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Diss Factsheets

Administrative data

Endpoint:
eye irritation: in vitro / ex vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
April 2017
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2017
Report date:
2017

Materials and methods

Test guideline
Qualifier:
according to guideline
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 (incl. QA statement)

Test material

Constituent 1
Chemical structure
Reference substance name:
Malonic acid
EC Number:
205-503-0
EC Name:
Malonic acid
Cas Number:
141-82-2
Molecular formula:
C3H4O4
IUPAC Name:
propanedioic acid
Test material form:
solid: crystalline
Details on test material:
Batch No: 20160723Purity: 99.5 %
Specific details on test material used for the study:
SupplierSponsor Test Item nameMalonic Acid Supplier CodeNot Applicable Supplier batch/lot number20160723 CAS number141-82-2PurityNot Communicated Expiry DateIndefinite Physical stateWhite crystalline solid Storage ConditionsRoom TemperatureSolubilityN/A neat solid application Administration methodTopical application Concentration testedNeat XCellR8 test item codeOXK0002 Study test item codeTA1

Test animals / tissue source

Species:
human
Details on test animals or tissues and environmental conditions:
MatTek’s EpiOcularTM system consists of normal, human-derived keratinocytes which have been cultured to form a stratified, squamous epithelium similar to that found in the cornea. Cultured on specially prepared cell culture inserts using serum-free culture medium, the cells differentiate to form a multi-layered structure with progressively stratified, but not cornified cells which closely parallel the corneal epithelium (for information see www.mattek.com). QC results for the specific lot of models received (Lot# 23777) were checked in-house for MatTek acceptance ranges with the following outcome: Morphology - PASS Tissue viability - PASS Skin barrier function (ET50 value for 0.3% Triton X-100) where ET50 is the time taken for 0.3% Triton X-100 to reduce the viability of the skin model to 50% relative to the negative control) - PASS Sterility testing showed no contamination during long term antibiotic and antimycotic free culture - PASS

Test system

Vehicle:
unchanged (no vehicle)
Controls:
yes, concurrent positive control
yes, concurrent negative control
Details on study design:
The test item was first checked for its potential to for MTT interference and solvent interference (water and isopropanol).Overview of main test procedure:Day 0: On the day of receipt, EpiOcularTM tissues were pre-incubated overnight at 37°C, 5% CO2, 95% relative humidity.Day 1: Exposure to and removal of test and reference items (50 mg of test item or 50μl of reference items for 6h± 15 minutes, followed by a 25 ± 2 minutes post-treatment immersion, and 18 hours ± 15 minutes post-treatment incubation).Day 2: MTT viability test, readings at 570 nm without reference filter#Data analysis for this study was performed following XCellR8 SOP L0069: “EpiOcularTM Eye Irritation Test (OECD TG492)”, using XCellR8 Form F0068: Data Analysis for EpiOcularTM Eye Irritation Test. This is a Microsoft Excel workbook (validated in-house, February 2015) containing formulae to process the raw data as per OECD TG492/SOP L0069. The final data output is a percentage viability value for EpiOcularTM models exposed to the test item relative to the negative control.

Results and discussion

In vitro

Results
Irritation parameter:
other: Percentage of viability (relative to negative control)
Value:
3.815
Negative controls validity:
valid
Positive controls validity:
valid

Any other information on results incl. tables

Viability measurements after 6h (± 15 min) of application and 18h (± 15 min) post-incubation of test and reference items.

Condition Tissue #

Raw data

Blank corrected data

Mean OD % of viability

aliquot 1

aliquot 2

aliquot 1

aliquot 2

 

NC

Tissue 1

1.416

1.435

1.272

1.291

1.282

95.243

 

Tissue 2

1.389

1.507

1.245

1.363

1.304

96.916

 

Tissue 3

1.55

1.64

1.406

1.496

1.451

107.841

PC

Tissue 1

0.537

0.546

0.393

0.402

0.398

29.543

 

Tissue 2

0.425

0.446

0.281

0.302

0.292

21.665

 

Tissue 3

0.455

0.455

0.311

0.311

0.311

23.114

TA1

Tissue 1

0.191

0.182

0.047

0.038

0.043

3.159

 

Tissue 2

0.187

0.199

0.043

0.055

0.049

3.642

 

Tissue 3

0.198

0.215

0.054

0.071

0.063

4.645

NC: negative control (sterile H2O), PC: Positive control (neat Methyl Acetate), TA1: Malonic Acid.

Mean and SD of viability measurements and of viability percentages after 6h (± 15 min) of application and 18h (± 15 min) post-incubation.

Name

Code

mean of OD

SD of OD

Mean of viability (%)

SD of viability (%)

CV %

Classification

Sterile water

NC

1.346

0.092

100.000

6.84

6.842

Non-Irritant

Methyl Acetate

PC

0.333

0.056

24.774

4.193

16.926

Irritant

Malonic Acid

TA1

0.051

0.010

3.815

0.758

19.874

Irritant

 

Applicant's summary and conclusion

Interpretation of results:
Category 1 (irreversible effects on the eye) based on GHS criteria
Conclusions:
A test item is considered to be irritant to the eye (i.e. would require labelling as either GHS 1 or 2) if the eye model viability after exposure and post-treatment incubation is ≤ 60%.The percentage of viability obtained with the test item Malonic Acid was 3.815%, therefore it has to be considered as at least irritant to the eye.The current assay is not intended to differentiate between GHS class 1 and GHS class 2 or R36 and R41 (degree of stromal damage). In view of the low percentage viability, obtained in the test; and in comparison with other short chain dicarboxylic acids for which in vivo data is available, malonic acid should be classified as Eye Damage 1
Executive summary:

In this study, the eye irritation potential of Malonic Acid was assessed in vitro according to OECD Test 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). After 6h exposure on the surface of EpiOcularTM reconstructed ocular epithelium and 18h post-incubation time, the viability of the tissues was assessed and compared to a negative control. The percentage viability obtained was 3.815 %.