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
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 Resin 5
- Substance type: UVCB
- Physical state: beige solid granules
- 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 Resin 5 is very low ( 0.23 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 Resin 5 will show a high systemic exposure after oral administration. The absorption will furthermore be lowered by the relatively large molecular weight of this substance (not defined), limiting the passage through biological membranes. Its highly lipophilic character (logPow = 7.46) indicates that uptake by micellular solubilisation may be of particular importance. For risk assessment purposes the oral absorption of Corsair Resin 5 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 Resin 5 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). Absorbed Corsair Resin 5 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.

No particle size distribution of Corsair Resin 5 is available as the substance is put on the market as a wax ink stick. Taking this into account, as well as the low vapour pressure of Corsair Resin 5 (1.33 x 10-8 Pa (at 20°C)), any inhalatory exposure to the substance will be limited. If however Corsair Resin 5 reaches the pulmonary tract, its very low water solubility (0.23 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 Resin 5 will be absorbed to a high extent after inhalation via the lungs, for risk assessment purposes the inhalation absorption of Corsair Resin 5 is set at 100% as a worst case assumption.

Corsair Resin 5 being a solid with a high molecular weight (not defined) 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[1]and logPow > 4) are met, 10% dermal absorption of Corsair Resin 5 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 Resin 5 after dermal and inhalatory absorption.

References:

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.


[1]Although the Molecular Weight is not defined, it is clear from the data provided by the sponsor that the MW of Corsair Resin 5 is > 500.

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%