Sodium D-glycero-D-gulo-heptonate

Basic toxicokinetics

Administrative data

Endpoint:

basic toxicokinetics

Type of information:

other: A screening assessment was done based on all available information

Adequacy of study:

key study

Study period:

The assessment was conducted in May 2013.

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Relevent studies were analysed by a qualified toxicologist with a view to fulfilling the requirements of REACH Annex VIII (8.8.1)

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2013

Materials and methods

Objective of study:

toxicokinetics

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

In accordance with REACH Annex VIII (8.8.1) an assessment of toxicokinetic behaviour has been conducted to the extent that can be derived from the relevant available information. The assessment is based on the Guidance on information requirements and chemical safety assessment R.7c: Endpoint specific guidance (ECHA, November 2012)

GLP compliance:

no

Remarks:

not relevent for assessment

Test material

Test material information

Constituent 1

Reference substance name:

Sodium D-glycero-D-gulo-heptonate

EC Number:

235-849-8

EC Name:

Sodium D-glycero-D-gulo-heptonate

Cas Number:

13007-85-7

Molecular formula:

C7H14O8.Na

IUPAC Name:

sodium 2,3,4,5,6,7-hexahydroxyheptanoate (non-preferred name)

Test material form:

solid: particulate/powder

Remarks:

migrated information: powder

Details on test material:

Details on the test material used in the studies assessed are presented in the respective endpoint study records. Studies were conducted on two materials the actual test material (sodium d-glycero-d-gulo-heptonate) and the structurally similar material (sodium glucoheptonate). For more details of why we are using read across please see section 13.

Radiolabelling:

no

Results and discussion

Toxicokinetic / pharmacokinetic studies

Details on absorption:

Screening assessment:
Although the test item is lipophobic in nature the high water solubility (34.0-36.0% at 20 °C + 0.5°C; Butler, 2013 a) and small molecular size of the substance could allow absorption through passive diffusion. This would suggest that the gastro-intestinal tract provides a route of absorption, following oral administration, before entering the circulatory system via the blood.

Limited absorption may also take place via the skin due to small molecular size and water solubility.

The low vapour pressure value (3.5 x 10-5 Pa at 25°C; Tarran, 2013 b) shows that the substance is not available as a vapour therefore inhalation is not a significant route of exposure.

Details on distribution in tissues:

Screening assessment:
Once absorbed, the substance may be distributed in serum due to the water solubility and may therefore be distributed systemically. The lack of evidence to suggest the test item is a sensitizer suggests that it does not bind to circulatory proteins. The high water solubility and low log octanol/water partition coefficient value would also suggest that the test item does not accumulate in body fat.

Details on excretion:

There is no evidence to indicate the route of excretion but high water-soluble products are not favourable for biliary excretion and therefore urinary excretion may well be a significant route for this material. Any test item that is not absorbed will be excreted in the faeces.

Metabolite characterisation studies

Metabolites identified:

not measured

Details on metabolites:

The results of the repeated dose reproductive screening study did not show evidence to indicate any test item influenced hepatic metabolism (McRae, 2013). The results of the genotoxicity assays have shown no evidence that genotoxicity is either enhanced or diminished in the presence of the S9 metabolising system (Thompson, 2013; Morris, 2013).

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information): other: see conclusions section
The available information suggests that absorption of the test substance from the gastrointestinal tract can take place. Some absorption may also take place via the skin. Once absorbed, the substance would be distributed in the serum and urine is the significant route of excretion. There is no evidence suggesting that the test substance may be metabolised, however no studies have been conducted to identify metabolites.

Executive summary:

The substance is an off white crystalline solid and the molecular weight is 248.1631 g/mol. The low vapour pressure value (3.5 x 10^-5 Pa at 25°C; Tarran, 2013 b) and the predicted negative for explosive and oxidising properties (Tarran, 2013 a) shows that the substance is non volatile therefore inhalation is not a significant route of exposure. The substance has a low log octanol/water partition coefficient value (Log10 Pow -3.81; Butler, 2013 b) and high water solubility (34.0- 36.0% at 20 °C + 0.5°C; Butler, 2013 a). The available acute oral study and the supporting evidence of the repeated dose reproductive screening study with a structurally similar product showed limited evidence of absorption, metabolism and excretion (Sanders, 2013 a; McRae, 2013). The test item was non-mutagenic in bacteria (Thompson, 2013) or in the mouse from a structurally similar product (Flanders, 2013) and non-clastogenic in mammalian cells in vitro from a structurally similar product (Morris, 2013). The test item is not a skin sensitizer and is not considered to be a dermal irritant or corrosive (Henzell, 2013; Warren, 2013 a; Warren 2013 b).