Fatty acids, C14-18 and C16-18-unsatd., maleated, reaction products 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 based on a series of physicochemical, environmental and toxicology studies with WS400107 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:

2014

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, environmental and toxicology studies with WS400107. 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

Test material form:

liquid: viscous

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-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 of in-vivo studies 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 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, WS400107, is a complex mixture of components. The low water solubility (< 1 mg/L at 20°C), high lipophilicity (Log10Pow > 6.2 at 25°C) and, to some extent, the molecular weight (ca. 300 – 800) of WS400107 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 2012, Chapter R.7c: Endpoint specific guidance]. Consequently the above physicochemical properties of WS400107 are considered to limit its systemic availability both, after topical and after oral administration.

However, in view of the sensitization response attained in a Local Lymph Node Assay (LLNA) in mice at non-irritating test concentrations of WS400107, some dermal absorption must have occurred. This may have been only a small fraction of the administered test material.

In addition, absorption of WS400107, or at least a small fraction thereof, after oral gavage administration was concluded from changes in a number of blood plasma parameters indicative of altered hepatic function after five weeks of treatment at 400 or 1000 mg/kg/day in an oral repeat dose toxicity study. In the absence of confirmatory histopathology findings, the changes in blood plasma parameters were not considered to be toxicologically relevant. Dose related adverse effects on bodyweight gain and food consumption were observed in male animals in this study at 400 and 1000 mg/kg/day. Treatment related macroscopic and microscopic pathology findings in the intestines in this study were considered to result from ingestion of the test material by macrophages.

Inhalation exposure to WS400107 is unlikely, because it has a very low vapour pressure (4 x 10E-3 Pa at 25°C) and decomposes without boiling (above ca. 155°C) both 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 WS400107 or components thereof.

Details on excretion:

There is no indication in the available study results regarding the excretion of WS400107 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