1,4-dioxane-2,5-dione

Hydrolysis

Description of key information

In the present study the migration of lactic acid from L-lactide as well as the respective hydrolysis rate was determined at different temperatures. At room temperature the halflife of L-lactide was 3 h. At 80°C the halflife of the test susbtance was only 0.13 h and at 60°C it was determined at 0.45 h. Thus, L-lactide is considered to be fast hydrolysed in aqueous solutions.

Key value for chemical safety assessment

Half-life for hydrolysis:

3 h

at the temperature of:

21 °C

Additional information

JUSTIFICATION FOR READ-ACROSS

There are no data for glycolide hydrolysis, therefore hydrolysis is assessed by read-across to the structural similar L-Lactide. A brief justification for read-across is given below.

Hypothesis for the analogue approach

This read-across is based on the hypothesis that source and target substances have similar structural features. The target substance, glycolide, is a cyclic diester which originates from condensation of two molecules glycolic acid, an alpha-hydroxy carboxylic acid. Glycolide is assumed to be unstable in aqueous solutions. Similarly, L-Lactide (source substance) exhibits the same structure except two additional methyl-groups on C3 and C6. L-Lactide is known to be hydrolysed resulting in two molecules lactic acid. Hydrolysis of glycolide results in its breakdown product/constituent glycolic acid. Many studies investigating physicochemical or environmental endpoints are mainly conducted in water, thus, these studies use the hydrolysis product glycolic acid as active ingredient. Testing of glycolide in aqueous solutions is therefore assumed to reveal the same results as compared to glycolic acid. 

Hydrolysis

No study was available for the determination of hydrolysis as function of pH for the target substance glycolide. However, there is data available from the structurally similar substance L-Lactide, which consists only of two more methyl-groups as compared to glycolide. These methyl-groups are not considered to modify the ring structure leading to a greater tension of the 4-ring (sp³sp²) and therefore not to an increase in hydrolysis. Also, a deceleration of hydrolysis is unlikely.  

The water solubility of glycolide as well as its partition coefficient, vapour pressure and its biodegradability are considered to be not measurable due to its hydrolysis behaviour. Additionally, the physico-chemical properties which are considered to be related to glycolides stability in aqueous solutions were estimated by QSAR predictions because measurement was technically not feasible. Studies for enzymatic degradation are not available, neither for the target nor for the source substance, however, data from published studies (metabolism in humans, rats and rabbit) indicate that glycolic acid (glycolate) is mainly metabolised to glyoxylate, which is renally excreted. Another product of glycolic acid during intermediary metabolism is oxalic acid which is an essential part of nucleotide metabolism. Similarly, in plants and also in algae glycolate is part of the carbon fixation during photosynthesis. During photosynthetic carbon fixation in many species, carbon is drawn from intermediates in the Calvin cycle to make glycolate. Before the carbon can re-enter the cycle it must be processed through the glycolate pathway. During this processing, some part of the carbon is lost as CO₂(common textbooks of plant biochemistry, Oliver D.J., 1981).

Common breakdown products:

Since the target substance glycolide is assumed to hydrolyse in aqueous solutions it can be supposed that aquatic organisms/bacteria are exposed to the breakdown product/constituent glycolic acid. Additionally, the source substance L-Lactide degrades to the breakdown product/constituent lactic acid. Both compounds are readily metabolised not only by terrestrial but also by aquatic vertebrates and invertebrates. The metabolism expected to occur within these organisms is degradation through the intermediary metabolism either carbohydrate metabolism in vertebrates or CO₂fixation in plants/bacteria. In contrast to lactic acid, glycolic acid is mainly excreted unchanged but to a lesser extent also metabolised to e.g. by carbohydrate metabolism. Lactic acid is known to be produced physiologically under anaerobic conditions, however, in the presence of sufficient oxygen, lactic acid enters carbohydrate metabolism.

Conclusion

Based on available data the read-across is justified with high confidence because similarly to the source substance the target substance is hydrolytically not stable, thus, tests performed in aqueous solutions or in water are supposed to be conducted with the breakdown product/constituent glycolic acid.

Thus, based on the available data, it can be concluded that the hydrolysis behaviour of the target and the source substance is nearly identical and that the results of studies obtained with glycolic acid are considered as being adequate to fulfil the information requirement of regulation (EC) 1907/2006, Annex VII, 9.2 for the target substance glycolide.

 

References:

Oliver, David J. "Role of glycine and glyoxylate decarboxylation in photorespiratory CO2 release."Plant physiology 68.5 (1981): 1031-1034.