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EC number: 812-681-9 | CAS number: 1215310-75-0
- 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
Skin sensitisation
Administrative data
- Endpoint:
- skin sensitisation: in vivo (LLNA)
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- Feb 2016 - Sep 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:
- EU Method B.42 (Skin Sensitisation: Local Lymph Node Assay)
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 429 (Skin Sensitisation: Local Lymph Node Assay)
- GLP compliance:
- yes
- Type of study:
- mouse local lymph node assay (LLNA)
Test material
- Reference substance name:
- 4-methanesulfonyl-2-(trifluoromethyl)benzaldehyde
- EC Number:
- 812-681-9
- Cas Number:
- 1215310-75-0
- Molecular formula:
- C9H7F3O3S
- IUPAC Name:
- 4-methanesulfonyl-2-(trifluoromethyl)benzaldehyde
- Test material form:
- solid: particulate/powder
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.
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 cageenrichment.
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:
- propylene glycol
- Concentration:
- 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.
- No. of animals per dose:
- 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.
GROUP* INDUCTION
1 (1-6) Vehicle control Vehicle: Propylene glycol/water (7/3, v/v)
2 (7-12) Positive control 0.5% 1-Chloro-2,4-Dinitrobenzene (DNCB)
3 (13-18) Experimental 0.5% test item concentration
4 (19-24) Experimental 5% test item concentration
5 (25-30) Experimental 50% test item concentration
*. Six females per group, animal numbers given between brackets. - Details on study design:
- 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.
Four young adult animals were selected and two test item concentrations were tested, each on
two animals. Concentrations of 25% and 50% were tested and the highest concentration was
the maximum concentration as required in the test guidelines.
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, no
examinations were performed after the animals were sacrificed on Day 4 and scoring for
irritation included scoring for oedema.
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.
Induction - Days 1, 2 and 3
For the experimental animals, the dorsal surface of both ears was epidermally treated
(25 μL/ear) with the test item, approximately the same time each day. The concentrations were
mixed thoroughly using a magnetic stirrer immediately prior to dosing. The control animals
were treated as described for the experimental animals, except that, instead of the test item, the
vehicle or positive control item was administered.
Weighing of ear punches and lymph nodes - Day 4
Approximately 24 hours after the last treatment, all animals were sacrificed by intra-peritoneal
injection with pentobarbital (0.2 mL/animal Euthasol® 20% (AST Farma BV, Oudewater, The
Netherlands)).
Both ears (left and right) were punched in the apical area using a biopsy punch (Stiefel, Ø 8 mm
=> 0.5 cm2). For each animal both punches were immediately weighed pooled per animal using
an analytical balance after which the punches were discarded.
Both auricular draining lymph nodes (left and right) of mice were excised. The relative sizes of
the nodes (as compared to normal) were estimated by visual examination and abnormalities of
the nodes and surrounding area were recorded. For each animal both lymph nodes were pooled
and immediately weight using an analytical balance.
Determination of total cell-counts of lymph nodes – Day 4
Following excision and weighing of the nodes, single cell suspensions of lymph node cells
(LNC) were prepared in phosphate buffered saline (PBS) by gentle separation through stainless
steel gauze (diameter 200 μm mesh). LNC were collected in approximately 0.7 mL of PBS in
a 24 wells plate that was kept on ice as much as possible.
Cell counts were determined using a Coulter Counter (Beckman Coulter, The Netherlands). - Positive control substance(s):
- other: 0.5% 1-Chloro-2,4-Dinitrobenzene (DNCB)
- Statistics:
- Calculations were performed in MS EXCEL and statistical analysis was performed with
GraphPad Prism 4 (Kruskal-Wallis test, followed by the Mann Whitney test).
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:
- 0.5% QAW039-C2
- Remarks on result:
- not measured/tested
- Key result
- Parameter:
- SI
- Test group / Remarks:
- 5% QAW039-C2
- Remarks on result:
- not measured/tested
- Key result
- Parameter:
- SI
- Test group / Remarks:
- 50% QAW039-C2
- Remarks on result:
- not measured/tested
- Key result
- Parameter:
- other: Ear weight index
- Value:
- 1
- Test group / Remarks:
- 0.5% QAW039-C2
- Key result
- Parameter:
- other: Ear weight index
- Value:
- 1
- Test group / Remarks:
- 5% QAW039-C2
- Key result
- Parameter:
- other: Ear weight index
- Value:
- 1
- Test group / Remarks:
- 50% QAW039-C2
- Key result
- Parameter:
- other: LN weight index
- Value:
- 1.26
- Test group / Remarks:
- 0.5% QAW039-C2
- Key result
- Parameter:
- other: LN weight index
- Value:
- 0.98
- Test group / Remarks:
- 5% QAW039-C2
- Key result
- Parameter:
- other: LN weight index
- Value:
- 1.05
- Test group / Remarks:
- 50 % QAW039-C2
- Key result
- Parameter:
- other: Cell count index
- Value:
- 1.38
- Test group / Remarks:
- 0.5% QAW039-C2
- Key result
- Parameter:
- other: Cell count index
- Value:
- 1.05
- Test group / Remarks:
- 5% QAW039-C2
- Key result
- Parameter:
- other: Cell count index
- Value:
- 1.22
- Test group / Remarks:
- 50 % QAW039-C2
Any other information on results incl. tables
Pre-screen test
Erythema was noted for one animal at 50% on Day 3 only. No signs of systemic toxicity were noted.
Based on the results, the highest test item concentration selected for the main study was a 50% concentration.
No erythema of the ears was noted after visual examination in all of animals. Yellow
testsubstance remnants on the dorsal surface of the ears did not hamper scoring for erythema.
Visual examination of the nodes revealed that the nodes of two animals treated at 0.5% and
two animals treated at 50% were enlarged when compared to the vehicle control group. No
macroscopic abnormalities of the surrounding areas were noted in any of the animals.
Statistically significant body weight loss was noted in the 50% group in comparison to the
vehicle control. Since there were no clinical observations attributable to treatment with
QAW039-C2 and the body weight loss was only slight this was considerd not to have affected
the study.
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.
QAW039-C2 did not cause any relevant changes in ear weight up to a concentration of 50% in
Propylene glycol/water (7/3, v/v).
QAW039-C2 did no show a statistically significant difference when compared to vehicle and
did not show a dose response for LN weights or LN counts. The threshold for LN weights and
LN counts was exceeded at the lowest concentration (0.5%). These high values of the lowest
dose groups were mostly caused by one animal.
Applicant's summary and conclusion
- Interpretation of results:
- GHS criteria not met
- Conclusions:
- Since the high values of the lowest dose groups for LN weights and LN counts were mostly caused by one animal and no dose reponse or statistical significant difference was shown, no sensitizing was ascribed to QAW039-C2 in the murine LLNA TIER I.
Further, based on the ear weight results, no irritating potential as ascribed to QAW039-C2 in the murine LLNA TIER I.
Based on these results QAW039-C2 would not be regarded as a skin sensitizer according to the recommendations made in the test guidelines. It does not have to be classified and has no obligatory labelling requirement for sensitization by skin contact according to the Globally Harmonized System of Classification and Labelling of Chemicals (GHS) of the United Nations (2015) (including all amendments).
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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