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EC number: 203-716-3 | CAS number: 109-89-7
Genetic toxicity: in vivo
Administrative data
- Endpoint:
- in vivo mammalian somatic cell study: cytogenicity / erythrocyte micronucleus
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- Dec 2002 - Mar 2003
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- test procedure in accordance with generally accepted scientific standards and described in sufficient detail
Data source
Referenceopen allclose all
- Reference Type:
- publication
- Title:
- Unnamed
- Year:
- 2 003
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 2 003
- Report date:
- 2011
Materials and methods
- Principles of method if other than guideline:
- Peripheral blood samples were obtained from male and female B6C3F1 mice at the end of a 14-week toxicity study. Smears were immediately prepared and fixed in absolute methanol, stained with a chromatin-specific fluorescent dye mixture of Hoechst 33258/pyronin Y and coded. Slides were scanned at 630 or 1000 times magnification using a semi-automated image analysis system to determine the frequency of micronuclei in 10000 normochromatic erythrocytes (NCEs) in each of 10 animals per dose group. A detailed discussion of this assay can be found in MacGregor et al. (1990).
- GLP compliance:
- no
- Type of assay:
- micronucleus assay
Test material
- Reference substance name:
- Diethylamine
- EC Number:
- 203-716-3
- EC Name:
- Diethylamine
- Cas Number:
- 109-89-7
- Molecular formula:
- C4H11N
- IUPAC Name:
- diethylamine
Constituent 1
- Specific details on test material used for the study:
- - Physical state: colorless liquid with a strong ammonia odor
- Analytical purity: approximately 99.9%
- Lot/batch No.: BE/07/01
- Stability under test conditions: no degradation of the bulk chemical was detected
- Storage condition of test material: at controlled room temperature
Test animals
- Species:
- mouse
- Strain:
- B6C3F1
- 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: 23.3 g (mean), female: 19.8 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
- Details on exposure:
- GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: Inhalation chamber (Harvord Systems Division of Lab Products, Inc. Aberdeen, MD)
- Method of conditioning air: glass beads in a heated glass coloum for vapourization
- Air flow rate: 15 air changes /h - Duration of treatment / exposure:
- 14 weeks (93 days exposure)
- Frequency of treatment:
- 6 hours per day, 5 days per week
Doses / concentrationsopen allclose all
- Dose / conc.:
- 8 ppm (nominal)
- Remarks:
- analytical concentration 8 ± 0.3 ppm
- Dose / conc.:
- 16 ppm (nominal)
- Remarks:
- analytical concentration 15.9 ± 0.6 ppm
- Dose / conc.:
- 32 ppm (nominal)
- Remarks:
- analytical concentration 32 ± 1.3 ppm
- Dose / conc.:
- 62 ppm (nominal)
- Remarks:
- analytical concentration 62.2 ± 2.3 ppm
- Dose / conc.:
- 125 ppm (nominal)
- Remarks:
- analytical concentration 126 ± 5 ppm
- No. of animals per sex per dose:
- 5
- Control animals:
- yes
Examinations
- Tissues and cell types examined:
- Peripheral blood
Justification: According to the OECD 474, the use of peripheral blood is a valid alternative in mice, if the treatment time exceeds 4 weeks. Since the animals were treated for 90 days, peripheral blood can be used instead of bone marrow. - Statistics:
- The frequency of micronucleated cells among normochromatic cells was analysed by statistical software package that tested for increasing trend over exposure groups using a one-tailed Cochran-Armitage trend test followed by pairwise comparisons between each exposure group and the control group.
Results and discussion
Test results
- Sex:
- male/female
- Genotoxicity:
- negative
- Toxicity:
- no effects
- Vehicle controls validity:
- valid
- Negative controls validity:
- not specified
- Positive controls validity:
- not specified
Any other information on results incl. tables
Tab. 1 Frequency of Micronuclei in Mouse Peripheral Blood Erythrocytes
Dose (ppm) | Micronucleated Normochromatic Erythrocytes / 1000 cells | |
| Male | Female |
0 | 2.80 ± 0.30 | 2.60 ± 0.29 |
8 | 4.60 ± 0.60 | 2.50 ± 0.61 |
16 | 4.10 ± 0.48 | 2.20 ± 0.25 |
32 | 3.30 ± 0.34 | 3.50 ± 0.57 |
62 | 4.00 ± 0.52 | 3.80 ± 0.60 |
125 | 2.60 ± 0.33 | 2.20 ± 0.25 |
No significant increase in micronucleated NCEs was observed in males or females and all tested dose groups.
The results from the vehicle control group as well as all treated groups were within the negative control range of micronucleated cells obtained by the lab (1.8 - 5.3 for males, 0.7 - 5.1 for females). The data have been compiled in the table below.
Tab. 2: Results for the vehicle control groups obtained by ILS Inc.
Year | Report | Male | Female | RoE |
2011 | TR564 | 2 +/- 0.61 | 1.8 +/- 0.25 | Inhalation |
2014 | TR581 | 2.4 +/-0.33 | 2.5 +/-0.35 | Inhalation |
2008 | TR552 | 3.4 +/-0.54 | 4 +/- 0.47 | Inhalation |
2009 | TR 542 | 2.4 +/- 0.69 | 2.3 +/- 0.4 | Inhalation |
2007 | TR 543 | 5.3 +/- 0.5 | 5.1 +/- 0.46 | Inhalation |
2011 | TR 567 | 2.8 +/- 0.2 | 1.7 +/- 0.2 | gavage |
2011 | TR 570 | 1.9 +/-0.19 | 0.7 +/- 0.2 | gavage |
2011 | TR565 | 4.6 +/- 0.58 | 3.7 +/- 0.46 | feed |
2011 | tox076 | 1.8 +/- 0.29 | 2 +/- 0.26 | gavage |
No concurrent positive control was included, but positive results have been reported by the laboratory. E.g, inhalation exposure for 90-days with α-Methylstyrene results in 9.1 micronucleated NCEs / 1000 NCEs in peripheral blood (TR 543).
Applicant's summary and conclusion
- Conclusions:
- There was no increase in the percentage of micronucleated cells compared to the vehicle control group. Additionally, all results were within the negative control range. Consequently, the substance did not cause chromosome damage in this study.
- Executive summary:
In a micronucleus assay with B6C3F1 mice, peripheral blood samples were obtained from 5 male/female animals at the end of a 93 days inhalation toxicity study (6 hours per day, 5 days per week; doses of 0, 8, 16, 32, 62, 125 ppm). No significant increase in micronucleated normochromatic erythrocytes was observed in males or females and all tested dose groups.
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