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EC number: 611-575-8 | CAS number: 577953-88-9
- 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
Long-term toxicity to fish
Administrative data
- Endpoint:
- fish early-life stage toxicity
- Type of information:
- experimental study
- Adequacy of study:
- key study
- 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 210 (Fish, Early-Life Stage Toxicity Test)
- GLP compliance:
- yes
Test material
- Reference substance name:
- 2-[1-[[1-[3-[2-[(7-Chloro-2-quinolyl)]vinyl]phenyl]-3-[2-(1-hydroxy-1-methyl-ethyl)phenyl]-propyl]sulfanylmethyl]cyclopropyl]acetic acid sodium salt
- EC Number:
- 604-813-7
- Cas Number:
- 151767-02-1
- IUPAC Name:
- 2-[1-[[1-[3-[2-[(7-Chloro-2-quinolyl)]vinyl]phenyl]-3-[2-(1-hydroxy-1-methyl-ethyl)phenyl]-propyl]sulfanylmethyl]cyclopropyl]acetic acid sodium salt
- Test material form:
- solid: particulate/powder
Constituent 1
- Specific details on test material used for the study:
- Name: montelukast sodium
Synonyms: MK-0476, active ingredient of SINGULAIR®
Lot No.: XTA-719
CAS No.: 151767-02-1
Purity: 100.4 (tested as 100%)
Recertification Date: 1 July 2013
Upon receipt at Springborn Smithers, the test substance (SSL No. 4647) was stored at room temperature in the original container in a dark ventilated cabinet
Sampling and analysis
- Analytical monitoring:
- yes
- Details on sampling:
- Prior to the start of the definitive exposure, samples from one replicate of each treatment level and control solution were collected and analyzed for montelukast. In addition, a sample of the diluter stock solution was analyzed twice prior to test initiation. Results of the pretest analyses were used to judge whether sufficient quantities of montelukast were being delivered and maintained in the exposure aquaria in order to initiate the early life-stage exposure.
During the in-life phase of the definitive study, water samples were removed from alternating replicates (A, B, C and D) of each treatment level and the control ontest day 0, 4 (hatch), 8, 15, 22 and 32. All test samples were removed from the approximate midpoint of each aquarium using a pipette. A sample of the stock solution was also analyzed at each sampling interval during the definitive study period. In addition, three quality control (QC) samples were prepared at each sampling interval and remained with the exposure solution samples throughout the analytical process. These QC samples were prepared in dilution water at nominal concentrations similar to the exposure concentration range. Results of the analyses of the QC samples were used to judge the precision and the quality control maintained during the analysis of exposure solution samples
Test solutions
- Vehicle:
- no
- Details on test solutions:
- A 25 mg/mL diluter stock solution was prepared prior to test initiation and as needed throughout the definitive exposure by placing, for example, approximately 0.2500 g of test substance in a 10 mL volumetric flask and diluting to volume with dilution water. The resultant solution was observed to be clear and yellow in color following preparation.
Prior to test initiation, a Harvard syringe pump was calibrated to deliver 0.0241 mL/cycle of the stock solution (25 mg/mL) into the diluter's chemical mixing chamber, which also received 1.94 L of dilution water per cycle. The mixing chamber was positioned over a magnetic stir plate and was partially submerged within an ultrasonic water bath to aid in mixing the stock solution with the dilution water. The solution contained in the mixing chamber constituted the highest nominal test concentration (0.31 mg/L) and was sequentially diluted (50%) to provide the remaining nominal exposure concentrations (0.16, 0.078, 0.039 and 0.019 mg/L).
A set of control vessels was also established which contained the same dilution water and was maintained under the same conditions as the treatment level vessels, but contained no montelukast
Test organisms
- Test organisms (species):
- Pimephales promelas
- Details on test organisms:
- Fathead minnow eggs were obtained from brood stock maintained at Springborn Smithers for more than 25 years. The brood stock originated from the U.S. Environmental Research Laboratory, Duluth, Minnesota. Fathead minnow from reputable commercial suppliers have been periodically added to the Springborn Smithersgene pool. No outbreak of disease has occurred and no medications have been used to treat the brood stock in the last fifteen years. The water flowing to the culture unit was from the same source as the dilution water used during the early life-stage exposure.
Study design
- Test type:
- flow-through
- Water media type:
- freshwater
- Limit test:
- no
- Total exposure duration:
- 32 d
- Remarks on exposure duration:
- 32-day duration (28 days post-hatch)
- Post exposure observation period:
- Dead and live embryos were counted daily until hatching was complete and dead eggs were
removed during this observation period. Day of hatch was considered to be exposure day 4,
when no more than 10% unhatched viable embryos remained in any control or treatment level
egg incubation cup. Calculations of hatching success of organisms were based on the number of
live, dead or deformed larvae per incubation cup after hatching was complete (day 4) compared
to the number of embryos per cup on test day 0.
The 28-day post-hatch larval exposure was initiated on the day of hatch (test day 4). On test
day 4, the surviving larvae present in each incubation cup were thinned to 15 organisms per
replicate/60 organisms per treatment level or control and placed into each respective exposure
aquarium. During the post-hatch exposure period, dead larvae were removed when observed and
behavior and appearance of the larval fish were observed and recorded daily. Larval survival
was estimated daily throughout the post-hatch period. At 28 days post-hatch exposure (test termination), the percentage of larval survival was
determined.
Test conditions
- Hardness:
- CaCO3 of 66 to 84 mg/L
- Test temperature:
- 23 to 25 ºC throughout the exposure
- pH:
- pH range of 6.0 to 7.2
- Dissolved oxygen:
- 5.0-8.7 mg/L
- Conductivity:
- 330 to 390 µmhos/cm
- Nominal and measured concentrations:
- NOMINAL TEST CONCENTRATIONS: 0.019, 0.039, 0.078, 0.16 and 0.31 mg/L
MEAN MEASURED CONCENTRATIONS: 0.019, 0.041, 0.073, 0.14 and 0.27 mg/L - Details on test conditions:
- The exposure of fathead minnow embryos and larvae to montelukast was initiated when the embryo incubation cups were distributed to each of the test aquaria The eggs were impartially distributed to the egg incubation cups in the following manner: Twenty-four labeled incubation
egg cups containing control water were placed in a water bath maintained at 25 ± 2ºC. A Carolina dish containing the eggs was placed in the same water bath. The eggs were impartially placed in the egg cups five at a time until each cup contained 30 eggs. To initiate the study, the incubation cups, each containing 30 eggs, were then suspended in the respective exposure aquaria (one cup per replicate vessel). At study initiation, the embryos were < 24 hours old.
Mortality of less than 1% was observed in the brood stock during the 48-hour period prior to exposure initiation - Reference substance (positive control):
- no
Results and discussion
Effect concentrationsopen allclose all
- Key result
- Duration:
- 32 d
- Dose descriptor:
- NOEC
- Effect conc.:
- 0.073 mg/L
- Nominal / measured:
- meas. (geom. mean)
- Conc. based on:
- test mat.
- Basis for effect:
- other: percent live normal fry, total length and dry weight
- Key result
- Duration:
- 32 d
- Dose descriptor:
- LOEC
- Effect conc.:
- 0.14 mg/L
- Nominal / measured:
- meas. (geom. mean)
- Conc. based on:
- test mat.
- Basis for effect:
- other: Most sensitive iinidcators were percent live normal fry, total length and dry weight
- Details on results:
- An 18-day (14 days post-hatch) preliminary test was conducted exposing 30 fathead minnow embryos per replicate (< 24 hours old) to concentrations of 0.019, 0.039, 0.078, 0.16 and 0.31 mg/L and a dilution water control. Based on these results nominal concentrations of 0.019,0.039, 0.078, 0.16 and 0.31 mg/L were selected for the definitive exposure.
The diluter system which prepared and delivered the test solutions to the exposure aquaria functioned properly during the pretest period and throughout the definitive study. Analysis of the exposure solutions during the pretest period established that the appropriate concentrations of montelukast (ranging from 87 to 103% of nominal concentrations) were maintained in the exposure solutions and that the delivery apparatus maintained the expected concentration gradient (approximately 50% dilution factor) of the test substance. Analysis of the stock solution during the pretest period resulted in a measured concentration range of 92 to 140% of nominal. No undissolved test substance (e.g., precipitate) was observed in the diluter system (e.g., mixing chamber and chemical cells) or exposure solutions.
Analysis of the QC samples resulted in measured concentrations which were consistent with the predetermined recovery range and ranged from 90.5 to 114% (N = 18) of the nominal fortified levels (0.00500 to 0.350 mg/L). Based on these results, it was demonstrated that satisfactory precision and quality control were maintained during the analysis of exposure solutions.
At the completion of hatch (day 4), hatching success in the control averaged 86%. Embryo hatching success in the 0.019, 0.041, 0.073, 0.14 and 0.27 mg/L treatment levels was 79, 79, 76, 74 and 83%, respectively. Williams' Test determined no significant difference in embryo hatching success among organisms exposed to any treatment level tested compared to the hatching success of the control organisms (86%).
At the completion of the hatching period (day 4), the percent of normal larvae in the control averaged 100%. The percent of normal larvae in the 0.019, 0.041, 0.073, 0.14 and 0.27 mg/L treatment levels averaged 96, 99, 98, 81 and 82%, respectively. Steel’s Many-One Rank Test determined a significant difference in the percent of normal larvae among organisms exposed to the 0.14 and 0.27 mg/L treatment levels compared to the percent of normal larvae in the control
(100%).
Applicant's summary and conclusion
- Validity criteria fulfilled:
- yes
- Conclusions:
- Based on mean measured concentrations and the most sensitive indicators of toxicity in this study (i.e., percent life normal fry, total length and dry weight), the No Observed-Effect Concentration (NOEC) was determined to be 0.073 mg/L. The Lowest-Observed-Effect Concentration (LOEC) for montelukast and fathead minnow was determined to be 0.14 mg/L.
- Executive summary:
The objective of this study was to determine the No-Observed-Effect Concentration (NOEC) of montelukast to fathead minnow (Pimephales promelas) embryos and larvae under flow-through conditions. The endpoints evaluated were embryo hatching success, defined as percentage of embryos that produce live normal fry at hatch, survival at test termination, and larval growth (total length and dry weight).
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