Registration Dossier

Diss Factsheets

Administrative data

Endpoint:
basic toxicokinetics
Type of information:
other: Toxicokinetic Assessment
Adequacy of study:
key study
Study period:
February 28, 2008
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Toxicokinetic Assessment by a certified toxicologist.

Data source

Referenceopen allclose all

Reference Type:
study report
Title:
Unnamed
Year:
2008
Report date:
2008
Reference Type:
other: amendment
Title:
Unnamed
Year:
2011

Materials and methods

Objective of study:
other: Assessment of toxicokinetic behaviour
Test guideline
Qualifier:
according to guideline
Guideline:
other: ECB EU Technical Guidance Document on Risk Assessment, 2003
GLP compliance:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material Pentaerythritol, reaction product with fatty acids, C8 to 18 (even numbered) and/or branched and/or unsaturated
- Description: Pale yellow liquid

Results and discussion

Main ADME results
Type:
absorption
Results:
For risk assessment purposes, 10% oral and dermal absorption is used and 100% inhalation absorption is used.

Any other information on results incl. tables

The toxicokinetic assessment is based on the physical/chemical properties as determined for the test substance and it is anticipated that these properties are
representative for all constituents in this substance.
The water solubility is very low (<1 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 the test substance will show a high systemic exposure after oral
administration. The absorption will furthermore be lowered by the relatively large molecular weight (approx. 930) of
this substance limiting the passage through biological membranes. Its highly lipophilic character (logPow > 5.1)
indicates that uptake by micellular solubilisation may be of particular importance. For risk assessment purposes the
oral absorption of the test substance is set at 10%. The results of the toxicity studies do not provide reasons to
deviate from this proposed oral absorption factor.
No significant cleavage of the ester bounds is to be expected in the gastro-intestinal tract, due to the limited
water solubility. In the case absorption of the test substance occurs, cleavage of the ester bonds and
conjugation is to be expected (1). The test substance, the resulting metabolites and conjugation products will be
excreted via feces (high molecular substances) or via urine (low molecular substances).
The low vapour pressure (< 8.40 x 10-7 Pa) indicates that the availability of the substance for inhalation will be
limited. However, once present in the respiratory tract, the low water solubility (<1 mg/L) indicates a potential for
accumulation, while its lipophilic character (logPow > 5.1) indicates the potential for absorption directly across the
respiratory tract epithelium. For risk assessment purposes the inhalation absorption of the test substance is set at
100% as a worst case assumption.
The low water solubility (<1 mg/L) and its highly lipophilic character (logPow > 5.1) do not facilitate dermal
absorption. Following the relatively high molecular weight of the substance (approx. 930), it can be concluded that the
criteria for 10% dermal absorption as given in the Reach guidance (MW > 500 and logPow > 4) are met. Therefore, 10% dermal
absorption of the test substance is proposed for risk assessment purposes. The results of the toxicity studies do
not provide reasons to deviate from this proposed dermal absorption factor, although the slight skin irritating properties
might reduce the skin barrier and hence enhance dermal absorption. 
Based on the present available data, no additional conclusions can be drawn on the metabolism and excretion of
the test substance after dermal and inhalatory absorption.

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information): other: The absorption factors for risk assessment purposes have been set by a certified toxicologist: absorption oral 10%, absorption dermal 10% and absorption inhalation 100%
For risk assessment purposes:
Absorption oral = 10%
Absorption dermal = 10%
Absorption inhalation = 100%