2-Octen-1-ylsuccinic anhydride, mixture of cis and trans

Endpoint summary

Link to relevant study record(s)

Reference

Endpoint:

basic toxicokinetics

Type of information:

other: paper-based review of toxicokinetics

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Performed according to ECHA Technical Guidance, R.7. Information requirements and the chemical safety assessment, 2010.

Objective of study:

toxicokinetics

Qualifier:

no guideline available

Principles of method if other than guideline:

Performed according to ECHA Technical Guidance, R.7. Information requirements and the chemical safety assessment, 2010.

GLP compliance:

no

Type:

metabolism

Results:

The substance readily hydrolyses, and the corresponding dicarboxylic acid is formed. For OSA, the hydrolysis product is octenyl succinic acid.

Details on absorption:

As the compound is a viscous liquid or semisolid with moderately high octanol/water partition coefficients and are sparingly soluble in water, upon oral exposure the chemical substance would be absorbed by the gastrointestinal tract. The structural and physical properties ncluding comparatively high molecular weight, the presence of long-chain tetrapropenyl moieties and sparingly water solubility, is expected to reduce the rate and extent of dermal absorption, thus dermal absorption rate is likely low. A high boiling point, low vapor pressure, and high viscousity suggests the substance would have a low propensity to form vapors or aerosols, so the inhalation absorption rate is also likely low.

Details on distribution in tissues:

Following absorption, distribution can occur to highly perfused organs such as the kidney. The lack of target organ toxicity other than the kidney is an indication that this substance is not widely distributed in the body.

Details on excretion:

The substance is sparingly water soluble, rapidly hydrolytically degraded to dicarboxylic acids, and based on excretion data for other acid anhydrides, is eliminated quickly with a half time that would indicate little bioaccumulation potential.

Details on metabolites:

The substance reacts easily with water (hydrolysis), and the corresponding dicarboxylic acid is formed. The formation of acid explains the irritating effects on the skin and the mucous membranes of the eyes. Acid anhydride groups reacts readily with amino acids and this reaction explains their conjugation with human serum albumin an explains the irritating effects in the forestomach after oral administration. In an Ames assay, metabolic activation with rat liver enzymes does not result in formation of metabolites which are mutagenetic.

The ASA category compounds are viscous liquid or semisolid substances with low octanol/water partition coefficients and sparingly soluble to insoluble water solubilities. These characteristics indicate that alkenyl succinic anhydrides are slightly lipophilic, and thus, capable of passive diffusion across biological membranes. ASA category members are also hydrolytically unstable and the resulting species are known to react with proteins. Thus it can be predicted that upon oral exposure these chemical substances would be absorbed by the gastrointestinal tract with an absorption rate >50%. The structural and physical properties of each compound including comparatively high molecular weight, the presence of long-chain tetrapropenyl moieties and sparingly water solubility, is expected to reduce the rate and extent of dermal absorption, thus dermal absorption rate is likely <10%. The alkenyl succinic anhydrides have relatively high boiling points, low vapor pressure, and are viscous liquids and thus have a low propensity to form vapors or aerosols, therefore exposure via inhalation is not likely and the inhalation absorption rate is also likely < 10%. Following absorption distribution can occur to highly perfused organs such as the kidney. The lack of target organ toxicity other than the kidney is an indication that members of the ASA category are not widely distributed in the body. Alkenyl succinic anhydrides are hydrolyzed to dicarboxylic acids and excreted in urine as the corresponding acids. While ASA category members are sparingly water soluble, they hydrolytically degrade to dicarboxylic acids and based on excretion data for other acid anhydrides are eliminated with a half time that would indicate little bioaccumulation potential.

Conclusions:

Interpretation of results (migrated information): no bioaccumulation potential based on study results
This substance has low water solubility, a moderate octanol/water partition coefficient, and low vapour pressure. It is rapidly hydrolyzed (within minutes) to the corresponding butanedioic acid. The substance may be absorbed from the gastrointestinal tract, but dermal and inhalation absorption are low. Distribution may occur to highly perfused organs, but a lack of target organ toxicity (other than kidney) for tripropenyl succinic anhydride indicates that the substance is not widely distributed in the body. Reactivity of the hydrolysed substance likely occurs in the local environment. The substance is excreted in the urine as the corresponding acid with a half-life that would indicate little bioaccumulation potential.

Description of key information

The substance has low water solubility, moderate octanol/water partition coefficient, and low vapour pressure.  It may be absorbed from the gastrointestinal tract, but has low absorption via the skin and respiratory tract.  It may be distributed to organs, but is quickly hydrolysed and eliminated in the urine.  Metabolism/hydrolysis is to the dioic acid.

Key value for chemical safety assessment

Bioaccumulation potential:

no bioaccumulation potential

Absorption rate - oral (%):

100

Absorption rate - dermal (%):

10

Absorption rate - inhalation (%):

10

Additional information

The ASA category compounds are viscous liquid or semisolid substances with moderate octanol/water partition coefficients and sparingly soluble to insoluble water solubilities. These characteristics indicate that alkenyl succinic anhydrides are slightly lipophilic, and thus, capable of passive diffusion across biological membranes. ASA category members are also hydrolytically unstable and the resulting species are known to react with proteins. Thus it can be predicted that upon oral exposure these chemical substances would be absorbed by the gastrointestinal tract with an absorption rate >50%. The structural and physical properties of each compound including comparatively high molecular weight, the presence of long-chain tetrapropenyl moieties and sparingly water solubility, is expected to reduce the rate and extent of dermal absorption, thus dermal absorption rate is likely <10%. The alkenyl succinic anhydrides have relatively high boiling points, low vapor pressure, and are viscous liquids and thus have a low propensity to form vapors or aerosols, therefore exposure via inhalation is not likely and the inhalation absorption rate is also likely < 10%. Following absorption distribution can occur to highly perfused organs such as the kidney. The lack of target organ toxicity other than the kidney is an indication that members of the ASA category are not widely distributed in the body. Alkenyl succinic anhydrides are hydrolyzed to dicarboxylic acids and excreted in urine as the corresponding acids. While ASA category members are sparingly water soluble, they hydrolytically degrade to dicarboxylic acids and based on excretion data for other acid anhydrides are eliminated with a half time that would indicate little bioaccumulation potential.