Naphthenic acids, copper salts

Endpoint summary

Description of key information

No skin sensitisation study with naphthenic acids, copper salts is available, thus the skin sensitisation potential will be addressed with existing data on the individual moieties copper and naphthenate.

Naphthenic acids, copper salts is expected to show signs of dermal sensitisation, since the constituent naphthenic acids has shown skin sensitisation potential in a guinea pig maximisation test. This finding is also supported by QSAR prediction. Thus, naphthenic acids, copper salts is to be classified according to regulation (EC) 1272/2008 as skin sensitising Cat. 1 (H317).

Key value for chemical safety assessment

Skin sensitisation

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (sensitising)

Additional information:

Copper

Available animal data on the skin sensitisation properties of copper (II) oxide and copper coated flakes have been considered against EU classification criteria as contained in Annex VI of Directive 67/548/.  The available animal data do not meet the criteria requiring these substances to be classified for skin sensitisation. Considering the lower solubility and bioaccessability of copper powders compared to copper oxides and copper flakes, the data are read-across to copper (powders and massive forms) do not require classification for skin sensitisation.

Naphthenate

Both data from published experimental studies and QSAR prediction for sensitisation were used in a Weight of Evidence approach:

- A Guinea pig maximisation test (GPMT) test in 6-week-old female Hartley guinea pigs was performed with Naphthenic acids and salts (copper, zinc and cobalt naphthenate) (Yamano et al, 2006). The first induction dose was set at 1%, while the second induction dose was 25%. Two weeks after the second induction, 0.1 ml aliquots of the 7 chemicals in vehicles (0.5% in petroleum ether for CuN, CoN. ZnN and NA) were applied to a shaved area of the flank for challenge. Each site was scored 48 hours after challenge. Naphthenic acid resulted in 4/5 animals with clear reactions at 48 hours, therefore it is considered to be sensitizing for skin.

- In an LLNA test, 6- to 8-week-old female mice were exposed to Naphthenic acids and salts (copper, zinc and cobalt naphthenate ) in a petroleum ether and olive oil (4 : 1) through application to the dorsum of both ears for 3 consecutive days (Yamano et al, 2006). On the 5° & 6° day, 4, 5- bromo-7-deoxyuridine (BrdU) was administered intraperitoneally to each mousse to measure the LLNA stimulation index. At the time of lymph node excision, the thickness of the ears was measured at the edge of the right pinna. There was an increase of the stimulation index, which was accompanied with an increase in the irritation index, therefore the results are not conclusive about the sensitizing properties of naphthenic acid under the conditions of the LLNA test, however a positive reaction is not excluded.

- Finally, skin sensitisation was predicted using the VEGA QSAR sensitisation model which is an extension of the original CAESAR model. Since naphthenic acids do not have a fixed composition, the prediction was performed on a broad selection of different possible structures in accordance with the substance identification. As can be seen from the results, almost of the molecules in Naphthenic acids were indicated to be sensitisers. Only two molecules were indicated to be a non-sensitiser with a low applicability domain index (ADI). Most molecules fell in the applicability domain (with ADI >=0.8) and thus the prediction can be assumed to be reliable.

Naphthenic acids, copper salts

Naphthenic acids, copper salts is expected to show signs of dermal sensitisation, since the constituent naphthenic acids has shown skin sensitisation potential in a guinea pig maximisation test. This finding is also supported by QSAR prediction. Thus, naphthenic acids, copper salts is to be classified according to regulation (EC) 1272/2008 as skin sensitising Cat. 1 (H317). Further testing is not required. For further information on the toxicity of the individual assessment entities, please refer to the relevant sections in the IUCLID and CSR.

Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

Naphthenic acids, copper salts is expected to show signs of dermal sensitisation, since the constituent naphthenic acids has shown skin sensitisation potential in a guinea pig maximisation test. Thus, naphthenic acids, copper salts is to be classified according to regulation (EC) 1272/2008 as skin sensitising Cat. 1 (H317).