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Reference
Endpoint:
basic toxicokinetics
Type of information:
other: Toxicokinetic Assessment
Adequacy of study:
key study
Study period:
July 2010 - August 2010
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Toxicokinetic Assessment by a certified toxicologist.
Qualifier:
according to guideline
Guideline:
other: Guidance on information requirements and chemical safety assessment Chapter R.7c: Endpoint specific guidance
Qualifier:
according to guideline
Guideline:
other: ECB EU Technical Guidance Document on Risk Assessment, 2003
GLP compliance:
yes (incl. QA statement)
Type:
absorption
Results:
absorption oral 50%, absorption dermal 10% and absorption inhalation 100%

TOXICOKINETIC ASSESSMENT

The water solubility of Blown linseed oil is very low (< 1 mg/L). Since in general a compound needs to be dissolved before it can be taken up from the gastro-intestinal tract, it is unlikely that Blown linseed oil will show a high systemic exposure after oral administration. However, its highly lipophilic character (log Po/w > 6) indicates that uptake by micellular solubilisation may be of particular importance. For risk assessment purposes oral absorption of Blown linseed oil is set at 50%. The results of the toxicity studies do not provide reasons to deviate from this proposed oral absorption factor.

Once absorbed, distribution throughout the body will be limited due to its low water solubility. Intracellular concentration is expected to be higher than extracellular concentration based on its lipophilic character. Absorbed Blown linseed oil might undergo conjugation. The conjugates will either be excreted via the bile (high molecular weights compounds) or the urine (low molecular weight compounds).

Due to the very low vapour pressure (< 1.33 x 10-8 Pa) and the high boiling point (reaction and/or decomposition at >300°C) it is not to be expected that Blown linseed oil will reach the nasopharyncheal region or subsequently the tracheobranchial or pulmonary region. If Blown linseed oil reaches the tracheobranchial region it is likely that uptake of Blown linseed oil by crossing the alveolar and capillary membranes will take place based on its highly lipophilic character (log Po/w > 6). However, the low water solubility of Blown linseed oil (< 1 mg/L) indicates that absorption from the respiratory tract will be limited. Overall, although it is unlikely that Blown linseed oil will be available to a high extent after inhalation via the lungs, for risk assessment purposes the inhalation absorption of Blown linseed oil is set at 100%.

Blown linseed oil being a liquid has the potential to partition from the stratum corneum into the epidermis. However, the highly lipophilic character (log Po/w > 6) and the low water solubility (< 1 mg/L) of the substance indicate that the transfer between the stratum corneum and the epidermis will be impaired. Although the data are insufficient (no molecular weight available) to meet the criteria for 10% dermal absorption as given in the TGD, a dermal absorption of 10% is proposed for risk assessment purposes based on the available information. The results of the toxicity studies do not provide reasons to deviate from this proposed dermal absorption factor.

Conclusions:
The absorption factors for risk assessment purposes have been set by a certified toxicologist: absorption oral 50%, absorption dermal 10% and absorption inhalation 100%

For risk assessment purposes:
Absorption oral = 50%
Absorption dermal = 10%
Absorption inhalation = 100%

Description of key information

Short description of key information on absorption rate:

Blown linseed oil being a liquid has the potential to partition from the stratum corneum into the epidermis. However, the highly lipophilic character (log Po/w > 6) and the low water solubility (< 1 mg/L) of the substance indicate that the transfer between the stratum corneum and the epidermis will be impaired. Although the data are insufficient (no molecular weight available) to meet the criteria for 10% dermal absorption as given in the TGD, a dermal absorption of 10% is proposed for risk assessment purposes based on the available information. The results of the toxicity studies do not provide reasons to deviate from this proposed dermal absorption factor.

Key value for chemical safety assessment

Absorption rate - dermal (%):
10

Additional information

The absorption factors for risk assessment purposes have been set by a certified toxicologist: absorption oral 50%, absorption dermal 10% and absorption inhalation 100%.

Once absorbed, distribution throughout the body will be limited due to its low water solubility. Intracellular concentration is expected to be higher than extracellular concentration based on its lipophilic character. Absorbed Blown linseed oil might undergo conjugation. The conjugates will either be excreted via the bile (high molecular weights compounds) or the urine (low molecular weight compounds).