

Additional information

Experimental bioaccumulation data is not available for Reaction product of 1,3,5-Triazine-2,4,6-triamine, polymer with formaldehyde, methylated and C16-18 fatty alcohols. The substance is produced in a tonnage below 100 t/a, and therefore a bioaccumulation test is not required and a BCF value is not available. Thus, the evaluation of the bioaccumulation potential of the substance is based on a Weight of Evidence (WoE), combining all available related (testing and non-testing) data. This is in accordance with REACh Regulation (EC) No 1907/2006, Annex XI General rules for adaptation of the standard testing regime set out in Annexes VII to X, 1.2, to cover the data requirements of Regulation (EC) No. 1907/2007 Annex IX and X (Guidance on information requirements and chemical safety assessment Chapter R.7c: Endpoint specific guidance, R.7.11.5.3, page 123 ff (ECHA, 2012)).

The integrated assessment and testing strategy outlined in the REACh Guidance on Information Requirements and Chemical Safety Assessment Chapter R.11: PBT/vPvB assessment (2017) was used as a basis for the Bioaccumulation assessment of the substance. According to these criteria the substance meets the screening criterion of high partition coefficients (log Kow) of > 7.9 (KOWWIN v1.68). However, as explained in detail below, due to information from the toxikokinetic assessment, QSAR predictions and physicochemical properties, the substance is not expected to bioaccumulate.

 

Uptake/Absorption and Distribution

The toxicokinetic assessment indicates a low dermal absorption potential due to the low water solubility of < 15 µg/L, the high log Pow value of > 7.97 and the high molecular weight of the substance (600.85-1077.76 g/mol). This indicates a low probability of the substance to cross biological membranes (ECHA 2017). Inhalative uptake is also considered negligible due to the very low vapour pressure (< 0.0001 Pa). Overall, however, oral absorption of the substance is likely. Micellular solubilisation can take place due to the high log Pow (> 4) and the low water solubility (< 1 mg/L,) of the substance (ECHA, 2017). If the substance is taken up orally, distribution of the compound within an organism depends on its physico-chemical properties; especially the molecular weight, the lipophilic character and the water solubility. The high molecular weight of the UVCB substance (600.85-1077.76 g/mol) does not favour a high distribution potential. Furthermore, for large and complex structures a high degree of conformational flexibility is assumed. Dimitrov et al. (2002) revealed a tendency of decreasing log BCF in combination with an increase in conformational flexibility of molecules. The authors assume that this effect is related to an enhancement of the entropy factor on membrane permeability of chemicals. There is a high probability that the substance exists in a conformation which would in this case reduce the potential for membrance permeation.

 

Metabolism

Information on metabolism of the constituents of the substance also indicate low bioaccumulation potential. Three representative constituents of the complex UVCB substance were selected for the prediction of the metabolites, using the OECD QSAR toolbox v4.2 (OECD, 2018). With this QSAR tool the metabolites that may result from enzymatic activity in the liver, enzymatic hydrolysis and by intestinal bacteria in the gastrointestinal tract were predicted.

Between 23 and 62 hepatic metabolites and 22 to 41 metabolites due to enzymatic hydrolysis (acidic) were predicted for the represented constituents. The evaluation of the toxicokinetic behaviour indicates that, after absorption by the gastrointestinal (GI) tract, hydroxylations of the C16- and C18-alkyl side chains takes place, thereby increasing the water solubility of the lipophilic compounds which makes the chemical structures more susceptible to further metabolism in the liver and, ultimately, excretion via urine. Between 166 and 505 metabolites for the three representative constituents were predicted to result from all kinds of microbiological metabolism. Most metabolites were found to be a consequence of the degradation of the molecule in multiple steps. For further details on the toxicokinetic behavior please refer to the toxicokinetic statement in IUCLID section 7.1.

In addition, various QSAR models that predict bioconcentration factors (BCF) for the constituents of the substance were taken into account as supporting information. The following BCF values were calculated:

1.23 – 19.5 L/Kg (Vega v.1.1.4, BCF model (KNN/Read-Across) v.1.1.0)

0.76 – 7 L/Kg (Vega v.1.1.4, BCF model (CAESAR) v.2.1.14)

3 - 11 L/Kg (Vega v.1.1.4, BCF model (Meylan) v.1.0.3)

0.893 – 1.3 L/Kg (EPISUITE v.4.11, Arnot-Gobas BCF & BAF Methods (including biotransformation rate estimates))

These very low BCF values ranging between 0.76 and 19.5 L/Kg, reveal a low bioaccumulation potential of the substance and support the toxicocinetics outcome concerning a high rate of biotransformation after uptake. Furthermore the Profiler “Lipinski rule OASIS” from the OECD QSAR Toolbox v.4.3 claims all constituents as little bioavailable. The Profiler “Example Prioritization Scheme (PBT)” does not predict the constituents as bioaccumulative.

In addition one long term toxicity study with mammals is available. The oral repeated dose toxicity of the substance was tested over 28 days according to the OECD guideline 422. No toxicity effects were observed in the study up to the highest tested concentration of 1000 mg/Kg bw/day. This complete absence of effects is a further indication that the substance is either chronically non-toxic and/or that it is not taken up to a significant extent.

 

Environmental behaviour

The substance bears a very low water solubility of 15 µg/L (OECD 105) and moderate to high log Koc values ranging between 3.58 and 12.45 (MCI, KOCWIN v2.00). These parameters indicate that the constituents of the substance will mainly adsorb to suspended organic particles, dissolved organic matter and to some degree biota in the aquatic environment (Jaffé, 1991) and will not be easily bioavailable to aquatic organisms. A potential uptake of the substance by organisms of the pelagic zone can occur mainly via food ingestion since the substance may adsorb to solid particles. Benthic or sediment-dwelling organisms may take up the substance by ingestion of contaminated sediment. However, the substance is expected to be significantly eliminated in sewage treatment plants due to its high adsorption potential and the very low water solubility (Guidance on information requirements and chemical safety assessment, Chapter R.7a (ECHA, 2012)). Insoluble substances are largely removed in the primary settling tank and fat trap during the clarification and sedimentation process of waste water treatment (according to the Guidance on information requirements and chemical safety assessment, Chapter R7.b (ECHA, 2012)). Only small amounts of the substance may therefore enter the secondary treatment and get in contact with activated sludge. Further adsorption to sewage sludge will additionally eliminate the substance from the water column during this process. On this basis exposure and therefore availability of the substance by aquatic organisms through the water phase is very limited, which reduces the probability of uptake and accumulation (e.g., see McKim et al, 1984; Björk, 1995; Haitzer et al., 1998).

 

Conclusion

Reaction product of 1,3,5-Triazine-2,4,6-triamine, polymer with formaldehyde, methylated and C16-18 fatty alcohols is characterized by a low water solubility (< 15 µg/L at 20 °C and pH 6.3; OECD 105), a high estimated log Kow (> 7.9 (KOWWIN v1.68) and high molecular weight (>600 g/mol). Based on the physico/chemical properties such as low water solubility and a high potential for adsorption a reduced availability in water is expected. The highly lipophilic character of the substance indicates a tendency to distribute into cells, particularly fatty tissues. This tendency is, however, reduced by the high molecular weight of the substance which significantly reduces the absorption due to steric hindrance to cross biological membranes. If the substance is taken up by an organism, oral absorption is the most likely route. The substance is enzymatically metabolised, yielding hydroxylated breakdown products that are further metabolised in the liver and ultimately excreted via urine. Bioaccumulation in organisms is therefore considered very low. This is further supported by calculated BCF values, none of which raise concern over bioaccumulative behaviour. Long-term toxicity data with mammals did not show any toxicity effects supporting the assumption of no bioaccumulation potential by the substance.

Taking all this information into account, it can be concluded in a weight of evidence approach that the bioaccumulation of Reaction product of 1,3,5-Triazine-2,4,6-triamine, polymer with formaldehyde, methylated and C16-18 fatty alcohols is low.