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EC number: 254-751-6 | CAS number: 40018-26-6
- 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
Acute Toxicity: inhalation
Administrative data
- Endpoint:
- acute toxicity: inhalation
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 2004-10-26 to 2004-11-24
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 2 005
- Report date:
- 2005
Materials and methods
Test guidelineopen allclose all
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 403 (Acute Inhalation Toxicity)
- Version / remarks:
- May 1981
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- EPA OPPTS 870.1300 (Acute inhalation toxicity)
- Version / remarks:
- August 1998
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- EU Method B.2 (Acute Toxicity (Inhalation))
- Version / remarks:
- 1992
- Deviations:
- no
- GLP compliance:
- yes (incl. QA statement)
- Test type:
- traditional method
- Limit test:
- yes
Test material
- Reference substance name:
- 1,4-dithiane-2,5-diol
- EC Number:
- 254-751-6
- EC Name:
- 1,4-dithiane-2,5-diol
- Cas Number:
- 40018-26-6
- Molecular formula:
- C4H8O2S2
- IUPAC Name:
- 1,4-dithiane-2,5-diol
- Test material form:
- solid: particulate/powder
Constituent 1
Test animals
- Species:
- rat
- Strain:
- other: Crl, CD® (SD) IGS BR
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Females (if applicable) nulliparous and non-pregnant: yes
- Age at study initiation: 8-12 weeks
- Weight at study initiation: 200-350 g, exception two males with an initial weight of 357 g and 360 g, respectively.
- Housing: in groups of five by sex in solid-floor polypropylene cages with stainless steel lids, furnished with softwood flakes (Datesand Ltd., cheshire, UK) and provided with environmental enrichment items: wooden chew blocks (B&K Universal Ltd., Hull, UK) and cardboard "fun-tunnels" (Datesand Ltd., Cheshire, UK)
- Diet (e.g. ad libitum): ad libitum, with exception of the treatment period EU Rodent Diet 5LF2, BCM IPS Limited
- Water (e.g. ad libitum): ad libitum
- Acclimation period: at least five days
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21 ± 2
- Humidity (%): 55 ± 15
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12
Administration / exposure
- Route of administration:
- inhalation: dust
- Type of inhalation exposure:
- nose only
- Vehicle:
- air
- Mass median aerodynamic diameter (MMAD):
- >= 2.16 - <= 3.07 µm
- Geometric standard deviation (GSD):
- >= 2.26 - <= 2.81
- Remark on MMAD/GSD:
- Inhalable Fraction (% < 4 µm):
Group 1: 62.4, Group 2: 72.6, Group 3: 70.5 - Details on inhalation exposure:
- GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: SAG 410 Solid Aerosol Generator (TOPAS GmbH, Dresden, Germany) located adjacent to the exposure chamber.
- Exposure chamber volume: approximately 30 litres (dimensions: 28 cm diameter x 50 cm high)
- Method of holding animals in test chamber: Each rat was held in a tapered, polycarbonate restraining tube fitted onto a single tier of the exposure chamber and sealed by means of a rubber ‘O’ ring
- Method of particle size determination: The particle size of the generated atmosphere inside the exposure chamber was determined three times during each exposure period using a Marple Personal -Cascade Impactor (Schaefer Instruments Ltd, Oxon., UK). Samples were taken from the animals’ breathing zone and a suitable, known volume of exposure chamber air was drawn through it using a vacuum pump. The collection substrates and backup filter were weighed before and after sampling and the weight of test material, collected at each stage, calculated by difference.The mean amount for each stage was used to determine the cumulative amount below each cut-off point size. In this way, the proportion (%) of aerosol less than 10.6, 6.8, 3.7, 1.3, 0.87 and 0.3 µm was calculated.
The resulting values were converted to probits and plotted against Log10; cut-point size. From this plot, the Mass Median Aerodynamic Diameter (MMAD) was determined (as the 50% point) and the geometric standard deviation was calculated. In addition the proportion (%) of aerosol less than 4 µm (considered to be the inhalable portion) was determined.
- Treatment of exhaust air: The extract from the exposure chamber passed through a ‘scrubber’ trap and was comrected with a high efficiency filter to a metered exhaust system
- Temperature, humidity: huminity ranged between 40 and 55%, the temperature was between 18 and 21 °C
TEST ATMOSPHERE
- Samples taken from breathing zone: yes
CLASS METHOD (if applicable)
- Rationale for the selection of the starting concentration: The traditional method with limit dose was used as recommended by the OECD guideline. - Analytical verification of test atmosphere concentrations:
- yes
- Remarks:
- The collection substrates and backup filter were weighed before and after sampling and the weight of test material, collected at each stage, calculated by difference.
- Duration of exposure:
- 4 h
- Concentrations:
- Achieved (analytical) concentrations:
2.17, 1.02 and 0.347 mg/L
Nominal concentrations: 4.30, 1.52 mg/L and N/A for the lowest concentration - No. of animals per sex per dose:
- 5
- Control animals:
- no
- Details on study design:
- - Duration of observation period following administration: 14 days
- Frequency of observations and weighing: on days 0, 7 and 14
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, organ weights, mortality, necropsy - Statistics:
- Using the mortality data obtained, an estimate of the acute inhalation median lethal concentration (LC50) and 95% confidence limits of the test material were calculated using validated toxicity data analysis software (ToxCalc v5.0 (Tidepool Scientific Software, McKinleyville, Ca, USA)). All values were calculated using the Maximum Likelihood Regression method (Finney, 1971).
Results and discussion
Effect levelsopen allclose all
- Key result
- Sex:
- male/female
- Dose descriptor:
- LC50
- Effect level:
- 0.477 mg/L air
- Based on:
- test mat.
- 95% CL:
- > 0.335 - < 0.615
- Exp. duration:
- 4 h
- Key result
- Sex:
- female
- Dose descriptor:
- LC50
- Effect level:
- 0.522 mg/L air
- Based on:
- test mat.
- 95% CL:
- > 0.275 - < 0.767
- Exp. duration:
- 4 h
- Key result
- Sex:
- male
- Dose descriptor:
- LC50
- Effect level:
- 0.44 mg/L air
- Based on:
- test mat.
- 95% CL:
- > 0.26 - < 0.614
- Exp. duration:
- 4 h
- Mortality:
- At the highest concentration, i.e. 2.17 mg/L all animals died. At the concentration of 1.02 mg/L 3 female out of five and 4 male rats out of five died. At the lowest concentration of 0.347 mg/L 2 out of five animals died in both sexes.
- Clinical signs:
- other: Common abnormalities noted during the study included increased respiratory rate, laboured respiration, noisy respiration, gasping respiration, hunched posture, piloerection and wet fur. There were frequent instances of ataxia and red/brown staining around
- Body weight:
- Three male and four female animals showed bodyweight loss during week 1. Five animals survived to show normal development during week 2 (two males and three females) whilst a further female showed additional weight loss during this second week.
- Gross pathology:
- For six animals necropsied at terminal kill, no abnormalities were detected. Amongst the other surviving animals the following macroscopic abnormalities were detected:
Lungs -- pale, abnormally red, dark patches, dark foci;
Stomach - gaseous distension;
Small Intestine - gaseous distension;
Large Intestine - gaseous distension.
Amongst animals that died or were humanely killed during the study the following macroscopic abnormalities were detected at necropsy:
Lungs - haemorrhagic, fluid filled, pale, pale patches, abnormally dark, dark patches, caudal lobe of right lung dark and enlarged;
Liver - dark, accentuated lobular pattern;
Stomach - gaseous distension;
Small Intestine - gaseous distension;
Large Intestine - gaseous distension.
Any other information on results incl. tables
Table 1: Particle size distribution
Group Number | Mean Achieved Atmosphere Concentration (mg/L) | Mean Mass Median Aerodynamic Diameter (µm) | Inhalable Fraction (% < 4µm) | Geometric Standard Deviation |
1 | 2.17 |
3.07 | 62.4 | 2.33 |
2 | 1.02 | 2.16 | 72.6 | 2.81 |
3 | 0.347 | 2.59 | 70.5 | 2.26 |
Applicant's summary and conclusion
- Interpretation of results:
- Category 2 based on GHS criteria
- Conclusions:
- In the present study conducted according to OECD guideline 403 (May 1981), 15 female and 15 male Sprague-Dawley rats were exposed to 2.17, 1.02 and 0.347 mg test substance/L air in a nose-only apparatus for 4h. The surviving animals were then observed for 14 days. Mortality was detected in all groups. In all animals increased respiratory rate was noted, at the higher concentrations also laboured respiration, gasping respiration and and in the further course also a decrease of respiratory rate was detected. From these results the following LC50 values were obtained:
All animals LC50 = 0.477 (0.335 - 0.615) mg/L
Thus, the test material needs to be classified in Category 2 "fatal if inhaled" according to Regulation (EC) No 1272/2008 (CLP) and the Globally Harmonized System for Classification and Labelling of Chemicals (GHS)
Males LC50 = 0.440 (0.260 - 0.614) mg/L
Females LC50 = 0.522 (0.275 - 0.767) mg/L
Based on these data the substance needs to be classified according to Regulation (EC) No 1272/2008 (CLP) and the Globally Harmonized System for Classification and Labelling of Chemicals (GHS) into Category 2 " Fatal if inhaled" with respect to acute inhalation toxicity.
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