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Description of key information

The substance has an affinity for fatty tissues however does not bioaccumulate due to metabolic breakdown.

Key value for chemical safety assessment

Bioaccumulation potential:
no bioaccumulation potential

Additional information

The substance has a high pKa value and is therefore protonated at physiological pH (see attached document). The protonated substance has a log Koc of 4.01 and therefore shows a moderate affinity for the compartment of the fatty tissues. The molecule contains several sites for metabolism (e.g. for hydrolysis, oxidation) and allows ring opening and degradation of the aliphatic chains. It is therefore considered that both metabolic conversion (which is lowering the Koc) and metabolic breakdown counteract to the trend for bioaccumulation. In summary the substance is unlikely to bioaccumulate.

The substance applied orally interacts with the tissues of the gastrointestinal tract and due to its high pKa value locally distorts hemostasis. This effect is likely responsible for the local effects observed in the gastrointestinal tract. Due to the increase of pH along the gastrointestinal tract from stomach (pH < 4) to duodenum (pH 8.3) an increasing amount (~ +80%) of the subtance becomes available in the non-protonated form (see attached calculation). Neutralization of the molecule favours its passage through the mucous membrane in the upper gastrontestinal tract. Following absorption the pH drops again to the value of the plasma (pH 7.4) and may be responsible for systemic & local effects.

Metabolism: The substance is considered to be susceptible for oxidation at the double bond of the aliphatic chain and at the nitrogen atoms of the ring. This leads to ring opening and subsequent breakdown of the molecule.