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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.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: 629-620-5 | CAS number: 13534-99-1
- 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:
- May 2016 - June 2017
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 2 017
- Report date:
- 2017
Materials and methods
Test guidelineopen allclose all
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 429 (Skin Sensitisation: Local Lymph Node Assay)
- Qualifier:
- according to guideline
- Guideline:
- EPA OPPTS 870.2600 (Skin Sensitisation)
- GLP compliance:
- yes
- Type of study:
- mouse local lymph node assay (LLNA)
Test material
- Reference substance name:
- 3-bromopyridin-2-amine
- EC Number:
- 629-620-5
- Cas Number:
- 13534-99-1
- Molecular formula:
- C5 H5 Br N2
- IUPAC Name:
- 3-bromopyridin-2-amine
- Test material form:
- solid
Constituent 1
In vivo test system
Test animals
- Species:
- mouse
- Strain:
- Balb/c
- Sex:
- female
- Details on test animals and environmental conditions:
- Mouse, Balb/c strain, inbred, SPF-Quality. 30 females (nulliparous and non-pregnant), six females per group.
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 Charles River Den Bosch archives.
Study design: in vivo (LLNA)
- Vehicle:
- other: DAE433
- Concentration:
- Initially, four young adult animals were selected and two test item concentrations were tested, each on two animals. Concentrations of 25% and 60% were tested and the highest concentration was the maximum concentration that could be prepared homogeneously.
Based on the results of the initially treated animals, four additional animals were treated in a similar manner with two lower concentrations (2% and 5%) at a later stage. Based on these results, two additional animals were treated in a similar manner (10%) at a later stage.
Preparations (w/w) were prepared within 4 hours prior to dosing and homogeneity was assessed by visual inspection of the solutions. No adjustment was made for specific gravity of the vehicle.
Correction of the purity/composition of the test substance is not applicable, since the test method requires a logical concentration range rather than specific dose levels to be dosed. - No. of animals per dose:
- GROUP* INDUCTION
1 (1-6) Vehicle control Vehicle: DAE433
2 (7-12) Positive control 0.5% 1-Chloro-2,4-Dinitrobenzene (DNCB)
3 (13-18) Experimental 0.05% test item concentration
4 (19-24) Experimental 0.5% test item concentration
5 (25-30) Experimental 5% test item concentration
*. Six females per group, animal numbers given between brackets. - Details on study design:
- Pre-screen test
A pre-screen test was conducted in order to select the highest test item concentration to be used in the main study. In principle, this concentration should cause no systemic toxicity and may give well-defined irritation (maximally grade 2) at the highest.
Initially, four young adult animals were selected and two test item concentrations were tested, each on two animals. Concentrations of 25% and 60% were tested and the highest concentration was the maximum concentration that could be prepared homogeneously.
Based on the results of the initially treated animals, four additional animals were treated in a similar manner with two lower concentrations (2% and 5%) at a later stage. Based on these results, two additional animals were treated in a similar manner (10%) at a later stage.
The test system, procedures and techniques were the same to those used in the main study, with the exceptions that Makrolon MII type cages (height 14 cm) were used for group housing, the animals were 8 weeks old, no examinations were performed after the animals were sacrificed on Day 4 and scoring for irritation included scoring for oedema according the scheme below:
Oedema formation:
No oedema .................................................................................……………………….……………….. 0
Slight oedema (barely perceptible) ......................................................………………………………..... 1
Moderate oedema....................................……………………................................................................. 2
Severe oedema…..................................................................................................................................... 3
Main study
Three groups of six animals were treated with one test item concentration per group. The highest test item concentration was selected from the pre-screen test. One group of six animals was treated with vehicle and one group with the positive control item. - Positive control substance(s):
- other: 0.5% 1-Chloro-2,4-Dinitrobenzene (DNCB)
- Statistics:
- In case of a positive finding, a linear regression was used to calculate the concentration corresponding to the respective threshold. The calculation for the LN hyperplasia threshold concentration was performed with the respective LN cell count threshold index. In case of inconclusive cell count results, LN weight data were used to calculate the threshold concentration. This classification scheme (see Table) is derived from results obtained with standard irritants and contact allergens (Ulrich P, Streich J, Suter W (2001)). Calculations were performed in MS EXCEL and statistical analysis was performed with GraphPad Prism 4 (Kruskal-Wallis test, followed by the Mann Whitney test).
Table Classification of LLNA results
Mode Strong Moderate Weak
Rules for ear skin irritation TC < 0.1 % 0.1% ≤ TC < 5% 5% ≤ TC
Rules for LN hyperplasia TC < 1 % 1% ≤ TC < 5 % 5% ≤ TC
TC: threshold concentration.
The results were evaluated according to the Globally Harmonized System of Classification and Labelling of Chemicals (GHS) of the United Nations (2015).
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.
In vivo (LLNA)
Resultsopen allclose all
- Key result
- Parameter:
- SI
- Test group / Remarks:
- 0.05% QAW039-C1
- Remarks on result:
- not measured/tested
- Key result
- Parameter:
- SI
- Test group / Remarks:
- 0.5% QAW039-C1
- Remarks on result:
- not measured/tested
- Key result
- Parameter:
- SI
- Test group / Remarks:
- 5% QAW039-C1
- Remarks on result:
- not measured/tested
- Key result
- Parameter:
- other: Ear weight index
- Value:
- 1.01
- Test group / Remarks:
- 0.05% QAW039-C1
- Key result
- Parameter:
- other: Ear weight index
- Value:
- 1.03
- Test group / Remarks:
- 0.5% QAW039-C1
- Key result
- Parameter:
- other: Ear weight index
- Value:
- 1.02
- Test group / Remarks:
- 5% QAW039-C1
- Key result
- Parameter:
- other: LN weight index
- Value:
- 1.03
- Test group / Remarks:
- 0.05% QAW039-C1
- Key result
- Parameter:
- other: LN weight index
- Value:
- 1.06
- Test group / Remarks:
- 0.5% QAW039-C1
- Key result
- Parameter:
- other: LN weight index
- Value:
- 1.09
- Test group / Remarks:
- 5% QAW039-C1
- Key result
- Parameter:
- other: Cell count index
- Value:
- 1.2
- Test group / Remarks:
- 0.05% QAW039-C1
- Key result
- Parameter:
- other: Cell count index
- Value:
- 1.2
- Test group / Remarks:
- 0.5% QAW039-C1
- Key result
- Parameter:
- other: Cell count index
- Value:
- 1.33
- Test group / Remarks:
- 5% QAW039-C1
- Cellular proliferation data / Observations:
- No irritation of the ears was noted after visual examination in the majority of animals, except for the very slight irritation of two animals treated at 0.05% and one animal treated at 5% on Day 3. The very slight irritation was considered not to have a toxicologically significant effect on the activity of the nodes. No further relevance was attached to this finding. Visual examination of the nodes revealed that all the nodes of the experimental animals were considered normal in size when compared to the vehicle control group. No macroscopic abnormalities of the surrounding areas were noted in any of the animals.
Body weights and body weight gain of experimental animals remained in the same range as controls over the study period. There were no clinical observations attributable to treatment with QAW039-C1.
QAW039-C1 did not cause any relevant changes in ear weight or LN weight up to a concentration of 5% in DAE433.
QAW039-C1 exceeded the LN count threshold at 5% with a statistically significant difference when compared to vehicle but did not show a clear dose response curve.
Applicant's summary and conclusion
- Interpretation of results:
- Category 1B (indication of skin sensitising potential) based on GHS criteria
- Conclusions:
- In conclusion, QAW039-C1 appeared to be a moderate sensitizer (based on a threshold concentration for cell counts of 4.3%) without irritating potential in the murine LLNA TIER I.
Based on these results:
according to the recommendations made in the test guidelines (including all amendments), QAW039-C1 would be regarded as skin sensitizer.
- according to the Globally Harmonized System of Classification and Labelling of Chemicals (GHS) of the United Nations (2015) (including all amendments), QAW039-C1 should be classified as skin sensitizer (Category 1B).
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.