3,5-dimethyl-1,2-dioxolane-3,5-diol

Endpoint summary

Description of key information

Physico-chemical characteristics show the substance is highly water soluble, and has a low logKow. This is inline with the biological, including some toxicological effects seen in repeated oral dose study in rats. Hydrolysis studies showed that at a pH value of 7 the half-life (t½) for 2,4 -pentanedione peroxide at a temperature of 20°C was calculated to be 200 hours; at a pH value of 9 the half-life (t½) for 2,4 -pentanedione peroxide at a temperature of 20°C was calculated to be 12.5 hours; and at pH value 4 no reliable results were observed so no information on hydrolysis can be given.

Specific test data are not available on the toxicokinetics of the test item. However, the evidence for the absorption/distribution of the test item is available in rats, mice and rabbits.
In a 28-day repeated oral gavage study with rats, based on treatment-related microscopic findings of squamous hyperplasia and hyperkeratosis of forestomach, as well as mucosal necrosis of glandular stomach in males and females treated with 1000 mg/kg/day a No-Observed-Adverse-Effect-Level

(NOAEL) of 300 mg/kg body weight/day of 2,4-Pentanedione, peroxide was established for the rat. Other test item-related (non-adverse and typically adaptive) microscopic findings noted included hypertrophy of mucosal epithelium of duodenum, centrilobular hepatocellular hypertrophy and extramedullary erythrocytic hemopoiesis (i.e. erythropoiesis) in femur bone marrow, enhanced hyaline droplets in renal proximal tubules, and tubular basophilia in the kidney. Hematology and clinical biochemistry parameter changes showed mild aberrations in lipid metabolism.
These changes support the absorption of the test item from the gastrointestinal tract of the rat, and the distribution into internal organs at sufficient concentrations of the test item (or its metabolites) to cause biological effects in a generally dose-dependent manner.
In NMRI BR mice used in the in vivo micronucleus test, a single intraperitoneal injection of the test item resulted in dose-dependent clinical signs of toxicity (ataxia) at 375 to 1500 mg/kg body weight revealing the absorption and distribution of the test item within the body.
The sensitization study results from the Himalayan rabbits showed that the epicutaneously applied test item was effective in eliciting a positive immune system response on the skin (“strong sensitizer”) suggesting dermal absorption occurs.

No data are available on the metabolism and elimination from the body, but the substance is presumed to be metabolized, detoxified and eliminated in urine (and in feces if oral exposure occurs).

Key value for chemical safety assessment

Bioaccumulation potential:

no bioaccumulation potential

Absorption rate - oral (%):

100

Absorption rate - dermal (%):

25

Absorption rate - inhalation (%):

100

Additional information

Specific data are not available on the toxicokinetics, metabolism and distribution of the test substance.

 

The pure peroxide is not commercially available. The test substance as tested was a ~30% mixture of peroxide containing solvent and stabilizer. Evidence of absorption and distribution of the test item can be inferred from the availablein vivo studies in rats (repeated oral gavage), mice (single intraperitoneal injection), and guinea pigs (single intradermal injection / epidermal application).

 

Oral Absorption

Due to the low molecular weight, high water solubility and low log Pow values, the test substance is expected to pass through aqueous pores or be carried through the epithelial barriers by the bulk passage of water. 

 

In a 28-day repeated oral gavage study with rats, based on treatment-related microscopic findings of squamous hyperplasia and hyperkeratosis of forestomach, as well as mucosal necrosis of glandular stomach in males and females treated with 1000 mg/kg/day, a No-Observed-Adverse-Effect-Level (NOAEL) of 300 mg/kg body weight/day of 2,4-Pentanedione, peroxide was established. Other test item-related (non-adverse and typically adaptive) microscopic findings noted included hypertrophy of mucosal epithelium of duodenum, centrilobular hepatocellular hypertrophy, extramedullary erythrocytic hemopoiesis (i.e. erythropoiesis) in femur bone marrow, enhanced hyaline droplets in renal proximal tubules, and tubular basophilia in the kidney. Hematology and clinical biochemistry parameter changes showed mild aberrations in lipid metabolism.

 

These results are considered as the evidence for absorption of the test substance from the gastrointestinal tract of the rat, and distribution into internal organs at sufficient concentrations (either the test substance or metabolites) causing effects at tissue and cellular levels in a generally dose-dependent manner.

 

Intraperitoneal: Although the micronucleus test results were negative in mice after a single intraperitoneal injection, in preliminary experiments, the absorption, distribution, and clinical effects of the test substance were implied from the dose-dependent (375 to 1500 mg/kg body weight) behavioral changes (e.g., lethargy, ventro-lateral recumbency, and ataxia) seen within the first 2 hours of dosing the animals.

 

Dermal Absoption Based on the physical properties (molecular weight, and water solubility, low Kow), the test item is expected to have a some degree of dermal absorption. The sensitization study concluded that the test substance is a sensitizer in guinea pigs showing that the test substance is absorbed from the skin in sufficient concentration to cause a positive immune system effect, which is a systemic response. However, the substance is not irritating to skin and increased absorption due to damaged skin is therefore not very likely. An acute dermal study showed a high LD50 (>2000 mg/kg). Therefore, dermal absorption was considered to be 25% for long term systemic DNEL calculations.

Inhalation:

The vapor pressure of the peroxide was 6.28 Pa at 20^oC. Inhalation is not expected to be a major route of exposure. .

The test substance is biodegradable. No information is available on the metabolism or elimination of the test substance in animals.