Registration Dossier

Administrative data

Endpoint:
basic toxicokinetics
Type of information:
other: theoretical approach
Adequacy of study:
key study
Reliability:
other: not applicable
Rationale for reliability incl. deficiencies:
other: Study is based on expert judgement.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2008
Report Date:
2008

Materials and methods

Objective of study:
other: toxicokinetic assessment
Principles of method if other than guideline:
A theoretical approach of the toxicokinetic properties of the substance based on the available physico-chemical properties and toxicological data..
GLP compliance:
no
Remarks:
not applicable

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): Corsair Clear #12
- Substance type: Soft waxy beige solid
- Physical state: Solid
- Stability under test conditions: stable
- Storage condition of test material: At room temperature in the dark

Results and discussion

Preliminary studies:
See below.

Any other information on results incl. tables

The water solubility of Corsair Clear #12 is very low (<0.282 mg/L). Since in general a substance needs to be dissolved before it can be taken up from the gastro-intestinal tract, it is unlikely that Corsair Clear #12 will show a high systemic exposure after oral administration. The absorption will furthermore be lowered by the relatively large molecular weight of this substance (1763-2891), limiting the passage through biological membranes. Its highly lipophilic character (logPow > 6.5) indicates that uptake by micellular solubilisation may be of particular importance. For risk assessment purposes the oral absorption of Corsair Clear #12 is set at 10%. The results of the toxicity studies do not provide reasons to deviate from this proposed oral absorption factor. The anticipated cleavage of Corsair Clear #12 in the gastro-intestinal tract (see below) however results in molecules with different physical/chemical characteristics. The proposed 10% oral absorption may thus not be applicable for these breakdown products; moreover, based on the reduced molecular weight and the anticipated higher polarity, the oral absorption of some of these molecules might be above 10%.

In the gastro-intestinal tract the molecule might undergo breakdown (cleavage of amide-bond amidases, hydrolysis of ester). Absorbed Corsair Clear #12 might be subject to Phase I and Phase II reactions (1). Distribution through the body will be limited due to the low water solubility and the high molecular weight. Because of the high molecular weight, the conjugates will predominantly be excreted via the bile.

Based on its physical form (soft waxy beige solid) and very low vapour pressure (1.38 x 10-6 Pa – 3.49 x 10-5 Pa) it is not to be expected that this substance will reach the nasopharyngeal region or subsequently the tracheobronchial or pulmonary region. If however any Corsair Clear #12 is inhaled, its very low water solubility (<0.282 mg/L) indicates a potential for accumulation, while its lipophilic character (logPow > 6.5) indicates the potential for absorption directly across the respiratory tract epithelium. Although it is unlikely that Corsair Clear #12 will be absorbed to a high extent after inhalation via the lungs, for risk assessment purposes the inhalation absorption of Corsair Clear #12 is set at 100% as a worst case assumption.

Corsair Clear #12 being a solid with a high molecular weight (1763-2891) has no real potential for dermal absorption. Furthermore, its low water solubility and highly lipophilic character do not facilitate dermal absorption. As the criteria for 10% dermal absorption as given in the TGD (2) (MW > 500 and logPow > 4) are met, 10% dermal absorption of Corsair Clear #12 is proposed for risk assessment purposes. The results of the toxicity studies do not provide reasons to deviate from this proposed dermal absorption factor.

Based on the present available data, no additional conclusions can be drawn on the distribution, metabolism and excretion of Corsair Clear #12 after dermal and inhalatory absorption.

1. A. Parkinson. In: Casarett and Doull’s Toxicology, The basic science of poisons. Sixth edition. Ed. C.D. Klaassen. Chapter 6: Biotransformation of xenobiotics. McGraw-Hill, New York, 2001.

2. ECB EU Technical Guidance Document on Risk Assessment, 2003.

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information): bioaccumulation potential cannot be judged based on study results
For risk assessment purposes the following absorption factors were derived:
oral absorption factor: 10%
dermal absorption factor: 10%
inhalation absorption factor: 100%