Fatty acids, C16-18, 1,2-ethanediylbis(oxy-2,1-ethanediyl) esters

Endpoint summary

Additional information

There are no data available on the terrestrial toxicity of Fatty acids, C16-18, 1,2-ethanediylbis(oxy-2,1-ethanediyl) esters (3EO) (CAS 91031-45-7). In order to fulfil the standard information requirements set out in Annex VI - IX, in accordance with Annex XI, 1.5, of Regulation (EC) No 1907/2006, read-across from structurally related substances was conducted.

In accordance with Article 13 (1) of Regulation (EC) No 1907/2006, "information on intrinsic properties of substances may be generated by means other than tests, provided that the conditions set out in Annex XI are met.” In particular for human toxicity, information shall be generated whenever possible by means other than vertebrate animal tests, which includes the use of information from structurally related substances (grouping or read-across).

Having regard to the general rules for grouping of substances and read-across approach laid down in Annex XI, Item 1.5, of Regulation (EC) No 1907/2006 whereby physicochemical, toxicological and ecotoxicological properties may be predicted from data for reference substance(s) by interpolation to other substances on the basis of structural similarity, the substances listed below are selected as reference substances and the available endpoint information is used to predict the same endpoints for Fatty acids, C16-18, 1,2-ethanediylbis(oxy-2,1-ethanediyl) esters (3EO) (CAS 91031-45-7).

Ecotoxicological parameters for the terrestrial toxicity of the target substance Fatty acids, C16-18, 1,2-ethanediylbis(oxy-2,1-ethanediyl) esters (3EO) and the source substances are presented in the following table.

	Target	Source 4	Source 5
CAS	91031-45-7	68583-51-7	853947-59-8
Chemical Name	Fatty acids, C16-18, 1,2-ethanediylbis(oxy-2,1-ethanediyl) esters (3EO)	Decanoic acid, mixed diesters with octanoic acid and propylene glycol	Butylene glycol dicaprylate / dicaprate
MW	388.58; 416.63; 626.99; 683.1	328.49 - 384.59	342.52 - 398.63
Fatty acids chain length	C16-18	C8-10	C8-10
Type of glycol	Triethylene glycol	1,2-propylene glycol	1,3-butylene glycol
Toxicity to soil macroorganisms except arthropods	RA: CAS 68583-51-7 RA: CAS 853947-59-8	LC0 (14 d) ≥ 1000 mg/kg dw	LC50 (14 d) > 1000 mg/kg dw
Toxicity to terrestrial arthropods	Waiving based on CSA	--	--
Toxicity to terrestrial plants	RA: CAS 853947-59-8	--	EC50 (21 d) 263.79 mg/kg
Toxicity to soil microorganisms	Weight of Evidence (WoE)	--	--

Lack of data for a given endpoint is indicated by “--“.

CSA: Chemical Safety Assessment

The above mentioned substances are considered to be similar on the basis of the structural similar properties and/or activities. The available endpoint information is used to predict the same endpoints for Fatty acids, C16-18, 1,2-ethanediylbis(oxy-2,1-ethanediyl) esters (3EO) (CAS 91031-45-7). A detailed justification for the grouping of chemicals and read-across is provided in the technical dossier (see IUCLID Section 13). This justification shows that there is convincing evidence that these chemicals lie in the overall common profile of this analogue approach. The key points, which are relevant for read-across of environmental effects, that the target and source substances share are:

 

Common functional groups: The target and the source substances are characterized by ester bond(s) between an aliphatic diol (triethylene glycol (TG), ethylene glycol (EG), propylene glycol (PG) or 1,3-butyleneglycol (1,3-BG)) and one or two carboxylic fatty acid chains;

 

Similar physico-chemical properties: For the purpose of read-across of eco-toxicity data, the most relevant physico-chemical parameter are physical state (appearance), vapour pressure, octanol/water partition coefficient and water solubility. All substances have in common, an trend of decreasing water solubility with increasing molecular weight, fatty acid chain length and degree of esterification (< 0.05 mg/L), increasing log Kow (1.78 – 16.39), high log Koc (3.18 - 8.80) and low vapour pressure (VP: < 0.0001 Pa).

 

Common properties for environmental fate & eco-toxicological profile of the target or source substances of this analogue approach: Considering the low water solubility and the potential for adsorption to organic soil and sediment particles, the main compartment for environmental distribution is expected to be the soil and sediment. Nevertheless, persistency in these compartments is not expected since the target substance and the source substances are readily biodegradable. Evaporation into air and the transport through the atmospheric compartment is not expected since the target substance and the source substances are not volatile based on the low vapor pressure. The source substances, representing the target substance, did not show any effects on aquatic organisms in acute and chronic tests up to the limit of water solubility. Moreover, bioaccumulation is assumed to be low based on metabolism data.

 

Similar metabolic pathways: fatty acid esters with an aliphatic alcohol are anticipated to be initially metabolised via enzymatic hydrolysis to the corresponding free fatty acids and the free glycol alcohols such as triethylene glycol, ethylene glycol and propylene glycol. Triethylene glycol, ethylene and propylene glycol are rapidly absorbed from the gastrointestinal tract and distributed within the body (ATSDR, 1997; ICPS, 2001; WHO, 2002; ATSDR, 2010). Following hydrolysis, absorption and distribution of the alcohol component, triethylene glycol has been shown to be excreted via the urine to a high extent without further metabolisation (NTIS, 1984). Ethylene and propylene glycol have been shown to undergo rapid biotransformation in liver and kidney and to be converted subsequently to carbon dioxide via different processes (ATSDR, 1997, 2010; IPCS, 2001). Following absorption into the intestinal lumen, fatty acids are re-esterified with glycerol to TAGs and metabolised in the liver in phase I and II metabolism. Fatty acids also undergo a process termed beta-oxidation that involves the sequential cleavage of two-carbon units, released as acetyl-CoA through a cyclic series of reaction catalysed by several distinct enzyme (Lehninger, 1970; Stryer, 1996).

 

Discussion

Three studies are available investigating effects on different species of the terrestrial compartment for the source substances decanoic acid, mixed diesters with octanoic acid and propylene glycol (CAS 68583-51-7) and butylene glycol dicaprylate / dicaprate (CAS 853947-59-8). The target and the source substances are characterized by similar physico/chemical parameters like low water solubility (< 0.05 mg/L), high log Koc (> 3) and high log Kow (> 5), indicating a similar behaviour in the environment. They are all esters of triethylene glycol, propylene glycol or 1,3-butylene glycol with varying fatty acid chain lengths (C8-C18 and C18 unsaturated) and thus, a similar metabolic pathway is expected. Consequently, bioaccumulation is not expected due to rapid metabolisation. Available read-across data in accordance to Regulation (EC) No 1907/2006 Annex XI, 1.5 from the structurally related source substances butylene glycol dicaprylate / dicaprate (CAS 853947-59-8) and decanoic acid, mixed diesters with octanoic acid and propylene glycol (CAS 68583-51-7) did not show any mortality to earthworms (Eisenia fetida) in acute terrestrial toxicity tests according to OECD 207 and EU Method C.8, respectively (LC50 > 1000 mg/kg soil dw). Testing of the toxicity on earthworm evaluates the exposure to the test substance via soil pore water, surface contact as well as by ingestion of soil particles. A long-term test is considered not be relevant as the results of the chemical safety assessment according to Annex I of Regulation (EC) No 1907/2006 did not indicate the need to investigate further the effects of the substance on terrestrial organisms. The substance has been shown to be readily biodegradable and therefore does not have a potential for persistence and thus no indirect chronic exposure of the soil. Additionally, no toxicity was observed in the standard acute toxicity tests to aquatic organisms on the three trophic levels (fish, daphnia, algae). Since indirect exposure is ruled out due to the ready biodegradability of the substance, only direct exposure could pose a risk. A higher solubility would imply that if exposure were to occur this substance would not only be adsorbed to soil particles (log Koc >5) but also concentrations may exist within the soil pore water also. The smaller fatty acid chain length increases the water solubility and therefore the bioavailability in the pore water. Water solubility is negatively correlated with the C-chain length of the fatty alcohol and fatty acid (Lide, 2005). Therefore, it is possible to extrapolate from a read-across substance with higher water solubility since it has an increased bioavailability in the pore water and can therefore be seen as a worst case for absorption via pore water (ECHA, 2012a). A plant study with butylene glycol dicaprylate/dicaprate according to OECD 208 with three species from different taxonomic groups resulted in effects on the freshweight of Avena sativa with an EC50 of 263.79 mg/kg soil. This endpoint was the most sensitive among others tested in the available study. All tested plant species showed the same effects, which are not typical phytotoxic effects as known for plant protection products (e.g. chlorosis and necrosis). The effects are resembled more growth depression like caused by a permanent water deficiency from the beginning of germination. Observed effects might have been caused by obstruction of water uptake through the roots by physical hindrance of uptake. Using a substance with a smaller fatty acid chain length represents a worst case for the uptake via pore-water as it is assumed that the water solubility increases with decreasing C-chain lengths.

No studies are available investigating the effects on soil microorganisms. Therefore, all available related data is combined in a Weight of Evidence (WoE) approach, which is in accordance to the REACh Regulation (EC) No 1907/2006, Annex XI, 1.2, to adapt the data requirements of Regulation (EC) No 1907/2006 Annex VII - IX (ECHA guidance section R.7.11.5.3, page 121).

Reliable read-across data for toxicity to aquatic microorganisms for the source substances supports the determination of a lack of toxicity to soil microorganisms. No inhibition of respiration rate of aquatic microorganisms was observed in any of the available studies for the source substances. The Guidance Document (ECHA, 2012b, page 125) states that a test on soil microbial activity will only be additionally necessary for a valid PNEC derivation if inhibition of sewage sludge microbial activity has occurred and this is clearly not the case. This is supported by further evidence from literature data. This data showed that soil microorganism communities are well capable of degrading fatty acid esters (Hita et al., 1996 and Cecutti et al., 2002) and use them as energy source (Banchio & Gramajo, 1997). Based on the available information, effects on soil microorganisms are not expected to be of concern, and consequently, no further testing is required.

Acute studies with terrestrial organisms from different taxonomic groups are regarded sufficient for the assessment of terrestrial toxicity since the target substance and the source substances are readily biodegradable and chronic aquatic data indicated no effects up to the limit of water solubility. Moreover, the relevant routes of uptake of the substance from the soil are covered by the available studies.

 

A detailed reference list is provided in the technical dossier (see IUCLID, section 13) and within CSR.