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Diss Factsheets

Administrative data

Description of key information

Malonic acid was mildly irritating in an in vivo study in rats, but not sufficient for classification under EU CLP.

In an in vitro eye irritation test, malonic acid was considered to be irritating. Although the test is not able to distinguish between category 1 and category 2 eye damage or irritation, in view of the low cell viability, and the low pH of this substance, it has been classified as Eye Damage Category 1.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records
Reference
Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Remarks:
Study was conducted prior to GLP and OECD guideline implementation
Qualifier:
according to guideline
Guideline:
other: US DOT (Transport-Classification) Guidelines
Principles of method if other than guideline:
The study was performed before GLP- and OECD-testing guidelines were available and in force. The intact and abraded skin of 120 albino rabbits was employed for this study. A series of 6 rabbits was used for testing each substance.
GLP compliance:
no
Remarks:
Study carried out prior to introduction of GLP
Species:
rabbit
Strain:
not specified
Type of coverage:
occlusive
Preparation of test site:
abraded
Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
0.5g
Duration of treatment / exposure:
4 hours
Observation period:
4, 24 and 48 hours
Number of animals:
6
Details on study design:
A series of 6 rabbits was used for testing this substance. Hair was clipped using angora clippers. Four areas of the back, placed approximately 10 cm apart, were designated for the application of the patches. Areas 2 and 3 were abraded by making 4 epidermal incisions (two perpendicular to two others). The patches consisted of 1.5 inch x 1.5 inch 12 ply gauze squares. The patches were secured to the area by thin bands of adhesive tape (occlusive application). The material to be tested (0.5 g) was introduced beneath the patch. The entire trunks of the animals were then wrapped in clear plastic trunk bands. Upon removal of the pactches, the resulting reactions were evaluated on the basis of weighted scores.
Irritation parameter:
primary dermal irritation index (PDII)
Basis:
mean
Score:
1.3
Reversibility:
fully reversible within: 48 hours
Irritation parameter:
erythema score
Basis:
mean
Time point:
24/48 h
Score:
0.6
Max. score:
2
Reversibility:
fully reversible within: 48 hrs
Irritation parameter:
edema score
Basis:
mean
Time point:
24/48 h
Score:
0
Max. score:
0

Primary Irritation Study

 

 

Erythema-Eschar observation

Edema observation

 

Rabbit #

Skin

4 hr

24 hr

48 hr

4 hr

24 hr

48 hr

Average

1

Intact

2

1

0

0

0

0

1.17

 

Abraded

2

1

0

1

0

0

2

Intact

2

1

0

0

0

0

1.33

 

Abraded

2

1

0

1

1

0

3

Intact

2

1

0

0

0

0

1.0

 

Abraded

2

1

0

0

0

0

4

Intact

2

2

0

0

0

0

2.0

 

Abraded

2

2

1

1

1

1

5

Intact

2

1

0

0

0

0

1.0

 

Abraded

2

1

0

0

0

0

6

Intact

2

1

0

0

0

0

1.17

 

Abraded

2

1

0

1

0

0

Primary Irritation Index of Compound 1.3 (Mild primary irritant)

 

 

Individual Scores – rabbit no

Skin Reaction

Reading (hours)

1

2

3

4

5

6

Erythema/Eschar

4

2

2

2

2

2

2

24*

1

1

1

2

1

1

48*

0

0

0

0

0

0

72

 

 

 

 

 

 

Total of *

 

1

1

1

2

1

1

Mean values of *

 

0.5

0.5

0.5

1.0

0.5

0.5

 

Edema

4

0

0

0

0

0

0

24*

0

0

0

0

0

0

48*

0

0

0

0

0

0

72

0

0

0

0

0

0

Total of *

 

0.0

0.0

0.0

0.0

0.0

0.0

Mean values of *

 

0.0

0.0

0.0

0.0

0.0

0.0

 

Overall mean of * for Erythema/Eschar = 0.6

Overall mean of * for Edema = 0.0

Interpretation of results:
GHS criteria not met
Conclusions:
Only erythema (score 2) was noted in all 6 animals 4h hours after removal of the patch. After 24 hours, score 1 and 2 were still noted in the animals after removal of the patch. These findings were completely reversible within 48 hours. No oedema were observed during the test period. Therefore, Malonic acid is mildly irritating to rabbit skin (primary irritation index 1.3).
Executive summary:

Malonic acid is mildly irritating to rabbit skin, but not sufficient for CLP classification.

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
Study period:
April 2017
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
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)
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
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
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.
Irritation parameter:
other: Percentage of viability (relative to negative control)
Value:
3.815
Negative controls validity:
valid
Positive controls validity:
valid

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

 

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 %.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Justification for classification or non-classification