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EC number: 211-541-9 | CAS number: 660-68-4
- 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
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: Scientific study according to NTP standard protocol that fully meets documentation requirements.
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 2 011
- Report date:
- 2011
Materials and methods
Test guideline
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 413 (Subchronic Inhalation Toxicity: 90-Day Study)
- GLP compliance:
- yes
- Limit test:
- no
Test material
- Reference substance name:
- Diethylamine
- EC Number:
- 203-716-3
- EC Name:
- Diethylamine
- Cas Number:
- 109-89-7
- Molecular formula:
- C4H11N
- IUPAC Name:
- N-ethylethanamine
- Test material form:
- other: free base liquid
- Details on test material:
- Diethylamine was obtained from Alkyl Amines Chemicals, Ltd. (Maharashtra, India) in one lot (BE/07/01) that was used in the 2-week, 3-month, and 2-year studies. Identity and purity analyses were conducted by the analytical chemistry laboratory at Research Triangle Institute (RTI) (Research Triangle Park, NC), the study laboratory at Battelle Toxicology Northwest (Richland, WA), Galbraith Laboratories, Inc. (Knoxville, TN), and Chemir/Polytech Laboratories, Inc. (Maryland Heights, MO) (Appendix I). Reports on analyses performed in support of the diethylamine studies are on file at the National Institute of Environmental Health Sciences.
The chemical, a colorless liquid with a strong ammonia odor, was identified as diethylamine using infrared and nuclear magnetic resonance spectroscopy and gas chromatography (GC) coupled with mass spectrometry.
Karl Fischer titration indicated 275 ppm water. Elemental analyses for carbon, hydrogen, and nitrogen were in agreement with the theoretical values for diethylamine. GC indicated one major peak and no impurities with areas greater than 0.1% of the total peak area. The overall purity of lot BE/07/01 was determined to be approximately 99.9%.
To ensure stability, the bulk chemical was stored at controlled room temperature in the original shipping containers (55-gallon metal drums). Periodic reanalyses of the bulk chemical were performed during the 2-week, 3-month, and 2-year studies using GC, and no degradation of the bulk chemical was detected.
Constituent 1
Test animals
- Species:
- rat
- Strain:
- Fischer 344
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Taconic Farms, Inc. (Germantown, NY)
- Age at study initiation: approximately 6 weeks
- Weight at study initiation: males: 110 g (mean), female: 93 g (mean)
- Housing: individually in stainless steel wire bottom (Lab Products, Inc., Seaford, DE), changed weekly and rotated daily
- Diet: NTP-2000 irradiated wafers (Zeigler Brothers, Inc., Gardners, PA), available ad libitum, except during exposure periods
- Water: Tap water (Richland municipal supply) via automatic watering system (Edstrom Industries, Waterford, WI), available ad libitum
- Acclimation period: 12 days
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22±3 °C (72°±3 °F)
- Humidity (%): 50% ± 15%
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12
Administration / exposure
- Route of administration:
- inhalation: vapour
- Type of inhalation exposure:
- whole body
- Remarks:
- inhalation chamber
- Vehicle:
- other: unchanged
- Details on inhalation exposure:
- Diethylamine was pumped onto glass beads in a heated glass column where it was vaporized. Heated nitrogen flowed through the column and carried the vapor into a short vapor distribution manifold. Concentration in the manifold was determined by the chemical pump rate and nitrogen flow rate. The pressure in the distribution manifold was kept fixed to ensure constant flow through the manifold and into all chambers as the flow of vapor to each chamber was adjusted.
Individual Teflon® delivery lines carried the vapor from the manifold to three-way exposure valves at the chamber inlets. The exposure valves diverted vapor delivery to the exposure chamber exhaust until the generation system was stable and exposures were ready to proceed. A metering valve with a flow indicator at the manifold controlled the flow rate to each chamber. To initiate exposure, the chamber exposure valves were rotated to allow the vapor to flow to each exposure chamber inlet duct where it was further diluted with HEPA®-filtered, conditioned air to achieve the desired exposure concentration.
The study laboratory designed the inhalation exposure chamber (Harford Systems Division of Lab Products, Inc., Aberdeen, MD) so that uniform vapor concen-trations could be maintained throughout the chamber with the catch pans in place. The total active mixing volume of each chamber was 1.7 m3. A small particle detector was used with and without animals in the exposure chambers to ensure that diethylamine vapor, and not aerosol, was produced. No particle counts above the minimum resolvable level (approximately 200 particles/cm3) were detected. - Analytical verification of doses or concentrations:
- yes
- Details on analytical verification of doses or concentrations:
- The on-line gas chromatograph was checked throughout the day for instrument drift against an on-line standard of diethylamine in nitrogen supplied by a standard generator. The on-line gas chromatograph was calibrated by a comparison of chamber concentration data to data from grade samples that were collected with acrylic ester adsorbent gas sampling tubes, extracted with methylene chloride containing triethylamine as an internal standard, and analyzed using an off-line gas chromatograph. Known values of chamber atmosphere were sampled at a constant flow rate ensured by a calibrated orifice. The off-line gas chromatograph was calibrated with gravimetrically prepared standards of diethylamine and the internal standard (triethylamine) in methylene chloride.
- Duration of treatment / exposure:
- 93 days
- Frequency of treatment:
- 6 h/d, 5 d/w
Doses / concentrationsopen allclose all
- Dose / conc.:
- 8 ppm (analytical)
- Remarks:
- (corresponding to 24 mg/m3)
- Dose / conc.:
- 16 ppm (analytical)
- Remarks:
- (corresponding to 49 mg/m3)
- Dose / conc.:
- 32 ppm (analytical)
- Remarks:
- (corresponding to 97 mg/m3)
- Dose / conc.:
- 62 ppm (analytical)
- Remarks:
- (corresponding to 188 mg/m3)
- Dose / conc.:
- 125 ppm (analytical)
- Remarks:
- (corresponding to 379 mg/m3)
- No. of animals per sex per dose:
- 10
- Control animals:
- yes
- Details on study design:
- - Dose selection rationale: Because exposure to 250 or 500 ppm diethylamine for 16 days caused significantly decreased body weights in rats, a high concentration of 125 ppm was selected for both sexes in the 3-month study. Although nasal lesions were present in rats exposed to 125 ppm for 16 days, these lesions were generally mild and were not likely to compromise the 3-month study. Diethylamine exposure concentrations of 0, 8, 16, 32, 62, and 125 ppm were selected for both sexes of rats in the 3-month study.
Examinations
- Observations and examinations performed and frequency:
- CAGE SIDE OBSERVATIONS: Yes
- Time schedule: twice daily
DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: twice daily
BODY WEIGHT: Yes
- Time schedule for examinations: days 0, 7 and weekly afterwards
OPHTHALMOSCOPIC EXAMINATION: No data
HAEMATOLOGY: Yes
- Time schedule for collection of blood: days 0, 23 and 93
- Anaesthetic used for blood collection: Yes
- How many animals: all
- Parameters examined: Erythrocyte count, Mean corpuscular volume, Hemoglobin, Packed cell volume, Mean corpuscular hemoglobin, Mean corpuscular hemoglobin concentration, Erythrocyte morphologic assessment, Leukocyte count, Leukocyte differential, Reticulocyte count, Platelet count and morphologic assessment
CLINICAL CHEMISTRY: Yes
- Time schedule for collection of blood: days 0, 23 and 93
- How many animals: all
- Parameters examined: Sorbitol dehydrogenase (SDH), Alkaline Phosphatase (ALP), Creatine Kinase (CK), Creatinine, Total Protein, Albumin, Urea Nitrogen (BUN), Total Bile Acids, Alanine Aminotransferase (ALT), Glucose
URINALYSIS: No data
NEUROBEHAVIOURAL EXAMINATION: No data
OTHER: Organs weighed were heart, right kidney, liver, lung, right testis, and thymus - Sacrifice and pathology:
- GROSS PATHOLOGY: Yes, a complete necropsy was performed on all treated and control animals that either died or were sacrificed
HISTOPATHOLOGY: Complete histopathology was performed on 0 and 125 ppm core study rats. In addition to gross lesions and tissue masses, the following tissues were examined to a no-effect level: adrenal gland, bone with marrow, brain, clitoral gland, esophagus, eyes, Harderian gland, heart, large intestine (cecum, colon, rectum), small intestine (duodenum, jejunum, ileum), kidney, larynx, liver, lungs, lymph nodes (bronchial, mandibular, mediastinal, and mesenteric), mammary gland, nose, ovary, pancreas, parathyroid gland, pituitary gland, preputial gland, prostate gland, salivary gland, skin, spleen, stomach (forestomach and glandular), testis with epididymis and seminal vesicle, thymus, thyroid gland, trachea, urinary bladder, and uterus.
Results and discussion
Results of examinations
- Details on results:
- CLINICAL SIGNS AND MORTALITY
All rats survived to the end of the study. The only clinical finding was a single occurrence of a torso lateral ulcer/abscess in a 125 ppm male.
BODY WEIGHT AND WEIGHT GAIN
Final mean body weights and body weight gains of all exposed groups were similar to those of the chamber control groups.
HAEMATOLOGY
There were no exposure-related changes in hematology endpoints.
CLINICAL CHEMISTRY
There were no exposure-related changes in clinical chemistry endpoints.
ORGAN WEIGHTS
The relative kidney weights of all groups of exposed females were increased and were significantly greater than those of the chamber controls, except in the 32 ppm group. The relative liver weight of 125 ppm males was significantly increased.
HISTOPATHOLOGY: NON-NEOPLASTIC
Exposure-related histopathology findings in rats were limited to the nose and were seen primarily in rats exposed to 62 or 125 ppm. These lesions included turbinate necrosis, suppurative inflammation, respiratory epithelial hyperplasia, squamous metaplasia of the respiratory epithelium, and olfactory epithelial atrophy.
There were no inflammatory changes of the eye as had been observed in the 2-week study at higher concentrations.
OTHER FINDINGS
There was a dose-related decrease seen in the motility of sperm from male rats with the values of those exposed to 32, 62, or 125 ppm diethylamine being significantly lower (5-26%) than those of the chamber controls; no significant differences were observed in the estrous cyclicity of female rats administered 32, 62, or 125 ppm diethylamine when compared to the chamber controls.
Effect levels
open allclose all
- Key result
- Dose descriptor:
- NOAEC
- Remarks:
- systemic
- Effect level:
- 16 ppm
- Based on:
- test mat.
- Remarks:
- equivalent to 49 mg/m3 and 0.049 mg/L air
- Sex:
- male
- Basis for effect level:
- other: sperm motility
- Key result
- Dose descriptor:
- NOAEC
- Remarks:
- systemic
- Effect level:
- 125 ppm
- Based on:
- test mat.
- Remarks:
- equivalent to 379 mg/m3 and 0.379 mg/L air
- Sex:
- female
- Basis for effect level:
- other: no adverse systemic effcets observed up to the highest dose tested
- Key result
- Dose descriptor:
- NOAEC
- Remarks:
- local
- Effect level:
- 16 ppm
- Based on:
- test mat.
- Remarks:
- equivalent to 49 mg/m3 and 0.049 mg/L air
- Sex:
- male/female
- Basis for effect level:
- histopathology: non-neoplastic
Target system / organ toxicity
- Key result
- Critical effects observed:
- yes
- Lowest effective dose / conc.:
- 32 ppm
- System:
- respiratory system: upper respiratory tract
- Organ:
- nasal cavity
- Treatment related:
- yes
- Dose response relationship:
- yes
Applicant's summary and conclusion
- Conclusions:
- DEA was studied in a subchronic study in rats using the NTP standard protocol. From the data a NOAEC for systemic and local toxicity of 16 ppm (corresponding to 49 mg/m3) was established.
- Executive summary:
Diethylamine (DEA) provides a suitable surrogate for diethylamine hydrochloride. DEA was studied in a subchronic study in rats using the NTP standard protocol. The report is publicly avaialable on the NTP website (TR 566).
In the study groups of 10 male and 10 female rats were exposed to diethylamine vapor at concentrations of 0, 8, 16, 32, 62, or 125 ppm (corresponding to 24, 49, 97, 188 and 379 mg/m3, respectively), 6 hours plus T90 (12 minutes) per day, 5 days per week for 14 weeks. All rats survived to the end of the study. Mean body weights of all exposed groups were similar to those of the chamber control groups. There were significant exposure concentration-related decreases in sperm motility in 32, 62, and 125 ppm males; there were no significant differences in the lengths of estrous cycles between chamber control and exposed groups of females. Exposure-related nasal lesions were seen primarily in rats exposed to 62 or 125 ppm, but occurred already at 32 ppm, although not reaching the level of statistical significance. These lesions included turbinate necrosis, suppurative inflammation, respiratory epithelial hyper-plasia, squamous metaplasia of the respiratory epithelium, and olfactory epithelial atrophy.
From the data a NOAEC for systemic and local toxicity of 16 ppm (corresponding to 49 mg/m3) could be established.
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