1,3-dioxolane

Basic toxicokinetics

Administrative data

Endpoint:

basic toxicokinetics

Type of information:

other: assessment based on available information

Adequacy of study:

key study

Study period:

June 2010

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: non GLP-assessment report

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2010

Report date:

2010

Materials and methods

Objective of study:

other: toxicokinetic assessment

Test guideline

Qualifier:

no guideline required

Principles of method if other than guideline:

Assessment of all available data

GLP compliance:

no

Test material

Test material information

Constituent 1

Reference substance name:

1,3-dioxolane

EC Number:

211-463-5

EC Name:

1,3-dioxolane

Cas Number:

646-06-0

Molecular formula:

C3H6O2

IUPAC Name:

1,3-dioxolane

Details on test material:

- Name of test material (as cited in study report):1,3-Dioxolane
- Physical state:liquid
- Analytical purity:99.99%

Test animals

Species:

other: none

Strain:

other: none

Administration / exposure

Route of administration:

other: oral, dermal and inhalation

Vehicle:

unchanged (no vehicle)

Details on exposure:

see assessment

Results and discussion

Any other information on results incl. tables

The partition coefficient of 1,3-Dioxolane is about 0 (log Pow = -0.37), meaning that the substance is about as soluble in water as in octanol. This property of the substance is favourable for absorption. In addition, also the low molecular weight (MW= 74.08) and the high water solubility of 1,3-Dioxolane are favourable for uptake from the gastro-intestinal tract. The combination of low molecular weight with high water solubility are indicative for posible passage of the substance through aqueous pores (1). For risk assessment purposes, the oral absorption is set at 100%. The results of the toxicity studies do not provide reason to deviate from this proposed oral absorption.

 

Once absorbed, widely distribution of 1,3-Dioxolane in the body is expected based on its low molecular weight. The high water solubility together with the low molecular weight is indicative for the possibility of diffussion through aqueous channels and pores. Once absorbed, 1,3-Dioxolane is likely to be metabolised (2). Excretion wil be mainly via urine (3).

 

The relatively low boiling point (76˚C) and relatively high vapour pressure (10.1 x 10³Pa) of 1,3-Dioxolane are indicative for volatility, and it is likely that the substance will reach the nasopharyngeal region or subsequently the tracheobronchial region. When 1,3-Dioxolanees the tracheobrochial region, absorption through aqueous pores may take place, taking the molecular weight of <200 into account. Its slightly hydrophilic character (log Pow = -0.37) is also favourable for crossing the alveolar and capillary membranes, and the high water solubility of 1,3-Dioxolane is favourable for dissolution of the substance in the mucus lining of the respiratory tract. If 1,3-Dioxolane is inhaled, significant absorption of the substance is to be expected. Based on physical/chemical properties of the substance the inhalation absorption of 1,3-Dioxolane is assumed to be 100%. However, data from inhalation studies with beagle dogs in which the uptake of inhaled 1,3-Dioxolane vapour (500 ppm) was studied, show that the total uptake of inhaled 1,3-Dioxolane vapor is below 100% (4,5). The average total uptake of inhaled 1,3-Dioxolane by dogs after exposure to 500 ppm vapour was 48% during normal breathing and 41% during rapid breathing (5). Based on the results of these studies in dogs, the inhalation absorption of 1,3-Dioxolane for risk assessment purposes is set at 50%.

 

1,3-Dioxolane, being a liquid, has the potential to partition from the strateum corneum into the epidermis, which is also enhanced by the high water solubility. The slightly lipophilic character (log Pow –0.37) of 1,3-Dioxolane indicates that the transfer between the stratum corneum and the epidermis will be likely. Based on the molecular weight (74.08) and and the log Pow, the criteria for 10% dermal absorption as given in the TGD (3) (MW > 500 and log Pow < -1 or > 4) are not met, and hence a dermal absorption of 100% is proposed for risk assessment purposes. The results of the toxicity studies and the corrosive character of the substance do not provide reasons to deviate from this proposed dermal absorption factor.

 

Based on the available data, no additional conclusions can be drawn on the metabolism and excretion of 1,3-Dioxolane after dermal and inhalatory absorption.

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information): other: - For risk assesment purposes, the oral absorption is set at 100%. For risk assessment purposes the inhalation absorption is set at 50%. For risk asssessment purposes the dermal absorption is set at 100%.
For risk assesment purposes, the oral absorption is set at 100%.
For risk assessment purposes the inhalation absorption is set at 50%.
For risk asssessment purposes the dermal absorption is set at 100%.