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EC number: 204-029-1 | CAS number: 113-48-4
- 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
Repeated dose toxicity: inhalation
Administrative data
- Endpoint:
- sub-chronic toxicity: inhalation
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- March - September 1993
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 1 994
- Report date:
- 1994
Materials and methods
Test guideline
- Qualifier:
- according to guideline
- Guideline:
- EPA OPP 82-4 (90-Day Inhalation Toxicity)
- GLP compliance:
- yes
Test material
- Reference substance name:
- N-(2-ethylhexyl)-8,9,10-trinorborn-5-ene-2,3-dicarboximide
- EC Number:
- 204-029-1
- EC Name:
- N-(2-ethylhexyl)-8,9,10-trinorborn-5-ene-2,3-dicarboximide
- Cas Number:
- 113-48-4
- Molecular formula:
- C17H25NO2
- IUPAC Name:
- N-(2-ethylhexyl)-8,9,10-trinorborn-5-ene-2,3-dicarboximide
- Reference substance name:
- (E)-1,4-Bis(2-ethylhexylamino)-2-butene-1,4-dione
- Molecular formula:
- C20H38N2O2
- IUPAC Name:
- (E)-1,4-Bis(2-ethylhexylamino)-2-butene-1,4-dione
- Reference substance name:
- 1-(2-ethylhexyl)-1H-pyrrole-2,5-dione
- Molecular formula:
- C12H19NO2
- IUPAC Name:
- 1-(2-ethylhexyl)-1H-pyrrole-2,5-dione
- Test material form:
- liquid
- Details on test material:
- Purity and characterisation analysis conducted on the following sample; Supplier: McLaughlin Gormley King ; Batch Number: AB9500
Constituent 1
impurity 1
impurity 2
- Specific details on test material used for the study:
- Test Material: MGK® 264
Supplier: Mclaughlin Gormley King Company
8810 Tenth Avenue North
Minneapolis, Minnesota 55427
Date Received: 30 September 1991 and 21 January 1993
Lot No.: 3843
Active Ingredient: 98% MGK® 264 Insecticice Synergist
Description: Liquid
Expiration Date: None. Test material Was shown to be stable for the duration of the study.
Test animals
- Species:
- rat
- Strain:
- Sprague-Dawley
- Details on species / strain selection:
- Sprague-Dawley - derived (CD®) [CD® - Crl: (CD®)BR]
Supplier: Charles River Breeding Laboratories, Inc.Kingston, New York 124E4 - Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- age at receipt - 6 weeks
age at initiation - 8 weeks
Non exposure periods: Animals were doubly housed in suspended stainless steel wire mesh cages during the first week of the acclimation period and individually house thereafter
Food was ad libitum; Purina Ceritified Rodent Chow® #5002 meal, Purina Mil's Inc., St. Louis,MO. Fresh food presenied as required.
water was ad libitum; by automated watering system (Elizabethtown Water Campany).
Approximately 12 hour · light/dark cycle (7 AM to 7 PM) via automatic timer. Temperature and relative humidity were monitored and recorded twice daily and
maintained, to the maximum extent possible, within the range presented below.
Temp: Desired: 20-24°C
Actual : 22 ± 1 °C (X ± S. D.)
Humidity: Desired: 40-70%
Actual: 54 ± 9% (X ± S.D.)
During Exposure: Animals were individually housed in stainless steel, wire mesh cages within a 1L glass and stainless steel exposure chamber. no water/food
Temp: Desired: 20-24°C
Actual : 24 ± 1 °C (X ± S. D.)
Humidity: Desired: 40-60%
Actual: 50 ± 1% (X ± S.D.)
Administration / exposure
- Route of administration:
- inhalation: aerosol
- Type of inhalation exposure:
- whole body
- Vehicle:
- air
- Mass median aerodynamic diameter (MMAD):
- 1.1 µm
- Geometric standard deviation (GSD):
- 2.3
- Remarks on MMAD:
- It was concluded that the liquid aerosol was highly respirable to the rat with a similar MGK 264 particle size amongst all the test material exposed groups.
- Details on inhalation exposure:
- Appropriate amounts of MGK® 264 were placed into a 3-neck flask resting in a heating mantle regulated by a variable autotransformer. House-line air was delivered through a regulator and backpressure gauge via 1/4" plastic tubing to a plastic T-tube where it split the airflow to the generation and dilution systems. For the generation system the air was directed from the T - tube, to a Nupro® metering valve, Dwyer® flowmeter and Matheson® backpressure gauge. The air was then carried to a 1 or 2-barrel Laskin nebulizer contained inside a 3-neck flask. For the dilution system, air was directed d to a Nupro® metering valve and Dwyer® flowmeter where it converged at a glass T-Tube with the generation air to generate the test atmosphere. The resultant liquid aerosol was directed into the chamber which housed the animals. The animals remained in the chamber for 30 minutes following the exposure to allow the chamber to clear, using room air at the same airflow rate used during exposure.
- Analytical verification of doses or concentrations:
- yes
- Remarks:
- Gravimentrical determinations were made 4 times per chamber per day and gas chromatatography was performed once per chamber per day.
- Details on analytical verification of doses or concentrations:
- The nominal concentration was determined by weighing the generation apparatus containing the test material before and after the exposure and dividing the difference in these weights by the total volume of air delivered during exposure (volumetric flow rate times total exposure time).
- Duration of treatment / exposure:
- 6 hours per day
Exposure levels were determined gravimetrically (four times per chamber per day) and by Gas Chromatography (GC) (one time per chamber per day). Particle size distribution measurements of the liquid aerosol were made once per chamber/day using a Delron DCI-6 cascade impactor. - Frequency of treatment:
- 5 days per week, for 13 weeks
Doses / concentrationsopen allclose all
- Dose / conc.:
- 0 mg/m³ air (nominal)
- Remarks:
- Group 1 and 2
- Dose / conc.:
- 10 mg/m³ air (nominal)
- Remarks:
- Group 3
- Dose / conc.:
- 40 mg/m³ air (nominal)
- Remarks:
- Group 4
- Dose / conc.:
- 135 mg/m³ air (nominal)
- Remarks:
- Group 5
- Dose / conc.:
- 400 mg/m³ air (nominal)
- Remarks:
- Group 6
- Dose / conc.:
- 400 mg/m³ air (nominal)
- Remarks:
- Group 7
- No. of animals per sex per dose:
- 15/sex/group
- Control animals:
- yes, concurrent vehicle
Examinations
- Observations and examinations performed and frequency:
- Physical observations for abnormal signs were performed once during each exposure for all animals; detailed physical examinations were conducted on all animals once pretest and weekly thereafter. Ophthalmoscopic examinations were performed on all animals pretest and once prior to scheduled sacrifice. Body weight measurements were recorded twice pretest, weekly thereafter and just prior to scheduled sacrifice. Food consumption measurements were conducted once pretest and weekly thereafter. Blood samples for analysis of hematology and clinical chemistry parameters were withdrawn just prior to the scheduled sacrifices. Following 13 weeks of exposure, 7 (groups I and VI) or 8 (Groups II and VII) animals/sex/group were sacrificed. Recovery animals were allowed a 13 week recovery period prior to sacrifice. Selected organs were weighed and organ/body and organ/brain weight ratios calculated for all animals. Complete macroscopic postmortem examination of selected tissues were conducted on all animals.
- Sacrifice and pathology:
- Following 13 weeks of exposure, 7 (groups I and VI) or 8 (Groups II and VII) animals/sex/group were sacrificed. Recovery animals were allowed a 13 week recovery period prior to sacrifice.
- Statistics:
- Body weight, change in body weight from Week 0, food consumption, haematology and clinical chemistry parameters, organ weights, organ/body and organ/brain weight ratios were analyzed. Mean values of the two control groups (I and II) and mean values of the two high dose groups (VI and VII) were compared in order to show comparable results regarding test material effects. When combined, the mean values of all exposure groups were compared to control at each time interval.
Results and discussion
Results of examinations
- Clinical signs:
- effects observed, treatment-related
- Description (incidence and severity):
- In-Chamber Observations: The only clearly test material related observation recorded during the exposures was decreased activity. This was seen in almost all animals in the high exposure groups over the entire study.
Weekly Detailed Observations: Weekly detailed observations noted dose-related incidences of red facial stains, nasal discharge and excessive salivation in both sexes. Excessive salivation occurred almost exclusively at the high exposure level and primarily during the first two weeks of the study. The red facial stains and nasal discharge were present over the entire exposure period. Red nasal discharge or staining is a common finding in inhalation studies. The animals were essentially all within normal limits during the recovery period. - Mortality:
- mortality observed, non-treatment-related
- Description (incidence):
- One control group male was found dead on Day 46 of the study. One high exposure level male was sacrificed moribund during the recovery period. Neither of these deaths is considered to be test material related.
- Body weight and weight changes:
- no effects observed
- Food consumption and compound intake (if feeding study):
- no effects observed
- Food efficiency:
- not examined
- Water consumption and compound intake (if drinking water study):
- not examined
- Ophthalmological findings:
- no effects observed
- Haematological findings:
- no effects observed
- Clinical biochemistry findings:
- no effects observed
- Urinalysis findings:
- not examined
- Behaviour (functional findings):
- not examined
- Immunological findings:
- not examined
- Organ weight findings including organ / body weight ratios:
- no effects observed
- Gross pathological findings:
- no effects observed
- Neuropathological findings:
- not examined
- Histopathological findings: non-neoplastic:
- effects observed, treatment-related
- Description (incidence and severity):
- Microscopic morphologic abnormalities considered to be related to the whole-body exposure to MGK® 264 were seen in the nasoturbinal tissues, nasopharynx and in the larynx of both males and females. In the nasoturbinates, these changes were seen and included an increased severity of hypertrophy/hyperplasia of goblet cells in the respiratory epithelium of males and a slight increase in the severity of intracytoplasmic eosinophilic material in the epithelium covering the respiratory and/or olfactory mucosa in males and females. In the nasopharynx, an increased incidence of hypertrophy/hyperplasia of the goblet cells in the epithelium lining the nasopharynx was seen in the males and females of the high exposure group. In the larynx, an increased severity of subacute (chronic active)/chronic inflammation was seen in the high exposure group. Squamous/squamoid metaplasia/hyperplasia of the pseudostratified columnar epithelium, frequently keratinized, of the larynx was seen in all treated groups (almost all animals) but not in any control animals. Hyperplasia and hyperkeratosis of the stratified squamous epithelium was seen in groups receiving exposures of 135 or 400 mg/m3. These changes were considered to be a direct local effect of the test material. At the end of the month post exposure recovery period, all of these findings had for all practical purposes, completely reversed.
- Histopathological findings: neoplastic:
- no effects observed
Effect levels
- Key result
- Dose descriptor:
- NOAEL
- Effect level:
- ca. 135 mg/m³ air (nominal)
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- clinical signs
- histopathology: non-neoplastic
Target system / organ toxicity
- Key result
- Critical effects observed:
- no
- Lowest effective dose / conc.:
- 400 mg/m³ air (nominal)
- System:
- respiratory system: upper respiratory tract
- Organ:
- larynx
- other: nasoturbinates and nasopharynx
Any other information on results incl. tables
Tabulated data are presented in the final report which is attached to this end point summary.
Applicant's summary and conclusion
- Conclusions:
- Exposures to MGK® 264 as a liquid aerosol for 6 hours/day, 5 days/week for 13 weeks at levels of 10, 40, 135 and 400 mg/m3, produced test material related increases in red facial stains and nasal discharge in all test material exposure groups and excessive salivation in the high exposure group. Decreased activity was seen in the high exposure group during the exposures.
Body weight gain, food consumption, ophthalmology, hematology and clinical chemistry parameters, organ weights and organ/body weight ratios were not affected by these exposures.
Microscopic findings related to the test material included reversible changes in the nasoturbinates, nasopharynx and larynx.
All of these microscopic results were considered to be localized, normal adaptive responses to an aerosol exposure, and not indicative of systemic toxicity. Therefore, 135 mg/m3 was considered to be a NOAEL No-observable-adverse-effect-level). - Executive summary:
The toxicity of MGK 264 was assessed when administered by whole-body inhalation as a liquid aerosol to rats for 6 hours per day, 5 days per week for 13 weeks. The target concentrations in this study weere 0 (control; double group), 10, 40, 135 and 400 (double group) mg/m3. The highest concentration in the study represented the maximum exposure level of MGK 264 which could be generated at the appropriate particle size in the 1000 litre chambers that were used in the study. Recovery animals were included in the control and high exposure groups and were examined after a 13 week recovery period.
Exposure levels were determined gravimetrically (4 times per day) and by gas chromatography (once per day). Particle size distribution measurements of the liquid aerosol were made once per chamber/day.
The animals were observed for clinical signs during each exposure and weekly for detailed physical examinations. Body weight measurements were recorded pre-test and weekly. Ophthalmoscopy examinations were performed pre-test and at the end of the study. Blood samples wre withdrawn for haematological and clinical chemistry examinations before the scheduled sacrifices at the end of the treatment or recovery periods. At necropsy examination, selected organs were weighed, a full list of organs were harvested and processed for histopathological examination.
The mean active ingredient exposure concentrations were determined to be 0, 0, 10±2 (mean± standard deviation), 43±6, 135±19, 400±28 and 407±41 mg/m3 for
Groups I to VII, respectively. Particle size distribution determinations indicated the test aerosol atmosphere was respirable in size to the rat.
Particle size distribution determinations showed, on average, the mass median aerodynamic diameter to be 1.1 microns with a geometric standard deviation of
2.3.
MGK 264 related changes were limited to reduced activity and excessive salivation during exposure in the high exposure groups and histopathological changes in the nasoturbinates, nasopharynx and larynx of the high exposure group. These changes which were reversible, were indicative of a localised, normal adaptive responses to an aerosol exposure and not indicative of systemic toxicity. The decreased activity was not considered to be a major detrimental response. On this basis, 135 mg/m3 was considered to be a NOAEL (no-observable-adverse-effect-level).
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