Fatty acids, tall-oil, compds. with oleylamine

Basic toxicokinetics

Administrative data

Endpoint:

basic toxicokinetics, other

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 WS400101. Predictions were made based on physical-chemical properties and results of toxicological studies.

Data source

Reference

Reference Type:

other: Expert report

Title:

Unnamed

Year:

2016

Materials and methods

Test material

Test material information

Constituent 1

Applicant's summary and conclusion

Conclusions:

Bioaccumulation is rather unlikely (based on different observations assessed in a weight of evidence approach)

Executive summary:

The substance WS400101 is a complex mixture of components. It is the salt (physical mixture) of fatty acids, tall oil, and octadec-9-enylamine. Below some physical-chemical properties are listed:

- Molecular weight: approx. 270 Da, each for tall oil fatty acids and octadec-9-enylamine (both C18 components)

- Water solubility: < 1 mg/l

- Boiling point: decomposes before boiling, decomposition starts at ca. 140°C

- Log Pow: > 6.2 at pH 4; log Pow < 2.6 at pH 7 and pH 9

- Vapour pressure : 5 x 10E-3 Pa at 25°C

 

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

 

In the ECHA document “Guidance on information requirements and chemical safety assessment Chapter R.7c: Endpoint specific guidance, 2014” guidance is provided which physical-chemical properties commonly determine dermal, oral and respiratory absorption of substances.

 

Dermal absorption

 

The substance, WS400101, is a complex mixture of primarily C18 fatty acids and octadecenylamine with molecular weights of approx. 270 Da. Molecules with MW < 500 Da may be absorbed through the skin. However, the low water solubility will limit absorption across the skin. Nevertheless, dermal absorption of at least some part of the test material or components thereof was concluded from the observation of skin irritation and a strong skin sensitising potential observed in the Local Lymph Node Assay in mice.

 

Oral absorption

 

The low water solubility and the lipophilic properties of the substance at acidic pH values are expected to limit its absorption in the stomach. At neutral and slightly basic pH values the substance becomes more hydrophilic and may be absorbed in the digestive tract. Effects were observed in the duodenum and jejunum as well as in mesenteric lymph nodes indicating exposure of these tissues. The cationic component of the salt, octadecenylamine, is known to cause such effects. Systemic effects were not observed after up to five weeks of oral exposure.

 

Respiratory absorption

 

WS400101 has very low vapour pressure and decomposes before boiling. The substance is highly viscous at room temperature. Accordingly, inhalation is an unlikely route of human exposure.

 

Distribution and metabolism

 

There is no information available on distribution and metabolism of WS400101 in the available studies.

 

Excretion

 

There is no information available on excretion of WS400101 in the available studies.

 

Bioaccumulation potential

 

Based on all available information no final conclusion on a bioaccumulation potential can be drawn. However, based on the chemical composition, the physical-chemical properties and the toxic effects observed in the repeat dose oral toxicity study (with the read-across source substance) the following fate in the animal body is likely:

1) the salt of fatty acids and octadecenylamine becomes less lipophilic at neutral pH and above and thus is expected to dissociate (to a cetain degree) in the digestive tract and body fluids;

2) fatty acids may be absorbed in the digestive tract whereas octadecenylamine exhibits toxic effects in the intestinal tract as observed in the repeat dose oral toxicity study with the read-across source substance and as reported for other long-chain primary alkyl amines including octadecenylamine.

Therefore, it is rather likely that WS400101 will not bioaccumulate because of dissociation of the salt in the digestive tract at neutral to basic pH values. At these pH values the constituents are more hydrophilic not having an accumulation potential.