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Description of key information

The test substance is expected to be absorbed to some extent in the rat and dog, distributed, metabolized and excreted with no indication of accumulation.

Key value for chemical safety assessment

Bioaccumulation potential:
no bioaccumulation potential

Additional information

The following prediction for the metabolic fate of the test substance can be made: The test substance has amphiphilic properties and is expected to be well absorbed from the gastrointestinal tract and consequently bioavailable to some extent. Metabolic degradation of Phase I hydrolysis is assumed, generating 2,2,6,6-Tetramethylpiperidin-4-ol (HTMP) and sebacic acid (decanedioic acid) as the main metabolites, leading to phase II reactions and rapid urinary and/or biliary elimination.

The metabolite HTMP showed much less affinity to Ca-channel and acetylcholine receptors than the parent compound. This is reflected the absence of cardio-/neurotoxicity after oral administration in contrast to parenteral treatment or in-vitro study designs [1, 2].

This prediction is in line with the results of the acute toxicity studies in rats and repeat-dose toxicology studies in both rats and dogs showing low acute toxicity and absence of relevant findings after repeated administration in clinical pathology and post mortem examinations. In dogs only, hepatocellular hypertrophy of a minimal degree was observed. In rats deaths occurred at excessive dosages of ≥ 600 mg/kg, accompanied by clinical signs of poor general condition, that in single cases could also be interpreted as signs of neurotoxicity. All other findings seen can be attributed to palatability problems in the in-feed studies in rats and dogs.

1. Glossmann H et al. (1993) Proc. Nat. Acad. Sci. USA, Vol 90, 9523 -9527

2. Sotonyi P et al. (2004) Tox. Sciences 77, 368 -374