Hexanoic acid

Endpoint summary

Additional information

Justification for grouping of substances and read-across of the Fatty acids category

The Fatty acids category covers aliphatic (fatty) acids, which all contain the carboxylic acid group attached to an aliphatic acid chain. The category contains mono-constituent substances and UVCB substances being compositions of these substances.

Mono-constituent substances are predominantly saturated, even-numbered acids, in the carbon range C6 to C22. Other mono-constituent fatty acids include:

- odd-numbered acids: heptanoic acid C7 and nonanoic acid C9;

- unsaturated acids: elaidic acid C18:1, oleic acid C18:1, linoleic acid C18:2, conjugated linoleic acid C18:2, linolenic acid C18:3 and erucic acid C22:1;

- dicarboxylic acids: azelaic acid C9d and sebacic acid C10d.

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, 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, 40 substances are allocated to the category of Fatty acids.

Grouping of substances into this category is based on:

(1) common functional groups: all members of the Fatty acids category are carboxylic acids with a linear aliphatic tail (chain), which is either saturated or unsaturated. The carbon chain lengths varies between C6 and C22 (uneven/even-numbered); and

(2) common precursors and the likelihood of common breakdown products via biological processes, which result in structurally similar chemicals: the members of the Fatty Acids category result from the hydrolysis of the ester linkages in a fat or biological oil (both of which are triglycerides), with the removal of glycerol. Fatty acids are almost completely absorbed after oral intake by the intestinal mucosa and distributed throughout the body. Fatty acids are an energy source. They are either re-esterified into triacylglycerides and stored in adipose tissues, or oxidized to yield energy primarily via the β-oxidation pathway. The excretion products are carbon dioxide and water after metabolism; and

(3) constant pattern in the changing of the potency of the properties across the category: the available data show similarities and trends within the category in regard to physicochemical, environmental fate, ecotoxicological and toxicological properties. For those individual endpoints showing a trend, the pattern in the changing of potency is clearly and expectedly related to the length of the fatty acid chains.

A detailed justification for the grouping of chemicals and read-across is provided in the technical dossier (see IUCLID Section 13).

Environmental fate for the Fatty acids category

The data set for biodegradation includes experimental biodegradation studies as well as data obtained by QSAR. As summarized in the category justification, the members of the fatty acid category can be regarded as readily biodegradable since the vast majority of the experimental results revealed ready biodegradability which was supported by reliable QSAR predictions. The consistent positive test results over the whole category supersede single negative results. In conclusion, aliphatic fatty acids comprising C6-C22 carbon chain length are judged to be readily biodegradable. This judgment is consistent with the hazard assessment presented in the OECD SIDS (2009) for the category “Aliphatic Acids Category” where aliphatic fatty acids with a carbon chain length in the range of C6 – C22 were described to be readily biodegradable. Hydrolysis is not a relevant degradation pathway for these substances, due to their ready biodegradability and/or their poor water solubility.

The range of log Kow values in the category suggests that fatty acids with chain lengths greater than C12 may be expected to have tendency of a higher bioaccumulation. However, this takes into account physicochemical properties of chemicals and only indicates their intrinsic potential, but not its behaviour in the environment (not considering, e.g., biodegradation), and in living organisms (not considering, e.g. metabolism). Fatty acids are naturally stored in form of triacylglycerols primarily within fat tissue until they are used for energy production and therefore fatty acids are considered to present no risk to aquatic organisms with respect to the bioconcentration or biomagnification.

Within the fatty acids category the Koc values increase with increasing chain length and decreasing water solubility as well, in which fatty acids with a chain length greater than C12 shows values above log Koc < 3 indicating potential for adsorption to solid organic particles, whereas fatty acids with a chain length of C12 and smaller are unlikely to adsorb to sediment. Nevertheless, all substances are readily biodegradable, indicating that persistency in the environment (water phase, sediment or soil) is not expected.

The volatilization potential of the Fatty acids category members is negligible (Vapour pressure < 5.6 Pa at 25 °C). Nevertheless, if released into the atmosphere, the substances are expected to be rapidly photodegraded in view of their estimated half-lives in air, ranging from 0.892 to 23.24 hours (calculation with AOPWIN 1.92). Based on the above information, accumulation in air, subsequent transportation through the atmosphere and deposition into other environmental compartments is not anticipated.

Ecotoxicological properties for the Fatty acids category

Within the Fatty acids category data are available for acute and chronic toxicity to different aquatic species for category members, which are soluble in water (carbon chain length C6 - C10) and also for category members, which are poorly water soluble (carbon chain length C12 - C22).

The data for Fatty acids with a carbon chain length ofC6 - C10 show that with increasing chain length the water solubility of these substances decrease and acute as well as chronic effects increase. With regard to this increasing toxicity with increasing carbon chain length a read across from soluble fatty acids with longer chain length for fatty acids with shorter chain length is applicable.

Toxicity on microorganisms was not observed for fatty acids independent from carbon chain length.

Aquatic toxicity of hexanoic acid (CAS 142-62-1)

For data gaps on hexanoic acid, a read-across approach to heptanoic acid (CAS 111 -14 -8) was applied. If no data for heptanoic acid were available, read across was facilitated to a fatty acid with even longer carbon chain length (octanoic acid C8 CAS 124-07-2, sodium laurate C12 CAS 629-25-4) based on the worst case consideration that toxicity will increase with carbon chain length.

For hexanoic acid itself valid acute toxicity studies on fish are available and a study with sodium laurate was used to cover the chronic endpoint for fish. Studies with heptanoic acid were used to cover the acute and chronic endpoints for invertebrates and algae. Furthermore, a study conducted with decanoic acid C10 was used as read across for toxicity on microorganisms.

The acute data (LC/EC50) for the three trophic levels were in a similar range of 56.4 mg/L – 88 mg/L. The most sensitive species were algae, followed by invertebrates and fish.

Comparing the long-term effects determined for three trophic levels (fish, invertebrates and algae), fish showed the lowest NOEC for long-term exposure (NOEC of 2.0 mg/L).

Toxicity on microorganisms of hexanoic acid is not to be expected. This assumption is based on a study on Pseudomonas putida (cell multiplication inhibition test). In this test an EC10 of 912 mg/L was determined.