Registration Dossier

Administrative data

Description of key information

The key study for skin irritation is read across from trisodium citrate (CAS 68-04-2) in which the test substance not irritating to rabbit skin according to EU criteria (Roche, 1995; rel 1). For eye irritation, positive findings for trizinc dicitrate were observed in an in vitro test according to OECD 492 while no effect was observed in a second in vitro test (BCOP, OECD 437).

Key value for chemical safety assessment

Skin irritation / corrosion

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records
Reference
Endpoint:
eye irritation: in vitro / ex vivo
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Study according to OECD guideline with GLP
Qualifier:
according to
Guideline:
other: OECD Guideline for the Testing of Chemicals, Part 492, adopted 28. Jul. 2015 , “Reconstructed Human Cornea-like Epithelium (RhCE) Test Method for Identifying Chemicals Not Requiring Classifica-tion and Labelling for Eye Irritation or Serious Eye Damage"
Deviations:
no
GLP compliance:
yes (incl. certificate)
Remarks:
Laus GmbH
Species:
other: normal, human-derived keratinocytes
Details on test animals or tissues and environmental conditions:
Commercially available OCL-200-EIT / OCL-212-EIT EpiOcularTM tissue kit.
Vehicle:
unchanged (no vehicle)
Controls:
other: Neg. Controls: demin. H2O, pos. Controls: Methyl acetate
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied: 50.4 mg
Duration of treatment / exposure:
6h
Observation period (in vivo):
post-treatment incubation: 18 h
Number of animals or in vitro replicates:
2 Tissues (according to guideline)
Details on study design:
Mean optical density was measured and viability was calculated according to guideline
Irritation parameter:
other: %viability
Run / experiment:
Mean after 24 h
Value:
4.7
Vehicle controls validity:
not examined
Negative controls validity:
valid
Positive controls validity:
valid
Irritant / corrosive response data:
After treatment with the test item, the relative absorbance values were reduced to 4.7 %.
This value is well below the threshold for eye irritation potential (≤ 60%).
Other effects:
All validity criteria were met. The criterion for optical density of the negative control was fulfilled: The OD value was 1.5 (> 0.8 and < 2.5).
The positive control induced a decrease in the relative absorbance as compared to the negative control to 32.1%.
Variation within the replicates was acceptable (<20 %).
For these reasons, the result of the test is considered as valid.
Interpretation of results:
other: GHS category 1 or 2
Remarks:
Criteria used for interpretation of results: OECD GHS
Conclusions:
Under the conditions of the test system, trizinc dicitrate is considered as eye irritant in the EpiOcularTM Eye Irritation Test (OECD 492).
Executive summary:

The test item trizinc dicitrate was applied to a three-dimensional human cornea tissue model in duplicate for an exposure time of 6 h.

The solid test item was applied to each tissue. After treatment with the test item, the relative absorbance values were reduced to 4.7 %.

This value is well below the threshold for eye irritation potential (≤ 60%).

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

There were no available data for the irritation potential of trizinc dicitrate to the skin. While it is evident from the data on trisodium citrate that the skin and eye irritation attributable to the citrate is low, the irritation potential of zinc needed to be investigated. EU Risk Assessment reports on other zinc compounds (peer reviewed and reliable) were used to assess the zinc irritation potential in addition to the available information on the citrate.

Zinc sulphate, zinc distearate and zinc chloride which are analogous in their physico chemical properties to those of trizinc dicitrate, were considered as suitable for read across to trizinc dicitrate as supporting studies for irritation potential of zinc. The best available information for read across was derived from zinc sulphate (CAS 7733-02-0); the EU Risk Assessment Report (RAR) on zinc sulphate reports no irritation of the test substance to the skin. However, zinc sulphate is found irritating to the eye and labelled as R41 (risk of serious damage to eyes).

The irritant effects are likely to be due to the low pH of zinc sulphate, although the pH of the test substance is not reported in the RAR. No data on eye irritation was available for zinc distearate.or zinc chloride. The existing information from citrate salts reports no irritant effects and the pH of trizinc dicitrate itself is 5.4 which does not predict irritation effects. Trizinc dicitrate classification decision for skin irritation was therefore based on zinc phosphate (CAS 7770 -90 -0) which is found not irritating to the eye, as reported in the zinc phosphate RAR.

Furthermore, it should be taken into account that zinc compounds have been used for over decades in a variety of pharmaceutical and cosmetic products (some of them even in dermatological preparations against skin irritation) without any reported effects suggesting irritant properties.

This section contains substantially new data.
Effects on eye irritation: irritating

Justification for classification or non-classification

Based on the available information, classification or labelling for eye irritation (Category 2) is required for trizinc dicitrate, in accordance with current EU Directive 67/548/EEC or Regulation 1272/2008.