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Administrative data

Link to relevant study record(s)

Reference
Endpoint:
basic toxicokinetics, other
Type of information:
other: theoretical assessment based on all available info
Adequacy of study:
key study
Study period:
February 2008
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: non-GLP assessment report
Objective of study:
other: toxicokinetic assessment
Qualifier:
no guideline required
Principles of method if other than guideline:
Assessment of all available data
GLP compliance:
no
Species:
other: none, theoretical assessment
Strain:
other: none, theoretical assessment
Route of administration:
other: oral, dermal and inhalation
Vehicle:
other: not applicable
Details on exposure:
see assessment
Type:
absorption
Results:
For risk assessment purposes, the oral, dermal, and inhalation absorption is set at 100%

The relatively small molecular weight (184.28), the water solubility (7.31 g/L) and the moderate logPow (between 0 and 4) of the substance indicates that uptake from the gastro-intestinal (GI) tract can take place through aqueous pores and by passive diffusion. In general, a substance needs to be dissolved before it can be taken up from the gastro-intestinal tract after oral administration (1). It is therefore likely that Ditetrahydrofurylpropane will be absorbed to a high extent from the GI tract. For risk assessment purposes therefore, the oral absorption of Ditetrahydrofurylpropane is set at 100%. The results of the toxicity studies do not provide reasons to deviate from this proposed oral absorption percentage.

Following absorption, Ditetrahydrofurylpropane being a small water-soluble molecule is expected to distribute widely through the body. Based on its lipophylic character, Ditetrahydrofurylpropane is likely to distribute into cells and the intracellular concentration might be higher than the extracellular concentration. Based on its relatively low molecular weight (184.28), excretion is expected to be predominantly via urine (2).

The water solubility (7.31 g/L) of Ditetrahydrofurylpropane indicates that the substance will dissolve in the mucus lining of the respiratory tract and subsequently be absorbed through aqueous pores (taking the molecular weight <200 into account). The log Pow (> 0) indicates a potential for absorption directly across the respiratory tract epithelium. As it is likely that Ditetrahydrofurylpropane will be absorbed to a high extent after inhalation via the lungs, for risk assessment purposes the inhalation absorption for this substance is set at 100%.

Ditetrahydrofurylpropane being a water soluble liquid (7.31 g/L) has the potential to be dermal absorbed as the surface moisture of the skin will not limit the availability. The logPow of 2.7 favours dermal absorption (values between 2 and 3 are optimal). Furthermore, the moderately skin irritating properties of the substance may result in damage of the skin and thus enhance penetration. Based on these properties, 100% dermal absorption of Ditetrahydrofurylpropane is proposed for risk assessment purposes; being in accordance with the criteria as given in the REACH Guidance on information requirements and chemical safety assessment (3) (10% dermal absorption if MW > 500 and log Po/w < -1; otherwise 100% dermal absorption). The results of the skin sensitisation study confirm that dermal absorption will take place.

Based on the present data, no additional conclusions can be drawn on the distribution, metabolism and excretion of Ditetrahydrofurylpropane after dermal and inhalatory absorption.

Conclusions:
The evaluation of currently available information on Ditetrahydrofurylpropane led to the following toxicokinetic assessment:
- For risk assessment purposes, the oral absorption is set at 100%.
- For risk assessment purposes the inhalation absorption is set at 100%.
- For risk asssessment purposes the dermal absorption is set at 100%.

Description of key information

The evaluation of currently available information on Ditetrahydrofurylpropane led to the following toxicokinetic assessment:

For risk assessment purposes, the oral absorption is set at 100%.

For risk assessment purposes the inhalation absorption is set at 100%.

For risk asssessment purposes the dermal absorption is set at 100%.

Key value for chemical safety assessment

Bioaccumulation potential:
low bioaccumulation potential
Absorption rate - oral (%):
100
Absorption rate - dermal (%):
100
Absorption rate - inhalation (%):
100

Additional information

The relatively small molecular weight (184.28), the water solubility (7.31 g/L) and the moderate logPow (between 0 and 4) of the substance indicates that uptake from the gastro-intestinal (GI) tract can take place through aqueous pores and by passive diffusion. It is therefore likely that Ditetrahydrofurylpropane will be absorbed to a high extent from the GI tract. For risk assessment purposes therefore, the oral absorption of Ditetrahydrofurylpropane is set at 100%. The results of the toxicity studies do not provide reasons to deviate from this proposed oral absorption percentage.

Following absorption, Ditetrahydrofurylpropane being a small water-soluble molecule is expected to distribute widely through the body. Based on its lipophylic character, Ditetrahydrofurylpropane is likely to distribute into cells and the intracellular concentration might be higher than the extracellular concentration. Based on its relatively low molecular weight (184.28), excretion is expected to be predominantly via urine.

The water solubility (7.31 g/L) of Ditetrahydrofurylpropane indicates that the substance will dissolve in the mucus lining of the respiratory tract and subsequently be absorbed through aqueous pores (taking the molecular weight <200 into account). The log Pow (> 0) indicates a potential for absorption directly across the respiratory tract epithelium. As it is likely that Ditetrahydrofurylpropane will be absorbed to a high extent after inhalation via the lungs, for risk assessment purposes the inhalation absorption for this substance is set at 100%.

Ditetrahydrofurylpropane being a water soluble liquid (7.31 g/L) has the potential to be dermal absorbed as the surface moisture of the skin will not limit the availablility. The logPow of 2.7 favours dermal absorption (values between 2 and 3 are optimal). Furthermore, the skin irritating properties of the substance may result in damage of the skin and thus enhance penetration. Based on these properties, 100% dermal absorption of Ditetrahydrofurylpropane is proposed for risk assessment purposes; being in accordance with the criteria as given in the TGD (1) (10% dermal absorption if MW > 500 and log Po/w < -1; otherwise 100% dermal absorption). The results of the skin sensitisation study confirm that dermal absorption will take place. Based on the present data, no additional conclusions can be drawn on the distribution, metabolism and excretion of Ditetrahydrofurylpropane after dermal and inhalatory absorption.