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EC number: 695-187-4 | CAS number: 166524-75-0
- 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:
- 23 April 2001 to 1 May 2001
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- other: see 'Remark'
- Remarks:
- Study conducted in compliance with agreed protocols, with no or minor deviations from standard test guidelines and/or minor methodological deficiencies, which do not affect the quality of the relevant results. The study report was conclusive, done to a valid guideline and the study was conducted under GLP conditions.
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 2 001
- Report date:
- 2001
Materials and methods
Test guideline
- Qualifier:
- according to guideline
- Guideline:
- other: ICCVAM NIH No. 99-4494 (The Murine Local Lymph Node Assay: a Test Method for Assessing the Allergic Contact Dermatitis Potential of Chemicals/Compounds)
- Deviations:
- not specified
- GLP compliance:
- yes
- Type of study:
- mouse local lymph node assay (LLNA)
Test material
- Reference substance name:
- 5-ethoxy-2-({5-ethoxy-7-fluoro-[1,2,4]triazolo[1,5-c]pyrimidin-2-yl}disulfanyl)-7-fluoro-[1,2,4]triazolo[1,5-c]pyrimidine
- EC Number:
- 695-187-4
- Cas Number:
- 166524-75-0
- Molecular formula:
- C14H12F2N8O2S2
- IUPAC Name:
- 5-ethoxy-2-({5-ethoxy-7-fluoro-[1,2,4]triazolo[1,5-c]pyrimidin-2-yl}disulfanyl)-7-fluoro-[1,2,4]triazolo[1,5-c]pyrimidine
- Test material form:
- solid: particulate/powder
- Remarks:
- migrated information: powder
- Details on test material:
- - Name of test material (as cited in study report): 2,2'-dithiobis (5-ethoxy-7-fluoro [1,2,4] triazolo [1,5c] pyrimidine)
- Appearance: yellowish solid powder
Constituent 1
In vivo test system
Test animals
- Species:
- mouse
- Strain:
- Balb/c
- Sex:
- female
- Details on test animals and environmental conditions:
- TEST ANIMALS
- Age at study initiation: 9 weeks
- Weight at study initiation: 18.1 - 22.2 g
- Housing: 2 per cage for a two day period then individually thereafter. Cages have wire mesh floors and are suspended above catch pans.
- Diet: Certified Rodent Diet, ad libitum
- Water: municipal water ad libitum
- Acclimation period: 7 days
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21.8 - 22.0 °C
- Humidity (%): 47.6 - 52.8 %
- Air changes (per hr): 12 - 15 air exchanges per hour
- Photoperiod (hrs dark / hrs light): 12 hours light / 12 hours dark (lights on 0600 to 1800)
IN-LIFE DATES: From 27 April 2001 to 1 May 2001
Study design: in vivo (LLNA)
- Vehicle:
- dimethylformamide
- Concentration:
- 0.3, 1 and 3 % test material in N,N,-dimethylformamide (DMF)
- No. of animals per dose:
- 6 mice per dose
- Details on study design:
- SCREEN STUDY
A screen study was conducted to determine the minimally irritating concentration (MIC) - the highest concentration that produces approximately a 10 % ear swelling response.
- Compound solubility: the test material was not soluble in acetone:olive oil; therefore, DMF was the vehicle of choice for this study.
- Dosing solutions: the maximum amount of test material that could be suspended in DMF was 3.5 %. Therefore, concentrations for the screen were set at 3.5, 1.2, 0.35, 0.12, 0.035 and 0.012 % test material in DMF.
- Method: for the screen, six animals per group received 12.5 µL of the appropriate dosing solution on the dorsal and ventral portions of the left ear and an equal amount of DMF on the dorsal and ventral portions of the right ear. Prior to the administration of the dosing solutions and 24 hours after the last application, the thickness of each ear was measured using a micrometer. The MIC for the subsequent LLNA was set at 3.0 %.
MAIN STUDY
ANIMAL ASSIGNMENT AND TREATMENT
Groups of 6 mice were topically exposed to one of three suspensions of test material in DMF (0.3, 1 and 3 %) for three consecutive days. Additional groups of 6 animals were exposed to the vehicle alone or a positive control. All mice received 12.5 µL of the appropriate treatment on the dorsal and ventral portion of both ears.
Five days following the initiation of the LLNA, all mice received an intravenous injection, via the lateral tail vein, of 250 µL of phosphate buffered saline (PBS) containing 20 µCi of tritiated thymidine. Approximately 5 hours later, the mice were sacrificed and the draining auricular lymph nodes were excised and pooled for each mouse. A single cell suspension of lymph node cells was prepared by gentle mechanical disaggregation in PBS. The lymph node cells were washed twice in PBS and were placed in 5 % trichloroacetic acid (TCA) for approximately 70 hours. The cells were spun down and reconstituted in 5 % TCA and the tritiated thymidine incorporation was measured on a beta-scintillation counter as disintegrations per minute (dpm) per mouse.
CRITERIA USED TO CONSIDER A POSITIVE RESPONSE
A test material with a Stimulation Index of 3 or more can be considered a skin sensitiser. - Positive control substance(s):
- other: 1 % dinitrochlorobenzene in DMF
- Statistics:
- The positive controls and treatment groups were compared to the vehicle control group using a one-way analysis of variance.
Results and discussion
- Positive control results:
- Animals treated with the positive control produced a SI of 30.9 ± 4.6, which is consistent with the material being a known contact sensitiser.
In vivo (LLNA)
Resultsopen allclose all
- Parameter:
- SI
- Remarks on result:
- other: Treatment with the vehicle, DMF, resulted in a SI of 1.0 ± 0.1. Animals treated with 0.3, 1 or 3 % test material in DMF all produced an SI of less than 3. See Tables 1 and 2.
- Parameter:
- other: disintegrations per minute (DPM)
- Remarks on result:
- other: See Table 1.
Any other information on results incl. tables
Table 1: Individual dpm and SI
Treatment |
Animal no. |
dpm |
SI |
0.3 % test material in DMF |
2213 |
848.15 |
3.53 |
2214 |
272.88 |
1.14 |
|
2215 |
235.68 |
0.98 |
|
2216 |
460.91 |
1.92 |
|
2217 |
79.66 |
0.33 |
|
2218 |
390.47 |
1.63 |
|
Average |
381.29 |
1.59 |
|
Standard error |
107.8 |
0.4 |
|
1 % test material in DMF |
2219 |
393.59 |
1.64 |
2220 |
205.07 |
0.85 |
|
2221 |
386.45 |
1.61 |
|
2222 |
No sample* |
No sample* |
|
2223 |
237.98 |
0.99 |
|
2224 |
274.95 |
1.15 |
|
Average |
299.61 |
1.25 |
|
Standard error |
38.5 |
0.2 |
|
3 % test material in DMF |
2225 |
463.50 |
1.93 |
2226 |
1175.13 |
4.90 |
|
2227 |
146.38 |
0.61 |
|
2228 |
178.37 |
0.74 |
|
2229 |
382.07 |
1.59 |
|
2230 |
420.53 |
1.75 |
|
Average |
461.00 |
1.92 |
|
Standard error |
152.4 |
0.6 |
|
Vehicle control (DMF) |
2201 |
162.86 |
0.68 |
2202 |
331.29 |
1.38 |
|
2203 |
112.98 |
0.47 |
|
2204 |
231.19 |
0.96 |
|
2205 |
321.86 |
1.34 |
|
2206 |
279.76 |
1.17 |
|
Average |
239.99 |
1.00 |
|
Standard error |
36.0 |
0.1 |
|
1.0 % dinitrochlorobenzene in DMF |
2207 |
6951.56 |
28.97 |
2208 |
12011.33 |
50.05 |
|
2209 |
5908.15 |
24.62 |
|
2209 |
8697.52 |
36.24 |
|
2210 |
3999.27 |
16.66 |
|
2211 |
6868.63 |
28.62 |
|
Average |
7406.24 |
30.86# |
|
Standard error |
1114.1 |
4.6 |
An average background dpm of 82.80 was subtracted from each dpm determination
*sample tube broken
# significantly different from the vehicle control
Body Weights
Only 7 of the 18 animals treated with test material gained weight over the course of the study, There was no explanation for the body weight loss observed over the course of this study (see Table 2).
Table 2: Summary of Stimulation Index and % Body Weight Gain
Treatment group |
SI ± SE |
% Body Weight Gain ± SE |
Vehicle |
1.0 ± 0.1 |
-0.2 ± 1.4 |
1.0 % Dinitrochlorobenzene* |
30.9 ± 4.6# |
-0.4 ± 1.5 |
3 % Test material* |
1.6 ± 0.4 |
0.6 ± 1.1 |
1 % Test material* |
1.3 ± 0.2 |
0.4 ± 1.2 |
0.3 % Test material* |
1.9 ± 0.6 |
-1.5 ± 0.9 |
* in DMF
# significantly different from the vehicle control
SI = Stimulation index
SE = Standard error
Irritation
The ear swelling response was variable but no treatment produced ear swelling much above 10 %. Treatment with the test material also produced no erythema.
Applicant's summary and conclusion
- Interpretation of results:
- not sensitising
- Remarks:
- Migrated information Criteria used for interpretation of results: EU
- Conclusions:
- Under the conditions of the study the test material was not considered to be a a contact sensitiser at concentrations ≤3 %.
- Executive summary:
A study was conducted to assess the test material as a potential contact sensitiser to female BALB/c mice in a Local Lymph Node Assay (LLNA) in accordance with the standardised guideline ICCVAM NIH No. 99-4494.
Following a screening study to assess the minimum irritating concentration (MIC), the LLNA study was performed using 3, 1 and 0.3 % test material in DMF. The test material (12.5 µL) was applied to the dorsal and ventral portion of the ears of six mice once a day for three consecutive days. In addition, six mice per group were treated with the vehicle or a positive control, 1 % dinitrochlorobenzene in DMF.
Five days following the initiation of the LLNA, all mice received intravenous injections, via their lateral tail vein, of 20 µCi of tritiated thymidine in 250 µL of phosphate buffer saline. Five hours later, the mice were sacrificed and their auricular lymph nodes were excised. Single cell suspensions of the lymph nodes were prepared and the radioisotope incorporation was measured on a beta-scintillation counter as disintegrations per minute (dpm) per mouse.
The mice treated with DMF produced a SI of 1.0 ± 0.1. The proliferative response of the animals treated with 1 % dinitrochlorobenzene produced a SI of 30.9 ± 4.6 which is consistent with a positive response and was significantly different from the mice treated with DMF. The SIs of mice treated with 3, 1 and 0.3 % of the test material in DMF were all less than 3.0.
Therefore, under the conditions of this study, the test material is not considered to be a contact sensitiser at concentrations ≤3 %.
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