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Long-term toxicity to aquatic invertebrates

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Description of key information

No toxicological effects on aquatic invertebrates are expected up to the water solubility; based on read-across

Key value for chemical safety assessment

Additional information

As no studies are available for this test substance, 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 ecotoxicity, 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 substances may be considered as a category provided that their physicochemical, toxicological and ecotoxicological properties are likely to be similar or follow a regular pattern as a result of structural similarity. The long term toxicity on invertebrates in accordance to Regulation (EC) No 1907/2006, Annex IX 9.1 Aquatic toxicity was tested on the read across substance, Fatty acids, C16-18 and C18-unsaturated, branched and linear, “Monomer acid” (CAS No. 68955-98-6). As UVCB substances derived from natural sources, both Fatty acids, C16-18 and C18-unsaturated, branched and linear, “Monomer acid” and Isooctadecanoic acid, as all members of this category are chemically similar, as they are all essentially a complex mixture of C16 - C18 or C18 unsaturated and saturated, branched and linear fatty acids with varying structural geometric isomers C16 -C18 unsaturated fatty acids as Octadecanoic acid branched and linear.

The key points that the members share are:

  • Common origin of C16-18 unsaturated fatty acids
  • Similar/overlapping structural features (no hydrolysable groups, all members have a homologous composition of fatty acids with a C16 - C18 carbon chain in diverse forms, that are susceptible to oxidation of metabolic process)
  • Similar metabolic pathways (same ADME pathways of fatty acids, absorbed fatty acids undergo rapid metabolism (via ß- or ω-oxidation) and excretion either in the expired CO2 or as a hydroxylated or conjugated metabolite in the urine in the case of cyclic fatty acids)
  • Similar physico-chemical properties (4 < log Koc < 5, the log Kow is judged to be > 4, the poor solubility in water)
  • Common properties for environmental fate & eco-toxicologcial profile of the two sub-categories (readily biodegradable, no toxicological effects up to the water solubility limit for aquatic organisms)
  • Common levels and mode of human health related effects

Please refer to IUCLID Chapter 6.1 for more details on the category justification for aquatic toxicity and to section 13 for the complete category justification.

The selection of Fatty acids, C16-18 and C18-unsaturated, branched and linear (CAS No. 68955-98-6) as representative test substance for the sub-category “monomers” was an iterative process of combination of different aspects:

The water solubility of Fatty Acids, C16-18 and C-18, unsatd., branched and linear, measured as the sum solubility of all the components of the test material was estimated to be 15.0 mg/L at 20°C. However, the water solubility based on its two major constituents is 0.6 mg/L at 20°C. Media preparation trials, conducted for the chronic daphnia study, demonstrated that solubility was below 5 mg/L. The actual solubility of the UVCB substance is therefore assumed to be below 15 mg/L. As the substance is expected to have the highest solubility within the subcategory, it represents a worst case scenario in terms of bioavailability.

The only difference between this member of the sub-category and all other members is the degree of saturation or hydrogenation, respectively. In fact, all substances are closely similar. Based on an evaluation conducted using the OECD Toolbox, the degree of saturation is estimated to not have any effect on the toxicity profile of C18 fatty acids. The profiles for C18 fatty acids containing 0, 1 or 2 double bonds are the same in terms of lack of structural alerts, toxic hazard classification by Cramer, aquatic toxicity mode of action by OASIS, aquatic toxicity classification by ECOSAR, etc. For the unsaturated fatty acids additional organic functional groups are indicated (allyl, alkene), but these are not coupled to any structural alerts for protein binding. Experimental data on the long-term toxicity of 16/18C fatty acids to daphnia seem to indicate that unsaturated fatty acids even have slightly higher toxic potential compared to the corresponding saturated fatty acids (MOE, 2008; MOE 2003, entered under IUCLID section 5.1.4). This observation could possibly be explained by the fact that additional steps are required for the β-oxidation process, when double bonds are present, and more energy is thus needed for the metabolism of unsaturated fatty acids (Berg, Tymoczko and Stryer, 2002). Based on this information, Fatty Acids, C16-18 and C-18, unsaturated, branched and linear can be considered as a worst case read-across substance. Additionally, the production volume of the unsaturated form is much higher than the other members. Therefore, one can assume that the risk of any exposure would be highest here due to large production volumes. Whereas, Octadecanoic acid branched and linear, is more or less to be considered as an intermediate for the production of Isooctadecanoic acid, therefore one would expect a more limited exposure to the aquatic environment. Isooctadecanoic acid also has a lower expected production volume.

Based on all aspects discussed above, it was decided to test Fatty Acids, C16-18 and C-18, unsaturated, branched and linear as representative member of the sub-category 1 “predominantly monomers”.

The study conducted with Fatty acids, C16-18 and C18-unsatd., branched and linear, “Monomer acid” (CAS No. 68955-98-6) was performed according to the OECD guideline 211 under GLP conditions. As the test substance is a UVCB and poorly soluble in water, the test solutions were prepared as water accommodated fractions (WAF) with differential loadings. The test organism Daphnia magna was exposed to the test substance at loadings of 0.1, 0.5, 1.25 and 5.0 mg/L for 21 days. The analytical monitoring of the test concentrations showed that the test substance was present in the test solutions and that the WAFs were stable. Based on preliminary media preparation trials, 5.0 mg/L was the highest concentration at which a stable WAF could be obtained.

However, as experienced in the pretests the test substance is a poorly soluble UVCB substance, and the fatty acid cluster of the original test item differs from the soluble part in the WAF fraction, due to the different solubilities of the constituents. Therefore, as the analytical concentrations do not reflect the concentration of the original test substance, they cannot be used to derive effect values.

No significant effect on reproduction was observed in any of the treatment groups. The NOELR for both cumulative number of offspring and age at first brood was determined to be ≥ 5.0 mg/L.

The effect of the test substance on the length of the daphnids was significant at the three highest test concentrations. However, the observed reduction in growth was very small and obviously only turned out to be significant due to the very consistent length of the animals (low standard deviation) from the lowest treatment and the control groups. Additionally, as stated in the ECHA guidance, the purpose of the test is to determine the effect of the test substance on the reproductive output and the ecologically most relevant response variable is the total number of living offspring produced per parent animal. The hazard assessment is therefore based on the NOELR for reproduction. Moreover, the EC10 for length is also > 1 mg/L and thus does not influence classification.

Based on this result and the structural and profile similarity of the two substances, Isooctadecanoic acid is not expected to have toxic effects on aquatic organisms.

References:

Berg, J.M., Tymoczko, J.L. and Stryer, L. (2002) Biochemistry, 5th edition, W.H. Freeman and Company

Ministry of the Environment, Government of Japan (2003). Daphnia magna, reproduction test by oleic acid. Food Research Laboratories. Report No. 14053. 2003-03-31.

Ministry of the Environment, Government of Japan (2008). Daphnia, reproduction toxicity test for palmitic acid. Mitsubishi Chemical Safety Institute Ltd.,Laboratory. Report No. A050381. 2008-02-14.