A mixture of: bis(2,2,6,6-tetramethyl-1-octyloxypiperidin-4-yl)-1,10-decanedioate; 1,8-bis[(2,2,6,6-tetramethyl-4-((2,2,6,6-tetramethyl-1-octyloxypiperidin-4-yl)-decan-1,10-dioyl)piperidin-1-yl)oxy]octane

Basic toxicokinetics

Administrative data

Endpoint:

basic toxicokinetics

Type of information:

other: assessment

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Because of limited data (which are provided by ECHA) it is difficult to make a full toxicokinetic assessment.

Data source

Reference

Reference Type:

other: Body responsible for the test

Title:

Unnamed

Year:

1991

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

other: ECHA Guidance on information requirements and chemical safety assessment, Chapter R.7c: Endpoint specific guidance, R.7.12 Guidance on Toxicokinetics

Deviations:

not specified

GLP compliance:

no

Test material

Test material information

Constituent 1

Reference substance name:

Reaction mass of bis[2,2,6,6-tetramethyl-1-(octyloxy)piperidin-4-yl] decanedioate and 1,1'-bis[2,2,6,6-tetramethyl-1-(octyloxy)piperidin-4-yl]10,10'-{octane-1,8-diylbis[oxy(2,2,6,6-tetramethylpiperidine-1,4-diyl)]}

IUPAC Name:

Reaction mass of bis[2,2,6,6-tetramethyl-1-(octyloxy)piperidin-4-yl] decanedioate and 1,1'-bis[2,2,6,6-tetramethyl-1-(octyloxy)piperidin-4-yl]10,10'-{octane-1,8-diylbis[oxy(2,2,6,6-tetramethylpiperidine-1,4-diyl)]}

Constituent 2

Reference substance name:

A mixture of: bis(2,2,6,6-tetramethyl-1-octyloxypiperidin-4-yl)-1,10-decanedioate; 1,8-bis[(2,2,6,6-tetramethyl-4-((2,2,6,6-tetramethyl-1-octyloxypiperidin-4-yl)-decan-1,10-dioyl)piperidin-1-yl)oxy]octane

EC Number:

406-750-9

EC Name:

A mixture of: bis(2,2,6,6-tetramethyl-1-octyloxypiperidin-4-yl)-1,10-decanedioate; 1,8-bis[(2,2,6,6-tetramethyl-4-((2,2,6,6-tetramethyl-1-octyloxypiperidin-4-yl)-decan-1,10-dioyl)piperidin-1-yl)oxy]octane

Cas Number:

129757-67-1

Molecular formula:

Constituent 1: C44H84N2O6 Constituent 2 : C80H150N4O12

IUPAC Name:

2,2,6,6-tetramethyl-1-(octyloxy)piperidin-4-yl 2,2,6,6-tetramethyl-1-{[8-({2,2,6,6-tetramethyl-4-[(10-oxo-10-{[2,2,6,6-tetramethyl-1-(octyloxy)piperidin-4-yl]oxy}decanoyl)oxy]piperidin-1-yl}oxy)octyl]oxy}piperidin-4-yl decanedioate; 2,2,6,6-tetramethyl-1-(octyloxy)piperidin-4-yl 2,2,6,6-tetramethyl-4-{[8-({2,2,6,6-tetramethyl-1-[(10-oxo-10-{[2,2,6,6-tetramethyl-1-(octyloxy)piperidin-4-yl]oxy}decanoyl)oxy]piperidin-4-yl}oxy)octyl]oxy}piperidin-1-yl decanedioate; bis[2,2,6,6-tetramethyl-1-(octyloxy)piperidin-4-yl] decanedioate

Constituent 3

Reference substance name:

Reaction mass of bis[2,2,6,6-tetramethyl-1-(octyloxy)piperidin-4-yl] decanedioate and 1,1'-bis[2,2,6,6-tetramethyl-1-(octyloxy)piperidin-4-yl]10,10'-{octane-1,8-diylbis[oxy(2,2,6,6-tetramethylpiperidine-1,4-diyl)]}

IUPAC Name:

Reaction mass of bis[2,2,6,6-tetramethyl-1-(octyloxy)piperidin-4-yl] decanedioate and 1,1'-bis[2,2,6,6-tetramethyl-1-(octyloxy)piperidin-4-yl]10,10'-{octane-1,8-diylbis[oxy(2,2,6,6-tetramethylpiperidine-1,4-diyl)]}

Administration / exposure

Route of administration:

oral: unspecified

Results and discussion

Toxicokinetic / pharmacokinetic studies

Details on absorption:

Oral/GI absorption: With a high molecular weight (Constituent 1: 737.15 g/mol; Constituent 2 : 1360.07 g/mol), high log P value ( log Pow >10) and very low water solubility (< 6mg/L) , substance is considered to not have oral/GI absorption. The oral toxicity data showing the LD50 > 2000 mg/kg bw/day indicates that no signs of systemic toxicity is present. It is to be expected that the oral bio-availability and the systemic exposure of substance will be very low.
Respiratory absorption - Inhalation: As substance is not soluble in water, has higher log P value, has low volatility, has a low vapour pressure and its viscosity is such that it is unlikely to form aerosol mists in use, it is expected that this chemical has no potential to be inhaled. Inhalation is not a significant route of exposure during use of substance.
Dermal absorption: With low water solubility and high molecular weight, dermal absorption of substance is anticipated to be very low. As Log P value is above 6, the rate of transfer between the stratum corneum and the epidermis will be slow and will limit absorption across the skin. Uptake into the stratum corneum itself may be slow.

Details on distribution in tissues:

28-day oral toxicity study recorded as follow: No premature mortalities occurred. The body-weight gain was not impaired as a result of the treatment. Prolognation of the prothrombin time, which however, was reversible in the animals from the recovery group, was observed among the males from the highest-dose group. Clinico-chemicals findings, organ weights and the macroscopic investigation did not reveal any substance-related changes. The histological examination revealed an increase in the extramedullar haematopoietic activity in the liver among the male animals from the high-dose group. No further substance-related changes (including neurological findings) were determined.

In 90-day oral toxicity study there was no macroscopic pathology and no histopathological finding after 13 weeks that was attributed to treatment. Microscopic examination indicated an increased incidence of inflammatory changes in the lungs of females give 1000 mg/kg/day. These were shown to be fully reversible. Also liver weight values were slightly high after 13 weeks in males that received 150 or 1000 mg/kg/day. This change showed full recovery.

It is expected that substance has a lower volume of distribution in the human body owing to its high molecular weight, which has less capability of distributing in tissues in body. Accumulation in fat or in other tissues is unlikely.

Details on excretion:

With a high molecular weight and low water solubility, substance may be excreted via bile. The excretion of compounds via bile is highly influenced by hepatic function as metabolites formed in the liver may be excreted directly into the bile without entering the bloodstream. Additionally, blood flow as such is a determining factor. Little is known about the determinants of biliary excretion in humans.

Metabolite characterisation studies

Metabolites identified:

not measured

Details on metabolites:

In view of its hydrophobicity, high molecular weight, high log P value, low volatility, absorption of CHIGUARD 101 is considered negligible. In the case absorption occurs, substance will be extensively metabolised in the liver and rapidly excreted via bile. Accumulation in the body during prolonged exposure will be very low.

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information): no bioaccumulation potential based on study results
Based on the expected kinetic behaviour in the body, substance will hardly be absorbed after oral administration, mainly because of its hydrophobicity and higher molecule weight. Absorption dermal and inhalation are anticipated to be low thanks to low water solubility and high lop P value. If absorption occurs, substance will be extensively metabolised in the liver and excreted via bile. Substance is predicted to have no bioaccumulation potential.