Registration Dossier

Administrative data

Endpoint:
basic toxicokinetics
Type of information:
other: expert statement
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
Well documented expert statement based on a series of physicochemical, environmental and toxicology studies with WS400102 in general performed according to technical guidelines and in compliance with GLP in internationally recognized contract research organizations.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2013
Report Date:
2013

Materials and methods

Principles of method if other than guideline:
Expert statement based on a series of physicochemical, environmental and toxicology studies with WS400102. Technical guidelines followed in these experimental studies are cited in the respective endpoint study records.

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
other: semi-solid, wax-like (at 20°C)
Details on test material:
- Name of test material: WS400102
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:

No specific study was performed on the absorption, distribution, metabolism, excretion (ADME) of this substance (WS400102), but data are currently available fromin vivoandin vitrotoxicology studies.

The substance WS400102 is a complex mixture of components (UVCB), a physical mixture / salt of tall-oil fatty acids and technical triethanolamine (TEA). Tall-oil fatty acids are derived from plant material with varying composition of mostly C18fatty acids, saturated, mono- and poly-unsaturated.

Absorption

WS400102 has low water solubility (249 mg/L at 20°C) and relatively high lipophilicity (Log10Pow2.1-5.0 at 25°C). The molecular weight ranges from approx. 150 Da to approx. 340 Da (monoester). Based on these properties some part of WS400102 would be expected to be absorbed after topical administration. Due to the fact that the substance is irritating to skin dermal penetration may be enhanced [ECHA 2008].

Absorption after oral administration of WS400102 is rather likely. Fatty acids or their glycerol esters are normal ingredients of food and are absorbed. Absorption of WS400102 after oral gavage administration is concluded from changes in a number of blood plasma parameters, increased liver weight and minimal changes in kidneys of females at 1000 mg/kg/day in the repeat dose toxicity study.

No data is available on absorption after inhalation. However, inhalation of any vapour from WS400102 is an unlikely route of human exposure, because the substance has very low vapour pressure (0.01 Pa at 25°C) and decomposes at high temperatures (> 227°C). Exposure of humans to an inhalable aerosol of WS400102 is also unlikely, because it is a highly viscous liquid limiting its availability as an inhalable aerosol.

Distribution

Based on the chemical composition of WS400102 it is expected that the fatty acids are absorbed and distributed in the body like any dietary fatty acids. TEA after absorption is expected to be freely distributed in tissues due to its high water solubility.

Metabolism

The tall-oil fatty acids contained in the UVCB substance WS400102 are expected to be metabolised like other fatty acids taken up with the daily diet. Mono-esters of fatty acids probably will be hydrolysed releasing fatty acids. Triethanolamine is well water soluble and thus probably will be excreted in urine.

Excretion

Triethanolamine is well water soluble and thus probably will be excreted in urine whereas fatty acids are expected to be metabolised like other dietary fatty acids. Thus, bioaccumulation of WS400102 or any components is rather unlikely.

Reference:           ECHA 2008, Chapter R.7c: Endpoint specific guidance