Fatty acids, C18-unsatd., trimers, compds. with oleylamine

Basic toxicokinetics

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 from an internationally recognized contract research organization. This expert statement has been based on a series of physicochemical and toxicology studies with WS400151 or a formulation of it, in general, performed according to technical guidelines and in compliance with GLP in internationally recognized contract research organizations.

Cross-reference

Reason / purpose for cross-reference:

reference to other study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2011

Materials and methods

Objective of study:

absorption

Test guideline

Qualifier:

no guideline required

Principles of method if other than guideline:

Expert statement based on a series of physicochemical and toxicology studies with WS400151 or a formulation of it. Technical guidelines followed in these experimental studies are cited in the respective endpoint study records.

GLP compliance:

no

Remarks:

Considered unnecessary for expert statement

Test material

Test material information

Constituent 1

Details on test material:

- Name of test material: WS400151 or a formulation of it
Further details on the test material used in the experimental studies referred to are presented in the respective endpoint study records.

Radiolabelling:

no

Test animals

Species:

other: Detailed in endpoint study records of in-vivo studies referred to in the present expert statement

Strain:

other: Detailed in endpoint study records of in-vivo studies referred to in the present expert statement

Sex:

male/female

Details on test animals or test system and environmental conditions:

Detailed in the endpoint study records of in-vivo studies referred to in the present expert statement.

Administration / exposure

Route of administration:

other: Detailed in endpoint study records of in-vivo studies referred to in the present expert statement

Vehicle:

other: Detailed in endpoint study records of in-vivo studies referred to in the present expert statement, if appropriate

Details on exposure:

Detailed in endpoint study records of in vitro and in-vivo studies referred to in the present expert statement.

Duration and frequency of treatment / exposure:

Detailed in endpoint study records referred to in the present expert statement.

Doses / concentrations

Remarks:

Doses / Concentrations:
Detailed in endpoint study records referred to in the present expert statement.

No. of animals per sex per dose / concentration:

Detailed in endpoint study records of in-vivo studies referred to in the present expert statement.

Control animals:

other: Detailed in in-vivo endpoint study records referred to in the present expert statement, if applicable

Positive control reference chemical:

Detailed in endpoint study records referred to in the present expert statement, if applicable

Details on study design:

Detailed in endpoint study records referred to in the present expert statement, if applicable

Details on dosing and sampling:

Detailed in endpoint study records referred to in the present expert statement, if applicable

Statistics:

Detailed in endpoint study records referred to in the present expert statement, if applicable. Not applicable for the present expert statement.

Results and discussion

Preliminary studies:

Not applicable

Toxicokinetic / pharmacokinetic studies

Details on absorption:

The test material, WS400151, is a complex mixture of components. The low water solubility (< 1 mg/L at 20°C), the high lipophilicity (Log10Pow > 5.7 at 20°C) and to some extent the molecular weight (ca. 280 – 810) of WS400151 would be expected to limit its rate of transfer between the stratum corneum and the lower epidermis and dermis after topical administration, and to limit its absorption after oral administration [ECHA, Chapter R.7c: Endpoint specific guidance]. Consequently the above physicochemical properties of WS400151 are considered to limit its systemic availability both, after topical and after oral administration. This is consistent with the absence of any signs of absorption or of relevant skin irritation in the available toxicity studies with WS400151, except the sensitization response attained in a Local Lymph Node Assay (LLNA) in mice at non-irritating test concentrations of WS400151. Therefore, in the latter study some dermal absorption must have occurred, although this may have been only a small fraction of the administered test material.

Inhalation exposure to WS400151 is unlikely, because it has a very low vapour pressure (5 x 10E-3 Pa at 25°C) limiting its availability under a vapour state, and because it is a highly viscous liquid limiting its availability as an inhalable aerosol.

Details on distribution in tissues:

There is no indication in the available study results regarding the metabolism or distribution of WS400151 or components thereof.

Details on excretion:

There is no indication in the available study results regarding the excretion of WS400151 or components thereof.

Metabolite characterisation studies

Metabolites identified:

not specified

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information): bioaccumulation potential cannot be judged based on study results
Systemic availability of WS400151 after topical or oral administration is expected to be limited, because of its low water solubility, high lipohilicity and to some extent its molecular weight (ca. 280 – 810). However, some dermal absorption of WS400151 or of a fraction of this complex mixture has been concluded from the sensitization response attained in a Local Lymph Node Assay (LLNA) in mice at non-irritating test concentrations.

Availability of WS400151 under a vapour state is unlikely, because of its low vapour pressure, and its availability as an inhalable aerosol is unlikely, because it is a highly viscous liquid.

All available study results gave no indication regarding the metabolic pathway, distribution or excretion of WS400151 or its bioaccumulation potential.