Naphthenic acids, copper salts

Endpoint summary

Description of key information

A basic toxicokinetics assessment was performed based on the REACH Guidance on data requirements. Basically, oral absorption was considered most appropriate and most consevative for testing based on physicochemical and toxicological endpoints. For the inhalation and dermal application route, 30% and 10% absorption were assessed to be realistic conservative values. For the assessment of distribution, metabolism and excretion of Naphthenic acids physicochemical and toxicological data are taken into account. Lower molecular weight fractions can be distributed to target organs, but elimination is considered to be possible via urine and faeces, therefore no accumulation takes place.

Key value for chemical safety assessment

Bioaccumulation potential:

no bioaccumulation potential

Absorption rate - oral (%):

100

Absorption rate - dermal (%):

10

Absorption rate - inhalation (%):

30

Additional information

According to chapter R.7C (p145) of the endpoint specific guidance of REACH, physicochemical data may be used for a qualitative TK assessment. The data below were used for a qualitative toxicokinetic assessment.

SUMMARY

Absorption of Naphthenic acids was assessed as follows based on physicochemical/toxicological data:

-  Naphthenic acids is a UVCB since it is isolated as a petroleum fraction. It is a mixture of many different isomers of cycloalkyl carboxylic acids with varying physicochemical properties according to the proportions of the individual components in its composition. The full range covers C6-C30 chain length, whereas the typical range covers the C10-C19 chain length.The substance is a viscous pale yellow to dark amber liquid and is considered insoluble to slightly soluble in water (around 88 mg/L). It has a very low vapor pressure (maximum 5,8 Pa)

-  Although poorly soluble, Naphthenic acids fractions have a limited molecular weight (116.16-432.74 for the full range and 170.25-294.48for the typical range) and rather high partition coefficients, ranging from (2.0- 13.2 for the full range and 3.8-7.9 for the typical range), which allows to assume that it will be absorbed via lipid uptake mechanisms. Results from the oral repeated dose toxicity studies, with liver weight and histopathological changes as major findings, indicate that there is a significant fraction that is absorbed via the GI tract.

-  Based upon the very low vapour pressure and its high viscosity, it is very unlikely that naphthenic acids are exposed to the respiratory tract. Deposition on the mucus layer is further not expected based on the low water solubility; as a consequence further penetration is not expected. In conclusion, exposure by inhalation is very unlikely. Taking into account this information, 30% respiratory absorption is taken as a worst case estimation.

- Based upon the high Log P values and low vapour pressure, dermal absorption is considered possible. However, the extent of dermal penetration, permeation and systemic absorption is considered to be limited. For this purpose, calculations were performed both for the major acidic and non-acidic fractions of Naphthenic acids including dermal permeability coefficient and maximum dermal flux, and comparison was made with absorption values of reference substances. It can be concluded that 10% can be considered to be a realistic conservative value for dermal absorption. A justification report was written (attached).

 

For the assessment of distribution, metabolism and excretion of Naphthenic acids physicochemical and toxicological data are taken into account.

-  Based upon the low molecular weight fraction and high log P, but mainly based on the target organs identified after oral application (e.g. liver), distribution is evident. 

-  The highly lipophilic character of the various fractions in Naphthenic acids and the increased liver weights and adaptive histology in the sub-chronic study point to an increased liver metabolism which will render more water-soluble metabolites of Naphthenic acids.

-   From the assumptions above, excretion via the urine or other body fluids (e.g. bile) is considered to be possible. It might be expected that the non-absorbed fraction of naphthenic acids will be eliminated via the faeces together with a small fraction eliminated via the bile excretion. The absorbed Naphthenic acids fractions after metabolisation will be more water soluble molecules so that they can be excreted via the kidneys. Therefore it is not considered to accumulate.