[ω-hydroxy-C16 (saturated and unsaturated) and C16 (unsaturated)] fatty acids

Categories

Category name:

(ω-hydroxy) fatty acids and fatty acid esters, C14-18 (saturated and unsaturated linear) produced via fermentation

Justifications and discussions

Category definition:

The substance category "(ω-hydroxy) fatty acids and fatty acid esters, C14-18 (saturated and unsaturated linear)" is defined as a group of UVCB substances which are produced and excreted by an Escherichia coli K-12 organism in an aqueous fermentation process. A mixture of long-chain fatty acids is extracted from the fermentation broth using a solvent, and separated by centrifugation. The solvent is then evaporated, leaving the purified oleochemical product.

The fatty acids produced by the E. coli organism all have a linear unbranched structure. Each constituent has a carboxyl functional group at the terminal end of the carbon chain, which is common to organic fatty acids and amino acids. More than 50% of the UVCB substance is comprised of hydroxylated fatty acid species containing a hydroxyl group at one terminal end of the molecule. The UVCB substance consists of both unsaturated and mono-saturated constituents. The category is characterized by no detectable levels of any poly-unsaturated fatty acids. All of the quantified constituents are comprised of only carbon, hydrogen, and oxygen. In summary, the category substances are comprised of linear long-chain organic fatty acids and esters differentiated only by saturation and number of terminal carboxyl or hydroxyl groups.

All of the members of the substance category are produced by the same E. coli fermentation process. The only difference in their production is the solvent used to facilitate extraction and purification. Some solvents (e.g. methanol or ethanol) resulting in esterification of some carboxylic fatty acid constituents. Other solvents do not result in esterification, resulting in a higher concentration of free fatty acids in the final UVCB composition. The member substances share at least ca. 8.5% composition, with the difference in the remaining constituents being only an ester at the terminal end of the carbon chain instead of carboxyl group(s) described previously.

Category rationale:

The substance category is characterized by UVCB substances comprised of structurally similar long-chain fatty acids and their esters. The UVCB constituents all have a linear unbranched structure with aliphatic tails of 14 to 18 carbons. Each constituent has at least one carboxyl functional group at the terminal end of the carbon chain, which is common to organic fatty acids and amino acids. All of the quantified constituents are comprised of only carbon, hydrogen, and oxygen. Uncharacterized constituents are most likely high molecular weight lipid polymers formed by the conjugation of the long-chain fatty acids.

Partition coefficient - Substances in this category are extracted from the fermentation broth by a process which necessarily selects for compounds with similar solubility and partitioning characteristics. The long-chain fatty acids produced by the E. coli are similarly partitioned into a solvent and separated together during centrifugation. Thus, the manufacturing process selects for constituents with similar partitioning characteristics. Therefore, these substances are considered to be members of the same category with respect to their n-octanol/water partition coefficients.

Biodegradation - Substances in this category consist of long-chain fatty acids and their esters extracted from a biological fermentation process. All of the quantified constituents are comprised of only carbon, hydrogen, and oxygen arranged in linear unbranched structures with 14-18 carbon chain lengths. These UVCB substances consisting of linear organic fatty acids and their esters are expected to exhibit nearly identical behavior with respect to biodegradation.

Acute oral toxicity - Substances in this category consist of long-chain fatty acids which are either naturally synthesized by or obtained through the food chain of a broad range of organisms and have been positively identified in algae, plant cuticular waxes, seeds, fish, avian eggs, edible nuts, and berries. Palmitic acid (C16:0) is synthesized endogenously and serves essential cellular functions in humans. Palmitic acid and oleic acid (C18:1) comprise more than half of the fatty acid content in human breast milk. Dietary ingestion of long-chain saturated and unsaturated organic fatty acids is not known to result in acute toxicity. A literature review of rodent feeding studies published in 2016 summarized consistent tolerance for a diet high in long-chain fatty acids. The rats and mice in these studies routinely survive the full 4-12 week duration of the study on a diet providing 40-70% of dietary energy from vegetable oils. The particular solvent used to extract these UVCB constituents is not expected to have any significant differential impact on their acute oral toxicity and thus these substances are considered to be members of the same category with respect to the acute oral toxicity endpoint.

Sensitization - The constituents that comprise the UVCB substances in this category are ubiquitous in biological systems. Linear long chain fatty acid compunds (C14-18) and their esters are not known to cause sensitization in mammals. No reports of allergic contact dermatitis related to the constituents of these substances were identified in the literature. In fact, there is a significant body of ongoing clinic research investigating the potential benefits of long-chain fatty acids in reducing inflammatory conditions. Given the chemical structures of the constituents and the absence of allergy case reports in spite of the ubiquity of long-chain fatty acids in biological systems, these UVCB substances are considered to be members of the same category with respect to sensitization effects.

Genetic toxicity - The constituents that comprise the UVCB substances in this category are ubiquitous in biological systems. Linear long chain fatty acid compunds (C14-18) and their esters are not known to react with DNA or exhibit any mutagenic properties. Therefore, these UVCB substances are considered to be members of the same category with respect to genetic toxicity effects.