Registration Dossier
Registration Dossier
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EC number: 203-921-8 | CAS number: 111-92-2
Genetic toxicity: in vivo
Administrative data
- Endpoint:
- in vivo mammalian somatic cell study: cytogenicity / bone marrow chromosome aberration
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
Cross-reference
- Reason / purpose for cross-reference:
- reference to same study
- Remarks:
- DRF included in same report
Reference
- Endpoint:
- acute toxicity: oral
- Type of information:
- experimental study
- Adequacy of study:
- weight of evidence
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: Poorly documented study report but acceptable for classification
- Reason / purpose for cross-reference:
- reference to same study
- Remarks:
- Main study (MNT)
- Qualifier:
- no guideline followed
- Principles of method if other than guideline:
- Single oral dose to male and female mice. Animals were observed for mortality and clinical signs for two days.
The results were used as a range finder for a consecutive micronucleus assay. - GLP compliance:
- not specified
- Species:
- mouse
- Strain:
- ICR
- Sex:
- male/female
- Route of administration:
- oral: gavage
- Vehicle:
- corn oil
- Doses:
- 100, 160, 250, 400 and 500 mg/kg bw
- No. of animals per sex per dose:
- 5
- Control animals:
- not specified
- Details on study design:
- - Duration of observation period following administration: 3 days
- Key result
- Sex:
- male/female
- Dose descriptor:
- LD50
- Effect level:
- 305 mg/kg bw
- Mortality:
- Mortality occurred within two days of dose administration as follows: 2/5 female mice at 250 mg/kg, 2/5 male mice and 5/5 female mice at 400 mg/kg and 5/5 male mice and 5/5 female mice at 500 mg/kg.
- Clinical signs:
- no data
- Body weight:
- no data
- Gross pathology:
- no data
- Interpretation of results:
- Category 4 based on GHS criteria
- Conclusions:
- The LD50 of the test substance after single oral administration was found to be 305 mg/kg bw in mice.
- Executive summary:
The test substance was administered orally (gavage) to male and female mice (ICR) at 100, 160, 250, 400 and 500 mg test article/kg bw which was administered in a total volume of 20 ml test article-vehicle (corn oil) mixture/kg body weight. 5 animals per sex per dose were used. Mortality occurred within two days of dose administration as follows: 2/5 female mice at 250 mg/kg, 2/5 male mice and 5/5 female mice at 400 mg/kg and 5/5 male mice and 5/5 female mice at 500 mg/kg. The LD50 of the test substance after single oral administration was found to be 305 mg/kg bw in mice.
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 1 995
- Report date:
- 1995
Materials and methods
Test guideline
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 474 (Mammalian Erythrocyte Micronucleus Test)
- Deviations:
- no
- GLP compliance:
- yes
- Type of assay:
- mammalian erythrocyte micronucleus test
Test material
- Reference substance name:
- Dibutylamine
- EC Number:
- 203-921-8
- EC Name:
- Dibutylamine
- Cas Number:
- 111-92-2
- Molecular formula:
- C8H19N
- IUPAC Name:
- N-butylbutan-1-amine
- Details on test material:
- Di-n-butylamine
Constituent 1
Test animals
- Species:
- mouse
- Strain:
- ICR
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Harlan Sprague-Dawley, Inc., Frederick, MD
- Age at study initiation: 6-8weeks old
- Weight at study initiation: 27.4-35.8g (males) and 24.5-30.6g (females)
- Assigned to test groups randomly: yes
- Fasting period before study: no
- Housing: 5 of the same sex per cage
- Diet (e.g. ad libitum): Purina certified rodent chow 5002 ad libitum
- Water (e.g. ad libitum): tap water ad libitum
- Acclimation period: 5 days at least
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 23.3°C (74°F)
- Humidity (%): 50+/-20
- Photoperiod (hrs dark / hrs light): 12/12
Administration / exposure
- Route of administration:
- oral: gavage
- Vehicle:
- - Vehicle(s)/solvent(s) used: corn oil
- Supplier: Super G - Details on exposure:
- gavage at constant volume of 20 ml/kg.
- Duration of treatment / exposure:
- one
- Frequency of treatment:
- once
- Post exposure period:
- 5 mice/group were sacrified at 24, 48 and 72 hours (All 5 mice treated with Cyclophosphamide were sacrified at 24h).
Doses / concentrationsopen allclose all
- Dose / conc.:
- 0 mg/kg bw/day (nominal)
- Dose / conc.:
- 55 mg/kg bw/day (nominal)
- Dose / conc.:
- 110 mg/kg bw/day (nominal)
- Dose / conc.:
- 220 mg/kg bw/day (nominal)
- No. of animals per sex per dose:
- Vehicle control n=15 per sex
55 mg/kg n=15 per sex
110 mg/kg n=15 per sex
220 mg/kg n=20 per sex
Cyclophosphamide 60 mg/kg n=5 per sex - Control animals:
- yes, concurrent vehicle
- Positive control(s):
- cyclophosphamide
- Justification for choice of positive control(s): commonly used
- Doses / concentrations: 60 mg/kg in distilled water
- Supplier: Sigma Chemical Company
Examinations
- Tissues and cell types examined:
- bone marrow from femurs
- Details of tissue and slide preparation:
- Slides were fixed in methanol and colored with may-Grünwald-Giemsa.
- Evaluation criteria:
- 1000 polychromatic erythrocytes were scored for the presence of micronuclei.
The mean incidence of micronucleated polychromatic erythrocytes must not exceed 5/1000 polychromatic erythrocytes (0.5%) in the vehicle control.
The incidence of micronucleated polychromatic erythrocytes in the positive control group must be significantly increased relative to the vehicle control group (p<0.05). - Statistics:
- Kastenbaum-Bowman
Results and discussion
Test results
- Sex:
- male/female
- Genotoxicity:
- negative
- Toxicity:
- yes
- Vehicle controls validity:
- valid
- Negative controls validity:
- not applicable
- Positive controls validity:
- valid
- Additional information on results:
- - Mortality: 3/20 males and 1/20 females treated at 220 mg/kg died on the day of exposure.
- Clinical signs: noted on the days following dose administration, included lethargy in male and female mice at 55, 110, and 220 mg/kg.
- Reductions up to 19 % in the ration of polychromatic erythrocytes per total erythrocytes were observed. The number of micronucleated polychromatic erythrocytes per 1000 polychromatic erythrocytes in the dibutylamine treated grouop was not statistically increased relative to the respective negative controls.
Cyclophosphamide induced a significant increase in micronucleated polychromatic erythrocytes in both male and female mice (p<0.05).
Any other information on results incl. tables
Summary of bone marrow micronucleus study
| Treatment | Sex | Time (h) | Number of mice | PCE/total erythrocytes | Micronucleated polychromatic erythrocytes | |
| Number per 1000 PCE | Number per PCE scored | |||||
| corn oil 20ml/kg | M | 24 | 5 | 0,53 | 0,8+/-0,84 | 4/5000 |
| 48 | 5 | 0,58 | 1,4+/-1,14 | 7/5000 | ||
| 72 | 5 | 0,57 | 0,8+/-0,84 | 4/5000 | ||
| F | 24 | 5 | 0,7 | 2,0+/-1,00 | 10/5000 | |
| 48 | 5 | 0,59 | 1,0+/-0,71 | 5/5000 | ||
| 72 | 5 | 0,61 | 1,2+/-0,84 | 6/5000 | ||
| Bi-n-butylamine 55mg/kg | M | 24 | 5 | 0,54 | 0,6+/-0,55 | 3/5000 |
| 48 | 5 | 0,58 | 1,0+/-1,41 | 5/5000 | ||
| 72 | 5 | 0,65 | 1,2+/-0,84 | 6/5000 | ||
| F | 24 | 5 | 0,72 | 2,6+/-1,82 | 13/5000 | |
| 48 | 5 | 0,48 | 1,2+/-0,84 | 6/5000 | ||
| 72 | 5 | 0,62 | 0,6+/-0,89 | 3/5000 | ||
| Bi-n-butylamine 110mg/kg | M | 24 | 5 | 0,52 | 0,2+/-0,45 | 1/5000 |
| 48 | 5 | 0,65 | 1,0+/-0,71 | 5/5000 | ||
| 72 | 5 | 0,56 | 1,4+/-2,07 | 7/5000 | ||
| F | 24 | 5 | 0,66 | 0,0+/-0,00 | 0/5000 | |
| 48 | 5 | 0,51 | 1,8+/-0,84 | 9/5000 | ||
| 72 | 5 | 0,66 | 0,8+/-0,84 | 4/5000 | ||
| Bi-n-butylamine 220mg/kg | M | 24 | 5 | 0,52 | 0,8+/-0,84 | 4/5000 |
| 48 | 5 | 0,63 | 1,8+/-1,30 | 9/5000 | ||
| 72 | 5 | 0,57 | 1,4+/-1,14 | 7/5000 | ||
| F | 24 | 5 | 0,59 | 2,6+/-2,61 | 13/5000 | |
| 48 | 5 | 0,49 | 0,6+/-0,89 | 3/5000 | ||
| 72 | 5 | 0,56 | 1,0+/-0,71 | 5/5000 | ||
| Cyclophosphamide 60mg/kg | M | 24 | 5 | 0,54 | 17,4+/-3,21 | 87/5000* |
| F | 24 | 5 | 0,46 | 34,4+/-2,41 | 172/5000* | |
p<0.05
Applicant's summary and conclusion
- Conclusions:
- A GLP-compliant in vivo Mammalian Erythrocyte Micronucleus Test was performed according to OECD TG 474 in male/female ICR mice. The test substance was found to be negative regarding the endpoint genotoxicity.
- Executive summary:
An in vivo Mammalian Erythrocyte Micronucleus Test was performed according to OECD TG 474 (GLP-compliant) in male/female ICR mice. Treatment with the test substance was once orally via gavage at constant volume of 20 ml/kg. 5 mice per group were sacrified at 24, 48 and 72 hours (All 5 mice treated with Cyclophosphamide were sacrified at 24h). Results show that 3/20 males and 1/20 females treated at 220 mg/kg died on the day of exposure. Clinical signs on the days following dose administration, included lethargy in male and female mice at 55, 110, and 220 mg/kg were noted. Reductions up to 19 % in the ration of polychromatic erythrocytes per total erythrocytes were observed. The number of micronucleated polychromatic erythrocytes per 1000 polychromatic erythrocytes in the test substance treated group was not statistically increased relative to the respective negative controls. Cyclophosphamide induced a significant increase in micronucleated polychromatic erythrocytes in both male and female mice (p<0.05).
However, the test substance was found to be negative regarding the endpoint genotoxicity.
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