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EC number: 204-498-2 | CAS number: 121-79-9
- Life Cycle description
- Uses advised against
- Endpoint summary
- Appearance / physical state / colour
- Melting point / freezing point
- Boiling point
- Density
- Particle size distribution (Granulometry)
- Vapour pressure
- Partition coefficient
- Water solubility
- Solubility in organic solvents / fat solubility
- Surface tension
- Flash point
- Auto flammability
- Flammability
- Explosiveness
- Oxidising properties
- Oxidation reduction potential
- Stability in organic solvents and identity of relevant degradation products
- Storage stability and reactivity towards container material
- Stability: thermal, sunlight, metals
- pH
- Dissociation constant
- Viscosity
- Additional physico-chemical information
- Additional physico-chemical properties of nanomaterials
- Nanomaterial agglomeration / aggregation
- Nanomaterial crystalline phase
- Nanomaterial crystallite and grain size
- Nanomaterial aspect ratio / shape
- Nanomaterial specific surface area
- Nanomaterial Zeta potential
- Nanomaterial surface chemistry
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- Nanomaterial pour density
- Nanomaterial photocatalytic activity
- Nanomaterial radical formation potential
- Nanomaterial catalytic activity
- Endpoint summary
- Stability
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- Transport and distribution
- Environmental data
- Additional information on environmental fate and behaviour
- Ecotoxicological Summary
- Aquatic toxicity
- Endpoint summary
- Short-term toxicity to fish
- Long-term toxicity to fish
- Short-term toxicity to aquatic invertebrates
- Long-term toxicity to aquatic invertebrates
- Toxicity to aquatic algae and cyanobacteria
- Toxicity to aquatic plants other than algae
- Toxicity to microorganisms
- Endocrine disrupter testing in aquatic vertebrates – in vivo
- Toxicity to other aquatic organisms
- Sediment toxicity
- Terrestrial toxicity
- Biological effects monitoring
- Biotransformation and kinetics
- Additional ecotoxological information
- Toxicological Summary
- Toxicokinetics, metabolism and distribution
- Acute Toxicity
- Irritation / corrosion
- Sensitisation
- Repeated dose toxicity
- Genetic toxicity
- Carcinogenicity
- Toxicity to reproduction
- Specific investigations
- Exposure related observations in humans
- Toxic effects on livestock and pets
- Additional toxicological data
Endpoint summary
Administrative data
Description of key information
The skin irritant potential of propyl gallate (> 99.93% purity) was analysed according to OECD 439 using the EPISKIN-Standard Model™ (EPISKIN-SMTM). Hereby, the test item was applied topically. In this study under the given conditions the test item showed no irritant effects (70.3% mean relative tissue viability) after 15 min exposure and 42 h post-incubation.
The eye irritation potential of propyl gallate (> 99.93% purity) was examined according to OECD 437 using the BCOP model. As this test gave indefinite results, an in vivo study according to OECD 405 was performed showing a severe irritant effect of the test item in the rabbit eye.
Key value for chemical safety assessment
Skin irritation / corrosion
Link to relevant study records
- Endpoint:
- skin irritation: in vitro / ex vivo
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 2016-11-10 to 2017-01-26
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 439 (In Vitro Skin Irritation: Reconstructed Human Epidermis Test Method)
- Version / remarks:
- 28 July 2015
- Deviations:
- no
- GLP compliance:
- yes (incl. QA statement)
- Test system:
- human skin model
- Source species:
- human
- Cell type:
- non-transformed keratinocytes
- Justification for test system used:
- This test uses the EPISKIN-SM™ reconstructed human epidermis model (SkinEthic) which consists of normal human epidermal keratinocytes (NHEK) and therefore represents in vitro the target organ of the species of interest and closely mimics the biochemical and physiological properties of the upper parts of the human skin, i.e. the epidermis.
- Vehicle:
- unchanged (no vehicle)
- Details on test system:
- RECONSTRUCTED HUMAN EPIDERMIS (RHE) TISSUE
- Model used: EPISKIN-SM™ (SkinEthic)
- Tissue batch number(s): 16-EKIN-048
SkinEthic Kit:
- EPISKIN-SM™ plate containing 12 reconstructed epidermis units (area: 0.38 cm²); each reconstructed epidermis is attached to the base of a tissue culture insert with an O-ring set and maintained on nutritive agar for transport (Lot No.: 16-EKIN-048):
1x 12-well assay plate
1x flask of sterile maintenance medium (basic medium for incubations, Lot No.: 16-MAIN3-079)
1x flask of sterile assay medium (basic medium for use in MTT assays, Lot No.: 16-ESSC-051)
- Validity controls as provided by the supplier (SkinEthic):
Morphology:
Histology scoring (HES stained vertical paraffin sections, n = 6):
Specification ≥ 19.5
Result: 22.3 ± 0.3, CV = 1.2%
Well-differentiated epidermis consisting of a basal layer, several spinous and granular layers and a thick stratum corneum.
Barrier function:
IC50 determination (SDS concentration, MTT test, n= 14):
Specification ≥ 1.5 mg/mL
Result: 1.7 mg/mL
TEMPERATURE USED FOR TEST SYSTEM
- Temperature used during treatment / exposure: Room temperature
- Temperature of post-treatment incubation (if applicable): 37 ± 1 °C, 5.0 % CO2
REMOVAL OF TEST MATERIAL AND CONTROLS
- washed with DPBS
MTT DYE USED TO MEASURE TISSUE VIABILITY AFTER TREATMENT / EXPOSURE
- MTT solution
MTT stock solution: 3 mg/mL MTT (Sigma; Lot No.: MKBR6576V) in PBS (Gibco; Lot No.: 1722256)
MTT medium: MTT stock solution was diluted 1 + 9 with DMEM-based medium (final concentration 0.3 mg/mL)
- Acidic isopropanol
0.04 N HCl (AppliChem; Lot No.: 0000687102) in isopropanol (AppliChem; Lot No.: 0000694025)
- MTT concentration: 0.3 mg/mL
- Incubation time: 3 h
- Wavelength: 570 nm
- Filter bandwidth: ± 30 nm
NUMBER OF REPLICATE TISSUES: 3 tissues per dose group
PREDICTION MODEL / DECISION CRITERIA (choose relevant statement)
- The test substance is considered to be irritant to skin if the viability after 15 minutes exposure and 42 h post-treatment incubation is less than or equal to 50%.
- The test substance is considered to be non-irritant to skin if the viability after 15 minutes exposure and 42 h post-treatment incubation is greater than 50%. - Control samples:
- yes, concurrent negative control
- yes, concurrent positive control
- yes, concurrent MTT non-specific colour control
- Amount/concentration applied:
- TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 10 ± 2 mg + 5 µL aqua dest.
NEGATIVE CONTROL
- Amount(s) applied (volume or weight): 10 µL DPBS (Gibco, Cat No. 14040-091, Lot No.: 1737107)
POSITIVE CONTROL
- Amount(s) applied (volume or weight): 10 µL Sodium dodecyl sulfat (SDS; AppliChem, Art.-No. A1112,0500, CAS No.: 151-21-3, Lot No.: 40015277)
- Concentration (if solution): 5% in aqua dest. - Duration of treatment / exposure:
- 15 min ± 0.5 miin
- Duration of post-treatment incubation (if applicable):
- 42 ± 1 h
- Number of replicates:
- 3 tissues per dose group
- Irritation / corrosion parameter:
- % tissue viability
- Run / experiment:
- mean of three tissues
- Value:
- 70.3
- Negative controls validity:
- valid
- Positive controls validity:
- valid
- Remarks on result:
- no indication of irritation
- Other effects / acceptance of results:
- For detailed results see "Any other information on results" Table 1
- Interpretation of results:
- GHS criteria not met
- Conclusions:
- In this study under the given conditions the test item showed no irritant effects. The test item is therefore classified as “non-irritant” in accordance with UN GHS “No Category”.
- Executive summary:
In the present study the skin irritant potential of Propyl gallate (> 99.93% purity) was analysed according to OECD 439 using the EPISKIN-Standard Model™ (EPISKIN-SMTM), a reconstituted three-dimensional human epidermis model to distinguish between UN GHS “Category 2” skin irritating test substances and not categorized test substances (“No Category”) which may be considered as non-irritant. Hereby, the test item was applied topically. Cytotoxicity is expressed as the reduction of mitochondrial dehydrogenase activity measured by formazan production from MTT after a 15 min exposure and 42 h post-incubation period and compared to those of the concurrent negative controls.
In this study under the given conditions the test item showed no irritant effects (70.3% mean relative tissue viability). As the relative mean tissue viability after 15 min of exposure and 42 h post-incubation was > 50%, the test item is therefore classified as “non-irritant” in accordance with UN GHS “No Category”.
Reference
Results of thePre-Experiments
The mixture of 10 mg test item per 2 mL MTT medium showed reduction of MTT as compared to the solvent. The mixture turned blue/purple.
For quantitative correction of results the part of absorption due to the non-specific reduction of MTT (NSMTT) was determined by using killed tissues. Therefore, three killed tissues were treated with the test item (KT) and with the negative control DPBS (KU), respectively. NSMTT was calculated relative to the negative control of living tissues (NK) according to the following formula:
NSMTT [%] = [(ODKT- ODKU)/ODNK] * 100
Mean ODKT= 0.066
Mean ODKU= 0.032
Mean ODNK= 0.685
The calculated NSMTT was ≤ 30% (4.9%) relative to the negative control of livingepidermisand could therefore be used for determination of the true MTT metabolic conversion (TODTT) of the test item treated living tissues (TM) according to the following formula:
TODTT= ODTM- (ODKT- ODKU) (results see Table 1)
The mixtures of 10 mg of the test item per 90 µL aqua dest. and per 90 µL isopropanol showed no colouring detectable by unaided eye-assessment. Therefore, NSClivingequalled 0%. No additional controls were necessary.
Results of the main experiment
Table1: Result of the test Item
Name | Negative Control | Positive Control | Test Item | ||||||
Tissue | 1 | 2 | 3 | 1 | 2 | 3 | 1 | 2 | 3 |
Absolute OD570 | 0.606 0.643 |
0.671 0.728 |
0.737 0.726 |
0.096 0.102 |
0.076 0.084 |
0.096 0.093 |
0.540 0.546 |
0.558 0.565 |
0.372 0.382 |
OD570 (Blank corrected | 0.563 0.600 |
0.628 0.685 |
0.694 0.683 |
0.053 0.059 |
0.033 0.041 |
0.053 0.050 |
0.497 0.503 |
0.515 0.522 |
0.329 0.342 |
Mean OD570 of the Duplicates (Blank corrected) | 0.582 | 0.656 | 0.689 | 0.056 | 0.037 | 0.052 | 0.500 | 0.519 | 0.336 |
Total Mean OD570 of 3 Replicate Tissues (Blank corrected) | 0.642* | 0.048 | 0.451 | ||||||
SD OD570 | 0.055 | 0.010 | 0.101 | ||||||
TODIT | - | - | 0.417 | ||||||
Relative Tissue Viabilities [%] | 90.6 | 102.2 | 107.2 | 8.7 | 5.8 | 8.0 | 77.8 | 80.7 | 52.3 |
Mean Relative Tissue Viabilities [%] | 100.0 | 7.5** | 70.3 | ||||||
SD Tissue Viabilities [%]*** | 8.5 | 1.5 | 15.7 | ||||||
CV [% Viability] | 8.5 | 20.5 | 22.3 |
*Corrected mean OD570of the negative control corresponds to 100% absolute tissue viability.
**Mean relative tissue viability of the three positive control tissues is40%.
***Standard deviation (SD) obtained from the three concurrently tested tissues is≤ 18%.
Table 2: Test Acceptance Criteria
|
Value |
Cut off |
pass/fail |
Mean OD570 nmBlank |
0.043 |
< 0.1 |
pass |
Mean Absolute OD570 nmNK |
0.685 |
0.6 ≤ NK ≤1.5 |
pass |
Mean Relative Viability [%] PC |
7.5 |
≤ 40% |
pass |
Max. SD of % Viability [%] |
15.7 |
≤ 18% |
pass |
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed (not irritating)
Eye irritation
Link to relevant study records
- Endpoint:
- eye irritation: in vivo
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 2017-01-17 to 2017-04-24
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
- Justification for type of information:
- A Bovine Corneal Opacity and Permeability Assay (OECD Guideline number 437) with propyl gallate was performed (Eurofins Munich / BSL Munich Project No. 167610). Based on the results of this test further in vivo testing for assessing acute eye irritation/corrosion is necessary.
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 405 (Acute Eye Irritation / Corrosion)
- Version / remarks:
- 2 October 2012
- Deviations:
- no
- GLP compliance:
- yes (incl. QA statement)
- Species:
- rabbit
- Strain:
- New Zealand White
- Details on test animals or tissues and environmental conditions:
- TEST ANIMALS
- Source: Charles River Deutschland, 97633, Sulzfeld, Germany
- Age at study initiation: approximately 39 weeks old
- Weight at study initiation: >2 kg
- Housing: ABS-plastic or Noryl rabbit cages, floor 4200 cm2, in an air-conditioned room
- Diet (e.g. ad libitum): free access to autoclaved hay and to Altromin 2123 maintenance diet for rabbits, rich in crude fibre
- Water (e.g. ad libitum): free access to tap water (drinking water, municipal residue control, microbiological controls at regular intervals)
- Acclimation period: adequate acclimatisation period (at least 5 days) under laboratory conditions
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18 ± 3 °C
- Humidity (%): 55 ± 10%
- Air changes (per hr): at least 10 x / hour
- Photoperiod (hrs dark / hrs light): Artificial light, sequence being 12 hours light, 12 hours dark - Vehicle:
- unchanged (no vehicle)
- Controls:
- yes
- Amount / concentration applied:
- TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 g of test item was applied to the test site
- Duration of treatment / exposure:
- single treatment, 1h
- Observation period (in vivo):
- 72 hours
- Number of animals or in vitro replicates:
- 1 rabbit
- Details on study design:
- REMOVAL OF TEST SUBSTANCE
- Washing (if done): The treated eye was rinsed with physiological saline 0.9% NaCl 1 hour after the application.
- Time after start of exposure: 1 h
SCORING SYSTEM: Grading System for Ocular Lesion (for details see Table 1 in "Any other information on material and methods")
TOOL USED TO ASSESS SCORE: fluorescein - Irritation parameter:
- conjunctivae score
- Basis:
- animal #1
- Time point:
- 24/48/72 h
- Score:
- 1
- Max. score:
- 3
- Reversibility:
- not reversible
- Remarks:
- within 72 hours
- Irritation parameter:
- chemosis score
- Basis:
- animal #1
- Time point:
- 24/48/72 h
- Score:
- 2
- Max. score:
- 4
- Reversibility:
- not reversible
- Remarks:
- within 72 hours
- Irritation parameter:
- iris score
- Basis:
- animal #1
- Time point:
- 24/48/72 h
- Score:
- 2
- Max. score:
- 2
- Reversibility:
- not reversible
- Remarks:
- within 72 hours
- Irritation parameter:
- cornea opacity score
- Basis:
- animal #1
- Time point:
- 24/48/72 h
- Score:
- 2
- Max. score:
- 4
- Reversibility:
- not reversible
- Remarks:
- within 72 hours
- Irritant / corrosive response data:
- After the application into the eye of one male NZW rabbit the test item produced severe irritant occular effects (see Table 2 and Table 3 in "Any other information on results"). Local effects at the treated eye and clinical signs were observed (see Table 3). The inclined position of the head 72 hours after application is considered to be related to the local effects observed at the treated eye and not due to systemic effects of the test item. Before fluorescein examination at the end of the observation period of 72 hours the animal was euthanised for animal welfare reasons. Conjunctival redness, chemosis, hypersecretion, corneal effects and iris lesion were observed and described in Table 2.
- Other effects:
- - Lesions and clinical observations: after 1 hour slight hypersecretion, after 24 hours moderate hypersecretion, after 48 and 72 hours severe hypersecretion
- Interpretation of results:
- Category 1 (irreversible effects on the eye) based on GHS criteria
- Conclusions:
- In an in vivo acute eye irritation/corrosion study in one rabbit accroding to OECD 405, Propyl gallate produced severely irritant effects, which are not expected to reverse.
- Executive summary:
In a primary eye irritation study according to OECD 405, 0.1 g of propyl gallate (99.93 % purity) was applied into the conjunctival sac of one eye of 1 male, 39 weeks old, New Zealand White rabbit. The test substance remained in the eye for 1 hour and was rinsed afterwards with physiological saline (0.9 % NaCl). The animal then was observed for 72 hours. Irritation was scored by the method of Draize after 1, 24, 48 and 72 h.
Under the conditions of the present study, a single ocular application of the test item Propyl gallate to one rabbit at a dose of 0.1 g produced severely irritant effects including conjunctival redness, chemosis, hypersecretion, corneal effects and iris lesion (iridial response grade 2 for 72 hours), which are not expected to reverse.
In this study, propyl gallate is a severe eye irritant based on CLP criteria.
Reference
Table 2: Eye Irritation Scores - Animal No. 1
Observation |
Eye Irritation Scores Post-Application After |
||||||||
1(1h) |
2(24h) |
3(48h) |
4(72h) |
|
|||||
T |
C |
T |
C |
T |
C |
T |
C |
Average Score (24, 48 and 72 hours) |
|
Redness |
0 |
0 |
1# |
0 |
1 |
0 |
1 |
0 |
1.00 |
Chemosis |
2 |
0 |
2 |
0 |
2 |
0 |
2 |
0 |
2.00 |
Iris |
n.a.* |
0 |
2** |
0 |
2** |
0 |
2 |
0 |
2.00 |
cornea |
3 |
0 |
2 |
0 |
2 |
0 |
2 |
0 |
2.00 |
t= test item; c= control; #= upper rim of conjunctiva and nicticating membrane discoloured white; *=due to complete opacity of the cornea the iris was not visible and thus could not be evaluated; **= no reaction to light
Table 3: Clinical Signs - Animal No. 1
Time Post-Application | Local Findings / Comments | Systemic Findings | |
Test Item | Control | Test Item | |
1 h | slight hypersecretion | nsf | nsf |
24 h | moderate hypersecretion | nsf | nsf |
48 h | severe hypersecretion | nsf | nsf |
72 h | severe hypersecretion | nsf | head inclined § |
nsf= no specific findings; h= hour(s); §= euthanised for ethical reasons
Endpoint conclusion
- Endpoint conclusion:
- adverse effect observed (irreversible damage)
Respiratory irritation
Endpoint conclusion
- Endpoint conclusion:
- no study available
Additional information
The irritancy potential of propyl gallate to the skin was addressed by using a reconstituted three-dimensional human epidermis model according to OECD 439.
In the in vitro skin irritation test, the target substance (> 99.93% purity) showed no irritant effects (70.3% mean relative tissue viability) after 15 min exposure and 42 h post-incubation, classifying propyl gallate as non-irritant to the skin.
The eye irritation potential of propyl gallate was investigated using a BCOP test according to OECD 437 followed by an in vivo study according to OECD 405.
For the bovine corneal opacity and permeability assay (OECD 437), the test item was suspended with physiological saline to give a concentration of 20%. A mean in vitro irritation score of 29.65 was determined. The positive control; 20% imidazol in physiological saline, induced the appropriate responses, indicating the validity of the assay. According to the UN GHS criteria, this mean in vitro irritation score does not allow to make any prediction regarding classification of propyl gallate. For the purpose of classification, an in vivo study according to OECD 405 was performed.
In a primary eye irritation study according to OECD 405, 0.1 g of propyl gallate (99.93 % purity) was applied into the conjunctival sac of one eye of one male New Zealand White rabbit. The test substance remained in the eye for 1 hour and was rinsed afterwards with physiological saline (0.9 % NaCl). The animal then was observed for 72 hours. Irritation was scored by the method of Draize after 1, 24, 48 and 72 h.
Under the conditions of the present study, a single ocular application of the test item propyl gallate to one rabbit at a dose of 0.1 g produced severely irritant effects including conjunctival redness, chemosis, hypersecretion, corneal effects and iris lesion (iridial response grade 2 for 72 hours), which are not expected to reverse.
In this study, propyl gallate is a severe eye irritant based on CLP criteria.
Justification for classification or non-classification
A GLP guideline study (OECD 439) was conducted to evaluate the skin irritation potential of propyl gallate with negative results. Therefore, the test item does not warrant classification for skin irritation.
Based on the results of the primary eye irritation study according to OECD 405, propyl gallate does warrant classification for eye irritation category 1 (Eye Dam. 1, H318) according to CLP criteria.
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