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EC number: 617-769-9 | CAS number: 858956-08-8
- 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:
- 25 April - 1 May 2007
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 2 011
- Report date:
- 2011
Materials and methods
Test guideline
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 429 (Skin Sensitisation: Local Lymph Node Assay)
- Version / remarks:
- adopted: 2001
- Deviations:
- no
- GLP compliance:
- yes
- Type of study:
- mouse local lymph node assay (LLNA)
Test material
- Reference substance name:
- 6-amino-5-chloro-2-cyclopropylpyrimidine-4-carboxylic acid
- EC Number:
- 617-769-9
- Cas Number:
- 858956-08-8
- Molecular formula:
- C8H8ClN3O2
- IUPAC Name:
- 6-amino-5-chloro-2-cyclopropylpyrimidine-4-carboxylic acid
1
In vivo test system
Test animals
- Species:
- mouse
- Strain:
- other: CBA/JHsd
- Sex:
- female
- Details on test animals and environmental conditions:
- TEST ANIMALS
- Source: Harlan Sprague Dawley, Frederick, Maryland, USA
- Females (if applicable) nulliparous and non-pregnant: yes
- Age at study initiation: 9 weeks
- Weight at study initiation: 21.3 - 23.2 g
- Housing: 2 animals housed in stainless steel wire-mesh cages suspended above cage boards during quarantine, individual housed in stainless steel wire-mesh cages suspended above cage boards during dosing and resting phases of the study
- Diet: PMI® Nutrition International, LLC Certified Rodent LabDiet® 5002, ad libitum
- Water: ad libitum
- Acclimation period: at least 6 days
- Indication of any skin lesions: There were no indications of any ear abnormalities (e.g., torn, scratched), clinical signs of disease or injury.
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18 - 26
- Humidity (%): 30 - 70
- Photoperiod (hrs dark / hrs light): 12/12
Study design: in vivo (LLNA)
- Vehicle:
- dimethylformamide
- Concentration:
- 1, 5, 25 and 50%
- No. of animals per dose:
- 5
- Details on study design:
- PRE-SCREEN TESTS:
- Compound solubility: The test substance was prepared in vehicle. Due to insolubility of the test substance, doses greater than 50% were not evaluated.
- Systemic toxicity: Animals were observed for changes in body weight and weight gain and any gross signs of disease or injury.
MAIN STUDY
ANIMAL ASSIGNMENT AND TREATMENT
- Name of test method: ³H-thymidine incorporation determined by beta counter
- Criteria used to consider a positive response: A stimulation index (SI) was derived for each experimental group by dividing the mean dpm of each experimental group by the mean dpm of the vehicle control group. A response is considered positive when the SI is ≥ 3.0 together with consideration of dose response and, where appropriate, statistical significance.
TREATMENT PREPARATION AND ADMINISTRATION: 25 µL of test substance preparations, vehicle or positive control were administered topically to the dorsum of each mouse ear for 3 consecutive days (test days 0-2). Test days 3-4 were days of rest followed by intravenous injection of 20 μCi of ³H-Thymidine per mouse on test day 5. Approximately 5 h after the injection, animals were sacrificed by carbon dioxide asphyxiation, draining auricular lymph nodes were removed, and single cell suspensions were prepared. The single cell suspensions were incubated at 2-8 °C overnight. On test day 6, the single cell suspensions were counted on a beta counter. The counts per minute (cpm) data were converted to disintegrations per minute (dpm). - Positive control substance(s):
- hexyl cinnamic aldehyde (CAS No 101-86-0)
- Statistics:
- Body weight and body weight gain:
Preliminary test: Levene’s test for homogeneity and Shapiro-Wilk test for normality
If preliminary test is not significant: One-way analysis of variance followed by Dunnett's test
If preliminary test is significant: Kruskal-Wallis test followed by Dunn's test
Lymph node dpm data:
Preliminary test: Test for lack of trend or Levene’s test for homogeneity and Shapiro-Wilk test for normality
If preliminary test is not significant: Sequential application of the Jonckheere-Terpstra trend test or One-way analysis of variance followed by Dunnett's test
If preliminary test is significant: Preliminary tests for pairwise comparison or Kruskal-Wallis test followed by Dunn's test
Significance was judged at p < 0.05 except for dpm data that were judged at p < 0.01. Lymph node dpm data were transformed to Log to obtain normality or homogenous variances.
When possible, an EC3 value for the SI data was derived from linear interpolation of points on the dose-response curve immediately above and below the 3-fold threshold. The equation used for calculation of EC3 was:
EC3 = c + [(3 - d)/(b - d)] × (a - c)
where:
a = the lowest concentration giving stimulation greater than 3
b = the actual SI caused by a
c = the highest concentration failing to produce an SI of 3
d = the actual SI caused by c
Results and discussion
- Positive control results:
- A 25% concentration of the positive control produced a SI of 13.28 and thus a dermal sensitization response in mice.
In vivo (LLNA)
Resultsopen allclose all
- Key result
- Parameter:
- SI
- Value:
- 1.8
- Test group / Remarks:
- 1%
- Key result
- Parameter:
- SI
- Value:
- 1.69
- Test group / Remarks:
- 5%
- Key result
- Parameter:
- SI
- Value:
- 2.29
- Test group / Remarks:
- 25%
- Key result
- Parameter:
- SI
- Value:
- 1.62
- Test group / Remarks:
- 50%
- Cellular proliferation data / Observations:
- CELLULAR PROLIFERATION DATA
No statistically significant increases in cell proliferation measurements compared to the vehicle control group were observed at any test concentration. Stimulation indices of less than 3.0 were observed at all test concentrations.
DETAILS ON STIMULATION INDEX CALCULATION
A stimulation index (SI) was derived for each experimental group by dividing the mean dpm of each experimental group by the mean dpm of the vehicle control group.
EC3 CALCULATION
Not calcuable for this study.
CLINICAL OBSERVATIONS
Dehydration was observed in one animal in the positive control group on test day 2. This mouse was found dead on test day 3. Gross necropsy revealed no abnormalities.
BODY WEIGHTS
No statistically significant differences in mean body weights and body weight gains compared to the vehicle control group were observed at any test concentration.
Any other information on results incl. tables
Table 1: Results of the Stimulation Index data
Group |
Test material |
number of animals |
Individual (dpm) |
Stimulation Index |
1 |
Vehicle control |
5 |
414.25 186.25 456.25 1658.25 299.25 |
|
Mean ± Standard deviation (dpm) |
602.85 ± 599.30 |
- |
||
2 |
Test substance 1% |
5 |
1585.25 632.25 1070.25 1368.25 765.25 |
|
Mean ± Standard deviation (dpm) |
1084.25 ± 399.35 |
1.80 |
||
3 |
Test substance 5% |
5 |
1702.25 899.25 485.25 1332.25 684.25 |
|
Mean ± Standard deviation (dpm) |
1020.65 ± 494.02 |
1.69 |
||
4 |
Test substance 25% |
5 |
2341.25 695.25 667.25 1730.25 1481.25 |
|
Mean ± Standard deviation (dpm) |
1383.05 ± 713.05 |
2.29 |
||
5 |
Test substance 50% |
5 |
1666.25 852.25 499.25 526.25 1342.25 |
|
Mean ± Standard deviation (dpm) |
977.25 ± 513.68 |
1.62 |
||
6
|
Positive control 25%* |
4** |
6195.25 ** 9308.25 7374.25 9136.25 |
|
Mean ± Standard deviation (dpm) |
8003.50 ± 1488.98 |
13.28 |
* Data were not included in the statistical analysis of the test substance groups
** One mouse was found dead on test day 3
dpm: disintegrations per minute
Table 2: Mean body weight and body weight gains of female mice
|
Mean body weight (g) ± Standard deviation |
|||||
Day |
Group 1 |
Group 2 |
Group 3 |
Group 4 |
Group 5 |
Group 6 |
|
vehicle control |
Test substance 5% |
Test substance 25% |
Test substance 50% |
Test substance 1% |
Positive control 25% |
0 |
22.2 ± 0.6 |
22.3 ± 0.6 |
22.3 ± 0.7 |
22.4 ± 0.6 |
22.0 ± 0.5 |
22.4 ± 0.8 |
5 |
22.3 ± 0.9 |
22.3 ± 0.8 |
22.0 ± 0.5 |
21.8 ± 1.2 |
21.4 ± 0.5 |
22.0 ± 0.7 |
|
Mean body weight gains (g) |
|||||
0-5 |
0.1 ± 0.8 |
-0.0 ± 0.4 |
-0.3 ± 0.8 |
-0.6 ± 0.8 |
-0.6 ± 0.8 |
-0.6 ± 1.3 |
Applicant's summary and conclusion
- Interpretation of results:
- other: CLP/EU GHS criteria not met, no classification required according to Regulation (EC) No. 1272/2008
- Conclusions:
- Under the conditions of the conducted LLNA test, the test substance did not exhibit sensitising properties.
CLP: not classified
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