2-piperazin-1-ylethanol

Basic toxicokinetics

Administrative data

Endpoint:

basic toxicokinetics, other

Remarks:

Expert statement

Type of information:

other: Expert statement

Study period:

2017-04-28

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Expert statement, no study available

Data source

Reference

Reference Type:

other: Expert Statement

Title:

Unnamed

Year:

2016

Report date:

2017

Materials and methods

Principles of method if other than guideline:

Expert statement

GLP compliance:

no

Test material

Test material information

Constituent 1

Reference substance name:

2-piperazin-1-ylethanol

EC Number:

203-142-3

EC Name:

2-piperazin-1-ylethanol

Cas Number:

103-76-4

Molecular formula:

C6H14N2O

IUPAC Name:

2-piperazin-1-ylethanol

Test material form:

liquid

Test animals

Details on test animals or test system and environmental conditions:

not applicable

Administration / exposure

Details on exposure:

not applicable

Duration and frequency of treatment / exposure:

not applicable

Doses / concentrations

Remarks:

not applicable

No. of animals per sex per dose / concentration:

not applicable

Positive control reference chemical:

not applicable

Details on study design:

not applicable

Details on dosing and sampling:

not applicable

Statistics:

not applicable

Results and discussion

Toxicokinetic / pharmacokinetic studies

Details on absorption:

Generally, oral absorption is favoured for molecular weights below 500 g/mol and log P values between -1 and 4. The very high water solubility enables the substance to dissolve readily in the gastrointestinal fluids and thus it may be considered that direct uptake into the systemic circulation through aqueous pores or via carriage of the molecules across membranes with the bulk passage of water takes place. Therefore, it can be concluded that 2-Piperazin-1-ylethanol likely becomes bioavailable following the oral route, as indicated by its physic chemical properties.

This assumption is confirmed by the results of the acute oral toxicity study. In the acute toxicity study, considerable mortalities were observed following administration of the highest dose of 5305 mg/kg bw, leading to the LD50 value of >4244 mg/kg bw.

Due to the low vapour pressure of 0.0096 hPa of 2-Piperazin-1-ylethanol it is unlikely that the substance will be available as a vapour. However, it this case, absorption via inhalation route would be possible due to the moderate log Pow value, enabling uptake directly across the respiratory tract epithelium by passive diffusion.

Dermal absorption can also take place, favoured by the log Pow value, and also by the small molecular weight of the substance.

Details on distribution in tissues:

The physicochemical properties of 2-Piperazin-1-ylethanol make systemic bioavailability very likely following oral, inhalative and dermal uptake. In general, the smaller the molecule, the wider the distribution.

After being absorbed into the body, 2-Piperazin-1-ylethanol is likely distributed into cells.

2-Piperazin-1-ylethanol is unlikely to have a bio-accumulative potential, because it is not highly lipophilic (log Pow is not greater than 4) and there are no other physic-chemical properties indicating bio-accumulating properties. Moreover, according to modelling, no bio-accumulation into organisms is expected.

Details on excretion:

Based on the physical-chemical properties and especially the low molecular weight and very high water solubility, predominantly rapid and complete excretion via the urine can be expected. This is also likely considering the propanoic component of the molecule.

The assumption of rapid excretion is supported by findings of the acute oral toxicity study as surviving animals recovered rapidly when treatment was determined.

Metabolite characterisation studies

Details on metabolites:

Based on its structure and as tertiary amine, 2-Piperazin-1-ylethanol is not considered to possibly undergo hydrolysis in contact with aqueous fluids. However, it is very difficult to predict the metabolic changes a substance may undergo on the basis of physico-chemical information alone.

2-Piperazin-1-ylethanol is a hydroxyalkyl substituted piperazine and as a tertiary amine the substance can be considered as metabolically relatively stable. Thus, no cleavage between the piperazine and the propanoic moiety can be expected. Therefore, the toxicokinetics behaviour of 2-Piperazin-1-ylethanol may be predominantly related to the alcoholic nature of the molecule. This means that the substance may be metabolized by alcohol dehydrogenase (ADH) to the propionic acid moiety via the aldehyde moiety.

Applicant's summary and conclusion

Conclusions:

Bioaccumulation of the substance is not to be excpected after continuous exposure based on expert statement.