Potassium N,N-dimethylglycinate

Basic toxicokinetics

Administrative data

Endpoint:

basic toxicokinetics

Type of information:

other: Expert statement

Adequacy of study:

key study

Study period:

2016-05-11

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:

2016

Materials and methods

Principles of method if other than guideline:

Expert statement

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Potassium N,N-dimethylglycinate

EC Number:

241-629-2

EC Name:

Potassium N,N-dimethylglycinate

Cas Number:

17647-86-8

Molecular formula:

C4H8NO2.K

IUPAC Name:

potassium 2-(dimethylamino)acetate

Details on test material:

- Chemical name: Glycine, N,N-dimethyl-, potassium salt

Administration / exposure

Details on exposure:

not applicable

Duration and frequency of treatment / exposure:

not applicable

Doses / concentrations

Remarks:

Doses / Concentrations:
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:

Oral route: 
Following oral administration, the likelihood of systemic absorption through the walls of the intestinal tract depends on several physicochemical substance properties. In order to obtain a conclusive judgement of a substance’s potential to be able to reach the systemic circulation, important physicochemical factors such as molecular weight, water solubility and the log Pow need to be considered. According to ECHA Guidance Document R.7c, the smaller the molecule the more easily it gets through the walls of the gastrointestinal tract (GI). Molecular weights below 500, like the molecular weight of the test substance, are favourable for absorption. In addition, the very low log Pow indicates that the test substance is very hydrophilic and the high water solubility facilitates the absorption of such a substance due to its ability to dissolve into the GI fluids and hence make contact with the mucosal surface. In addition, the very low log Pow indicates that the substance is very hydrophilic and the high water solubility facilitates the absorption of such a substance due to its ability to dissolve into the GI fluids and hence make contact with the mucosal surface. Thus, passive diffusion of the substance is possible due to its hydrophilic nature, but is limited by the rate at which the substance partitions out of the gastrointestinal fluid. However, substances with small molecular weights (less than 200) may pass through aqueous pores or be carried through the epithelial barrier by the bulk passage of water. With regard to the toxicological data, no signs of systemic toxicity were observed in the repeated-dose study (BASF 2016, 88R0456/01C029).

Inhalation route: 
The test substance has a low volatility potential due to its very low vapour pressure of 0.000001 hPa. Thus, inhalation as a vapour is very unlikely. However, absorption via inhalation as dust might be possible. Due to the high water solubility, dusts would readily dissolve into the mucus lining the respiratory tract. Such substances may be transported out of the deposition region with the mucus and swallowed or may pass the respiratory ephithelium via aqueous membrane pores. Thus, uptake of high amounts directly across the respiratory tract epithelium is not expected. No information from acute or repeated dose toxicity studies is available, which could provide information about the systemic distribution of the test substance after inhalation.

Dermal route: 
To assess the potential of a substance to cross the skin, basic physicochemical properties of the substance, i.e. molecular weight, water solubility and lipophilicity (log Pow), should be taken into account. The test substance has a very low molecular weight which favours the dermal uptake. Nevertheless, dermal uptake of the substance is expected to be low due to its hydrophilic properties and the barrier function of the stratum corneum against ions. With a water solubility above 10,000 mg/L and a log Pow value below 0 the substance may be too hydrophilic to cross the lipid rich environment of the stratum corneum. This assumption is supported by the toxicological data achieved by a skin sensitization study (BASF 2015, 58V0456/01X070) and two acute dermal toxicity studies (BASF 1979, 78/498). The studies did not reveal that relevant amounts were absorbed into the systemic circulation as no systemic effects were observed. Based on the findings on the intact skin, the test substance is not considered as a skin irritant with respect to edema or erythema but is considered as a slightly skin irritant only due to skin scales formation (not relevant for classification purposes). The latter does not enhance skin penetration.

Details on distribution in tissues:

As mentioned above, the physicochemical properties and toxicological data revealed that the test substance can become systemically available following oral exposure. Once absorbed, the distribution of the test substance via blood stream can be assumed. The small molecular weight of the substance supports a wide distribution. Due to its high water solubility and very low Pow value distribution in fatty tissues is unlikely. In general, the transport efficiency to body tissues is limited by the rate at which the test substances cross cell membranes. For instance, access of highly water soluble substances to the central nervous system (CNS) or testes is likely to be restricted by the blood-brain and blood-testes barriers (Rozman and Klaasen, 1996).

Details on excretion:

Excretion can occur via the urine especially for small (below 300 g/mol) and water-soluble substance and/or via biliary excretion predominantly for larger molecules. Based on the high water solubility and the low molecular weight of the test substance, excretion might occur primarily via urine.

Metabolite characterisation studies

Details on metabolites:

Biotransformation of a substance aimed to increase the hydrophilicity of lipophilic substances by Phase I (functionalization) and Phase II (conjugation) enzymes. Due to the high water solubility of the test substance, metabolic conversion is unlikely. In addition, based on the results of the Ames test (BASF 2015, 40M0456/01M019), Chromosome Aberration test (BASF 2016, 33M0456/01M020) and HPRT test (BASF 2015, 50M0456/01M022) it can be assumed that the test substance is not enzymatically activated (toxified) during the metabolism as the parent compound showed no higher toxicity compared to the metabolic activated substance.