Reaction mass of cerium dioxide and lanthanum oxide and lanthanum fluoride

Endpoint summary

Key value for chemical safety assessment

Skin sensitisation

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not sensitising)

Additional information:

A skin sensitisation study (Klimisch 1) is available on reaction mass of Cerium dioxide and Lanthanum oxide and Lanthanum fluoride. This study was therefore selected as key study. Further information on skin sensitisation potential is also available on the 2 main constituents of the reaction mass, Cerium dioxide and Lanthanum oxide (the sum of both representing approximately 80% of the total reaction mass). As these constituents showed similar physicochemical, toxicological, ecotoxicological and environmental properties, results of studies performed on both constituants are used as supporting evidence.

The sensitisation potential of reaction mass of Cerium dioxide and Lanthanum oxide and Lanthanum fluoride was evaluated on Hartley Crl: (HA) BR female Guinea-pigs by cutaneous application according to the Magnusson & Kligman method in compliance with GLP. This study was selected as the key study.

During the induction period, 10 females per treated group and 5 females per control group received pairs of intradermal injections of either Freund’s Complete Adjuvent (FCA) diluted to 50 % (v/v) with 0.9% NaCl (both groups), the reaction mass at 25% (w/w) in corn oil (treated group) or vehicle alone (control group), or the reaction mass at 25% (w/w) in corn oil in a mixture of FCA/0.9 % NaCl (50/50, w/w) (treated group) or vehicle at 50 % (w/v) in a mixture of FCA/0.9% NaCl (50/50, v/v) (control group). On day 7, the same skin site of both groups was pre-treated with sodium lauryl sulphate to receive one day later a 48-hour occlusive topical application of the reaction mass at 25 % (w/w) in olive oil for treated group or olive oil alone for the control group. The animals of both groups were challenged on day 22 with a 24-hour cutaneous occlusive application of the reaction mass at 25 % (w/w) in olive oil to the right flank and olive oil alone to the left flank. The cutaneous reactions were graded for erythema and oedema 24 and 48 hours after removal of the dressing. No cutaneous reactions were observed after the challenge application in both treated and control groups, on both flanks, at 24 and 48 hour after dressing removal.

Based on the results of this study, the reaction mass of Cerium dioxide and Lanthanum oxide and Lanthanum fluoride is not classified as sensitizing according to the criteria laid down in the Annex VI of the Directive 67/548/EEC or UN GHS/EU CLP.

The skin sensitization potential of cerium dioxide was assessed in vivo in two distinct tests (Klimisch 2): one Guinea-Pig Maximization Test (GPMT) and one Popliteal Lymph Node Assay (PLNA) in rats.

Results of both studies were consistent with the absence of skin sensitization potential for cerium dioxide. In the GPMT, no test animals were positive for sensitization and this was confirmed by performing histopathology. In the PLNA conducted on Brown-Norway rats, a rat strain well known for its high sensitivity to immunotoxicants, there were no significant differences in popliteal lymph node weights and tritiated thymidine incorporation, as well as blood Ig E concentrations, for animals treated up to 35 mg/kg bw, indicating that cerium dioxide is unlikely to be able to generate an antigen-specific immune response. Therefore cerium dioxide is considered not to be a skin sensitizer.

One reliable (Klimisch 2) study is also available for the skin sensitisation potential of lanthanum oxide (Ott, 2005). A traditional skin sensitisation test was performed according to a Maximization Test as described in EU Method B.6. Dunkin-Hartley Guinea pigs were treated by intradermal sensitisation and elicitation. Lanthanum oxide was found to be not sensitising to the skin at a concentration of 50% whilst the positive control substance, hexyl cinnamic aldehyde, demonstrated the validity of the test.

Skin sensitisation	Reaction mass	Cerium dioxide	Lanthanum oxide	Lanthanum fluoride
Conclusion	Not sensitising	Not sensitising	Not sensitising	-
Method	Guinea-Pig Maximization test	Guinea-Pig Maximization test + rat PLNA	Guinea-Pig Maximization test	Not tested as such

 

Migrated from Short description of key information:
No indication of skin sensitization potential in in vivo Guinea Pig Maximisation (Magnusson & Kligman) tests (reaction mass, cerium dioxide or lanthanum oxide) and no indication of antigenic-specific immune response in a Popliteal Lymph Node Assay in rats (cerium dioxide)

Respiratory sensitisation

Endpoint conclusion

Additional information:

No data available

Migrated from Short description of key information:
Not formally assessed but no indication of specific immunotoxicity in a 90-day inhalation study in rats performed with cerium dioxide, that is the majority constituent in the reaction mass of Cerium dioxide and Lanthanum oxide and Lanthanum fluoride

Justification for classification or non-classification

Based on the classification criteria of Annex VI Directive 67/548/EEC or UN GHS/EU CLP, and given the absence of positive reactions in a Guinea-Pig Maximisation Test, the reaction mass of Cerium dioxide and Lanthanum oxide and Lanthanum fluoride is not classified as a skin sensitiser. This conclusion is supported by results on the two main constituents of the reaction mass.

No reliable data are available for respiratory sensitisation, therefore no conclusion can be made on the classification for this endpoint.