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EC number: 221-761-7 | CAS number: 3228-02-2
- 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
- Nanomaterial dustiness
- Nanomaterial porosity
- Nanomaterial pour density
- Nanomaterial photocatalytic activity
- Nanomaterial radical formation potential
- Nanomaterial catalytic activity
- Endpoint summary
- Stability
- Biodegradation
- Bioaccumulation
- 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
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Endpoint summary
Administrative data
Description of key information
Key value for chemical safety assessment
Skin sensitisation
Link to relevant study records
- Endpoint:
- skin sensitisation: in vivo (LLNA)
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- From June 09 to 26, 2014
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- other: GLP study conducted in compliance with OECD Guideline No. 429 without any deviation.
- Reason / purpose for cross-reference:
- reference to same study
- Reason / purpose for cross-reference:
- reference to other study
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 429 (Skin Sensitisation: Local Lymph Node Assay)
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- EU Method B.42 (Skin Sensitisation: Local Lymph Node Assay)
- Deviations:
- no
- Principles of method if other than guideline:
- Not applicable
- GLP compliance:
- yes (incl. QA statement)
- Remarks:
- UK GLP Compliance Programme (inspected on March 12 to 14, 2014/ signed on May 12, 2014)
- Type of study:
- mouse local lymph node assay (LLNA)
- Species:
- mouse
- Strain:
- other: CBA/Ca (CBA/CaOlaHsd)
- Sex:
- female
- Details on test animals and environmental conditions:
- TEST ANIMALS
- Source: Harlan Laboratories UK Limited, Oxon, UK.
- Age at study initiation: 8-12 weeks
- Weight at study initiation: 15-23 g
- Housing: Animals were individually housed in suspended solid-floor polypropylene cages furnished with softwood woodflakes.
- Diet: Food (2014 Teklad Global Rodent diet supplied by Harlan Laboratories UK Ltd., Oxon, UK), ad libitum
- Water: Mains tap water, ad libitum
- Acclimation period: 5 days
ENVIRONMENTAL CONDITIONS
- Temperature: 19-25 °C
- Humidity: 30-70 %
- Air changes: Approximately 15 changes/h
- Photoperiod: 12 h dark / 12 h light
IN-LIFE DATES: From June 09 to 26, 2014 - Vehicle:
- dimethylformamide
- Concentration:
- Main test: 10, 25 and 50 % w/w in v/v in dimethyl formamide
- No. of animals per dose:
- 5
- Details on study design:
- RANGE FINDING TESTS:
- Using available information regarding the irritancy potential of the test item, a preliminary screening test was performed using one mouse. The mouse was treated by daily application of 25 µL of the test item at a concentration of 50% w/w in dimethyl formamide, to the dorsal surface of each ear for three consecutive days (Days 1, 2, 3). The mouse was observed twice daily on Days 1, 2 and 3 and once daily on Days 4, 5 and 6. Local skin irritation was scored daily; any clinical signs of toxicity, if present, were also recorded. The body weight was recorded on Day 1 (prior to dosing) and on Day 6.
- The thickness of each ear was measured using a Mitutoyo 547 300S gauge (Mitutoyo Corporation), pre dose on Day 1, post dose on Day 3 and on Day 6. Any changes in the ear thickness were noted. Mean ear thickness changes were calculated between time periods Days 1 and 3 and Days 1 and 6. A mean ear thickness increase of equal to or greater than 25% was considered to indicate excessive irritation and limited biological relevance to the endpoint of sensitization.
- Irritation: No signs of systemic toxicity, visual local skin irritation or irritation indicated by an equal to or greater than 25% increase in mean ear thickness were noted. Based on this information the dose levels selected for the main test were 50%, 25% and 10% w/w in dimethyl formamide.
MAIN STUDY
ANIMAL ASSIGNMENT AND TREATMENT
- Name of test method: Local Lymph Node Assay
- Criteria used to consider a positive response: The test item will be regarded as a sensitizer if at least one concentration of the test item results in a threefold or greater increase in 3HTdR incorporation compared to control values. Any test item failing to produce a threefold or greater increase in 3HTdR incorporation will be classified as a "non sensitizer."
TREATMENT PREPARATION AND ADMINISTRATION:
The test item was formulated within two hours of being applied to the test system. It is assumed that the formulation was stable for this duration.
25 µL of control or test material was applied topically on the dorsal surface of both ears using a micropipette daily for three consecutive days (Days 1-3). Five days following the first topical application of the test item or vehicle (Day 6) all mice were injected via the tail vein with 250 μL of phosphate buffered saline (PBS) containing 3H-methyl thymidine (3HTdR: 80 μCi/mL, specific activity 2.0 Ci/mmoL, ARC UK Ltd) giving a total of 20 μCi to each mouse. Five hours later animals were killed by carbon dioxide asphyxiation followed by cervical separation. The lymph nodes from each group were pooled and a single cell suspension was prepared. Cells were washed with phosphate buffered saline (PBS) and precipitated with 5% trichloroacetic acid (TCA) for 18 h at ca. 4 °C. The pellets were recovered by centrifugation and resuspended in 1 mL of TCA and transferred to a vial containing scintillation fluid. 3HTdR incorporation was measured by β-scintillation counting. The "Poly Q™" vials containing the samples and scintillation fluid were placed in the sample changer of the scintillator and left for approximately 20 minutes. The purpose of this period of time in darkness was to reduce the risk of luminescence, which has been shown to affect the reliability of the results. After approximately twenty minutes, the vials were shaken vigorously. The number of radioactive disintegrations per minute was then measured using the Beckman LS6500 scintillation system (Beckman Instruments Inc, Fullerton, CA, USA).
The proliferation response of lymph node cells was expressed as the number of radioactive disintegrations per minute per animal and as the ratio of 3HTdR incorporation into lymph node cells of test nodes relative to that recorded for the control nodes (Stimulation Index). - Positive control substance(s):
- hexyl cinnamic aldehyde (CAS No 101-86-0)
- Statistics:
- Data was processed to give group mean values for disintegrations per minute and standard deviations where appropriate. Individual and group mean disintegrations per minute values were assessed for dose response relationships by analysis of homogeneity of variance followed by one way analysis of variance (ANOVA). In the event of a significant result from the ANOVA, pairwise comparisons were performed between control and treated groups. For homogenous datasets Dunnett’s Multiple Comparison test was used and for non-homogenous datasets Dunnett’s T3 Multiple Comparison Method was used.
Probability values (p) were presented as follows:
P<0.001 ***
P<0.01 **
P<0.05 *
P≥0.05 (not significant) - Positive control results:
- A group of five animals was treated with 50 µL (25 µL per ear) of α-Hexylcinnamaldehyde, tech., 85% as a solution in dimethyl formamide at a concentration of 15 % v/v. A further control group of five animals was treated with dimethyl formamide alone. With a SI = 6.13, α-Hexylcinnamaldehyde, tech., 85% was considered to be a sensitiser under the conditions of the test.
- Parameter:
- SI
- Remarks on result:
- other: Stimulation index for 10, 25 and 50 % w/w in dimethyl formamide were 1.54, 0.87 and 2.64, respectively.
- Parameter:
- other: disintegrations per minute (DPM)
- Remarks on result:
- other: Mean DPM / animal for vehicle, 10, 25 and 50 % w/w in dimethyl formamide were 5572.02 ± 1392.25, 8596.86 ± 1496.42, 4857.37 ± 1206.38, 14710.49** ± 3151.28, respectively.
- Interpretation of results:
- not sensitising
- Remarks:
- Migrated information Criteria used for interpretation of results: EU
- Conclusions:
- Under the test conditions, Parathymol is not classified as a skin sensitiser according to the annex VI of the Regulation EC No. 1272/2008 (CLP) and of the Directive 67/548/EEC.
- Executive summary:
A study was performed to assess the skin sensitisation potential of test material in the CBA/Ca (CBA/CaOlaHsd) strain mouse following topical application of Parathymol to the dorsal surface of the ear. The method was conducted according to the OECD test guideline No 429 and in compliance with GLP.
In preliminary screening test, no signs of systemic toxicity, visual local skin irritation or irritation indicated by an equal to or greater than 25% increase in mean ear thickness were noted. Based on this information the dose levels selected for the main test were 50%, 25% and 10% w/w in dimethyl formamide.
Three groups, each of five animals, were treated with 50 µL (25 µL per ear) of Parathymol as a solution in dimethyl formamide at concentrations of 50%, 25% or 10% w/w. A further group of five animals was treated with dimethyl formamide alone. The animals were allowed to rest without dosing on days 4 and 5. On day 6, the proliferation of lymphocytes in the lymph node draining the application site was measured by incorporation of 3H-Methyl Thymidine.
The Stimulation Index values expressed as the mean radioactive incorporation for each treatment group divided by the mean radioactive incorporation of the vehicle control group are as follows:
Concentration
Mean dpm/animal
Stimulation Index
Result
Vehicle
5572.02 ± 1392.25
NA
N/A
10 %
8596.86 ± 1496.42
1.54
Negative
25 %
4857.37 ± 1206.38
0.87
Negative
50 %
14710.49** ± 3151.28
2.64
Negative
The historical positive control, α-Hexylcinnamaldehyde, gave a SI of 6.13, when tested at 15 % v/v. The test system was therefore considered to be valid.
There were no deaths. No signs of systemic toxicity or excessive local skin irritation were noted in the test or control animals during the test. Body weight change of the test animals between Day 1 and Day 6 were comparable to that observed in the corresponding control group animals over the same period.
Under the test conditions, Parathymol is not classified as a skin sensitiser according to the annex VI of the Regulation EC No. 1272/2008 (CLP) and of the Directive 67/548/EEC.
This study is considered as acceptable and satisfies the requirement for sensitisation endpoint.
Reference
Clinical Observations and Mortality Data
There were no deaths. No signs of systemic toxicity or excessive local skin irritation were noted in the test or control animals during the test.
Bodyweight
Body weight change of the test animals between Day 1 and Day 6 were comparable to that observed in the corresponding control group animals over the same period.
Table 7.4.1/1: Individual Disintegrations per Minute and Stimulation Indices
Concentration (% w/w) in Dimethyl formamide |
Animal Number |
dpm/ Animal a |
Mean dpm/Animal (Standard Deviation) |
Stimulation Index b |
Result |
Vehicle |
1-1 |
6657.79 |
5572.02 ± 1392.25 |
NA |
NA |
1-2 |
6380.88 |
||||
1-3 |
6713.45 |
||||
1-4 |
4119.44 |
||||
1-5 |
3988.54 |
||||
10 |
2-1 |
8472.55 |
8596.86 ± 1496.42 |
1.54 |
Negative |
2-2 |
9164.35 |
||||
2-3 |
10174.59 |
||||
2-4 |
9016.15 |
||||
2-5 |
6156.67 |
||||
25 |
3-1 |
6300.06 |
4857.37 ± 1206.38 |
0.87 |
Negative |
3-2 |
4006.05 |
||||
3-3 |
4270.75 |
||||
3-4 |
3699.31 |
||||
3-5 |
6010.68 |
||||
50 |
4-1 |
17291.74 |
14710.49** ± 3151.28 |
2.64 |
Negative |
4-2 |
10912.78 |
||||
4-3 |
11894.01 |
||||
4-4 |
17860.95 |
||||
4-5 |
15592.96 |
dpm = Disintegrations per minute; a = Total number of lymph nodes per animal is 2; b = Stimulation Index of 3.0 or greater indicates a positive result; na = Not applicable; ** = Significantly different from control group p<0.01
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed (not sensitising)
- Additional information:
- A key study was identified (Harlan, 2014).
This Local Lymph Node Assay was conducted according to the OECD test
guideline No 429 and in compliance with GLP.
In preliminary screening test, no signs of
systemic toxicity, visual local skin irritation or irritation indicated by
an equal to or greater than 25% increase in mean ear thickness were noted.
Based on this information the dose levels selected for the main test were
50%, 25% and 10% w/w in dimethyl formamide.
Three groups, each of five animals, were
treated with 50 µL (25 µL per ear) of Parathymol as a solution in dimethyl
formamide at concentrations of 50%, 25% or 10% w/w. A further group of
five animals was treated with dimethyl formamide alone.The animals were
allowed to rest without dosing on days 4 and 5. On day 6, the
proliferation of lymphocytes in the lymph node draining the application
site was measured by incorporation of3H-Methyl Thymidine.
The historical positive control,
α-Hexylcinnamaldehyde, gave a SI of 6.13, when tested at 15 % v/v. The
test system was therefore considered to be valid.
Stimulation index for 10, 25 and 50 % v/v
in dimethyl formamide were 1.54, 0.87 and 2.64 respectively.
There were no deaths. No signs of systemic
toxicity or excessive local skin irritation were noted in the test or
control animals during the test. Body weight change of the test animals
between Day 1 and Day 6 were comparable to that observed in the
corresponding control group animals over the same period.
Under the test conditions, Parathymol is
not classified as a skin sensitiser
Migrated from Short description of key information:
-LLNA, Skin sensitizer (OECD 429, GLP, K, Rel. 1)
Justification for selection of skin sensitisation endpoint:
Only one study available. The key-study is GLP-compliant and of high quality (Klimisch score = 1).
Respiratory sensitisation
Endpoint conclusion
- Endpoint conclusion:
- no study available
Justification for classification or non-classification
Harmonized classification:
The substance has no harmonized classification according to the Regulation (EC) No. 1272/2008.
Self-classification:
Based on the available data, Parathymol is not classified as skin sensitizer according to the Regulation (EC) No. 1272/2008 (CLP).
No data was available regarding respiratory sensitisation.
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