2-[2-(3-butoxypropyl)-1,1-dioxo-1,2,4-benzothiadiazin-3-yl]-5'-tert-butyl-2-(5,5-dimethyl-2,4-dioxo-1,3-oxazolidin-3-yl)-2'-[(2-ethylhexyl)thio]acetanilide

Bioaccumulation: aquatic / sediment

Description of key information

Regression based estimate: BCF = 442.1 L/kg (BCFBAF v3.01)
Arnot-Gobas: BCF = 78.98 L/kg (BCFBAF v3.01)

Additional information

No experimental data evaluating the bioaccumulation potential of 2-[2-(3-butoxypropyl)-1,1-dioxo-1,2,4-benzothiadiazin-3yl]-5'-tert-butyl-2-(5,5-dimethyl-2,4-dioxo-1,3-oxazolidin-3-yl)-2'-[(2-ethylhexyl)thio]acetanilide (UY-330) are available. According to the Guidance on information requirements and chemical risk assessment, Chapter R.11: PBT assessment (ECHA, 2012), for substances with a tonnage band ≤ 100 tonnes/year “normally a bioaccumulation test is not required and therefore a BCF value may not be available. In that case it should be considered if the available testing and non-testing data are sufficient to conclude on the B-properties for those substances < 100 t/y or if bioaccumulation testing is required to draw a reliable conclusion”.

Regarding 2-[2-(3-butoxypropyl)-1,1-dioxo-1,2,4-benzothiadiazin-3yl]-5'-tert-butyl-2-(5,5-dimethyl-2,4-dioxo-1,3-oxazolidin-3-yl)-2'-[(2-ethylhexyl)thio]acetanilide (UY-330), the information gathered on environmental behaviour and metabolism in combination with the QSAR-estimated BCF values provide evidence (in accordance with the 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. 1907/2006, Annex IX) to state that this substance is likely to fulfil the Bioaccumulative (B) but not the very Bioaccumulative (vB) criteria.

Based on a measured log Pow of > 6.2 and a calculated Log Pow of 8.8, UY-330 is considered to have a bioaccumulation potential in aquatic organisms, and therefore, precautionary classification in the environmental hazard category Chronic Aquatic 4 (according to Regulation No. 1272/2008) and R53 (Directive 67/548/EEC) is assigned to this substance. Nevertheless, UY-330 is not expected to have a BCF value above 5000 L/kg (very Bioaccumulative).

QSAR calculations have been performed using the BCFBAF v3.01 program in order to estimate the BCF values for this substance. The BCF value estimated via the regression method is 442.1 L/kg, whereas the BCF value estimated via the Arnot-Gobas method, including biotransformation is 78.98 L/kg (upper trophic level; Bieberstein, 2013). The main difference between these two methods is that the regression method is purely based on the partition coefficient value (log Kow) of the substance (8.8 in the case of UY-330). On the other hand, the Arnot-Gobas method considers additionally whole body primary biotransformation following the uptake of the substance in fish.

The available experimental mammalian data and QSAR predictions considered for the toxicokinetics statement in IUCLID section 7.1 indicate that UY-330 has a low bioaccumulation potential in mammals and that the fraction absorbed via the oral and dermal route will be rapidly metabolized and excreted. Furthermore, no systemic effects were observed both during the acute and subacute studies performed with rats, indicating that the substance has limited oral bioavailability (Hooiveld, 2003 and van Otterdijk, 2004). The lack of irreversible adverse effects in the 28-day oral repeated dose toxicity study (van Otterdijk, 2004) indicates that the substance will be metabolized and/or excreted rapidly. Even considering the extrapolation from mammals to fish physiology, the experimental data show that the substance is chronically non-toxic and provides strong evidence of the unlikelihood of the substance being very Bioaccumulative (vB).

Moreover, the PBT assessment guidance states that at log Kow values above 6, a decreasing relationship between log Kow and bioaccumulation potential is observed. One of the reasons that might explain this pattern is the reduced uptake of highly hydrophobic substances due to increasing molecular size. According to this same Guidance, if a substance has a molecular weight higher than 700 g/mol (as UY-330), this is an indicator showing that the BCF value will be below 5000 L/kg.

In conclusion, the information above provides strong evidence supporting the statement that UY-330 can be considered as not very Bioaccumulative (vB). Nevertheless, the Bioaccumulative (B) criterion cannot be excluded and it is considered for further assessment.