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EC number: 801-282-5 | CAS number: 1034343-98-0
- 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
Endpoint summary
Administrative data
Description of key information
Key: In vivo, skin sensitisation, guinea pig, OECD 406: not skin sensitising (Cada, 2020)
Key value for chemical safety assessment
Skin sensitisation
Link to relevant study records
- Endpoint:
- skin sensitisation: in vivo (non-LLNA)
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 30 Dec 2019 to 28 May 2020
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 406 (Skin Sensitisation)
- Version / remarks:
- adopted July, 1992
- Deviations:
- yes
- Remarks:
- There were occasional procedural deviations that were minor and did not impact the integrity or outcome of the study
- GLP compliance:
- yes
- Type of study:
- Buehler test
- Justification for non-LLNA method:
- 1.No LLNA test (OECD TG 429) was conducted for the purpose of this registration according to Regulation (EC) No 1907/2006, as an OECD TG 406 study on Graphene nano platelets was already available as this study was explicitly requested for national registration under the Canadian Environmental Protection Act, 1999.
2.For the testing of Graphene nano platelets, the OECD TG 429 method is not applicable. The testing according to OECD 429 requires the test item to be suspended or dissolved in solvents/vehicles and subsequently applied on the mouse ear for incubation. Due to physical-chemical properties of Graphene, this procedure is not feasible. Graphene is an insoluble solid and it is difficult to keep the substance on the mouse ear for a sufficiently long time (it is also impossible to keep an e-collar on mice as well as to bandage for topical administration).
These technical difficulties will most likely result in minimal or no topical administration and possible oral administration in the LLNA. In contrast, test item application via an occlusive patch enables testing of such substances in the Buehler method.
All in all, due to topical dose administration difficulties in the mouse the OECD 406, Buelher test is the method of choice. - Species:
- guinea pig
- Strain:
- Hartley
- Sex:
- male
- Details on test animals and environmental conditions:
- TEST ANIMALS
- Source: Charles River Laboratories, Inc.
- Age at study initiation: 8 weeks
- Weight at study initiation: 395–490 g
- Housing: Animals were housed individually with an enrichment device in polycarbonate cages with appropriate bedding.
- Diet: ad libitum (Envigo Teklad Certified Guinea Pig Diet)
- Water: ad libitum ( Municipal tap water)
- Acclimation period: an acclimation period of 7 days was allowed between receipt of the animals and the start of dosing
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21 ± 3 °C
- Humidity (%): 50 ± 20%
- Air changes (per hr): at least 10 air changes per hour
- Photoperiod (hrs dark / hrs light): a light dark cycle of 12 hours light/12 hours dark, except during Study protocol-designated procedures - Route:
- epicutaneous, occlusive
- Vehicle:
- other: saline 0.9%
- Concentration / amount:
- 0.25 + 0.01 g
- Day(s)/duration:
- dosing on day 1, day 8 and day 15 / for 6 hours ± 15 minutes
- Adequacy of induction:
- highest technically applicable concentration used
- No.:
- #1
- Route:
- epicutaneous, occlusive
- Vehicle:
- other: saline 0.9%
- Concentration / amount:
- 0.25 + 0.01 g
- Day(s)/duration:
- dosing on day 29 / for 6 hours ± 15 minutes
- Adequacy of challenge:
- other: highest technically applicable concentration used
- No. of animals per dose:
- treatment group: 20
naive control group: 10
positive control group: 10 - Details on study design:
- RANGE FINDING TESTS:
The test substance is not miscible in any substance and was found to be non-irritating at 0.5 g in a concurrent OECD 404 rabbit study, the maximal test amount according to the test guideline. For this skin sensitisation study in guinea pigs, 0.25 g was found to be the maximal achievable test amount to ensure adequate if not excessive dermal exposure during induction and challenge tests in this study in the same test area.
MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 3
- Exposure period: 6 hours ± 15 minutes
- Test groups: for the Graphene group, Graphene was applied (0.25 + 0.01 g) of gauze pre-wetted with 0.9% saline
- Control group: for the Naïve control group, 0.9% saline was applied; for the Positive control group, α-Hexylcinnamaldehyde was applied (0.4 mL)
- Site: dorsal flank area (Dose site 1)
- Frequency of applications: weekly (Days 1, 8, 15)
- Duration: 3 weeks
- Concentrations: 0.25 + 0.01 g Graphene
B. CHALLENGE EXPOSURE
- No. of exposures: 1
- Day(s) of challenge: Day 29
- Exposure period: 6 hours ± 15 minutes
- Test groups: for the Graphene group, Graphene was applied (0.25 + 0.01 g) of gauze pre-wetted with 0.9% saline
- Control group: for the Naïve control group, Graphene was applied (0.25 + 0.01 g) of gauze pre-wetted with 0.9% saline; for the Positive control group, α-Hexylcinnamaldehyde was applied (0.4 mL)
- Site: dorsal flank area (Dose site 2)
- Concentrations: same as induction phase
- Evaluation (hr after challenge): 24 and 48 h after removal of the dosing patch - Challenge controls:
- naive control group: 10 male animals, Graphene was applied (0.25 + 0.01 g) of gauze pre-wetted with 0.9% saline on day 29
positive control group: 10 male animals, α-Hexylcinnamaldehyde was applied (0.4 mL) on day 29 - Positive control substance(s):
- yes
- Positive control results:
- During the induction phase, the majority of α-Hexylcinnamaldehyde exposed (positive control) animals demonstrated slight or defined erythema after dose administration.
The test conducted was found to be reliable as >15% of animals in the positive control group demonstrated slight or defined erythema during the challenge phase at a previously un-dosed site (site 2, 5 out of 10 animals or 50% responded). - Reading:
- 1st reading
- Hours after challenge:
- 24
- Group:
- test chemical
- Dose level:
- 0.25g
- No. with + reactions:
- 0
- Total no. in group:
- 20
- Clinical observations:
- No test substance-related clinical signs (for further information please refer to 'Any other inoframtion on results')
- Remarks on result:
- no indication of skin sensitisation
- Reading:
- 2nd reading
- Hours after challenge:
- 48
- Group:
- test chemical
- Dose level:
- 0.25g
- No. with + reactions:
- 0
- Total no. in group:
- 20
- Clinical observations:
- No test substance-related clinical signs (for further information please refer to 'Any other inoframtion on results')
- Remarks on result:
- no indication of skin sensitisation
- Reading:
- 1st reading
- Hours after challenge:
- 24
- Group:
- negative control
- Dose level:
- 0.25g
- No. with + reactions:
- 0
- Total no. in group:
- 10
- Clinical observations:
- No test substance-related clinical signs (for further information please refer to 'Any other inoframtion on results')
- Remarks on result:
- no indication of skin sensitisation
- Reading:
- 2nd reading
- Hours after challenge:
- 48
- Group:
- negative control
- Dose level:
- 0.25g
- No. with + reactions:
- 0
- Total no. in group:
- 10
- Clinical observations:
- No test substance-related clinical signs (for further information please refer to 'Any other inoframtion on results')
- Remarks on result:
- no indication of skin sensitisation
- Reading:
- 1st reading
- Hours after challenge:
- 24
- Group:
- positive control
- Dose level:
- 0.4 mL
- No. with + reactions:
- 6
- Total no. in group:
- 10
- Clinical observations:
- No test substance-related clinical signs (for further information please refer to 'Any other inoframtion on results')
- Remarks on result:
- positive indication of skin sensitisation
- Reading:
- 2nd reading
- Hours after challenge:
- 48
- Group:
- positive control
- Dose level:
- 0.4 mL
- No. with + reactions:
- 5
- Total no. in group:
- 10
- Clinical observations:
- No test substance-related clinical signs (for further information please refer to 'Any other inoframtion on results')
- Remarks on result:
- positive indication of skin sensitisation
- Interpretation of results:
- other: EU GHS criteria not met
- Conclusions:
- Repeated dermal dosing of 0.25 g of graphene to male guinea pigs did not induce skin irritation during or after induction phase, and no dermal response was observed after challenge. These results show that graphene is not a skin sensitizer in guinea pigs.
- Executive summary:
Study design
This study was conducted in compliance with the FIFRA Good Laboratory Practice Standards of 40 CFR Part 160 and the generally applicable principles of the OECD, ENV/MC/CHEM (98) 17 as well as any applicable amendments. This study was conducted according to guidelines OPPTS 870.2600 and OECD 406.
The objective of this study was to assess the skin sensitization potential of Graphene in guinea pigs. This information was utilized for the assessment and evaluation of the toxic characteristics of the test substance.
Induction or challenge dosing was administered according to the following table:
Group
No. of Males
Induction Dose Regimen
Induction Dose Test Substance1
Challenge Dose Regimen
Challenge Dose Test Substance
1
10
1 time/week for 3 weeks (Days 1, 8, 15)
0.9% Saline
Day 29
0.9% Saline + 0.25 g Graphene
2
20
1 time/week for 3 weeks (Days 1, 8, 15)
0.9% Saline
+ 0.25 g GrapheneDay 29
0.9% Saline + 0.25 g Graphene
3
10
1 time/week for 3 weeks (Days 1, 8, 15)
0.4 mL α-HexylcinnamaldehydeDay 29
0.4 mL α-Hexylcinnamaldehyde
The dermal sensitization test was comprised of an induction and challenge phase. For the induction phase, the test substance was applied to an approximate 6 cm² area of skin of test substance group animals (n =20) every seven days for a total of three inductions (the same test site on the flank was used each time). The test substance remained in contact with the skin via closed patch occlusion for ~6 hours. A naïve control group (n= 10) was treated in the same manner during the induction phase with the exception that the control animals did not have test substance applied underneath the occlusive wrap. A positive control group (n= 10) was dosed concurrently with and in the same manner as the test substance-treated group. The positive control was α-Hexylcinnamaldehyde, a known mild-to-moderate sensitizer.
The challenge phase was completed two weeks after the last induction dose. The test substance-treated group (n= 20) and a naïve control group (n= 10) were dosed, as during the induction phase, with the test substance. These groups were treated on the opposite side from the application site for the induction phase. The dose sites were evaluated for erythema and edema at approximately 24 and 48 h after removing the challenge patch. The positive control group was dosed with α-Hexylcinnamaldehyde using the same procedures.
Results Multiple dermal exposure to graphene had no effect on mortality, clinical observations, dermal scoring, or body weights. The positive control test was validated by the presence of erythema in 50% of animals at a previously un-dosed skin site after challenge with α-Hexylcinnamaldehyde.
Conclusion
Repeated dermal dosing of 0.25 g of graphene to male guinea pigs did not induce skin irritation during or after induction phase, and no dermal response was observed after challenge. These results show that graphene is not a skin sensitizer in guinea pigs.
Reference
Clinical Observations:
There were no test substance-related clinical observations. Observations during the induction and challenge periods occurred in all dose groups (flaky skin), were found in a minimal number of animals (hair thinning or scab) or were expected based on the dose administration/wrapping procedure (yellow staining of the skin in the abdomen and/or perianal region).
Body Weights:
There were no test substance-related effects on body weights. All animals gained a satisfactory amount of weight during the induction and challenge periods and there were no statistical differences between any group at any time.
Dermal Scoring:
There were no test substance-related dermal effects observed. At all recorded time points, erythema and edema were scored as 0 at the dose site in both the control and the graphene dose groups during both the induction and challenge phases. During the induction phase, the majority of α-Hexylcinnamaldehyde exposed (positive control) animals demonstrated slight or defined erythema after dose administration.
The test conducted was found to be reliable as >15% of animals in the positive control group demonstrated slight or defined erythema during the challenge phase at a previously un-dosed site (site 2, 5 out of 10 animals or 50% responded).
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed (not sensitising)
- Additional information:
Study design
This study was conducted in compliance with the FIFRA Good Laboratory Practice Standards of 40 CFR Part 160 and the generally applicable principles of the OECD, ENV/MC/CHEM (98) 17 as well as any applicable amendments. This study was conducted according to guidelines OPPTS 870.2600 and OECD 406.
The objective of this study was to assess the skin sensitization potential of Graphene in guinea pigs. This information was utilized for the assessment and evaluation of the toxic characteristics of the test substance.
The dermal sensitization test was comprised of an induction and challenge phase. For the induction phase, the test substance was applied to an approximate 6 cm² area of skin of test substance group animals (n =20) every seven days for a total of three inductions (the same test site on the flank was used each time). The test substance remained in contact with the skin via closed patch occlusion for ~6 hours. A naïve control group (n= 10) was treated in the same manner during the induction phase with the exception that the control animals did not have test substance applied underneath the occlusive wrap. A positive control group (n= 10) was dosed concurrently with and in the same manner as the test substance-treated group. The positive control was α-Hexylcinnamaldehyde, a known mild-to-moderate sensitizer.
The challenge phase was completed two weeks after the last induction dose. The test substance-treated group (n= 20) and a naïve control group (n= 10) were dosed, as during the induction phase, with the test substance. These groups were treated on the opposite side from the application site for the induction phase. The dose sites were evaluated for erythema and edema at approximately 24 and 48 h after removing the challenge patch. The positive control group was dosed with α-Hexylcinnamaldehyde using the same procedures.
Results
Multiple dermal exposure to graphene had no effect on mortality, clinical observations, dermal scoring, or body weights. The positive control test was validated by the presence of erythema in 50% of animals at a previously un-dosed skin site after challenge with α-Hexylcinnamaldehyde.
Conclusion
Repeated dermal dosing of 0.25 g of graphene to male guinea pigs did not induce skin irritation during or after induction phase, and no dermal response was observed after challenge. These results show that graphene is not a skin sensitizer in guinea pigs.
Respiratory sensitisation
Endpoint conclusion
- Endpoint conclusion:
- no study available
Justification for classification or non-classification
Based on the results of the key study for in vivo skin sensitisation, the registered substance is not subject to classification as skin sensitiser in accordance with Regulation (EC) No 1272/2008.
Information on Registered Substances comes from registration dossiers which have been assigned a registration number. The assignment of a registration number does however not guarantee that the information in the dossier is correct or that the dossier is compliant with Regulation (EC) No 1907/2006 (the REACH Regulation). This information has not been reviewed or verified by the Agency or any other authority. The content is subject to change without prior notice.
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