N,N'-1,6-hexanediylbis(N-(2,2,6,6-tetramethyl-piperidin-4-yl)formamide

Basic toxicokinetics

Administrative data

Endpoint:

basic toxicokinetics

Type of information:

other: Assessment, based on physico-chemical properties of the compound and on toxicological data. Experimental toxicokinetic studies were not performed.

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Data source

Reference

Reference Type:

other: Assessment

Title:

Unnamed

Year:

2011

Materials and methods

Test guideline

Guideline:

other: Assessment on toxicokinetics

Test material

Test material information

Constituent 1

Reference substance name:

N,N'-1,6-hexanediylbis(N-(2,2,6,6-tetramethyl-piperidin-4-yl)formamide

EC Number:

413-610-0

EC Name:

N,N'-1,6-hexanediylbis(N-(2,2,6,6-tetramethyl-piperidin-4-yl)formamide

Cas Number:

124172-53-8

Molecular formula:

C26 H50 N4 O2

IUPAC Name:

N,N'-1,6-hexanediylbis(N-(2,2,6,6-tetramethyl-piperidin-4-yl)formamide

Applicant's summary and conclusion

Executive summary:

This Assessment is based on:

-Information on N,N'-Bis(2,2,6,6-tetramethyl-4-piperidyl)-N,N'-diformylhexamethylenediamine, provided in the Australian National Industrial Chemicals Notification and Assessment Scheme full public report (1997).

-ECHA Guidance on Information Requirements and Chemical Safety Assessment, R.7c, Chapter R.7.12: Guidance on Toxicokinetics (2008).

Experimental toxicokinetic studies have not been performed.

Absorption

Inhaltion: No signs of systemic toxicity (no mortality, no pathologic findings) were observed in an acute inhalation toxicity study in rats at a concentration of 5000 mg/m3, indicating that the compound is of low acute inhalation toxicity (bloody nasal crust formation and accelerated respiration were the only local effects observed). N,N'-Bis(2,2,6,6-tetramethyl-4-piperidyl)-N,N'-diformylhexamethylenediamine is a solid white crystalline powder with a melting point of 157.3 oC and a negligible vapor pressure under ambient conditions (approx. 10-8 Pa at 20 oC). Vapor inhalation, therefore, is a very unlikely route of exposure. The low log Pow of -2 (at pH 7, 25oC) is not favorable for absorption directly across the respiratory tract epithelium by passive diffusion. Thus, based on physicochemical and toxicological data, absorption after inhalation may be limited.

Dermal: N,N'-Bis(2,2,6,6-tetramethyl-4-piperidyl)-N,N'-diformylhexamethylenediamine is a solid white crystalline powder with a molecular weight of 450 g/mol a low log Pow of -2 (at pH 7, 25oC) and high water solubility of 13 g/l. The physicochemical data, molecular weight higher than 100, water solubility above 10g/l in combination with log Pow values below 0 indicate that dermal uptake for this substance is unlikely and will be low.

Oral: No signs of toxicity (no mortality, no pathologic findings, no clinical observations) were observed in an acute oral toxicity study in rats at a dose of 2200 mg/kg-bw. Low oral toxicity was reported in a sub acute toxicity study in rats with no effects on food consumption, body weight, clinical observations, gross lesions or histopathology at all doses investigated; 100, 300 and 1000 mg/kg-bw/day. A slight decrease of total protein and albumin concentration was fund in the serum of the high-dose females, however, a slight increase was observed in males. N,N'-Bis(2,2,6,6-tetramethyl-4-piperidyl)-N,N'-diformylhexamethylenediamine is a solid white crystalline powder with a molecular weight of 450 g/mol and high water solubility of 13 g/l. Absorption of very hydrophilic substances by passive diffusion may be limited by the rate at which the substance partitions out of the gastrointestinal fluid. The log Pow is low and pH dependent between -2 (at pH 7, 25oC) and 0.8 (at pH 9, 25oC). Since moderate log P values (between -1 and 4) are in general favorable for absorption by passive diffusion, some absorption by the gastrointestinal tract may be assumed. Overall, due to the physicochemical and toxicological data some adsorption is assumed after oral uptake for this substance.

Distribution and Metabolisation: Due to the given water solubility a wide distribution might be expected, based on the low Pow a distribution into cells is unlikely. Based on the negative results of the in vitro genotoxicity tests (salmonella/microsome test with and without metabolic activation, chromosome aberration test with and without metabolic activation) and the in vivo micronucleus test in mice after single oral dosing, it is concluded that DNA-reactive metabolits of N,N'-Bis(2,2,6,6-tetramethyl-4-piperidyl)-N,N'-diformylhexamethylenediamine will most probably not be generated in mammals.

Elimination: The high water solubility of 13 g/l and the low log Pow of -2 (at pH 7, 25oC) are not suggestive of accumulation of unchanged N,N'-Bis(2,2,6,6-tetramethyl-4-piperidyl)-N,N'-diformylhexamethylenediamine in fatty tissue subsequent to absorption from the gastrointestinal tract.

On the base of the a molecular weight of 450 g/mol and the water solubility it is assumed that excretion into urine might be the preferred route of elimination.