Sodium hydrogen glutamate

Basic toxicokinetics

Administrative data

Endpoint:

basic toxicokinetics

Type of information:

other: Toxicokinetic Assessment

Adequacy of study:

key study

Study period:

August 2010 - September 2010

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Toxicokinetic Assessment by a certified toxicologist.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2010

Report date:

2010

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

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

Test guideline 2

Qualifier:

according to guideline

Guideline:

other: ECB EU Technical Guidance Document on Risk Assessment, 2003

GLP compliance:

no

Test material

Test material information

Constituent 1

Reference substance name:

Sodium hydrogen glutamate

EC Number:

205-538-1

EC Name:

Sodium hydrogen glutamate

Cas Number:

142-47-2

Molecular formula:

C5H8NNaO4

IUPAC Name:

sodium hydrogen 2-aminopentanedioate

Details on test material:

- Name of test material (as cited in study report): Monosodium L-Glutamate monohydrate
- Description: White powder

Results and discussion

Main ADME results

Type:

absorption

Results:

absorption oral 10%, absorption dermal 10% and absorption inhalation 100%

Any other information on results incl. tables

TOXICOKINETIC ASSESSMENT

The dicarboxylic amino acid L-Glutamate is a major oxidative fuel for the gut. In addition, LGlutamate is an important precursor for other biologically active molecules, including glutathione, proline and arginine, and also functions as a key neurotransmitter (Reeds et al., 2000). Several studies have shown that L-Glutamate is extensively metabolized by the intestinal enterocytes. Studies by Windmueller and Spaeth using an in situ perfused rat intestine established that only small fractions of luminally administered L-Glutamate are absorbed into the mesenteric venous blood.(Windmueller and Spaeth, 1975, 1980). Subsequent studies in young pigs, preterm infants and adult humans have confirmed that dietary L-Glutamate is extensively metabolized by the intestine and that oxidation to CO2 is a major metabolic fate (Battezzati et al., 1995; Riedij et al., 2007; Stoll et al., 1999). The gut capacity for metabolism of dietary L-Glutamate is substantial, even when the intake is in excess of the normal level. Even when the dietary intake is increased three to four fold, a majority of the dietary L-Glutamate intake is metabolized by the gut, either for generation of ATP or conversion into other amino acids. Apart from CO2, most of the end-products of L-Glutamate metabolism are non-essential amino acids (Burrin et al., 2008). For risk assessment purposes oral absorption of Glutamate is set at 10%.

L-Glutamate and -ketoglutarate, an intermediate in the Krebs cycle, are interconvertible by transamination. L-Glutamate can therefore enter the Krebs cycle for energy metabolism. (Burrin et al., 2008).

Due to the low vapour pressure (< 0.00147 Pa) of the substance it is not to be expected that Glutamate will reach the nasopharyncheal region or subsequently the tracheobronchial or pulmonary region. Moreover, Monosodium L-Glutamate has a large MMAD of 148 μm and only 4.3% of the particles is below 10 μm. However, being a very hydrophilic substance with a molecular weight below 200, any Monosodium L-Glutamate reaching the lungs might be absorbed through aqueous pores. (ECHA, 2008) For risk assessment purposes, although it is unlikely that Monosodium L-Glutamate will be available to a high extent after inhalation via the

lungs due to the low vapour pressure and high MMAD, the inhalation absorption of Monosodium L-Glutamate is set at 100%.

Monosodium L-Glutamate with high water solubility and the log P value below 0 may be too hydrophilic to cross the lipid rich environment of the stratum corneum. Therefore, 10% dermal absorption of Monosodium L-Glutamate is proposed for risk assessment purposes.

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information): other: The absorption factors for risk assessment purposes have been set by a certified toxicologist: absorption oral 10%, absorption dermal 10% and absorption inhalation 100%
For risk assessment purposes:
Absorption oral = 10%
Absorption dermal = 10%
Absorption inhalation = 100%