Registration Dossier

Administrative data

Endpoint:
basic toxicokinetics, other
Type of information:
other: expert statement
Adequacy of study:
key study

Data source

Reference
Reference Type:
other: expert report
Title:
Unnamed
Year:
2017

Materials and methods

Principles of method if other than guideline:
Expert statement based on a series of physicochemical and toxicology studies with WS400130 or formulations of it.

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material: WS400130 or formulations of it
Further details on the test material used in the experimental studies referred to are presented in the respective endpoint study records.

Results and discussion

Applicant's summary and conclusion

Executive summary:

The substance WS400130 is a complex mixture of components (UVCB), it is liquid at room temperature. In the following table some physical-chemical properties of WS400130 are listed:

 

Molecular weight: 565 – 847 Da

Water solubility: < 1.15 mg/L

Boiling point: 245°C

Log Pow: > 5.5

Vapour pressure: 6 x 10-4 Pa at 25°C

 

The available physical-chemical information of the substance has been evaluated in combination with results from toxicological studies to assess the toxicokinetic behaviour. The ECHA “Guidance on information requirements and chemical safety assessment Chapter R.7c: Endpoint specific guidance 2017” document provides guidance, which physical-chemical properties commonly determine dermal, oral and respiratory absorption, distribution, metabolism and elimination of substances.

 

Dermal absorption

 

The substance WS400130 is a complex mixture of components with a broad range of molecular weight distribution. The low water solubility and the lipophilic properties of the substance (log Pow > 5.5) are expected to limit absorption across the skin. However, in view of the sensitization response attained in a Local Lymph Node Assay (LLNA) in mice at non-irritating test concentrations of WS400130, some dermal absorption must have occurred. This may have been only a small fraction of the administered test material.

 

Oral absorption

 

The low water solubility and the lipophilic properties of the substance WS400130 are expected to limit its absorption in the digestive tract. In the sub-chronic repeat dose study (OECD 408) with oral gavage dosing up to 1000 mg/kg body weight/day no systemic toxic effects were observed.

No final conclusion can be drawn on absorption of WS400130 after oral exposure. Absence of toxic effects in the sub-chronic oral study may be due to non-absorption in the digestive tract or to very low toxic properties of the substance.

 

Respiratory absorption

 

The substance WS400130 has very low vapour pressure. In addition, the substance is a viscous liquid and thus formation of inhalable aerosols is rather unlikely. Accordingly, inhalation is an unlikely route of human exposure.

 

Distribution, metabolism, excretion

 

There is no information available on distribution, metabolism and excretion of WS400130 in the available studies.

 

Bioaccumulation potential

 

The UVCB substance WS400130 is composed of molecules with relatively high molecular weight (565 -847 Da) and very low water solubility (< 1 mg/L) limiting its bioavailability. The log Pow is > 5.5. The individual substances contain ionisable groups (carboxyl and/or amino groups) that can be protonated or deprotonated resulting in very different lipophilicity of the molecules. It was demonstrated that only at low pH-values (pH 4) there is high lipophilicity whereas at increased pH-values (pH 9) lipophilicity of WS400130 is very much decreased [determined in the HPLC screening test according to OECD Guideline 121 (Estimation of the Adsorption Coefficient (Koc) on Soil and on Sewage Sludge using High Performance Liquid Chromatography)].

From this pH-dependence of lipophilicity and from absence of any systemic toxic effects in the oral sub-chronic repeat dose study at the highest dose level of 1000 mg/kg body weight /day it is concluded that at physiological pH-values, i.e. in the animal body, accumulation is very unlikely.