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Endpoint summary

Additional information

Hypothesis for the analogue approach

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, information shall be generated whenever possible by means other than vertebrate animal tests, through the use of alternative methods, for example, in vitro methods or qualitative or quantitative structure-activity relationship models or from information from structurally related substances (grouping or read-across).” According 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, substances may be considered as a group provided that their physicochemical and toxicological are likely to be similar or follow a regular pattern as a result of structural similarity. The substances within the analogue approach are considered to apply to these general rules and the similarity is justified on basis of scope of variability and overlapping of composition, representative molecular structure, physico-chemical properties and toxicological profiles. There is convincing evidence that these chemicals lie in the overall common profile of this analogue approach. The key points that the target and source substances share are:

·                    Common functional groups: Both, source and target are fatty acid amides. Most of the components of the target substance have alkyl chain ranging between C16 and C18, while the source substance is predominantly C22.

·                    Similar physico-chemical properties: For the purpose of read-across of (eco)toxicity data, the most relevant physico-chemical parameters are physical state (appearance), vapour pressure, octanol/water partition coefficient and water solubility. Both substances are solid and have in common a low water solubility (<0.0191 mg/L), high partition coefficient (log Pow >6.62) and a low vapour pressure (< 3 Pa at 25 °C).

·                    Similar metabolic pathways: The target and source substance are anticipated to be hydrolysed in the gastrointestinal tract and/or liver, resulting in the generation of free ammonia as well as free long-chain, saturated or unsaturated fatty acids (C16, C18 and C22). Hydrolysis represents the first chemical step in the absorption, distribution, metabolism and excretion pathways assumed to be similar between the target substance and the source substance. Following hydrolysis of fatty acid amides, fatty acids are readily absorbed by the intestinal mucosa and distribute systemically in the organism. They are either re-esterified into triacylglycerols and stored in adipose tissue, or enzymatically degraded in order to generate energy, primarily via β-oxidation and the subsequent catabolic pathways citric acid cycle and oxidative phosphorylation. Unsaturated fatty acids require additional isomerization prior to entering the β-oxidation cycle.

·                    Common properties for environmental fate & eco-toxicological profile of the target and source substance: Considering the low water solubility and the high potential for adsorption to organic soil and sediment particles, the main compartment for environmental distribution is expected to be soil and sediment.The available results demonstrate no acute or chronic toxicity of the substances up to the limit of water solubility. Based on the study results both substances are considered not toxic to aquatic organisms. Experimental data evaluating the toxicity of the target and source substance to soil/sediment organisms are not available. Since the substances are poorly water soluble an exposure of sediment organisms is considered unlikely.The Guidance on information requirements and chemical safety assessment, Chapter R7.b (ECHA, 2014) states that once insoluble chemicals enter a standard STP, they will be extensively removed in the primary settling tank and fat trap and thus, only limited amounts will get in contact with activated sludge organisms. Nevertheless, once this contact takes place, these substances are expected to be removed from the water column to a significant degree by adsorption to sewage sludge (Guidance on information requirements and chemical safety assessment, Chapter R.7a, (ECHA, 2014). Thus, discharged concentrations of this substance (if at all) into the aqueous/sediment and soil compartment are likely to be low. Based on the available information, toxicity to soil and sediment organisms is expected to be low. Evaporation into air and the transport through the atmospheric compartment are not expected since the target substance and the source substance are not volatile based on the low vapour pressure. Moreover, bioaccumulation is assumed to be low based on the results of the bioaccumulation assessment; the substances are not expected to bioaccumulate. Available data for the target and the source substance showed that the substances are not toxic to aquatic organisms as no effects were observed in acute and chronic studies up to the limit of water solubility (fish, aquatic invertebrates and algae). The target substance did not exhibit any effects on aquatic microorganisms. Therefore, effects on the microorganism community and the degradation process in sewage treatment plants are not anticipated.

·                    Common levels and mode of human health related effects: The available data indicate that the target and source substance have similar toxicokinetic behaviour (low bioavailability of the parent substance; anticipated hydrolysis of the amide bond followed by absorption, distribution, metabolism and excretion of the breakdown products) and that the constant pattern consists in a lack of potency change of properties. Thus, based on the available data, the target and the source substance of the analogue approach show a low acute oral, dermal and inhalation toxicity and no potential for skin or eye irritation and skin sensitisation. Furthermore, the target and source substance are not mutagenic or clastogenic and have no toxic effects on reproduction or intrauterine development.

Analogue approach justification

Ecotoxicity

Short term toxicity tests with species of 3 trophic levels are available for the target and the source substance. The results demonstrate no acute or chronic toxicity of the substances up to the limit of water solubility. Based on the study results both substances are considered not toxic to aquatic organisms. Experimental data evaluating the toxicity of the target and source substance to soil sediment organisms are not available. Since the substances are poorly water soluble an exposure of sediment organisms is considered unlikely. Acute and chronic aquatic studies indicate that the substances are not toxic to organisms. The substances are not expected to bioaccumulate. Based on the available information, toxicity to soil and sediment organisms is not expected to be of concern.

Table: Data matrix environmental toxicity

	Target Chemical	Source Chemical
Name/CAS #	Amides, C18, branched and linear	Erucamide/112-84-5
Fish acute toxicity 96h LC50 mg/L	Experimental result: LC50 >100 mg/L (nominal). No toxic effects up to limit of WS	Data waiving
Daphnia acute toxicity 48h EC50 mg/L	Data waiving	Experimental result: EC50 ≥0.13µg/L (measured). No toxic effects up to limit of WS
Long-term toxicity to fish	Data waiving	Experimental result: NOEC is ≥ 105 µg/L (measured). No long-term effects up to the limit of water solubility.
Long-term toxicity to aquatic invertebrates	Experimental result: NOEC is ≥ 0.0038 mg/L (measured. No long-term effects up to the limit of water solubility.	Experimental result: NOEC is ≥ 77 µg/L (measured). No long-term effects up to the limit of water solubility.
Algae toxicity 72h EC50/NOEC mg/L	Experimental result: EC50 >100 mg/L (nominal). No toxic effects up to limit of WS	Experimental result: EC50 >50 µg/L (measured). No toxic effects up to limit of WS

Aquatic toxicity

Data on the aquatic toxicity of Amides, C18, branched and linear are available for all three trophic levels (fish, aquatic invertebrates, algae). All available studies are compliant to GLP standards and were conducted according to internationally accepted guidelines. The generated data demonstrates no acute or chronic toxicity of the test substance up to the limit of water solubility.

The acute toxicity of the substance to fish was investigated in a study following OECD guideline 203. The determined LC50 was > 100 mg/L based on the nominal test substance concentration. The toxicity to aquatic algae was tested according to OECD guideline 201. The observed EC50 value was >100 mg/L (nominal). An acute toxicity study on aquatic invertebrates is not available. The toxicity to Daphnia was tested in a long-term study according to OECD 211. Based on the reproduction rate a NOEC ≥ 100 mg/L (nominal) was determined. Long-term toxicity testing to fish was not considered to be necessary since there was no evidence from the available data that fish are more sensitive compared to aquatic invertebrates.

A study investigating the toxicity of the substance to aquatic microorganisms is not available. The assessment is therefore based on the toxicity control of the ready biodegradation test. Inhibition of the microbial activity was not observed and thus a NOEC of 13.1 mg/L was determined.