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Description of key information

Testing on similar materials shows that irritancy of these salts are related to the irritancy of the parent acid.

On the basis that citric acid is considered potentially irritant to skin and eye (although noting REACH Registrants of citric acid seem to consider non-irritant), it is proposed to classify as Skin Irrit 2 and Eye Irrit 2

The susbtance is pH 5 suggesting weak acid.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Referenceopen allclose all

Endpoint:
skin irritation: in vitro / ex vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
60 minutes exposure with 42 hour post exposure incubation
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Justification for type of information:
Guideline study to GLP
Acetate salt is seen as a suitable surrgoate for citrate; the two acids are similar and are both water soluble under the conditions of testing
Citric acid is not classified as irritant to skin.
Reference:
Composition 0
Qualifier:
according to
Guideline:
OECD Guideline 439 (In Vitro Skin Irritation: Reconstructed Human Epidermis Test Method)
GLP compliance:
yes (incl. certificate)
Test material information:
Composition 1
Specific details on test material used for the study:
Batch RGA16-5628
Test system:
human skin model
Source species:
human
Cell type:
non-transformed keratinocytes
Justification for test system used:
This in-vitro model is considered a suitable substitute for live animals
Vehicle:
unchanged (no vehicle)
Details on test system:
Test item - single application of nominal 25 mg on top of each tissue (tissues pre-wetted with 25μl PBS)
Reference items – single application 30 μl of negative control (PBS) or positive control (SDS 5%).
Three tissues were used per condition (n=3).
Control samples:
yes, concurrent positive control
yes, concurrent MTT non-specific colour control
Amount/concentration applied:
25 mg applied neat to wetted surface
Duration of treatment / exposure:
60 minutes
Duration of post-treatment incubation (if applicable):
42 hours
Number of replicates:
3
Irritation / corrosion parameter:
% tissue viability
Run / experiment:
1
Value:
59
Vehicle controls valid:
yes
Negative controls valid:
yes
Positive controls valid:
yes
Remarks on result:
no indication of irritation
Other effects / acceptance of results:
The test item did not reduce the viability to 50% or below and should be considered as non-Irritant.
Interpretation of results:
GHS criteria not met
Conclusions:
The test item did not reduce the viability to 50% or below and should be considered as non-Irritant.
Executive summary:

Valid study confirming that the criteria to classify as irritant were not met. However, there was some reduction in viability suggesting a weak irritation potential

Endpoint:
skin irritation: in vitro / ex vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
60 minutes exposure with 42 hour post exposure incubation
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Justification for type of information:
Guideline study to GLP
Oxalate salt is seen as a suitable surrgoate for citrate; the two acids are similar and are both water soluble under the conditions of testing
Citric acid is not classified as irritant to skin.
Reference:
Composition 0
Qualifier:
according to
Guideline:
OECD Guideline 439 (In Vitro Skin Irritation: Reconstructed Human Epidermis Test Method)
GLP compliance:
yes (incl. certificate)
Test material information:
Composition 1
Specific details on test material used for the study:
Batch RGA16-5628
Test system:
human skin model
Source species:
human
Cell type:
non-transformed keratinocytes
Justification for test system used:
This in-vitro model is considered a suitable substitute for live animals
Vehicle:
unchanged (no vehicle)
Details on test system:
Test item - single application of nominal 25 mg on top of each tissue (tissues pre-wetted with 25μl PBS)
Reference items – single application 30 μl of negative control (PBS) or positive control (SDS 5%).
Three tissues were used per condition (n=3).
Control samples:
yes, concurrent positive control
yes, concurrent MTT non-specific colour control
Amount/concentration applied:
25 mg applied neat to wetted surface
Duration of treatment / exposure:
60 minutes
Duration of post-treatment incubation (if applicable):
42 hours
Number of replicates:
3
Irritation / corrosion parameter:
% tissue viability
Run / experiment:
1
Value:
6.3
Vehicle controls valid:
yes
Negative controls valid:
yes
Positive controls valid:
yes
Remarks on result:
positive indication of irritation
Interpretation of results:
Category 2 (irritant) based on GHS criteria
Conclusions:
The test item reduced the viability to less than 50% or below and should be considered as Irritant.
However, the viability was not sufficiently reduced to be considered as potentially corrosive.
Executive summary:

Valid study confirming that the criteria to classify as irritant were met.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (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:
guideline study
Justification for type of information:
Guideline study to GLP
Confirms irritancy of simple organic acid salts of chromium III
Reference:
Composition 0
Qualifier:
according to
Guideline:
OECD Guideline 492 (Reconstructed Human Cornea-like Epithelium (RhCE) Test Method for Identifying Chemicals Not Requiring Classification and Labelling for Eye Irritation or Serious Eye Damage)
GLP compliance:
yes
Test material information:
Composition 1
Irritation parameter:
in vitro irritation score
Run / experiment:
1
Value:
ca. 4.4
Vehicle controls valid:
yes
Negative controls valid:
yes
Positive controls valid:
yes
Other effects / acceptance of results:
The low viability is close to figures seen for Eye Dam 1.

Interpretation of results:
Category 2 (irritating to eyes) based on GHS criteria
Conclusions:
It is noted that this method alone cannot validate the division between Eye Dam 1 and Eye Irrit 2, but acetates are weak acids and although the class if substance will show significant effect in this in-vitro assay, impact on the cornea (ie Eye Dam 1) is not expected.
Citric acid is a weaker acid than acetic and this result suggests that Eye Irrit 2 is a valid classification.
Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Additional information

Justification for classification or non-classification

In-vitro testing for skin irritation indicates low level of irritation

Low pH suggests Eye Dam 1