1,4-dioxane-2,5-dione

Biodegradation in water: screening tests

Description of key information

The present test was performed according to OECD Test Guideline 301B, activated sludge was incubated with the source substance glycolic acid and the CO2 evolution was determined. Since the substance was degraded > 60% within the 10 days-window it is considered to be readily biodegradable.

Additonally, a QSAR prediction was performed using EPISuite/BIOWWIN software. 1,4 -Dioxane-2,5 -dione is considered to be readily biodegradable.

Key value for chemical safety assessment

Biodegradation in water:

readily biodegradable

Additional information

JUSTIFICATION FOR READ-ACROSS

There are no data for the assessment of biodegradability of Glycolide, therefore toxicity is assessed by read-across to the breakdown product of glycolide hydrolysis, glycolic acid. 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 biodegradation behaviour because the target substance, Glycolide, is a cyclic diester which originates from condensation of two molecules glycolic acid (source substance), an alpha-hydroxy carboxylic acid. Glycolide is assumed to be unstable in aqueous solutions. Hydrolysis of glycolide results in its breakdown product/constituent glycolic acid. Studies to determine biodegradation 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. 

Biodegradability

In a guideline study according to OECD 301B (Modified Sturm Test), the biodegradability of glycolic acid was determined. The biodegradation of 71.7 µL/L glycolic acid 78% at day 11. Thus, biodegradability was > 60% within a 0 -day window after exceeding the 10% level of biodegradability and the substance is considered to be readily biodegradable.

Additionally, a QSAR prediction with the target substance 1,4 -Dioxane-2,5 -dione was performed using EPISuite/BIOWWIN estimation software. Since, the target substance is a cyclic diester, the functional groups of the susbtance were included in the training set of structures for the BIOWWIN model. Thus, the substance falls within the applicability domain of the model and the results obtained by the QSAR prediction are considered reliable. 1,4 -Dioxane-2,5 -dione is readily biodegradable.

Hydrolysis

 In addition, 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 1,4-Dioxane-2,5-dione 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. Supplementary QSAR estimations were also performed for biodegradation. The results of these estimations revealed the same result like the experimental data from glycolic acid. Thus, the predictions are considered to be reliable and glycolide is assumed to be within the applicability domain of the used models.

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.

Similarily, 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 source substance glycolic acid. The metabolism expected to occur within these organisms is degradation through the intermediary metabolism either carbohydrate metabolism in vertebrates or CO₂fixation in plants/bacteria. Glycolic acid is mainly excreted unchanged but to a lesser extent also metabolised to e.g. by carbohydrate metabolism.

 

Conclusion

Based on available data the read-across is justified with high confidence because the target substance is hydrolytically not stable and consists of the source substance, thus tests performed in aqueous solutions or in water are supposed to be conducted with the source substance. Additionally, testing does not need to be conducted because the results from the studies performed with the source substance were supported by QSAR predictions of the ecotoxicological behaviour of glycolide.

Thus, based on the available data, it can be concluded that the results of the biodegradation study with the source substance are likely to predict the properties of the target substance and are considered as being adequate to fulfil the information requirement of Annex VII, 9.1.1 and 9.1.2.

 

References:

 

 

Oliver, David J. "Role of glycine and glyoxylate decarboxylation in photorespiratory CO2 release."Plant physiology68.5 (1981): 1031-1034.

 

As the results were above the pass level of 60% biodegradation, the substance is regarded as readily biodegradable in accordance with the Guidance on information requirements and chemical safety assessment, Chapter R.7b, Endpoint specific guidance.