Lysine hydrochloride

Basic toxicokinetics

Administrative data

Endpoint:

basic toxicokinetics

Type of information:

other: assessment based on available information

Adequacy of study:

key study

Study period:

September 2010

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Study is based on expert judgement. Non GLP assessment report.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2010

Report date:

2010

Materials and methods

Objective of study:

other: toxicokinetic assessment

Test guideline

Qualifier:

no guideline required

Deviations:

not applicable

Principles of method if other than guideline:

A theoretical approach of the toxicokinetic properties of the substance based on the available physicochemical properties and toxicological data.

GLP compliance:

no

Remarks:

not applicable

Test material

Test material information

Constituent 1

Reference substance name:

Lysine hydrochloride

EC Number:

211-519-9

EC Name:

Lysine hydrochloride

Cas Number:

657-27-2

Molecular formula:

C6H14N2O2.ClH

IUPAC Name:

lysine hydrochloride

Constituent 2

Reference substance name:

L-Lysine Monohydrochloride

IUPAC Name:

L-Lysine Monohydrochloride

Details on test material:

- Name of test material (as cited in study report): L-Lysine Monohydrochloride
- Substance type: Beige powder with lumps
- Physical state: Solid
- Analytical purity: 99.72%
- Batch : 0148
- Test substance storage : At room temperature in the dark
- Stability under storage conditions : Stable
- Expiry date : 28 May 2012

Results and discussion

Preliminary studies:

See below.

Any other information on results incl. tables

L-lysine is an essential amino acid. The L-isomer of lysine is the only form that is involved in protein synthesis, and one of the 20 standard amino acids common in animal proteins and required for normal functioning in humans. It has noted roles in building muscle protein, tissue repair and growth, and the body's production of hormones, enzymes, and antibodies (Longe 2005). Lysine is metabolised in mammals to give acetyl-CoA, via an initial transamination with α-ketoglutarate.

 

Amino acids are absorbed in the small intestines by carrier-mediated transport, and for most L-amino acids, transport has been shown to be active (Matthews, 1972). The active transport mechanisms appear to be situated in the plasma membrane of the mucosal poles of the absorptive cells, since amino acids are concentrated in the cells while transport is going on. Lysine transport is not completely sodium-dependent. For risk assessment purposes oral absorption of L-Lysine Monohydrochloride is set at 100%.

 

Due to the low vapour pressure (< 1.33´10^-8Pa) and large particle size of the substance it is not to be expected that L-Lysine Monohydrochloride will reach the nasopharyngeal region or subsequently the tracheobronchial or pulmonary region. As a very hydrophilic substance with a molecular weight below 200, any L-lysine reaching the lungs might be absorbed through aqueous pores. For risk assessment purposes, although it is unlikely that L-lysine will be available to a high extent after inhalation via the lungs due to the low vapour pressure and large particle size, the inhalation absorption of L-Lysine Monohydrochloride is set at 100%.

 

L-Lysine Monohydrochloride with water solubility above 10 g/l 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-Lysine Monohydrochloride is proposed for risk assessment purposes.

1.    Martinez, Amidon GL. Mechanistic approach to understanding the factors affecting drug absorption: a review of fundamentals. J Clin Pharmacol 2002; 42: 620-43.

2.    Guidance for the implementation of REACH. Guidance on information requirements and chemical safety assessment. Chapter R.7c: Endpoint specific guidance. European Chemical Agency, May 2008.

3.    A. Parkinson. In: Casarett and Doull’s Toxicology, The basic science of poisons. Sixth edition. Ed. C.D. Klaassen. Chapter 6: Biotransformation of xenobiotics, McGraw-Hill, New-York, 2001.

4.    Longe, J. L., 2005.The Gale Encyclopedia of Alternative Medicine. Detroit: Thomson Gale

5.    Matthews D.M.,1972. Intestinal absorption of amino acids and peptides. Proc. Nutr. Soc.31, 171

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information): other: oral and inhalation absorption factor set at 100%, dermal absorption factor set at 10%
For risk assessment purposes the following absorption factors were derived:
oral absorption factor: 100%
dermal absorption factor: 10%
inhalation absorption factor: 100%

Executive summary:

For risk assessment purposes the following absorption factors were derived:

oral absorption factor: 100%

dermal absorption factor: 10%

inhalation absorption factor: 100%