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EC number: 276-657-4 | CAS number: 72428-99-0
- 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
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- Nanomaterial aspect ratio / shape
- Nanomaterial specific surface area
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- 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
Skin sensitisation
Administrative data
- Endpoint:
- skin sensitisation: in vivo (non-LLNA)
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- other: well performed GLP and OECD guideline study
Cross-reference
- Reason / purpose for cross-reference:
- exposure-related information
Reference
- Endpoint:
- skin sensitisation: in vivo (LLNA)
- Type of information:
- experimental study
- Adequacy of study:
- supporting study
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- other: Guideline-conform study under GLP without deviations
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 429 (Skin Sensitisation: Local Lymph Node Assay)
- Deviations:
- no
- GLP compliance:
- yes
- Type of study:
- mouse local lymph node assay (LLNA)
- Species:
- mouse
- Strain:
- CBA
- Sex:
- female
- Details on test animals and environmental conditions:
- TEST ANIMALS: mice, CBA/CaOlaHsd
- Source: Harlan Laboratories B.V., Postbus 6174, 5960 AD Horst / The Netherlands
- Age at study initiation: 8 - 9 weeks
- Weight at study initiation: 17.3 - 22.5 g
- Housing: group caging
- Diet: pelleted standard diet (Harlan Laboratories B.V., 5960 AD Horst, The Netherlands), ad libidum
- Water: tap water, (Gemeindewerke, 64380 Rossdorf, Germany), ad libitum
- Acclimation period: At least 5 days prior to the start of dosing under test conditions after health examination. Only animals without any visible signs of illness were used for the study
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 + 2°C
- Humidity (%): 45-65 %
- Photoperiod (hrs dark / hrs light): artificial light 6:00 a.m. - 6:00 p.m.
- Bedding: granulated soft wood bedding (Rettenmaier & Söhne GmbH + Co. KG, 73494 Rosenberg, Germany)
- Vehicle:
- dimethylformamide
- Concentration:
- 5, 10, and 25%
- No. of animals per dose:
- 4
- Details on study design:
- RANGE FINDING TESTS:
To determine the highest non-irritant test concentration or the highest technically applicable concentration, a non-GLP pretest (study 1093403) was performed in two mice (pretest excluded from Statement of Compliance). The data showed that the highest test item concentration, which could be technically used, was a 25 % solution in DMF. In other vehicles tested, e.g propylene glycol, actone:olive oil (4+1), methyl ethyl ketone, ethanol (70%), and DMSO, a higher concentration could not be achieved. At the 25 % dilution the treated mouse did not show any signs of systemic toxicity.
Thus, the test item in the main study was assayed at 5, 10, and 25%. The highest concentration tested was the highest level that could be achieved whilst avoiding systemic toxicity and excessive local skin irritation as confirmed in the pre-experiment.
MAIN STUDY:
TOPICAL APPLICATION:
Each test group of mice was treated by topical (epidermal) application to the dorsal surface of each ear (left and right) with different test item concentrations of 5, 10, and 25% in DMF. The application volume, 25 µL was spread over the entire dorsal surface (~ 8 mm) of each ear once daily for three consecutive days. A futher group of mice was treated with an equivalent volume of the relevant vehicle alone (control animals).
ADMINISTRATION OF 3H-METHYL THYMIDINE AND DETERMINATION OF INCORPORATED 3H-METHYL THYMIDINE
Five days after the first topical application, all mice were intraveneously injected into a tail vein with radio-labelled thymidine (3HTdR). Approximately five hours after treatment with 3HTdR all mice were sacrificed and the draining lymph nodes were excised and pooled per group. Single cell suspensions of lymph node cells were prepared from pooled lymph nodes, which were subsequently washed with phosphate buffered saline and incubated with trichloroacetíc acid overnight. The proliferative capacity of pooled lymph node cells was determined by the incorporation of 3H-methyl thymidine measured in a scintillation counter.
INTERPRETATION OF RAW DATA
The proliferation response of lymph node cells is expressed as the number of radioactive disintegrations per minute per lymph node (DPM/node) and as the ratio of 3HTdR incorporated into lymph node cells of test lymph nodes relative to that recorded for control lymph nodes (stimulation index). Before DPM/node values were determined, mean scintillation-background DPM was subtracted from test and control raw data. A test item is regarded as a sensitiliser in the LLNA if the following criteria are fulfilled:
-First, that exposure to at least one concentration of the test item resulted in an incorporation of 3HTdR at least 3-fold or greater than that recorded in control mice, as indicated by the stimulation index.
-Second, that the data are compatible with a conventional dose response, although allowance must be made (especially at high topical concentrations) for either local toxicity or immunological suppression.
OBSERVATIONS
In addition to the sensitising reactions the following observations and data were recorded during the test and observation period:
Mortality / Viability: At least once daily from experimental start to necropsy.
Body weights: In the pre-test: prior to the first application and prior to sacrifice. In the main experiment: prior to the first application and prior to treatment with 3HTdR.
Ear thickness: In the pre-test prior to the first application of the test item (day 1), on day 3 and before sacrifice (day 6).
Ear weights: In the pre-test and main experiment after sacrifice; biopsy punches were taken from each ear.
Clinical signs (local / systemic): Clinical signs (local irritation at the application site or systemic toxicity) were recorded at least once daily. Especially the treatment sites were observed carefully. - Positive control substance(s):
- hexyl cinnamic aldehyde (CAS No 101-86-0)
- Statistics:
- The mean values and standard deviations were calculated in the body weight tables.
- Positive control results:
- Experiment performed in May 2007 using concentrations of 5, 10, and 25 % alpha-hexyl cinnamic aldehyde in acetone:olive oil (4:1). These concentrations yielded S.I.´s of 2.43, 4.07, 4.88, respectively.
The EC3 value calculated was 6.7 % (w/v).
The positive control substance alpha-hexyl cinnamic aldehyde was found to be a skin sensitizer under the described conditions, demonstrating the validity of the study. - Parameter:
- other: disintegrations per minute (DPM)
- Remarks on result:
- other: see depicted table below
- Interpretation of results:
- other: inconclusive
- Remarks:
- Criteria used for interpretation of results: EU
- Conclusions:
- The test item was found to be a skin sensitiser under the test conditions of this study. However, taking into account the inverse dose relationship and the borderline result obtained for the high dose of 25%, it cannot be excluded that the test item would show sensitising properties at higher concentrations or interferes with the test system in general. Thus, the result of this study remains inconclusive.
- Executive summary:
In order to study a possible skin sensitising potential of the test item, three groups each of four female mice were treated once daily with the test item at concentrations of 5, 10, and 25% in DMF by topical application to the dorsum of each ear for three consecutive days. A control group of four mice was treated with the vehicle (DMF) only. Five days after the first topical application the mice were injected intravenously into a tail vein with radio-labelled thymidine (3H-methyl thymidine). Approximately five hours after intravenous injection, the mice were sacrificed, the draining auricular lymph nodes excised and pooled per group. Single cell suspensions of lymph node cells were prepared from pooled lymph nodes, which were subsequently washed and incubated with trichloroacetic acid overnight. The proliferative capacity of pooled lymph node cells was determined by the incorporation of3H-methyl thymidine measured in ab-scintillation counter.
All treated animals survived the scheduled study period and no signs of systemic toxicity or local skin irritation were observed.
A test item is regarded as a sensitiser in the LLNA if the exposure to one or more test concentration resulted in a 3-fold or greater increase in incorporation of3HTdR compared with concurrent controls, as indicated by the Stimulation Index (S.I.). The estimated concentration of test item required to produce a S.I. of 3 is referred to as the EC3 value.
In this study Stimulation Indices of 3.26, 3.46, and 2.46 were determined with the test item at concentrations of 5, 10, and 25% in DMF. A dose response was not observed. The EC3 value could not be calculated, since an inverse dose relationship was observed.
Calculation and results of individual data; Vehicle: DMF
Test item concentration % |
Group |
Measurement DPM |
Calculation |
Result |
||
DPM-BGa) |
number of lymph nodes |
DPM per lymph nodeb) |
S.I. |
|||
24 |
--- |
--- |
--- |
--- |
24 |
--- |
24 |
--- |
--- |
--- |
--- |
24 |
--- |
2268 |
2244 |
8 |
280.5 |
1.00 |
2268 |
2244 |
7330 |
7306 |
8 |
913.3 |
3.26 |
7330 |
7306 |
7792 |
7768 |
8 |
971.0 |
3.46 |
7792 |
7768 |
5554 |
5530 |
8 |
691.3 |
2.46 |
5554 |
5530 |
2-4= Test Group
a) = The mean value was taken from the figures BG I and BG II
b) = Since the lymph nodes of the animals of a dose group were pooled, DPM/node was determined by dividing the measured value by the number of lymph nodes pooled
The EC3 value could not be calculated, since an inverse dose relationship was observed.
VIABILITY / MORTALITY
No deaths occurred during the study period.
CLINICAL SIGNS
No symptoms of local skin irritation at the ears of the animals and no signs of systemic toxicity were observed during the study period.
BODY WEIGHTS
The body weight of the animals, recorded prior to the first application and prior to treatment with 3HTdR, was within the range commonly recorded for animals of this strain and age.
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 2 014
- Report date:
- 2014
Materials and methods
Test guideline
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 406 (Skin Sensitisation)
- Deviations:
- no
- GLP compliance:
- yes
- Type of study:
- guinea pig maximisation test
- Justification for non-LLNA method:
- The OECD 406 method was employed because the OECD 429 was proven as "not feasible" due to the experience that no stable formulation on acceptable vehiles could be produced as shown in the referenced study.
Test material
- Reference substance name:
- Hydrogen [[[(2-ethylhexyl)amino]sulphonyl][[(3-methoxypropyl)amino]sulphonyl]-29H,31H-phthalocyaninesulphonato(3-)-N29,N30,N31,N32]cuprate(1-), compound with N,N'-di(o-tolyl)guanidine (1:1)
- EC Number:
- 276-657-4
- EC Name:
- Hydrogen [[[(2-ethylhexyl)amino]sulphonyl][[(3-methoxypropyl)amino]sulphonyl]-29H,31H-phthalocyaninesulphonato(3-)-N29,N30,N31,N32]cuprate(1-), compound with N,N'-di(o-tolyl)guanidine (1:1)
- Cas Number:
- 72428-99-0
- Molecular formula:
- C32H13CuN8O4S2.(SO3H)m.(C4H11NO)n.(C8H18N) (3-m-n).C15H17N3
- IUPAC Name:
- hydrogen [[[(2-ethylhexyl)amino]sulphonyl][[(3-methoxypropyl)amino]sulphonyl]-29H,31H-phthalocyaninesulphonato(3-)-N29,N30,N31,N32]cuprate(1-), compound with N,N'-di(o-tolyl)guanidine (1:1)
Constituent 1
In vivo test system
Test animals
- Species:
- guinea pig
- Strain:
- Dunkin-Hartley
- Sex:
- female
- Details on test animals and environmental conditions:
- TEST ANIMALS
- Source: HARLAN, Kreuzelweg 53,5961 NM HORST- The Netherlands
- Age at study initiation: 3 or 4 weeks old
- Weight at study initiation: 250 - 310 g
- Diet (e.g. ad libitum): SAFE, 106, ad libitum
- Water (e.g. ad libitum): drinking water (tap water from public distribution system), ad libitum
- Acclimation period: a minimum acclimatization period of 5 days
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-25
- Humidity (%): 30-70
- Air changes (per hr): at least ten
- Photoperiod (hrs dark / hrs light): 12/12
Study design: in vivo (non-LLNA)
Inductionopen allclose all
- Route:
- intradermal and epicutaneous
- Vehicle:
- other: Physiological saline for the intradermal injections and propylene glycol for the topical applications.
- Concentration / amount:
- Intradermal Induction: 10%, epicutaneous induction: 60%, epicutaneous challange: 30% or 60%
Challengeopen allclose all
- Route:
- epicutaneous, occlusive
- Vehicle:
- other: Physiological saline for the intradermal injections and propylene glycol for the topical applications.
- Concentration / amount:
- Intradermal Induction: 10%, epicutaneous induction: 60%, epicutaneous challange: 30% or 60%
- No. of animals per dose:
- GROUP 1 (negative control) : 5
GROUP 2 (treated) : 10 - Details on study design:
- 1st Intradermal Induction:
Day 0
After shearing the scapular zone, three (3) pairs of intradermal injections (ID) of 0.1 mL were performed on the scapular zone in such a way as an injection on each pair is placed to either side of the spine as follows:
GROUP 1 (Control):
• 2 ID: Freund's Complete Adjuvant diluted at 50 % in physiological saline
• 2 ID: physiological saline
• 2 ID: a mixture with equal volumes v/v:
- Freund's Complete Adjuvant at 50% and physiological saline
GROUP 2 (Treated):
• 2 ID: Freund's Complete Adjuvant diluted at 50 % in physiological saline
• 2 ID: test item at 10% in physiological saline,
• 2 ID: a test mixture in equal volumes v/v:
- Freund's Complete Adjuvant at 50% and the test item at 20% in physiological saline
2nd Topical Induction:
Day 7
The scapular zone of all the animals in each group, shorn beforehand, was brushed with a solution of sodium lauryl sulfate at 10% in thick vase line, in order to create a local irritation.
Day 8
A topical application under occlusive dressing for 48 hours was performed on the injection sites of each animal.
GROUP 1 (Control): 0.5 mL of propylene glycol
GROUP 2 (treated): 0.5 mL ofthe test item at 60%
Day 10
Occlusive dressing removal and rinsing with propylene glycol of treated group. - Challenge controls:
- Challenge phase
Day 21
The experimental procedure of this phase was identical for both groups GROUP 1 and 2: on the previously shorn dorso-Iumbar zone, an application, under occlusive dressing, was performed during 24 hours:
- 1 sample cup saturated with the test item diluted at 60% and 1 sample cup saturated with the test item diluted at 30%.
Day 22
Occlusive dressing removal. - Positive control substance(s):
- yes
- Remarks:
- alpha-Hexylcinnamaldehyde
Results and discussion
- Positive control results:
- 23 July 2013:
24h reading / Conc.12.5% / 70% of animals sensitized
48h reading / Conc 12.5% / 60% of animals sensitized
24h reading / Conc.6.25% / 70% of animals sensitized
48h reading / Conc 6.25% / 50% of animals sensitized
21 January 2014:
24h reading / Conc.12.5% / 50% of animals sensitized
48h reading / Conc 12.5% / 30% of animals sensitized
72h reading / Conc 12.5% / 30% of animals sensitized
24h reading / Conc.6.25% / 30% of animals sensitized
48h reading / Conc 6.25% / 20% of animals sensitized
72h reading / Conc 6.25% / 70% of animals sensitized
26 August 2014:
24h reading / Conc.12.5% / 80% of animals sensitized
48h reading / Conc 12.5% / 40% of animals sensitized
24h reading / Conc.6.25% / 40% of animals sensitized
48h reading / Conc 6.25% / 0% of animals sensitized
In vivo (non-LLNA)
Resultsopen allclose all
- Reading:
- 1st reading
- Hours after challenge:
- 24
- Group:
- negative control
- Dose level:
- Challange Concentration 60%
- No. with + reactions:
- 0
- Total no. in group:
- 5
- Remarks on result:
- other: Reading: 1st reading. . Hours after challenge: 24.0. Group: negative control. Dose level: Challange Concentration 60%. No with. + reactions: 0.0. Total no. in groups: 5.0.
- Reading:
- 2nd reading
- Hours after challenge:
- 48
- Group:
- negative control
- Dose level:
- Challange Concentration 60%
- No. with + reactions:
- 0
- Total no. in group:
- 5
- Remarks on result:
- other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: negative control. Dose level: Challange Concentration 60%. No with. + reactions: 0.0. Total no. in groups: 5.0.
- Reading:
- 1st reading
- Hours after challenge:
- 24
- Group:
- negative control
- Dose level:
- Challange Concentration 30%
- No. with + reactions:
- 0
- Total no. in group:
- 5
- Remarks on result:
- other: Reading: 1st reading. . Hours after challenge: 24.0. Group: negative control. Dose level: Challange Concentration 30%. No with. + reactions: 0.0. Total no. in groups: 5.0.
- Reading:
- 2nd reading
- Hours after challenge:
- 48
- Group:
- negative control
- Dose level:
- Challange Concentration 30%
- No. with + reactions:
- 0
- Total no. in group:
- 5
- Remarks on result:
- other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: negative control. Dose level: Challange Concentration 30%. No with. + reactions: 0.0. Total no. in groups: 5.0.
- Reading:
- 1st reading
- Hours after challenge:
- 24
- Group:
- test chemical
- Dose level:
- Challange Concentration 60%
- No. with + reactions:
- 0
- Total no. in group:
- 10
- Remarks on result:
- other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: Challange Concentration 60%. No with. + reactions: 0.0. Total no. in groups: 10.0.
- Reading:
- 2nd reading
- Hours after challenge:
- 48
- Group:
- test chemical
- Dose level:
- Challange Concentration 60%
- No. with + reactions:
- 0
- Total no. in group:
- 10
- Remarks on result:
- other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: Challange Concentration 60%. No with. + reactions: 0.0. Total no. in groups: 10.0.
- Reading:
- 1st reading
- Hours after challenge:
- 24
- Group:
- test chemical
- Dose level:
- Challange Concentration 30%
- No. with + reactions:
- 0
- Total no. in group:
- 10
- Remarks on result:
- other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: Challange Concentration 30%. No with. + reactions: 0.0. Total no. in groups: 10.0.
- Reading:
- 2nd reading
- Hours after challenge:
- 48
- Group:
- test chemical
- Dose level:
- Challange Concentration 30%
- No. with + reactions:
- 0
- Total no. in group:
- 10
- Remarks on result:
- other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: Challange Concentration 30%. No with. + reactions: 0.0. Total no. in groups: 10.0.
Any other information on results incl. tables
Sodium lauryl sulfate at 10% induced an irritant effect on the skin during the 2nd induction.
Applicant's summary and conclusion
- Interpretation of results:
- not sensitising
- Remarks:
- Migrated information Criteria used for interpretation of results: EU
- Conclusions:
- In conclusion, under these experimental conditions, 0 % of the test animals showed a sensitisation response. Therefore the test item does not have to be classified as a skin sensitizer in accordance with the Regulation EC No 1272/2008.
- Executive summary:
The aim of the study was to evaluate the possible allergenic activity of the test item after intradermal and topical administration in guinea pigs.
After induction (intradermic injection at 10% and topical application at 60%) of 10 Guinea Pigs of treated group with the test item and a 10-day rest phase, the challenge phase, under occlusive dressing for 24 hours, consisted to a single topical application of the test item diluted at 60% and at 30% in propylene glycol. The experimental protocol was established according to the OECD guideline No. 406 dated July 17th , 1992 and the test method B.6 of the council regulation No. 440/2008.
In the treated group (chalange dose of 60%), no cutaneous reaction attributable to allergy was recorded in animals after the challenge phase. In the control group (associated with the challange dose of 60%), no cutaneous intolerance reaction was recorded at 24 and 48 hours. A blue coloration, not preventing erythema quotation was noted at the level of all treated areas at 60%.
In the treated group (challange dose of 30%), no cutaneous reaction attributable to allergy was recorded in animals after the challenge phase. In the control group (associated with the challange dose of 30%), no cutaneous intolerance reaction was recorded at 24 and 48 hours.
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