Reaction product of "Fatty acids, C16-18 (even numbered) and C18-unsaturated" and "reaction mass of 1,3-alkanediol, 2-(hydroxymethyl)-2-[(methoxymethoxy)methyl]- and 1,3-heteromonocycle-5,5-dimethanol

Basic toxicokinetics

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

Reference

Reference 1

Reference Type:

study report

Title:

Unnamed

Year:

2008

Report date:

2008

Reference 2

Reference Type:

other: amendment

Title:

Unnamed

Year:

2012

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

Test material information

Constituent 1

Test material form:

liquid

Details on test material:

- Name of test material: Reaction products of Fatty acids, C16-18 and C18-unsatd. and reaction mass of 1,3-alkanediol, 2-(hydroxymethyl)-2-[(methoxymethoxy)methyl]- and 1,3-heteromonocycle-5,5-dimethanol
- Physical state: Light brown liquid

Results and discussion

Main ADME results

Type:

absorption

Results:

For risk assessment purposes, the oral and dermal absorption is set at 10% and the inhalation absorption at 100%.

Any other information on results incl. tables

The substance is a mixture of polyols reacted with fatty acids C16-18 and C18-unsaturated. This 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. As ionized substances do not easily pass the GI wall, the presence of free hydroxyl groups in the
molecule will further impair the absorption. Although no clear molecular weight can be defined, it is not to be
expected that the molecular size is that high that passage through biological membranes will further be lowered. 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 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 bound(s) is to be expected in the gastro-intestinal tract, due to the limited
water solubility. Also liberation of formaldehyde (from the cyclic monopentaformal and cyclic homopentaformal group) is
anticipated to be limited. In the case absorption of the test substance occurs, cleavage of the ester bonds and
conjugation is to be expected. 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 (< 1.47 x 10-3 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 > 6.5) 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 > 6.5) do not facilitate dermal
absorption. As the molecular weight cannot really be defined, it cannot be assessed whether or not the criteria
for 10% dermal absorption as given in the Reach guidance (MW > 500 and logPow >4) are met. However, based on the logPow> 6.5, a molecular weight most probably not far below 500 and the knowledge that in general dermal absorption is not higher
compared to oral absorption, 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.
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:

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