2,4,8,10-Tetraoxaspiro[5.5]undecane-3,9-diethanol, .beta.3,.beta.3,.beta.9,.beta.9-tetramethyl-

Basic toxicokinetics

Administrative data

Endpoint:

basic toxicokinetics

Type of information:

other: Summary of the assessment

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Assessement is based on Guideline studies

Data source

Reference

Reference Type:

other: Expert judgement based on guideline studies

Title:

Unnamed

Year:

2006

Materials and methods

Objective of study:

other: Assessment of toxicokinetic behaviour

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

The assessment is based on expert judgement.

GLP compliance:

no

Test material

Test material information

Constituent 1

Reference substance name:

-

EC Number:

485-230-3

EC Name:

-

Cas Number:

1455-42-1

Molecular formula:

Hill formula: C15H28O6 CAS formula: C15H28O6

IUPAC Name:

2-[9-(1-hydroxy-2-methylpropan-2-yl)-2,4,8,10-tetraoxaspiro[5.5]undecan-3-yl]-2-methylpropan-1-ol

Details on test material:

SPG (spiroglycol; 3,9-bis[1,1-dimethyl-2-hydroxyethyl]-2,4,8,10-tetraoxo-spiro [5,5] undecane;
CAS no 1455-42-1)
Molecular weight of 304 Daltons.
It is a white solid at room temperature

Radiolabelling:

no

Remarks:

Not applicable

Test animals

Species:

other: Not applicable

Strain:

other: Not applicable

Sex:

not specified

Administration / exposure

Route of administration:

other: Not applicable

Vehicle:

other: Not applicable

Duration and frequency of treatment / exposure:

Not applicable

Doses / concentrations

Remarks:

Doses / Concentrations:
Not applicable

No. of animals per sex per dose / concentration:

Not applicable

Control animals:

other: Not applicable

Results and discussion

Toxicokinetic / pharmacokinetic studies

Details on absorption:

As the amount of substance of respirable size is relatively low, few particles will reach the lung alveolus. Given the low vapour pressure of the substance, it is unlikely that vapour will be inhaled in significant quantities.

The substance has some water solubility and has a log P 1.63, thus it is likely to be absorbed orally and through the skin. However, the substance appears to be non-toxic, thus the in vivo studies do not confirm that absorption has taken place.

Details on distribution in tissues:

The log P indicates that the substance is likely to distribute in body water and not to bioaccumulate

Details on excretion:

Some conjugates are likely to be of sufficiently high molecular weight to suggest that they may be excreted in the bile of rat. Otherwise, the substance and metabolites are likely to be excreted in urine.

Metabolite characterisation studies

Details on metabolites:

As the substance is a glycol, it is likely to be converted to the acid and/or conjugated with glucuronic acid or sulphate

Any other information on results incl. tables

SPG (spiroglycol; 3,9-bis[1,1-dimethyl-2-hydroxyethyl]-2,4,8,10-tetraoxo-spiro [5,5] undecane; CAS no 1455-42-1) has a molecular weight of 304 Daltons. It is a white solid at room temperature, melting point 200^oC. The substance is of very low vapour pressure (2.1 x 10^-8Pa at 25^oC), is of limited solubility in water (168 mg/L) and has a log Pow of 1.63 at 30^oC. It is stable at pH 4, 7 or 9. The particle size distribution indicates that 91% are < 100 μm, 13.8 % < 10.2 μm and 5.4% <5.4 μm.

 

The substance is not classified as acutely toxic to rats, either when given orally or when given by inhalation. The substance is not classifiable in terms of skin and eye irritancy and skin sensitisation potential. The substance was negative in a bacterial point mutation assay and an assay for chromosomal aberrations. In the 28 day repeated dose study, rats received oral doses of 0, 15, 150 or 1000 mg/kg bw/d by gavage. There were no relevant toxicity findings. The no observed adverse effect level was stated as 1000 mg/kg bw/d.

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information): other: The log P indicates that the substance is likely to distribute in body water and not to bioaccumulate.
Absorption
As the amount of substance of respirable size is relatively low, few particles will reach the lung alveolus. Given the low vapour pressure of the substance, it is unlikely that vapour will be inhaled in significant quantities.

The substance has some water solubility and has a log P 1.63, thus it is likely to be absorbed orally and through the skin. However, the substance appears to be non-toxic, thus the in vivo studies do not confirm that absorption has taken place.

Distribution
The log P indicates that the substance is likely to distribute in body water and not to bioaccumulate.

Metabolism
As the substance is a glycol, it is likely to be converted to the acid and/or conjugated with glucuronic acid or sulphate.

Excretion
Some conjugates are likely to be of sufficiently high molecular weight to suggest that they may be excreted in the bile of rat. Otherwise, the substance and metabolites are likely to be excreted in urine.