Registration Dossier
Registration Dossier
Data platform availability banner - registered substances factsheets
Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.
The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.
Diss Factsheets
Use of this information is subject to copyright laws and may require the permission of the owner of the information, as described in the ECHA Legal Notice.
EC number: 811-180-2 | CAS number: 69249-22-5
- 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
Skin sensitisation
Administrative data
- Endpoint:
- skin sensitisation: in vivo (LLNA)
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 4 days
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- test procedure in accordance with generally accepted scientific standards and described in sufficient detail
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 2 016
- Report date:
- 2016
Materials and methods
- Principles of method if other than guideline:
- In the main study, six Balb/c female mice per group received topical test or control items on
the dorsum of both ears once a day on 3 consecutive days. Auricular lymph nodes were taken
24 hours after the last application. Endpoints: visual examination ears and sizes ear-draining
lymph nodes, body weight at treatment start and day of necropsy, ear weight (skin irritation),
ear-draining lymph node weights and cell counts (LN hyperplasia). Concentrations: vehicle
control Propylene glycol/water (7/3, v/v), positive control DNCB (1-Chloro-2,4-
Dinitrobenzene): 0.5% (w/w), and INC280-M3A: 5%, 0.5%, 0.05% (w/w). The vehicle was
selected on the basis of maximizing the solubility and the formulations appeared visually as
clear (0.05% or turbid (0.5% and 5%) solutions. - GLP compliance:
- yes (incl. QA statement)
- Type of study:
- mouse local lymph node assay (LLNA)
Test material
- Reference substance name:
- 6-bromo-1,2,4-triazin-3-amine
- Cas Number:
- 69249-22-5
- Molecular formula:
- C3H3BrN4
- IUPAC Name:
- 6-bromo-1,2,4-triazin-3-amine
- Test material form:
- solid: crystalline
Constituent 1
- Specific details on test material used for the study:
- Identification INC280-M3A
Appearance Slightly yellowish powder
Batch 1010006035
In vivo test system
Test animals
- Species:
- mouse
- Strain:
- Balb/c
- Sex:
- female
- Details on test animals and environmental conditions:
- Location: Specific Pathogen Free area: animal rooms A0.18.
Conditions: Environmental controls for the animal room were set to
maintain 18 to 24°C, a relative humidity of 40 to 70%, at least
10 air changes/hour, and a 12-hour light/12-hour dark cycle.
Any variations to these conditions were maintained in the raw
data and had no effect on the outcome of the study.
Animal caging:
Group housing in Makrolon cages (MIII type; height 18 cm)
containing sterilized sawdust as bedding material (Lignocel S
8-15, JRS - J.Rettenmaier & Söhne GmbH + CO. KG,
Rosenberg, Germany).
The acclimatization period was at least 5 days before the start
of treatment under laboratory conditions.
Cage enrichment: Paper (Enviro-dri, Wm. Lillico & Son (Wonham Mill Ltd),
Surrey, United Kingdom) and shelters (disposable paper corner
home, MCORN 404, Datesand Ltd, USA) were supplied as
cage-enrichment.
Food: Free access to pelleted rodent diet (SM R/M-Z from SSNIFF®
Spezialdiäten GmbH, Soest, Germany).
Water: Free access to tap-water.
Analysis of food, sawdust,
paper, shelters and water:
Results of analysis for diet (nutrients and contaminants),
sawdust, paper, shelters and water were assessed and did not
reveal any findings that were considered to have affected the
study integrity. All certificates and results of analysis are
retained in the WIL Research Europe archives.
Study design: in vivo (LLNA)
- Vehicle:
- other: Propylene glycol/water (7/3, v/v)
- Concentration:
- 5%, 0.5%, 0.05% (w/w).
- No. of animals per dose:
- 6
- Details on study design:
- In the main study, six Balb/c female mice per group received topical test or control items on
the dorsum of both ears once a day on 3 consecutive days. Auricular lymph nodes were taken
24 hours after the last application. Endpoints: visual examination ears and sizes ear-draining
lymph nodes, body weight at treatment start and day of necropsy, ear weight (skin irritation),
ear-draining lymph node weights and cell counts (LN hyperplasia). - Positive control substance(s):
- other: DNCB (1-Chloro-2,4- Dinitrobenzene): 0.5% (w/w)
- Statistics:
- The results of the LLNA were evaluated according to the following criteria. The following
thresholds were used: ear weight index: 1.05, LN weight: 1.2, LN cell count: 1.3 as advised by
the Sponsor.
1. Values which exceed these thresholds were considered positive
with no statistical significance, but a clear concentration-dependence
or when a statistically significant increase in one of the parameters occurs and a clear
concentration-dependence can be derived.
2. Values which are below these thresholds were considered positive when a statistical
significance occurs in one of the parameters together with a clear concentrationdependence.
3. Values were considered negative
in case of being below the thresholds and without a statistical significance.
in case of being below the thresholds, with a statistical significance, but without a clear
concentration-dependence.
in case of being above the thresholds, without statistical significance and without a clear
concentration-dependence.
Results and discussion
- Positive control results:
- The positive control item DNCB elicited a reaction pattern with increased LN hyperplasia,
which was in congruence with the expected mode of action of a contact allergen.
INC280-M3A meeted the ear weight threshold at the highest concentration with a statistically
significant difference when compared to vehicle. No clear dose response was found.
INC280-M3A exceeded the LN weight threshold at 0.5% and 5% with a statistically
significant difference when compared to vehicle. No clear dose response was found.
INC280-M3A exceeded the LN count threshold at all concentrations with a statistically
significant difference when compared to vehicle and showed a clear dose response.
In vivo (LLNA)
Resultsopen allclose all
- Parameter:
- other: Ear weight index
- Value:
- 1.05
- Test group / Remarks:
- 5% INC280-M3A
- Parameter:
- other: LN weight index
- Value:
- 1.31
- Test group / Remarks:
- 5% INC280-M3A
- Key result
- Parameter:
- other: Cell count index
- Value:
- 2.71
- Test group / Remarks:
- 5% INC280-M3A
- Remarks on result:
- other: P<0.01 treated groups vs control group
- Cellular proliferation data / Observations:
- INC280-M3A appeared to be a strong sensitizer, since the cell count index
exceeded the threshold of 1.3 at the lowest concentration of 0.05% (1.62), in the murine
LLNA TIER I.
Applicant's summary and conclusion
- Interpretation of results:
- Category 1A (indication of significant skin sensitising potential) based on GHS criteria
- Conclusions:
- According to the Globally Harmonized System of Classification and Labelling of Chemicals
(GHS) of the United Nations (2011) (including all amendments), INC280-M3A should be
classified as skin sensitizer (Category 1A). - Executive summary:
INC280-M3A: Assessment of contact sensitizing potential with the murine local lymph node
assay (TIER I).
The purpose of this study is to evaluate whether the test item induces contact hypersensitivity
in mice after three epidermal exposures of the animals under the conditions described in this
report. This study should provide a rational basis for risk assessment in man. The proposed
study complies with the test principle outlined in OECD Guideline 429 (2010), EC No
440/2008 Part B42 (2008) and EPA OPPTS 870.2600 (2003), except that these guidelines
describe a study plan using radioactive methods for the determination of cell proliferation.
Test item concentrations selected for the main study were based on results of a pre-screen test.
In the main study, six Balb/c female mice per group received topical test or control items on
the dorsum of both ears once a day on 3 consecutive days. Auricular lymph nodes were taken
24 hours after the last application. Endpoints: visual examination ears and sizes ear-draining
lymph nodes, body weight at treatment start and day of necropsy, ear weight (skin irritation),
ear-draining lymph node weights and cell counts (LN hyperplasia). Concentrations: vehicle
control Propylene glycol/water (7/3, v/v), positive control DNCB (1-Chloro-2,4-
Dinitrobenzene): 0.5% (w/w), and INC280-M3A: 5%, 0.5%, 0.05% (w/w). The vehicle was
selected on the basis of maximizing the solubility and the formulations appeared visually as
clear (0.05% or turbid (0.5% and 5%) solutions.
Formulation analyses confirmed that formulations of INC280-M3A in Propylene glycol/water
(7/3, v/v) were prepared accurately and homogenously, and were stable over at least 5 hours.
The positive control item DNCB elicited a reaction pattern with increased LN hyperplasia,
which was in congruence with the expected mode of action of a contact allergen.
INC280-M3A meeted the ear weight threshold at the highest concentration with a statistically
significant difference when compared to vehicle. No clear dose response was found.
INC280-M3A exceeded the LN weight threshold at 0.5% and 5% with a statistically
significant difference when compared to vehicle. No clear dose response was found.
INC280-M3A exceeded the LN count threshold at all concentrations with a statistically
significant difference when compared to vehicle and showed a clear dose response.
In conclusion, INC280-M3A appeared to be a strong sensitizer, since the cell count index
exceeded the threshold of 1.3 at the lowest concentration of 0.05% (1.62), in the murine
LLNA TIER I. Weak irritating potential was ascribed to INC280-M3A.
Based on these results according to the recommendations made in the test guidelines
(including all amendments), INC280-M3A would be regarded as skin sensitizer.
According to the Globally Harmonized System of Classification and Labelling of Chemicals
(GHS) of the United Nations (2011) (including all amendments), INC280-M3A should be
classified as skin sensitizer (Category 1A).
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.
Reproduction or further distribution of this information may be subject to copyright protection. Use of the information without obtaining the permission from the owner(s) of the respective information might violate the rights of the owner.