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EC number: 262-309-9 | CAS number: 60580-61-2
- 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
![](https://echa.europa.eu/o/diss-blank-theme/images/factsheets/A-REACH/factsheet/print_toxicological-information.png)
Skin sensitisation
Administrative data
- Endpoint:
- skin sensitisation: in vivo (LLNA)
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 2017-09-20 to 2017-10-18
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 2 018
- Report date:
- 2018
Materials and methods
Test guidelineopen allclose all
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 429 (Skin Sensitisation: Local Lymph Node Assay)
- Version / remarks:
- adopted 2010-07-22
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- EU Method B.42 (Skin Sensitisation: Local Lymph Node Assay)
- Version / remarks:
- 2008-05-30
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- EPA OPPTS 870.2600 (Skin Sensitisation)
- Version / remarks:
- 2003-03
- Deviations:
- no
- GLP compliance:
- yes (incl. QA statement)
- Remarks:
- signed 2015-06-05
- Type of study:
- mouse local lymph node assay (LLNA)
Test material
- Test material form:
- solid: particulate/powder
- Details on test material:
- State of aggregation at room temperature: white powder
Constituent 1
- Specific details on test material used for the study:
- STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: room temperature; protected from light; dry in closed containers
In vivo test system
Test animals
- Species:
- mouse
- Strain:
- other: CBA/OlaHsd
- Sex:
- female
- Details on test animals and environmental conditions:
- TEST ANIMALS
- Source: Envigo (formed partially from Harlan in September 2015), 5800 AN Venray, The Netherlands
- Females (if applicable) nulliparous and non-pregnant: yes
- Microbiological status of animals, when known: The animals were derived from a controlled full-barrier maintained breeding system (SPF).
- Age at study initiation: 8-9 weeks
- Weight at study initiation: Prescreen test:18.3 - 21 g, Main Study: 18.3 - 22.5 g
- Housing: The animals were kept in groups of 5 animals in IVC cages, type II L, polysulphone cages on Altromin saw fibre bedding
- Diet (ad libitum): Altromin 1324 maintenance diet for rats and mice
- Water ( ad libitum): Tap water, sulphur acidified to a pH value of approx. 2.8 (drinking water, municipal residue control, microbiological controls at regular intervals)
- Acclimation period: at least five days
- Indication of any skin lesions: No skin lesions observed
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3 °C
- Relative Humidity (%): 55 ± 10%
- Air changes (per hr): at least 10 x / hour
- Photoperiod (hrs dark / hrs light): 12/12
Study design: in vivo (LLNA)
- Vehicle:
- acetone/olive oil (4:1 v/v)
- Concentration:
- 12.5%, 25% and 50% (w/v)
Dose selection based on the results observed in the prescreen test: the maximum technically applicable concentration of the test item in the vehicle was
found to be 50% in AOO (4:1 (v/v) acetone / olive oil) - No. of animals per dose:
- 5 female mice per dose
- Details on study design:
- PRE-SCREEN TESTS:
- Compound solubility: The maximum technically applicable concentration was found to be 50% in AOO (4:1 (v/v) acetone / olive oil)
- A prescreen test was performed which was conducted under the same conditions as the main study, except there was no assessment of lymph node proliferation and fewer animals per dose group were used.
- The mice were observed daily for any clinical signs of systemic toxicity or local irritation at the application site.
- Body weights were recorded pre-test and prior to termination (day 6).
- Both ears were observed for erythema and scored.
- Ear thickness measurements were performed on day 1 (pre-dose), day 3 (approximately 48 hours after the first dose) and day 6 using a digital calliper. Excessive local irritation was indicated by an erythema score ≥ 3 and/or ear swelling of ≥ 25%. In addition to a 25% increase in ear thickness, a statistically significant increase in the treated mice compared to control mice was used to identify irritants in the LLNA.
- Four animals were treated by topical application on three consecutive days at the following concentrations to the entire dorsal surface of each ear:
Two animals were treated with a test item concentration of 50% (suspended in AOO)
Two animals were treated with a test item concentration of 25% (suspended in AOO)
One animal was treated with 100% AOO and served as negative control.
- Before the first application, approximately 48 hours after the first application and shortly before sacrificing the thickness of both ears of all animals was measured. During this period also all clinical signs were recorded. Cageside observations included spontaneous activity, lethargy, recumbent position, convulsions, tremors, apnoea, asphyxia, vocalisation, diarrhoea, changes in the skin and fur, eyes and mucous membranes (salivation, discharge).
Results:
- Neither signs of systemic toxicity nor signs of excessive irritation at any application site could be detected in any animal.
- The animal treated with 100% AOO (negative control) showed sticky fur at the application sites on day 4.
- All animals showed the expected weight development, which includes a weight loss of up to 2 g throughout the duration of the prescreen test.
MAIN STUDY
ANIMAL ASSIGNMENT AND TREATMENT
- Name of test method: The animals were randomly selected using the validated departmental computerised system E-WorkBook (version 10.1.2, ID Business Solutions Ltd.). Identification was ensured by cage number and individual marking (tail, no ear marking).
- Criteria used to consider a positive response: A substance is regarded as a 'sensitiser' in the LLNA if at least one concentration of the
test item results in a 3-fold or greater increase in 3H-methyl thymidine - incorporation into lymph node cells of the test group animals, relative to that recorded for the lymph nodes of control group animals (Stimulation Index equal to or greater than 3.0). The strength of the dose response, the statistical significance and the consistency of the vehicle and positive control responses may also be used when determining whether a borderline result is declared positive.
TREATMENT PREPARATION AND ADMINISTRATION:
Topical Application:
- Before the first application the thickness of both ears of all animals was measured using a digital caliper.
- Each mouse was treated by topical application of 25 μL of the selected solution to the entire dorsal surface of each ear.
- A second measurement of the ear thickness of all animals was carried out approximately 48 hours after the first application.
- Topical applications were performed once daily over three consecutive days. The first treatment day is defined as study day 1.
Administration of 3H-Methyl Thymidine:
- Five days after the first topical application (study day 6) all mice were dosed with 20 μCi 3H-methyl thymidine by intravenous injection (tail vein) of 250 μL of 3H-methyl thymidine, diluted with PBS to a working concentration of 80 μCi/mL.
Preparation of Cell Suspension:
- Approximately 5 hours after injection of 3H-methyl thymidine all mice were sacrificed by cervical dislocation.
- Shortly before sacrificing, scoring of ear erythema and the thickness of ears of all animals was measured for a third time.
- The draining auricular lymph nodes were excised, individually pooled for each animal (2 lymph nodes per animal) and collected in phosphate buffered saline (PBS).
- A single cell suspension of pooled lymph node cells was prepared by gentle mechanical disaggregation through polyamide gauze (200 mesh size)
- After washing the gauze with PBS the cell suspension was pelleted in a centrifuge. The supernatant was discarded and the pellets were resuspended with PBS. This washing procedure was repeated.
- Each pellet was resuspended in approx. 1 mL 5% TCA at approx. 4° C for approximately 18 hours. Each precipitate was once washed again, resuspended in 1 mL 5% TCA and 7 mL scintillation fluid (equivalent to OECD 429, in order to achieve a more efficient counting by reducing the background noise) was added. This solution was transferred into scintillation vials and stored at room temperature overnight.
Determination of Incorporated 3H -Methyl Thymidine:
- The 3H-methyl thymidine – incorporation was measured in a ß-counter and expressed as the number of disintegrations per minute (DPM).
- Similarly, background 3H-methyl thymidine levels were also measured (5% TCA) in order to determine a baseline. Determination of radioactivity was performed individually for each animal.
OBSERVATIONS:
- Prior to the start of treatment all animals were examined to ensure that they had no observable skin lesions.
- Prior to the application and once a day thereafter all animals were observed in order to detect signs of toxicity, including dermal irritation at site of application.
- The following clinical observations were observed and recorded: changes in nervous system function (e.g. pilo-erection, ataxia, tremors, and convulsions); changes in behaviour (e.g. aggressiveness, change in grooming activity, marked change in activity level); changes in respiratory patterns (i.e. changes in frequency and intensity of breathing such as dyspnoea, gasping, and rales), and changes in food and water consumption.
- Signs of lethargy and/or unresponsiveness and any clinical signs of more than slight or momentary pain and distress, or a >10% reduction in body weight from day 1 to day 6, and mortality were considered in the evaluation.
- The animals were weighed prior to the application and at the end of the test period (prior to the treatment with 3HTdR).
EVALUATION OF RESULTS:
- The proliferative 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 3H-methyl thymidine - incorporation into lymph node cells of test group animals relative to that recorded for control group animals (STIMULATION INDEX).
- Before DPM/NODE values were determined, background values were subtracted.
- EC3 values, calculated concentrations which induce stimulation indices of three, are determined by linear interpolation, EC3=c+[(3-d)/(b-d)]x(a-c), between two points of the stimulation indices axis, one above (a,b) and one below (c,d) the stimulation index of three.
- If all measured points are above or below the stimulation index of three, no EC3 value can be stated. - Positive control substance(s):
- other: 1 % phenylenediamine in acetone:olive oil (4/1 v/v)
- Statistics:
- According to OECD 429 the SI calculation may need to be carried out without outliers. Therefore, DPM data of all dose and control groups were screened for outliers using Grubbs’, Nalimov’s and Dixon’s test, respectively. Values that failed at least one of the tests were labelled as outliers and excluded for SI calculation.
Results and discussion
- Positive control results:
- The positive-control substance, 1 % phenylenediamine in acetone:olive oil (4/1 v/v), exceeded the stimulation index of 3 (mean SI 8.6) confirming the reliability of the test system.
In vivo (LLNA)
Resultsopen allclose all
- Parameter:
- SI
- Value:
- 1.6
- Variability:
- 0.4 (SD)
- Test group / Remarks:
- 12.5 % group
- Parameter:
- SI
- Value:
- 1.4
- Variability:
- 0.2 (SD)
- Test group / Remarks:
- 25 % group
- Parameter:
- SI
- Value:
- 1.3
- Variability:
- 0.7
- Test group / Remarks:
- 50 % group
- Cellular proliferation data / Observations:
- DETAILS ON STIMULATION INDEX CALCULATION
- The proliferative 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 3H-methyl thymidine - incorporation into lymph node cells of test group animals relative to that recorded for control group animals (STIMULATION INDEX).
- Before DPM/NODE values were determined, background values were subtracted.
- One measured DPM value (25% test item concentration) failed Grubbs’, Nalimov’s and Dixon’s outlier tests and was excluded for SI calculation.
EC3 CALCULATION
- Since all three stimulation indices were below the stimulation index of three, no EC3 value can be calculated.
- A dose-response relationship was not observed.
CLINICAL OBSERVATIONS:
- All animals survived throughout the test period without showing any clinical signs.
BODY WEIGHTS
- All animals showed the expected weight development, which includes a weight loss of up to 2 g throughout the study.
EAR THICKNESS:
- The means of the ear thickness per group showed no relevant difference compared to the negative control Please refer to the field "Any other information on results incl. tables" below.
Any other information on results incl. tables
Table 1: Mean ear thickness
Mean ear thickness |
day 1 |
day 3 |
day 6 |
12.5% test group |
18.4 mm |
19.1 mm |
19.0 mm |
25% test group |
18.2 mm |
19.0 mm |
18.3 mm |
50% test group |
18.1 mm |
19.4 mm |
18.5 mm |
negative control group |
18.3 mm |
19.4 mm |
19.2 mm |
Applicant's summary and conclusion
- Interpretation of results:
- GHS criteria not met
- Conclusions:
- Under the present test conditions, zinc 5-nitroisophthalate at concentrations of 12.5%, 25% or 50% (w/w) in acetone/olive oil (4/1 v/v) did not reveal any sensitising properties in the local lymph node assay and therefore should not be classified and labelled according to Regulation (EC) No.: 1272/2008 and its subsequent regulations.
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.
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