N,N'-bis(2,2,6,6-tetramethylpiperidin-4-yl)hexane-1,6-diamine

Endpoint summary

Key value for chemical safety assessment

Bioaccumulation potential:

no bioaccumulation potential

Additional information

No experimental data on toxicokinetics are available for the substance. The toxicokinetic behaviour of the test substance was assessed to the extent that can be derived from the relevant available data on physico-chemical and toxicological properties.

Relevant physico-chemical data

The test substance is a hindered amine light stabilizer with a purity of at least 99%. It is a solid substance at room temperature. The test substance has a molecular weight of 394.7, an n-octanol-water partition coefficient (log P_OW) of -2 at pH 7.3 and a water solubility of 1.76 g/L.

 

Toxicological profile

The test substance is corrosive to the eyes and the skin. Furthermore, experimental data showed neither skin sensitising potential in guinea pigs nor mutagenic potential in bacteria and mammalian cells.

The test substance is harmful after ingestion (LD50 = 820-880 mg/kg bw).

Oral treatment of rats for 28 or 90 consecutive days oral toxicity study in rats were performed that revealed only minor signs of systemic toxicity which were considered to be secondary due to the irritative effects. In the 90-day oral toxicity study in rats, a NOAEL (systemic) of 275 mg/kg bw/day was established, which was the highest dose administered. In addition, severe irritative effects in the GI tract were observed. Therefore, an additional NOEL for adverse effects on tissues in the gastro-intestinal and upper respiratory tracts with were primarily exposed to the test item was set at 44 mg/kg bw/day (lowest dose).

 

Assessment of toxicokinetic behaviour

The test substance is well soluble in water, has an n-octanol-water partition coefficient (log P_OW) of -2 at pH 7.3, and a molecular weight of 394.7. It is not readily biodegradable. A bioaccumulation potential is not expected. The physico-chemical properties of the test substance and consideration of Lipinsky’s rule of 5 (Lipinski, 2001) impose gastro-intestinal absorption, also supported by the water solubility. Repeat-dose toxicity studies up to 90 days of treatment predominantly revealed toxicity attributable to local irritation and only minor signs of systemic toxicity. This in turn indicates a low toxic potential and/or a low bioavailability of the test substance. Dermal permeation is expected to be negligible (Fitzpatrick, 2004). No inhalation toxicity data are available but the physico-chemical properties indicate that inhalative exposure might be possible (inhalable fraction represented less than 10% of the matter). Again, the irritation potential of the substance is a limiting factor with regards to studying toxicity via the respiratory route.

Upon oral administration, the test substance might be absorbed unchanged to some degree and is subject to hepatic metabolic degradation. Hydroxylation of the methyl carbon adjacent to the aliphatic ring(s), oxidative N-dealkylation leading to the amino-tetramethylpiperidine moiety followed by glucuronidation seems the plausible metabolic pathway (Derek / Meteor, (Q)SAR software version 11.0, Lhasa Ltd.). Subsequently, the substance will be excreted effectively. Presumably, urinary excretion of parent compound and the glucuronidation product(s) is the primary elimination pathway. Bioaccumulation as well as enzymatic reactions leading to toxic metabolites can be excluded.