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Description of key information

In accordance with Annex VIII of the Regulation (EC) 1907/2006 (REACH), an assessment of the toxicokinetic behaviour of the substance (as required in section 8.8.1) is performed to the extent that can be derived for the relevant available information.

A toxicokinetic assessment was performed based on the available physical-chemical data and toxicological information available. Additional metabolism information was gathered using the TIMES S9 rat liver metabolism simulator.

Key value for chemical safety assessment

Bioaccumulation potential:
low bioaccumulation potential
Absorption rate - oral (%):
50
Absorption rate - dermal (%):
25
Absorption rate - inhalation (%):
100

Additional information

In accordance with Annex VIII of the Regulation (EC) 1907/2006 (REACH), an assessment of the toxicokinetic behaviour of the substance (as required in section 8.8.1) is performed to the extent that can be derived for the relevant available information. A toxicokinetic assessment was performed based on the available physical-chemical data and toxicological information available. Additional metabolism information is provided using the TIMES rat liver S9 metabolism simulator.

Introduction

Tall oil, compound with diethanolamine (“the compound”) is a dark amber coloured paste and is a UVCB organic substance.

No experimental studies of the absorption, metabolism, distribution, or elimination of the compound in mammals are available. However, information is utilized from the physical chemical properties and the existing toxicology studies on the compound, or for other very similar materials, to infer as far as possible, the potential toxicokinetics of the compound.

 

Physicochemical properties

Systemic availability of the compound depends on its ability to be absorbed across body surfaces. Factors that affect this process include water solubility, lipophilicity (measured by the partition coefficient, Kow), degree of ionization (the dissociation constant, pKa), and molecular size. Given the large number of components within the compound, it has a molecular weight of 300-500 g/mol. It disperses in water. An attempt was made to investigate the water solubility; however, no experimental determination was possible. Sample solutions saturated in the range of 0.11 to 4.77% w/w resulted in the formation of stable, uniform dispersions at 20.0 ± 0.5 °C. As this suspended, excess, undissolved compound could not be removed by either centrifugation or filtration techniques, it was not possible to isolate clear, saturated sample solutions suitable for analysis. The observed behaviour in water was consistent with the proposed composition and the extremely low surface tension values (31.4 to 31.5 mN/m). Furthermore, the salt interaction with diethanolamine was beyond the scope of available prediction methods (computer software and/or QSAR methods) therefore no alternative estimation of the water solubility was possible. The dissociation constant was not technically feasible. The log Kow ranged from 4.39 to 7.27.

Absorption

Oral absorption

The acute oral LD50 was found to be greater than 2000 mg/kg bw in an OECD 420 rat oral gavage study, with no clinical signs and no effect on body weight observed. In addition, no gross abnormalities were observed at necropsy.  

In an 90 day oral study with one of the primary metabolites, there were systemic findings at some doses from which it might be inferred that some absorption took place.

Because of the moderate dispersibility of the material in water, absorption via the oral route is likely, but in the absence of quantitative information and because of the high Pow, 50% bioavailability after oral administration is assumed for the purposes of human risk assessment.

Dermal absorption

From an acute dermal study on the test substance, the LD50 > 2000 mg/kg in male and female rats.

Eye and skin irritation studies showed the compound to be irritating, and demonstrated the potential of the compound to reach at least the living layers of the skin and likely beyond.

Systemic effects in toxicology studies with diethanolamine clearly demonstrated dermal penetration potential of this component.

For the purposes of human risk assessment however, estimation of mammalian dermal absorption is made in accordance with principles adopted by the EFSA guidance on estimating dermal absorption of pesticide active substances (EFSA, 2012). On this basis, dermal absorption is estimated at 25% for undiluted compound.

Inhalation absorption

In the absence of any quantitative data, absorption of the compound following inhalation is considered to be 100%.

Distribution, Metabolism and Elimination

No test information is available to describe the distribution, metabolism or elimination of the compound, although repeat dose studies indicate at least exposure of the bone marrow. Metabolism data can be determined using the TIMES software with in vitro rat liver S9 model. The metabolism is based on the representative structure of oleic acid-DEA salt, one of the primary components of this UVCB. The expected metabolism pathway is shown in Figure 1 (attached) and has been generated in TIMES using the in vitro rat liver with S9 model. From this map it is clear the target substance is hydrolysed to two primary metabolites, Tall Oil (CAS # 8002-26-4, represented by SMILES notation CCCCCCCCC=CCCCCCCCC(O)=O for oleic acid, CAS # 112-80-1) and DEA (CAS # 111-42-2, SMILES Notation OCCNCCO). The Toolbox Metabolite Distribution for the in vitro rat liver with S9 model (Figure 2 attached) shows that none of the target substance remains. Instead based on liver S9 metabolism, the salt dissociates into the Tall Oil and the DEA components. Based on the Metabolite Distribution, the primary compounds that eventually remain are acetic acid (CAS # 64-19-7, Metabolism Map #98, quantity = 0.974), monoethanolamine (CAS # 2272-11-9, Metabolism Map # 316, quantity = 0.621), and O-glucuronidation of DEA (no CAS #, Metabolism Map # 484, quantity = 0.258), and aliphatic C-oxidation of oleic acid (no CAS #, Metabolism Map # 115, quanity = 0.142). However, all of the remaining metabolites are downstream of the two primary main metabolites, Tall Oil (represented by oleic acid) and DEA. Therefore, Tall Oil and diethanolamine (DEA) are appropriate read across substances when test data is not available on the target substance. The read across substances are explained further in the Read Across Justification Document (based on ECHA's Read Across Assessment Framework) found in Section 13.

Conclusion

For the purposes of human risk assessment oral absorption of the substance is estimated at 50%, inhalation absorption is estimated at 100% and dermal absorption is estimated at 25%. The TIMES metabolism software shows that the target substance is expected to hydrolyze into Tall Oil and DEA. Further metabolism is seen, but the metabolites are all downstream of Tall Oil and DEA. Therefore, Tall Oil and DEA are considered appropriate read across substances when test data on the target substance is not available.