Registration Dossier

Administrative data

Endpoint:
basic toxicokinetics
Type of information:
other: expert statement
Adequacy of study:
supporting study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: No studies are available on adsorption, distribution, metabolism and excretion of WS400128. Predictions were made based on physical-chemical properties and results of toxicological studies.

Data source

Reference
Reference Type:
other: Expert report
Title:
Unnamed
Year:
2015

Materials and methods

Principles of method if other than guideline:
.

Test material

Results and discussion

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information): bioaccumulation potential cannot be judged based on study results. However, a bioaccumulation potential is unlikely.
Executive summary:

WS400128 is a complex mixture of components (UVCB), it is liquid at room temperature.In the following table some physico-chemical properties of WS400128 are listed:

 

Endpoint

 

Molecular weight

360 – 940 Da

Water solubility

< 0.1 mg/L

Boiling point

Decomposes before boiling, decomposition starts above 170 °C.

Log Pow

> 6

Vapour pressure

4 x 10-4 Pa at 25°C

 

 

The available physico-chemical and toxicological information of the substance has been evaluated and used to assess the toxicokinetic behaviour.

 

The ECHA “Guidance on information requirements and chemical safety assessment Chapter R.7c: Endpoint specific guidance 2014” document provides guidance, which physico-chemical properties commonly determine dermal, oral and respiratory absorption, distribution, metabolism and elimination of substances.

 

Dermal absorption

 

The substance, WS400128, is a complex mixture of components with a broad range of molecular weight distribution. Molecules with MW < 500 Da may be absorbed through the skin. However, the low water solubility and the lipophilic properties of the substance (log Pow > 6) will limit absorption across the skin.

 

One or more of the components of WS400128 could have contributed to the slight increase in stimulation index in the Local Lymph Node sensitization Assay (LLNA). Dermal absorption of the test material or components thereof was concluded from these findings in the LLNA and from local staining and erythema, minor in degree and reversible, followed by reversible exfoliation/desquamation, in the acute dermal toxicity study at 2000 mg/kg.

 

Oral absorption

 

The low water solubility and the lipophilic properties of the substance will limit its absorption in the digestive tract. However, oral absorption of WS400128 or components thereof was concluded from minor histopathology findings in the kidneys attributed to treatment with WS400128 at 1000 mg/kg/day in the combined repeated dose oral toxicity study reproduction / developmental toxicity screening test (OECD 422). In the 90 day oral study some slight effects on blood parameters were observed as well as increased liver and kidney weights at 1000 mg/kg/day. These effects were no longer observed after a four week recovery period. There were no histopathological findings after 90 days of oral exposure.

 

Respiratory absorption

 

WS400128 has a very low vapour pressure and decomposes before boiling. Accordingly, inhalation is an unlikely route of human exposure.

 

Distribution and metabolism

 

There is no information available on distribution and metabolism of WS400128 in the available studies.

 

Excretion

 

The slight increase in incidence and severity of tubular casts and in incidence of cortical tubular basophilia in the kidneys in the OECD 422 study was interpreted to be an indication of excretion of WS400128, components and/or metabolites thereof.

  

Bioaccumulation potential

 

Based on all available information no final conclusion on a bioaccumulation potential can be drawn. However, based on the physico-chemical properties, the chemical composition and the very low toxicological potential observed in the animal tests the following fate in the animal body is very likely:

1) in an aqueous environment WS400128 forms micelles and thus it may not be available (or only to a small part) for absorption in the digestive tract;

2) the fatty acid esters may be hydrolysed in the digestive tract by digestive enzymes;

3) fatty acid esters that may be absorbed in the digestive tract may be be hydrolysed by esterases in the liver (and blood).

The products of hydrolysis, e.g. mono- and diesters of triethanolamine and free fatty acids, are more hydrophilic and thus do not have an accumulation potential.

 

Therefore, it is rather likely that WS400128 will not bioaccumulate because it is not absorbed in the digestive tract and directly excreted as such and/or it is (partially) hydrolysed to more hydrophilic substances not having an accumulation potential.