Registration Dossier

Administrative data

Endpoint:
basic toxicokinetics, other
Type of information:
other: Summary of available data
Adequacy of study:
key study
Reliability:
other: Expert statement

Data source

Materials and methods

Objective of study:
other: Assessment of toxicokinetic behaviour
Test guideline
Qualifier:
according to guideline
Guideline:
other: Expert statement
Principles of method if other than guideline:
Assessment of toxicokinetic behaviour

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
Expert statement, no test material needed

Results and discussion

Applicant's summary and conclusion

Conclusions:
Interpretation of results: No toxicologically relevant observations were made in any study performed
The substance is toxicologically not relevant. It is not classified according to Regulation (EC) 1272/2008. In any toxicological study performed there is no concern raised.
Executive summary:

 

No specific study was performed on the absorption, distribution, metabolism and/or excretion (ADME) of WS400572. Predictions on toxicokinetics were based on physical-chemical properties and results of toxicological studies.

The UVCB substance consists of condensation products of m-phenylenebis(methylamine) with condensation products of 4-methyl-m-phenylene diisocyanate with alcohols, C10-14 (even numbered). The molecular weights of the condensation products range from 801 Da to 913 Da. Water solubility is very low, < 0.1 mg/l. The water/octanol partition coefficient was calculated to amount to log Pow > 10. The vapour pressure was calculated resulting in a value of < 10-23Pa.

The physico-chemical and toxicological information on the substance has been used to assess its toxicokinetic behaviour according to the ECHA “Guidance on information requirements and chemical safety assessment Chapter R.7c: Endpoint specific guidance”.

 

The UVCB substance contains various molecules with alkyl chains of different length. The average molecular diameters have been determined using the Chem3D Pro software, as specified in the TGD on data requirements and chemical safety assessment, appendix R.11-1 annex 2. Average molecular diameters were calculated for molecules containing two C10 (component I), two C12 (component II), and two C14 alkyl chains (component III); results are are summarised in the following table.

 

Component

Molecular formula

Molecular weight [Da]

Average molecular diameter [nm]

Component I

C46H68N6O6

801

3.75

Component II

C50H76N6O6

857

3.66

Component III

C54H84N6O6

913

4.33

 

 

Dermal absorption

The low water solubility and high lipophilicity (log Pow > 10) together with the high molecular weight of the constituents of WS400572 limit absorption across the skin. In animal tests, dermal or eye irritation as well as a skin sensitising potential were not observed.

 

Oral absorption

The low water solubility and high lipophilicity (log Pow > 10) together with the high molecular weight of the constituents of WS400572 limit absorption in the digestive tract. In tests for acute oral toxicity and toxicity after repeated oral dosing, no effects were observed in rats receiving once 5000 mg/kg bodyweight or repeatedly 1000 mg/kg bodyweight/day, respectively.

 

Respiratory absorption

WS400572 is solid and has a very low vapour pressure. It decomposes before boiling. Accordingly, inhalation is an unlikely route of human exposure. In addition, the substance is not used as such but always is formulated in solvents thus excluding exposure to particles.

 

Distribution, metabolism, and excretion

There is no information available on distribution, metabolism, and excretion of WS400572 in the available studies.

 

Based on the physical-chemical properties bioavailability of the components of WS400572 is very restricted. Also bioaccumulation is rather unlikely because the different components of the UVCB substance have high molecular weights (> 800 Da), very high octanol/water partition coefficient (log Pow > 10), and average molecular diameters above 1.7 nm. These properties indicate extremely low transport across biological membranes and thus low likeliness of absorption and bioaccumulation of the substance.