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Key value for chemical safety assessment

Additional information

There were no experimental studies available investigating the toxicokinetic properties of glycine. Therefore, whenever possible, toxicokinetic behavior was assessed taking into account the available information on physicochemical and toxicological characteristics of glycine according to the “Guidance on information and chemical safety assessment Chapter R.7c: Endpoint specific guidance (ECHA, 2009)”.

Absorption

Glycine has a molecular weight of 75.07 g/mol and is a white crystalline solid with a water solubility of 250 g/L at 25°C. Its vapour pressure is estimated to be 0.000017065 Pa and its log Po/w is -3.21.

The acute oral toxicity of has been investigated in rats (Nemoto, 1977). The LD50 from this study was determined to be 9550 and 7930 mg/kg bw for male and female animals, respectively. Therefore, glycine is of very low toxicity. It is a natural occuring amino acid and the average adult ingests 3 to 5 g of glycine daily (HMDB, 2013). Glycine is very rapidly absorbed along the gastrointestinal tract via special carrier systems (Elmadfa and Leitzmann, 1998). The Danish QSAR Database also predicted bioavailability of glycine after oral ingestion.

The proportion of glycine having an inhalable particle size of less than 100 µm was determined to be 1.48%. Therefore, glycine is considered to be essentially non-inhalable.

A Dermwin v2.0 QSAR modeling estimated a dermal permeability constant Kp 4.37E-006 cm/h for glycine. Similar to the approach taken by Kroes et al. (2007), the maximum flux Imax (Imax = Kp [cm/h] x water solubility [mg/cm³]) was calculated, resulting in dermal absorption of 1 µg glycine/cm²/h. The Danish QSAR Database predicted a low dermal bioavailability as well (0.002 mg/cm²/event).

Distribution

Once absorbed, glycine will mainly be transported via the portal vein into the liver but also distributed within the whole body since it is involved in the body´s production of haem, DNA, phospholipids and collagen. The demand of glycine is therefore highest in terms of rapid growth (Müller-Esterl, 2004; Elmadfa and Leitzmann, 1998).

Metabolism

Glycine is a non-essential amino acid and can be biosynthesized in the body from the amino acid serine. In most organs, the enzyme serine hydroxymethyltransferase catalyses this transformation using tetrahydrofolate (THF), leading to methylene THF and glycine. Glycine can be degraded via three pathways. The predominant way in mammals involves the glycine cleavage system. This leads to the degradation of glycine into ammonia and CO2. In the second pathway, glycine is degraded in two steps. The first step is the reverse of glycine biosynthesis from serine with serine hydroxymethyl transferase. Serine is then converted to pyruvate by serine dehydratase. In the third route to glycine degradation, the amino acid is converted to glyoxylate by D-amino acid oxidase. Glyoxylate is then oxidized by hepatic lactate dehydrogenase to oxalate in an NAD+-dependent reaction (Lehninger 2005, Salway 2004).

The OECD QSAR application toolbox was used for a qualitative prediction of metabolites formed in liver, skin and gastrointestinal tract. It predicted 3 hepatic, 2 gastrointestinal and 6 skin metabolites. Among these metabolites, pyruvate, glycolic and oxalic acid could be identified.

Excretion

Glycine, which is not used for synthesis processes within the body will be excreted. Glycine and its metabolites are soluble in water and thus subjected to renal elimination. Significant faecal excretion of glycine is not expected.

References:

-Elmadfa and Leitzmann (1998) Ernährung des Menschen (3rd ed.). Stuttgart: Ulmer

-HMDB (Humand Metabolome Database) (2013): http://www.hmdb.ca/metabolites/HMDB00123

-Lehninger, AL (2005) Lehninger principles of biochemistry (4th ed.). New York: W.H. Freeman

-Müller-Esterl (2004) Biochemie (1st ed.). Munic: Elsevier GmbH

-Salway, JG (2004) Metabolism at a glance (3rd ed.). Alden, Mass.: Blackwell Pub.