N,N-bis(carboxymethyl)glycine, compound with 2-aminoethanol (1:3)

Basic toxicokinetics

Administrative data

Endpoint:

basic toxicokinetics in vivo

Type of information:

other: expert assessment

Adequacy of study:

key study

Study period:

2019

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: An assessment was performed based on available data on the substance and its constituents

Data source

Reference

Reference Type:

other: expert assessment

Title:

Unnamed

Year:

2019

Report date:

2019

Materials and methods

Test guideline

Qualifier:

no guideline required

Principles of method if other than guideline:

An assessment was performed based on available data on the substance and its constituents

GLP compliance:

no

Test material

Test material information

Constituent 1

Reference substance name:

N,N-bis(carboxymethyl)glycine, compound with 2-aminoethanol (1:3)

EC Number:

302-766-4

EC Name:

N,N-bis(carboxymethyl)glycine, compound with 2-aminoethanol (1:3)

Cas Number:

94134-01-7

Molecular formula:

C6H9NO6.3C2H7NO

IUPAC Name:

2-[bis(carboxymethyl)amino]acetic acid; tris(2-aminoethan-1-ol)

Test material form:

solid: bulk

Results and discussion

Main ADME results

Main ADME results 1

Type:

absorption

Results:

Following an exposure via the oral route the substance is expected to dissociate into its constituents. This is supported by experimental data on the substance. Dermal and inhalation routes are not considered relevant.

Main ADME results 2

Type:

distribution

Results:

Its constituents are expected to be well-distributed in a mammalian body. This hypothesis is supported by experimental data on the substance.

Main ADME results 3

Type:

metabolism

Results:

There is no data available on the registered substance and one of its constituents.

Main ADME results 4

Type:

excretion

Results:

There is no data available on the registered substance and one of its constituents.

Toxicokinetic / pharmacokinetic studies

Details on absorption:

- Oral exposure: It is expected that following an exposure to the substance via the oral route, the registered substance will dissociate into its constituents nitrilotriacetic acid and 2-aminoethanol. Available data on these constituents indicate that they will be absorbed in the gastrointestinal tract. Following an exposure to the registered substance via the oral route, deaths were observed at 2,000 mg/kg bw, as well as adverse effects associated with systemic toxicity and a bodyweight loss. These findings indicate that absorption occurred following an oral exposure.

- Inhalation exposure: There is no data available on the substance following an inhalation exposure, which is not considered as a relevant route of exposure taking into account the uses of the substance.

- Dermal exposure: There is no data available on the substance following a dermal exposure, which is not considered as a relevant route of exposure taking into account the uses of the substance.

Details on distribution in tissues:

Systemic effects observed following an oral exposure to the registered suggest a wide distribution in the body. Absorption of its constituents is expected to occur following an oral exposure. Both are hydrophilic compounds expected to be well-distributed in the body and unlikely to accumulate.

Details on excretion:

There is no data available on the elimination of the substance following an exposure via the oral, inhalation or dermal routes and the elimination of nitrilotriacetic acid. Respiration was identified as the main elimination route for 2-aminoethanol.

Metabolite characterisation studies

Metabolites identified:

not specified

Details on metabolites:

There is no data available on the metabolisation of the registered substance and Nitrilotriacetic acid. 2-aminoethanol is expected to be metabolised exhaled CO2, glycine, serine, choline, urea and uric acid.

Applicant's summary and conclusion

Conclusions:

An assessment was performed based on available data on the substance and its constituents.

Executive summary:

The absence of specific toxicokinetics data from animal testing means that it is not possible to make firm conclusions concerning the absorption, distribution, metabolisation and excretion of N,N’-bis(carboxymethylglycine) compound with 2-aminoethanol (1:3).

However, it is expected that the individual constituents of the substance will behave independently following oral and inhalation exposure and dermal penetration. Therefore the toxicokinetics behaviour of N,N’-bis(carboxymethylglycine) compound with 2-aminoethanol (1:3) is expected to be driven by the toxicokinetics behaviour of Nitrilotriacetic acid and 2-Aminoethanol.

It is expected that Nitrilotriacetic acid and 2-Aminoethanol will be absorbed and well distributed following an exposure via the oral route. The available experimental data on the registered substance supports the hypothesis that 2-aminoethanol and nitrilotriacetic acid are released in the body and well absorbed following an oral exposure. However, there is no data available allowing to confirm the distribution of the substance following absorption. Based on the uses of the substance no exposure via inhalation or the dermal route of N,N’-bis(carboxymethylglycine) compound with 2-aminoethanol (1:3) is expected.

No data is available on the metabolisation and elimination of Nitrilotriacetic acid and N,N’-bis(carboxymethylglycine) compound with 2-aminoethanol (1:3). 2-Aminoethanol was identified as being metabolised mainly into exhaled CO2.

It is not considered justified to perform animal studies on this substance to further investigate its toxicokinetics behaviour.