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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.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: 249-320-4 | CAS number: 28940-11-6
- 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:
- From August 12 to October 06, 2005
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- guideline study with acceptable restrictions
- Remarks:
- guideline study with acceptable restrictions GLP Study performed according to the old version of the OECD test guideline No. 429 (2002), therefore ear thickness measurements were not included in the pre-screen test. The substance being irritating to the skin, this deviation may have an impact on the reliability of the study results. However no visible signs of irritation were observed at any of the concentration tested, therefore the study results are considered as reliable. The rational for the choice of the maximal dose tested (30%) is not very clear and not well reported (technical reason linked to the physical state of the substance - solid - expected since no higher dose was tested in the pre-test).
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 2 005
- Report date:
- 2005
Materials and methods
Test guideline
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 429 (Skin Sensitisation: Local Lymph Node Assay)
- Version / remarks:
- Adopted 24 April 2002
- Deviations:
- yes
- Remarks:
- tested only up to 30% (rational not clear), no ear thickness measurements, Age: 6-7 weeks old instead of 8-12 weeks old. Humidity: 30-95% instead of 30-70%, no duration of acclimatation period, single caging, use of hair dryer.
- Principles of method if other than guideline:
- Not applicable
- GLP compliance:
- yes (incl. QA statement)
- Remarks:
- inspected on July 19 to 22, 2004 / signed on January 06, 2005
- Type of study:
- mouse local lymph node assay (LLNA)
Test material
- Reference substance name:
- 7-methyl-2H-benzo-1,5-dioxepin-3(4H)-one
- EC Number:
- 249-320-4
- EC Name:
- 7-methyl-2H-benzo-1,5-dioxepin-3(4H)-one
- Cas Number:
- 28940-11-6
- Molecular formula:
- C10H10O3
- IUPAC Name:
- 7-methyl-3,4-dihydro-2H-1,5-benzodioxepin-3-one
- Test material form:
- solid
- Details on test material:
- - Storage condition of test material: At room temperature, protected from light, tightly sealed
Constituent 1
- Specific details on test material used for the study:
- - Physical state: White solid
In vivo test system
Test animals
- Species:
- mouse
- Strain:
- other: CBA/CaOlaHsd
- Sex:
- female
- Details on test animals and environmental conditions:
- TEST ANIMALS
- Source: Harlan Netherlands, Horst, The Netherlands.
- Age at study initiation: 6-7 weeks (beginning of acclimatization)
- Weight at study initiation: 19.0 ± 1.1 g (mean)
- Housing: Animals were individually housed in Makrolon Type I, with wire mesh top
- Diet: Pelleted standard diet, ad libitum
- Water: Tap water, ad libitum
- Acclimation period: no duration reported
ENVIRONMENTAL CONDITIONS
- Temperature: 22 ± 3 °C
- Humidity: 30-95 %
- Photoperiod: 12 h dark / 12 h light
IN-LIFE DATES: From: August 24, 2005 To: September 27, 2005
Study design: in vivo (LLNA)
- Vehicle:
- acetone/olive oil (4:1 v/v)
- Concentration:
- Main test: 1, 10 and 30 % w/v in acetone/olive oil 4:1 (v/v)
- No. of animals per dose:
- 4
- Details on study design:
- RANGE FINDING TESTS:
- Compound solubility: Soluble at 30% in AOO 4:1.
- Irritation: No irritation effects were observed at the concentrations of 1, 10 and 30% after a single application.
- Systemic toxicity: 30% is the highest achievable concentration whilst avoiding systemic toxicity and excessive local irritation.
- Ear thickness measurements: not measured
- Erythema scores: not reported
MAIN STUDY
ANIMAL ASSIGNMENT AND TREATMENT
- Name of test method: pooled treatment group approach, using tritiated (3H)-methyl thymidine, according to the OECD 429 test guideline.
- Criteria used to consider a positive response: A test item is regarded as a sensitiser in the LLNA if the following criteria are fulfilled:
1) 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.
2) 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.
The decision to select a stimulation index (S.I.) of 3 as an arbitrary indication of sensitizing activity was made on the basis of investigations performed with a wide range of chemicals.
TREATMENT PREPARATION AND ADMINISTRATION:
- All formulations were prepared freshly before each dosing. Homogeneity of the test item in the vehicle was maintained during treatment with the magnetic stirrer.
- Groups of four mice were treated with the test material at concentrations of 1, 10 and 30 % w/v in acetone/olive oil 4:1. The mice were treated by daily application of 25 μL of the appropriate concentration of the test material to the dorsal surface of each ear for three consecutive days (Days 1, 2, 3). A further group of four mice received the vehicle alone in the same manner. A hair dryer was used to dry the ear's surface as quickly as possible to avoid loss of test item applied.
Each animal was injected via the tail vein with 250 μL of phosphate buffered saline (PBS) containing 20.4 μCi of 3H-methyl thymidine (3HTdR) on Day 6.
After five hours, all animals were killed by intraperitoneal injection of Na-thiopental and the draining (auricular) lymph node of each ear was excised. The nodes from the four mice were excised and pooled for each experimental group. A single cell suspension of lymph node cells (LNC) was prepared in PBS by gentle mechanical disaggregation through gauze. LNC were washed two times with PBS. To precipitate out the radioactive material, the LNC were resuspended in 3 mL of 5 % Trichloroacetic acid (TCA) and incubated approximately 18 h incubation at approximately 4 °C. The precipitate was then resuspended in 1 mL of 5% TCA and transferred to 10 mL of scintillation fluid (Ultima gold) and thoroughly mixed. 3HTdR incorporation was measured bon a β-scintillation counter. Similarly background 3HTdR levels were also measured in two aliqots of 5% TCA.
The proliferation response of lymph node cells was expressed as the number of radioactive disintegrations per minute per lymph node (DPM/node) and as the ratio of 3HTdR incorporation into lymph node cells of test nodes relative to that recorded for the control nodes (Stimulation Index). - 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.
- A statistical analysis was conducted for assessment of the dose-response relationship, and the EC3 value was calculated according to the equation
EC3 = (a-c) [(3-d)/(b-d)] + c
where EC3 is the estimated concentration of the test item required to produce a 3-fold increase in draining lymph node cell proliferative activity; (a, b) and (c, d) are respectively the co-ordinates of the two pair of data lying immediately above and below the S.I. value of 3 on the local lymph node assay dose response plot.
Results and discussion
- Positive control results:
- α-hexylcinnamaldehyde at 25 % induced skin sensitisation (SI = 4.0)
In vivo (LLNA)
Results
- Key result
- Parameter:
- SI
- Value:
- < 3
- Test group / Remarks:
- Stimulation index for 1, 10 and 30 % were 0.83, 0.83 and 1.25, respectively.
- Cellular proliferation data / Observations:
- CELLULAR PROLIFERATION DATA
DPM / group for vehicle, 1, 10 and 30 % were 6293.56, 5225.82, 5253.89 and 7843.85, respectively.
DETAILS ON STIMULATION INDEX CALCULATION
Stimulation index for 1, 10 and 30 % were 0.83, 0.83 and 1.25, respectively.
EC3 CALCULATION
The EC3 value could not be calculated wince all SI's are below 3.
CLINICAL OBSERVATIONS:
Mortality / Viability: No deaths occurred during the study period.
Clinical signs (local / systemic): No symptoms of local toxicity at the ears of the animals and no systemic findings were observed during the study period.
BODY WEIGHTS
The body weight of the animals recorded was within the range commonly recorded for animals of this strain and age.
Any other information on results incl. tables
Table 7.4.1/1: Results of skin sensitisation
Test item Concentration %(w/v) |
Group |
Measurement DPM |
Calculation |
|
|
Result |
DPM-BGa |
number of lymph nodes |
DPM per lymph nodeb |
S.I. |
|||
- |
BG I |
24.60 |
- |
- |
- |
- |
- |
BG II |
23.53 |
- |
- |
- |
- |
- |
CG 1 |
6293.56 |
6269.5 |
8 |
783.7 |
NA |
1 |
TG 2 |
5225.82 |
5201.8 |
8 |
650.2 |
0.83 |
10 |
TG 3 |
5253.89 |
5229.8 |
8 |
653.7 |
0.83 |
30 |
TG 4 |
7843.85 |
7819.8 |
8 |
977.5 |
1.25 |
BG = Background (1 ml 5% trichloroacetic acid) in duplicate
CG = Control Group
TG = Test Group
S.I. = Stimulation Index
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 all SI’s were below 3.
Applicant's summary and conclusion
- Interpretation of results:
- GHS criteria not met
- Conclusions:
- Under the test conditions, test material is not classified as a skin sensitiser according to the annex VI of the Regulation EC No. 1272/2008 (CLP) and to the GHS.
- Executive summary:
A study was performed to assess the skin sensitisation potential of test material in the CBA/CaOlaHsd strain mouse following topical application to the dorsal surface of the ear. The method was conducted according to the OECD test guideline No 429 and in compliance with GLP.
Following a preliminary screening test in which no clinical signs of toxicity and no signs of local irritation were noted at the achievable concentrations of 0.5, 1, 10 and 30 % (w/v), the dose levels of 1, 10 and 30% (w/v) were selected for the main test.
The study comprised three groups, each comprising four female animals, were treated with 50 μl (25 μl per ear) of test material as a solution in acetone/olive oil 4:1 at concentrations of 1, 10 and 30 % (w/v) for 3 consecutive days. A further control group of four animals was treated with acetone/olive oil 4:1 alone. The proliferative response of the lymph node cells (LNC) from the draining auricular lymph nodes was assessed five days following the initial application, by measurement of the incorporation of 3H-methyl Thymidine (3HTdR) by β-scintillation counting of LNC suspensions. The proliferation response of lymph node cells was expressed as the number of radioactive disintegrations per minute per group and as the ratio of 3HTdR incorporation into lymph node cells of test nodes relative to that recorded for the control nodes (Stimulation Index).
The SI obtained for 1, 10 and 30% v/v test item were 0.83, 0.83 and 1.25, respectively, which indicates that test item did not show the potential to induce skin sensitization. The EC3 value was therefore not calculated. There were no deaths. No signs of systemic toxicity were noted in the test or control animals during the test. Bodyweight changes of the test animals between prior to the first application and prior to treatment with 3HTdR were comparable to those observed in the corresponding control group animals over the same period.
The historical positive control, α-Hexylcinnamaldehyde, gave a SI of 4.00, when tested at 25 % w/v. The test system was therefore considered to be valid.
Under the test conditions, test material is not classified as a skin sensitiser in the Local Lymph Node Assay according to the annex VI of the Regulation (EC) No. 1272/2008 (CLP) and to the GHS.
This study is considered as acceptable and satisfies the requirement for sensitisation endpoint.
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.