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Description of key information

The substance Sodium 5-oxo-L-prolinate is an organic substance, a white to pale yellow powder at ambient temperature; it has the molecular formula C5H7NO3.Na and a molecular weight of 151 g/mol. It is very soluble in water (613 g/L at 20 °C) and has a Log POW < 1.0. Sodium 5-oxo-L-prolinate is a substituted proline and is basic in nature, with a (Q)SAR estimated pKa value of 9.94. 
As no specific studies on absorption, distribution, metabolism and excretion are available, the physico-chemical properties and the results of acute and repeat dose toxicity studies performed with Sodium 5-oxo-L-prolinate have been used to infer as far as possible, a toxicokinetic profile.
For risk assessment purposes, oral and inhalation absorption of Sodium 5-oxo-L-prolinate is assumed to be complete; dermal absorption is assumed at 1% as a worst-case estimate.
The substance will be widely distributed following absorption, and eventually utilised within the ‘γ-glutamyl cycle’ providing antioxidant for the body in the form of glutathione or for the synthesis of other amino acids.

Key value for chemical safety assessment

Bioaccumulation potential:
no bioaccumulation potential
Absorption rate - oral (%):
100
Absorption rate - dermal (%):
1
Absorption rate - inhalation (%):
100

Additional information

Introduction

As no specific studies on absorption, distribution, metabolism and excretion are available, the physico-chemical properties and the results of acute and repeat dose toxicity studies have been used to determine, as far as possible, a toxicokinetic profile for Sodium 5-oxo-L-prolinate.

Physicochemical properties

The substance Sodium 5-oxo-L-prolinate is an organic substance, a white to pale yellow powder at ambient temperature; it has the molecular formula C5H7NO3.Na and a molecular weight of 151 g/mol. It is moderately soluble in water (613 g/L at 20 °C) and has a Log POW of < 1.0. The vapour pressure is 0.54 kPa at 20 °C.

Sodium 5-oxo-L-prolinate is the sodium salt of an uncommon amino acid derivative in which the free amino group of glutamic acid or glutamine cyclises to form a lactam and is basic in nature, with a (Q)SAR estimated pKa value of 9.94.

Absorption

Oral absorption

The small molecular weight, together with the moderate water solubility and moderate Log POW all suggest readily absorption following oral administration, mainly through the intestinal tract where the pH is a little more basic.

In a published paper (Ishii et al., 1992), the substance was administered via the diet at extremely high dosages (up to 7000-8000 mg/kg bw/day) to rats for either 13 or 26 weeks; in addition to the control group (untreated diet), the study included a concurrent control receiving sodium at a level corresponding to that contained at the highest dose level. Treatment was well tolerated, without any signs of over toxicity or mortality. Changes included observation of soft faeces, up to week 9 of treatment, considered related to a transient insufficient adaptation of the intestinal tract due to the intake of food which contains large amount of highly-moisturizing test substance, increased water consumption, slight increase in urine pH value, and organ weight as well as microscopic changes in kidneys, which were comparable to the Na-treated controls and considered adaptive to the constant high load of sodium.

The ‘soft faces’, observed till week 9 of treatment, and the similarity of results obtained for the high dose animals and the Na-treated controls confirm that the substance was completely absorbed, and that it does not accumulate and possesses a highly favourable toxicological profile.

In addition, in a fully compliant recently performed OECD 421 study (Kiss, 2013), no adverse effects were noted for any of the parameters evaluated and the NOAEL/NOEL for parental, reproductive and developmental toxicity was the limit dose of 1000 mg/kg bw/day.

For risk assessment purposes, oral absorption is assumed to be complete.

Dermal absorption

The substance is reported to be a normal constituent of the stratum corneum, as one of the hygroscopic components of the water-soluble fraction that helps to maintain the moisture content of the corneum (Laden and Spotzes, 1967).

Nothing can be inferred from the acute dermal toxicity study, because, as in the case of oral administration, the LD50 was greater than the limit dose of 2000 mg/kg bw and no signs of local or systemic toxicity were noted.

The Log POW, lower than 1, also supports limited penetration into the stratum corneum, and hence dermal absorption.

For risk assessment purposes, dermal absorption is assumed at 1%, as a really worst-case estimate.

Inhalation absorption

The substance has a vapour pressure of 0.54 kPa at 20 °C and is marketed as a solution therefore inhalation exposure is not expected to occur. However, the moderate water solubility, low Log POW, and the likely complete absorption following oral administration, suggest that the substance can readily absorbed if inhaled.

In the absence of quantitative data, complete absorption following inhalation is assumed for risk assessment purposes.

Distribution

The small molecular weight (even smaller when the salt dissolves) and moderate water solubility suggest that the substance would be widely distributed within the body.

Metabolism

As indicated by the drinking behaviour of rats dosed at extremely high doses for up to 3 months, and adaptive changes in the kidney, sodium released from the salt is absorbed from the intestine and enters into the large physiological pool for this electrolyte existing within the body.

5-oxo-L-proline is the substrate of the enzyme 5-oxoprolinase that catalyzes the conversion of 5-oxoproline to glutamate in the presence of ATP, and is present mainly in the kidney but was also found in rat liver, spleen, lung, and brain (Van Der Werf et al., 1971).

Elimination

Sodium will be eventually excreted in the urine. 5-oxo-L-proline will be not excreted, but converted into glutamate and then utilised within the ‘γ-glutamyl cycle’ providing antioxidant for the body in the form of glutathione or for the synthesis of other amino acids.

Conclusion

For risk assessment purposes, oral and inhalation absorption of Sodium 5-oxo-L-prolinate is assumed to be complete; dermal absorption is assumed at 1% as a worst-case estimate.

References

Ishii H., Fujimoto T., Ninomiya K. & Torii K. (1992)

Toxicity Study of Sodium L-2-Pyrrolidone-5-carboxylate (PCA-Na) Administered to Rats in Diet for 13 and 26 Weeks

IYAKUHIN KENKYU, 23 (6), 717-736

Laden K. & Spotzes R. (1967)

Identification of a natural moisturizing agent in skin

J. Soc. Cosmet. Chem., 18, 351

Van Der Werf P., Orlowski M. & Meister A. (1971)

Proc. Nat. Acad. Sci. USA, 68 (12), 2982-2985