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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
Acute Toxicity: inhalation
Administrative data
- Endpoint:
- acute toxicity: inhalation
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 7 January 1994 to 31 January 1994
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- other: Study conducted to GLP 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.
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 1 994
- Report date:
- 1994
Materials and methods
Test guidelineopen allclose all
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 403 (Acute Inhalation Toxicity)
- Deviations:
- yes
- Remarks:
- (see below)
- Qualifier:
- according to guideline
- Guideline:
- EU Method B.2 (Acute Toxicity (Inhalation))
- Deviations:
- yes
- Remarks:
- (see below)
- Qualifier:
- according to guideline
- Guideline:
- EPA OPP 81-3 (Acute inhalation toxicity)
- Deviations:
- yes
- Remarks:
- (see below)
- Qualifier:
- according to guideline
- Guideline:
- other: The Acute Inhalation Toxicity Study Guidelines specified by the Japan Ministry of Agriculture, Forestry and Fisheries (MAFF, 1985)
- Deviations:
- yes
- Remarks:
- (see below)
- Principles of method if other than guideline:
- The animals were exposed to a limit test concentration of 6.07 mg/L. This concentration exceeded the limit test concentration of 5 mg/L however the mean mass median aerodynamic diameter for the aerosol was 3.02 µm, which was within the 1 to 4µm targeted range for a respirable atmosphere.
- GLP compliance:
- yes
- Test type:
- standard acute method
- Limit test:
- yes
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 [1,5-c]pyrimidine)
- Synonym: DEDS
- Appearance: light beige powder
Constituent 1
Test animals
- Species:
- rat
- Strain:
- Fischer 344
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Age at study initiation: The rats were approximately 12 weeks old when exposed to the test material.
- Weight at study initiation: Mean male bodyweight at the start of the test: 230.0 g (standard deviation 8.8); mean female bodyweight at the start of the test: 151.3 g (standard deviation 3.1).
- Fasting period before study: No.
- Housing: The animals were housed two per cage in stainless steel wire cages during acclimation. Animals were singly housed during the 2-week post-exposure period.
- Diet (e.g. ad libitum): Certified Rodent Chow was available ad libitum except during exposure.
- Water (e.g. ad libitum): Tap water (municipal water supply) was available ad libitum except during exposure.
- Acclimation period: 3 weeks prior to exposure.
ENVIRONMENTAL CONDITIONS
Animals were housed in a room designed to maintain adequate environmental conditions concerning temperature and relative humidity and regulated for the specific species under study
- Photoperiod (hrs dark / hrs light): A 12-hour photoperiod was employed throughout the study.
IN-LIFE DATES: From: 7 January 1994 To: 31 January 1994
Administration / exposure
- Route of administration:
- inhalation: aerosol
- Type of inhalation exposure:
- nose only
- Vehicle:
- air
- Details on inhalation exposure:
- GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Chambers
A 42 litre ADG nose-only chamber modified by the testing laboratory (30 cm diameter x 60 cm high) was used for this study. Compressed air supplied to the chamber was controlled by a system designed to maintain temperature at approximately 22 °C. The airflow was maintained at approximately 30 litres per minute, which was sufficient to provide the normal concentration of oxygen to the animals. The chamber was operated at a slight negative pressure relative to the surrounding area. Rats were exposed to the test material by a nose-only technique.
- Generation System
Aerosols were generated from powdered test material using a Jet Mill (Model 00 Jet-O-Mizer, Fluid Energy Aljet, Plumsteadville, PA). The nature of the test material was such that it easily and quickly bridged (would not flow to the auger screw) upon standing. Even with the feeder's built-in agitation, the test material would not feed once hand stirring ceased. Therefore, to maintain consistent chamber concentrations and feeding of the test material through the screw feeder to the jet mill, the contents of the feeder were continuously hand stirred. Also, to prevent any possible plugging of the jet mill, the test material was sieved prior to use using a U.S.A. standard testing sieve (opening 500 micrometers, 32 mesh).
- Chamber Monitoring
The air flow through the chamber was determined with a manometer. The manometer was calibrated with a gas meter (Model DTM-115, Singer Aluminum Diaphragm Meter, American Meter Division, Philadelphia, PA, USA) prior to the start of the study. Ambient room temperature, chamber humidity and chamber air flow values were recorded every 30 minutes during the 4 hour exposure period.
Chamber temperature, relative humidity and airflow were within expected values. Chamber relative humidity values in the range reported resulted from the use of compressed air as the total air supply through the dust generator to the chamber.
TEST ATMOSPHERE
- Mass Concentration
The mass concentration of aerosol present in the chamber was determined gravimetrically four times during the 4 hour exposure period. Each gravimetric sample was taken by drawing the chamber atmosphere, at a rate of 3 litres per minute for two minutes, through a vertical stainless steel tube which projected into the animal breathing zone and collecting the aerosol particles on a pre-weighed 0.45 micron Teflon filter (Schleicher and Schuell, Keene, NH). After each atmosphere sampling, the filter was reweighed to obtain the total weight of the particles. The time-weighted average (TWA) exposure concentration was calculated from these gravimetric measurements.
- Particle Size Determination
The aerodynamic particle size was determined twice during the exposure period. Each sample was taken by drawing samples from the animal breathing zone, at a rate of 3 litres per minute for two minutes, through a six-stage Cascade Impactor (Model 266, Sierra Instruments, Carmel Valley, CA, USA). The mass median aerodynamic diameter (MMAD) and geometric standard deviation (σg) were determined for each sample as well as the average of the two samples.
- MMAD (Mass median aerodynamic diameter) / GSD (Geometric st. dev.): MMAD of 3.02 µm, GSD 2.48. - Analytical verification of test atmosphere concentrations:
- yes
- Duration of exposure:
- 4 h
- Concentrations:
- 6.07 mg/L
- No. of animals per sex per dose:
- 5 animals per sex
- Control animals:
- no
- Details on study design:
- The animals were acclimated to the nose cones for a single four hour period on on the day preceding exposure to the test material.
- Duration of observation period following administration: 14 days.
- Frequency of observations and weighing: Animals were weighed and examined prior to exposure to the test material. All animals were observed during the exposure period and daily during the two-week post-exposure period. The observations included an evaluation of the fur, eyes, mucous membranes and respiration. Behaviour pattern and nervous system activity were also assessed by specific observation for tremors, convulsions, salivation, lacrimation and diarrhoea, as well as lethargy and other signs of altered central nervous system function. An additional daily observation and routine monitoring on weekends were limited to husbandry procedures required to ensure the availability of food and water. All rats were weighed on test days 2, 4, 8, 11, and 15 during the two-week post-exposure period.
- Necropsy of survivors performed: yes. All rats were submitted for a complete necropsy examination on test day 15. The rats were anaesthetised with methoxyflurane and euthanised. The necropsy included examination of the eyes with a microscope slide using fluorescent illumination. No tissues were saved. - Statistics:
- Means and standard deviations of animal bodyweights and chamber temperatures, relative humidities and airflows and chamber concentration (mean only) were calculated for descriptive purposes.
Results and discussion
Effect levels
- Sex:
- male/female
- Dose descriptor:
- LC50
- Effect level:
- > 6.07 mg/L air (analytical)
- Based on:
- test mat.
- Exp. duration:
- 4 h
- Remarks on result:
- other: MMAD 3.02 µm
- Mortality:
- No mortality was observed.
- Clinical signs:
- other: No clinical effects were observed during the exposure period or throughout the 14 day post-exposure period.
- Body weight:
- Mean bodyweights for male and female rats on test day 2 were decreased approximately 6 % from pre-exposure values. This initial weight loss is typical of the weight losses historically observed in this age and strain of rats exposed to non-lethal test atmospheres by the nose-only techniques used in this study. The animals subsequently gained weight throughout the remainder of the 2-week post-exposure period.
- Gross pathology:
- One female rat had a herniated left liver and a distended ovarian bursa both of which were spontaneous and not considered treatment-related. There were no visible lesions attributable to exposure noted in any of the animals necropsied on test day 15.
Any other information on results incl. tables
Table 1 Chamber Atmosphere Concentrations During Exposure
Exposure Time (minutes) |
Gravimetric Sample Concentration (mg/L)* |
TWA Analytical Concentration (mg/L) |
Temperature (°C)** |
Relative Humidity (%)** |
Chamber Air Flow (LPM)*** |
57 |
6.23 |
6.07 |
22.0 ± 0.0 |
10.1 ± 1.0 |
30 ± 0 |
141 |
5.46 |
||||
213 |
6.64 |
TWA: Time-weighted average
*Flow rates for gravimetric sampling were 3 litres per minute for 2 minutes
**Mean ± standard deviation, N = 8
***Mean ± standard deviation, N = 9
Table 2 Particle Size Data Determined Gravimetrically
Mass Obtained on Different Stages of the Cascade Impactor (mg) |
|||
Effective Cut-off Diameter (µm) |
Mean* |
Dataset A** |
Dataset B** |
17 11 6.1 3 1.3 0.68 0.45 |
0.294 0.399 1.409 4.406 2.552 0.507 0.930 |
0.281 0.428 1.494 4.897 2.781 0.502 1.036 |
0.306 0.369 1.324 3.915 2.323 0.511 0.824 |
Sum |
10.497 |
11.419 |
9.572 |
Cumulative Percent of Aerosol Particles Less Than Stated Size (%) |
|||
Effective Cut-off Diameter (µm) |
Mean* |
Dataset A** |
Dataset B** |
0.68 1.3 3 6.1 11 17 |
8.86 13.69 38.00 79.97 93.39 97.19 |
9.07 13.47 37.82 80.70 93.78 97.53 |
8.61 13.95 38.22 79.12 92.95 96.80 |
MMAD (µm) |
3.02 |
2.95 |
3.02 |
Sigma G |
2.48 |
2.37 |
2.48 |
* Mean of dataset A and dataset B values
**Flow rates were 3 litres/minute for 2 minutes (Datasets A and B obtained approximately 110 and 172 minutes into exposure).
MMAD assumes particles were from a log normal distribution. Particle size for probit values of 4, 5 and 6 is determined from a linear regression of the data. The MMAD is equivalent to a probit of 5 and the geometric standard deviation is equal to square root (Probit 6/Probit 4).
Table 3 Bodyweight Data (g)
Sex |
Animal Number |
Days on Test |
|||||
1 |
2 |
4 |
8 |
11 |
15 |
||
Male |
94A0001 94A0002 94A0003 94A0004 94A0005 |
217.3 225.2 231.6 238.7 237.0 |
207.3 212.0 219.0 225.6 218.9 |
219.4 223.6 228.0 236.6 229.0 |
234.6 233.5 240.9 247.6 246.1 |
242.5 243.2 248.7 252.2 252.6 |
252.1 251.8 258.6 259.2 260.1 |
Mean SD N |
230.0 8.8 5 |
216.6 7.1 5 |
227.3 6.4 5 |
240.5 6.4 5 |
247.8 4.8 5 |
256.4 4.1 5 |
|
Female |
94A0006 94A0007 94A0008 94A0009 94A0010 |
148.2 148.4 152.3 151.8 155.6 |
135.6 144.6 140.0 141.5 148.9 |
145.3 148.9 149.0 152.0 158.0 |
149.2 151.1 151.7 154.3 162.3 |
152.6 152.0 155.1 156.3 161.5 |
157.3 152.0 158.7 161.2 166.0 |
Mean SD N |
151.3 3.1 5 |
142.1 5.0 5 |
150.6 4.8 5 |
153.7 5.1 5 |
155.5 3.8 5 |
159.0 5.1 5 |
Applicant's summary and conclusion
- Interpretation of results:
- not classified
- Remarks:
- Migrated information Criteria used for interpretation of results: EU
- Conclusions:
- Under the conditions of this study, the 4 hour LC50 of the test material to male and female rats was greater than the concentration of 6.07 mg/L with a particle size distribution MMAD of 3.02 microns. As such, the test material requires no classification in accordance with EU criteria.
- Executive summary:
The acute inhalation toxicity of the test material was determined in accordance with the standardised guidelines OECD 403, EU Method B.2, FIFRA Guideline No. 81-3 and the Acute Inhalation Toxicity Study Guidelines specified by the Japan Ministry of Agriculture, Forestry and Fisheries (MAFF, 1985).
A group of 5 male and 5 female Fischer 344 rats was exposed to a limit test concentration of 6.07 mg/L of the test material for four hours in a nose-only inhalation chamber and observed for two weeks post-exposure.
The mean mass median aerodynamic diameter for the aerosol was 3.02 µm, with a geometric standard deviation of 2.48. Approximately 11 % of the total mass of particles was less than 1 micron in size and 80 % of the total mass was less than 6 microns in size.
All animals survived the exposure as well as the two-week post-exposure period. A mean body weight loss of approximately 6 % was noted in both male and female animals on the day following the exposure to the test material. These animals subsequently gained weight without any other exposure-related effects noted.
Under the conditions of this study, the 4 hour LC50 of the test material to male and female rats was greater than the concentration of 6.07 mg/L with a particle size distribution MMAD of 3.02 microns. As such, the test material requires no classification in accordance with EU criteria.
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