Hexanoic acid

Endpoint summary

Additional information

Justification for grouping of substances and read-across

The Fatty acids category covers aliphatic (fatty) acids, which all contain the carboxylic acid group attached to an aliphatic acid chain. The category containsmono-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).

Physico-chemical properties

Saturated mono-constituent fatty acids are solids in ambient conditions with an exception of the short chain ones: C6, C7, C8 and C9. In general, melting point increases with the chain length, but odd-numbered fatty acids are characterized by lower melting temperatures than preceding even-numbered ones, so that the sequence is C7-C6-C9-C8 (from -7 to +17 °C). In the range C10-22, melting point increases from 31 to 81 °C. Even higher are the values for dicarboxylic acids: 106.5 °C (azelaic acid) and 131 °C (sebacic acid). Non-saturated fatty acids are characterized by lower melting points: from -16.5 °C in the case of linolenic acid C18:3 to 45 °C for elaidic acid C18:1; the latter and erucic acid C22:1 (melting point of 34 °C) are the only solid fatty acids under ambient conditions in the category. The isomerisation trans-cis plays here a role: while C18:1-trans elaidic acid is solid, the cis-counterpart oleic acid is liquid (melting range from 9 to 16 °C). UVCB substances are solids or liquids, depending on the fractions of short-chain and unsaturated acids.

 

Boiling points are in the range from 203 °C (C6, hexanoic acid) to about 460 °C (Fatty acids, sunflower oil, conjugated). For certain, especially unsaturated, fatty acids, boiling points are often measured at reduced pressure, in order to avoid decomposition. Generally, boiling point increases with the chain length.

 

The vapour pressure pattern is a mirror image of the boiling point trend. For shorter chains (< C10), the values are low (< 0.1 hPa), and for longer chains (from C10) as well as dicarboxylic acid, very low and negligible. Saturation does not influence the boiling point and the vapour pressure as significantly as it is the case by the melting point.

 

The octanol-water partition coefficient, log Kow, is a quantity difficult for experimental determination, and in most cases weight of evidence approach, based on QSAR data, is used. Available QSAR models include Rekker approach (D’Amboise and Hanai, 1982) and EPISUITE KOWWIN (U.S. EPA, 2000). Partition coefficient increases with the chain length. For 4 substances: C6, C7 and two dicarboxylic ones, log Kow values are lower than 3. The highest value over the category is the one for C22 of 9.91.

Water solubility data is a mirror image of the log Kow data, from soluble C6 (10.3 g/L at 25 °C) up to values below 1 mg/L starting at C14. For the UVCBs, their data reflect the trends for single substances, depending on short and long chain fractions.

 

Dissociation constant (pKa) values including experimental and QSAR data (SPARC, Hilal et al, 1995) are at room temperatures 20-25 °C in the range from 4.55 (azelaic acid) to 5.70 (decanoic acid). The values predicted by SPARC are ca. 4.75 at 25 °C for monocarboxylic category substances.