Succinic anhydride

Endpoint summary

Key value for chemical safety assessment

Bioaccumulation potential:

no bioaccumulation potential

Additional information

Information regarding the toxicokinetics and percutaneous absorption of cyclic anhydrides is available in the published literature.

Toxicokinetics data on hexahydrophthalic anhydride and phthalic anhydride indicate that cyclic anhydrides are readily hydrolyzed to the corresponding dicarboxylic acid, which is mainly excreted in the urine and to a lesser extent in expired air after exposure via the inhalation route. Cyclic anhydrides share structural and physicochemical properties such that succinic anhydride would also be expected to show low systemic availability, particularly following inhalation exposure. The hydrolysis product of succinic anhydride is succinic acid, an endogenous substance and food ingredient, that is expected to be effectively excreted in urine. A separate toxicokinetics study on succinic anhydride is not proposed and cannot be justified based upon animal welfare considerations.

Percutaneous absorption of cyclic anhydrides was investigated using hexahydrophthalic anhydride as the test material. Hexahydrophthalic anhydride was shown to be minimally absorbed across human skin and similar results would be expected with succinic anhydride.

Succinic anhydride is structurally similar to maleic acid and it plays a biochemical role in the citrus acid cycle, where succinic anhydride is catalysed by succinate dehydrogenase, releasing electrons to the electron transport chain.

Succinic acid can also be oxidised to fumaric acid

The participation of malate, fumarate and succinate in the Kreb's cycle, the relative interchangeability of maleic and succinic acids via hydrolysis/hydrogenation and the derivation of succinic anhydride from maleic acid and anhydride, indicate it is reasonable to read-across from one form to another without anticipating large changes in toxicity profile.

The most common site of reactivity of cyclic anhydrides in biological systems is the initial site of contact. Like other cyclic acid anhydrides, succinic anhydride is readily hydrolyzed to a dicarboxylic acid (WHO, 2009). Dicarboxylic acids are known irritants and the formation of the acid is the basis for skin and eye irritation seen with succinic and other anhydrides (WHO, 2009).  

In addition, succinic acid is ubiquitous in prokaryotic and eukaryotic cells. Succinate is a substrate in the Krebs (citric acid) cycle and is metabolized by succinate dehydrogenase to fumarate, resulting in the generation of adenosine triphosphate. Succinic acid is an approved food additive in the EU (E 363) and is naturally found in beer and wine.