Zirconium, acetate lactate oxo ammonium complexes

Endpoint summary

Description of key information

No skin sensitisation study with zirconium, acetate lactate oxo ammonium complexes is available, thus the skin sensitisation potential will be addressed with existing data on the dissociation products zirconium, acetate, lactate and ammonium.

The substance zirconium, acetate lactate oxo ammonium complexes is not expected to show signs of dermal sensitisation, since the assessment entities zirconium, acetate, lactate and ammonium have not shown any skin sensitisation potential in experimental testing or QSAR modelling.

Key value for chemical safety assessment

Skin sensitisation

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not sensitising)

Additional information:

No skin sensitisation study with zirconium, acetate lactate oxo ammonium complexes is available, thus the skin sensitisation potential will be addressed with existing data on the dissociation products zirconium, acetate, lactate and ammonium.

 

Zirconium

One reliable (Klimisch 2) study was available for the skin sensitisation endpoint that is selected as the key study (TOSOH Corporation, 1999). The traditional skin sensitisation test was performed according to OECD guideline 406 and the Maximization Test of the Guideline for Toxicity Studies of Drugs (Notification No. 1 -24 of Pharmaceuticals and Cosmetics Division dated September 11, 1989). Female Guinea pigs of the Hartley strain received following treatment:

Intradermal sensitisation

1) Test agent group - E-FCA (equal volume (v/v) of "distilled injection water" and Freund's complete adjuvant (FCA) were mixed and emulsified in water-in-oil style - 2.5% test agent - 2.5% test agent/FCA emulsion

2) Control group - E-FCA

3) Positive control group - E-FCA - 0.1% DNCB/olive oil - 0.1% DNCB/FCA emulsion

Patch sensitisation

1) Test agent group - 25% test agent

2) Control group

3) Positive control group - 0.5% DNCB

Elicitation Treatment

1) Test group and control group - 25% test agent - 2.5% test agent

2) Positive control group - 0.1% DNCB

Zirconium dioxide was found to be not sensitising to the skin at level up to 25% whilst the positive control substance, DNCB, was found to have an extreme skin sensitising potential.

Based on the test results and according to the criteria of the CLP Regulation, zirconium dioxide should not be classified as a skin sensitiser.

 

Acetate

Based on the model outcome “acetic acid” may be considered as a non-sensitising substance in the sense of Regulation (EC) No 1907/2006. The substance of concern is within the applicability domain of the “VEGA - Skin Sensitisation model (CAESAR) – v.2.1.6”. Hence, the prediction is fully reliable to replace an in vivo skin sensitisation test to fulfil requirements for Regulation (EC) No 1907/2006 (REACH) Annex VII section 8.3.

 

Lactate

A registration dossier shall contain information on the human health hazard assessment (regulation 1907/2006, Art.10). However, it is considered that the information requirements for lactate/lactic acid as laid down in annex VII to IX can be fulfilled by adaptation of the standard testing regime according to Annex XI, points 1.1. and 1.2. as presented in the following:

As reported in the final report on the safety assessment of lactic acid and other substances (CIR, 1998) a maximization study was performed using guinea pigs (number of animals not stated) in which induction consisted of intradermal injection of 0.2% and topical application of 50% Lactic Acid; challenge consisted of intradermal injection of 0.2% and application of 10% (ESLUR, 1994a). Lactic Acid was not a sensitizer.

The sensitization potential of a 12% Ammonium Lactate lotion, pH 5.0-5.5, was examined using 10 guinea pigs (FDA, 1988). The first induction application consisted of 0.5 mL applications of undiluted material as well as 25 and 50% dilutions. The remaining two induction applications (one per week), as well as the two subsequent challenge applications (applied 2 and 3 weeks after the last induction dose), of 0.5 mL were undiluted lotion. The first induction dose and the two challenge doses were placed under occlusive patches for 24 h; the remaining two induction doses were placed under occlusive patches for 6 h. One animal was found dead on day 18 (reason not stated). No erythema was observed after induction or challenge applications, and 12% Ammonium Lactate lotion was not a sensitizer using guinea pigs.

Sensitisation by or intolerance to an abundantly available substance in the human body such as lactic acid would be grossly implausible and can therefore safely be excluded. No further animal testing is required.

Ammonium

A registration dossier shall contain information on the human health hazard assessment (regulation 1907/2006, Art.10). However, it is considered that the information requirements for ammonium as laid down in annex VII to IX can be fulfilled by adaptation of the standard testing regime according to Annex XI, points 1.1. and 1.2. as presented in the following:

As reported by the OECD SIDS for ammonium chloride (2003) a guinea pig maximization test conducted according to GLP [Hoechst AG, 1987b] in female guinea pigs (Pirbright-White) is available. In an attempt to induce the sensitised state the animals received an intradermal injection of a 5% solution (in saline) and the skin was also subsequently in covered contact for 24 hours with a 25% solution. When challenged 11 days after the end of the induction phase with a 24-hour covered patch of a 10% solution, two of the 20 guinea pigs (10 %) demonstrated a positive reaction after the challenge exposure (below the limit value of 30 %). The study showed that the substance had no sensitising potential.

Sensitisation by or intolerance to ammonium would be grossly implausible and can therefore safely be excluded. No further animal testing is required.

 

Zirconium, acetate lactate oxo ammonium complexes

The substance zirconium, acetate lactate oxo ammonium complexes is not expected to have a skin sensitising activity, since the assessment entities zirconium, acetate, lactate and ammonium have not shown any skin sensitisation potential in experimental testing or QSAR modelling. Further testing is not required. For further information on the toxicity of the individual moieties, 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

Since the assessment entities of zirconium, acetate lactate oxo ammonium complexes are not sensitising, zirconium, acetate lactate oxo ammonium complexes can safely be assumed to be non-sensitising. According to the criteria of regulation (EC) No 1272/2008 zirconium, acetate lactate oxo ammonium complexes does not have to be classified for skin sensitisation.