Glutamic acid

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:

Glutamic acid

EC Number:

200-293-7

EC Name:

Glutamic acid

Cas Number:

56-86-0

Molecular formula:

C5H9NO4

IUPAC Name:

glutamic acid

Details on test material:

- Name of test material (as cited in study report): L-Glutamic acid
- 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-glutamic acid is a major oxidative fuel for the gut. In addition, L-glutamic acid 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-glutamic acid 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-glutamic acid 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-glutamic acid 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-glutamic acid 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-glutamic acid 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-glutamic acid metabolism are nonessential amino acids (Burrin et al., 2008). For risk assessment purposes oral absorption of Lglutamic

acid is set at 10%.

L-glutamic acid and -ketoglutarate, an intermediate in the Krebs cycle, are interconvertible by transamination. L-glutamic acid 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 L-glutamic acid will reach the nasopharyncheal region or subsequently the tracheobronchial or pulmonary region. Moreover, L-glutamic acid has a large MMAD of 127 μm and only 2.66% of the particles is below 10 μm. However, being a very hydrophilic substance with a molecular weight below 200, any L-Glutamic acid reaching the lungs might be absorbed through aqueous pores. (ECHA, 2008) For risk assessment purposes, although it is unlikely that L-Glutamic acid 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 L-Glutamic acid is set at 100%.

L-Glutamic acid 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 L-Glutamic acid 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%