Registration Dossier
Registration Dossier
Diss Factsheets
Use of this information is subject to copyright laws and may require the permission of the owner of the information, as described in the ECHA Legal Notice.
EC number: 203-921-8 | CAS number: 111-92-2
- 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

Developmental toxicity / teratogenicity
Administrative data
- Endpoint:
- developmental toxicity
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 06 Nov 2007 - 26 Nov 2007
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
- Remarks:
- GLP compliant
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 2 010
- Report date:
- 2010
Materials and methods
Test guideline
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 414 (Prenatal Developmental Toxicity Study)
- Version / remarks:
- Jan 2001
- Deviations:
- no
- GLP compliance:
- yes (incl. QA statement)
- Remarks:
- Landesamt für Umwelt, Wasserwirtschaft und Gewerbeaufsicht, Kaiser-Friedrich-Straße 7, 55116 Mainz
- Limit test:
- no
Test material
- Reference substance name:
- Dibutylammonium chloride
- EC Number:
- 228-521-0
- EC Name:
- Dibutylammonium chloride
- Cas Number:
- 6287-40-7
- Molecular formula:
- C8H19N.ClH
- IUPAC Name:
- N-butylbutan-1-aminium chloride
Constituent 1
- Specific details on test material used for the study:
- SOURCE OF TEST MATERIAL
- Purity: 95 w-%
STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: Room temperature
- Stability under test conditions: analytical verifications of the stability of the test substance in demineralized water for a period of 7 d at room tempreature were carried out before study initiation
Test animals
- Species:
- rat
- Strain:
- Wistar
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Charles River Laboratories, Germany
- Age at study initiation: 10 - 12 weeks
- Housing: housed singly
- Diet (e.g. ad libitum): ad libitum, Kliba maintenance diet mouse/rat
- Water (e.g. ad libitum): ad libitum
- Weight at study initiation: 145.4 - 188.4 g
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-24°C
- Humidity (%): 30-70%
- Air changes (per hr): 15 times per hour
- Photoperiod (hrs dark / hrs light): 12/12
Administration / exposure
- Route of administration:
- oral: gavage
- Vehicle:
- water
- Details on exposure:
- The test substance solutions were prepared at the beginning of the administration period and thereafter at intervals of 7 days, which took into account the analytical results of the stability verification.
For the preparation of the solutions, appropriate amounts of the test substance was weighed in a beaker, topped up with drinking water and subsequently intensely mixed with a magnetic stirrer.
10 mL/kg bw were administered each day - Analytical verification of doses or concentrations:
- yes
- Details on analytical verification of doses or concentrations:
- The results of the analyses of the test substance solutions in drinking water confirmed the correctness of the prepared concentrations. The analytical values of the samples corresponded to the expected values within the limits of the analytical method, i.e. were always above 90% and below 110% of the nominal concentrations.
- Details on mating procedure:
- The animals were paired by the breeder("time-mated") and supplied on GD 0 (=detection of vaginal plug/sperm).
- Duration of treatment / exposure:
- Gestation day 6 - 19
- Frequency of treatment:
- Once daily
- Duration of test:
- Dams sacrificed on GD20
Doses / concentrationsopen allclose all
- Dose / conc.:
- 15 mg/kg bw/day (nominal)
- Remarks:
- concentration of the aqueous solution 150 mg/100mL
- Dose / conc.:
- 50 mg/kg bw/day (nominal)
- Remarks:
- concentration of the aqueous solution 500 mg/100mL
- Dose / conc.:
- 150 mg/kg bw/day (nominal)
- Remarks:
- concentration of the aqueous solution 1500 mg/100mL
- No. of animals per sex per dose:
- 25 female rats per dose
- Control animals:
- yes, concurrent vehicle
Examinations
- Maternal examinations:
- CAGE SIDE OBSERVATIONS: Yes
- Time schedule: daily
DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: daily
BODY WEIGHT: Yes
- Time schedule for examinations: GD 0, 1, 3, 6, 83 10, 13, 15, 17, 19 and 20
FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study): Yes
- With the exaption of day 0, the consumption o food was determined on the same days as body weight.
POST-MORTEM EXAMINATIONS: Yes
- Sacrifice on gestation day 20
MORTALITY was checked twice a day on working days and once a day on saturdays, sundays or public holidays
POST-MORTEM EXAMINATIONS: Yes
- Sacrifice on gestation day 20
- Organs examined: Liver, kidney, thyroid glands
other: Clinical pathology (hematology, clinical chemistry)
- Ovaries and uterine content:
- The ovaries and uterine content was examined after termination: Yes
Examinations included:
- Gravid uterus weight: Yes
- Number of corpora lutea: Yes
- Number of implantations: Yes
- Number of early resorptions: Yes
- Number of late resorptions: Yes
- Other: dead fetuses - Fetal examinations:
- All fetus was weighed, sexed and external tissues ans all orifices were examined macroscopically.
- External examinations: Yes: all per litter
- Soft tissue examinations: Yes: all per litter
- Skeletal examinations: Yes: all per litter - Statistics:
- DUNNETT-test
FISHER`S EXACT
WILCOXON-test
KRUSKAL-WALLIS test
Results and discussion
Results: maternal animals
General toxicity (maternal animals)
- Clinical signs:
- effects observed, treatment-related
- Description (incidence and severity):
- Dose 50 mg/lg bw: salivation
Dose 150 mg/kg bw: salivation; one dam showed distinct clinical signs of maternal toxicity such as abdominal position, convulsion, twitching and hypersensitivity after treatment on just one occasion during the tretment.
Salivation stopped with exposure on GD 20 but was not considered to be a sign of systemic toxicity (result of the unpleasant taste or local irritation of the upper digestive tract) - Mortality:
- no mortality observed
- Body weight and weight changes:
- no effects observed
- Description (incidence and severity):
- Body weight gain of the high-dose rats was statistically significantly reduced at initiation of treatment (GD 6-8, about 63% below the concurrent control value) but recovered afterwards. If calculated for the enire treatment phase (GD 6-19), the mean body weight gain of these rats was slightly ans non-signicantly below control (about 5%).
Body weight gain of the dams of test groups 1 and 2 (15 and 50 mg/kg bw/d) was comparable to the concurrent controls. All observable differences in these 2 groups in comparison to the controls are without any biological relevance. - 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:
- not examined
- Haematological findings:
- effects observed, treatment-related
- Description (incidence and severity):
- In the dams on GD 20 the red bood cell counts as well as the menoglobin and hematocit values were slightly, but statictically significantly increased beginning in the 50 mg/kg bw/d dose group.
- Clinical biochemistry findings:
- effects observed, treatment-related
- Description (incidence and severity):
- On GD 20, the medians of the alanine aminotransferase (ALT) activity were increased in the dams of the 150 mg/kg bw/d dose group. The inorganic phosphate levels were increased in the dams starting in the 50 mg/kg bw/d dose group. Correspondingly, the calcium levels were increased. This increase showed a statistically weakly significance already in the 15 mg/kg bw/d dose group. However, in this dose group the calcium increase was the only increased parameter in clinical pathology. Because of this exclusiveness, the calcium increase in this dose group was regarded as non-adverse. Beginning in the dams of the 50 mg/kg bw/d dose group the urea as well as the cholesterol values were increased.
- Urinalysis findings:
- not examined
- Behaviour (functional findings):
- not specified
- Immunological findings:
- not examined
- Organ weight findings including organ / body weight ratios:
- effects observed, treatment-related
- Description (incidence and severity):
- Absolute kidney weights were slightly, but significantly increased in the high-dose group (150 mg/kg bw/d). Neither clinical pathological correlates nor any corroborative gross lesions were noted in this dose group, thus this rather marginal increase of kidney weight was not considered as an adverse effect of systemic toxicity.
The mean gravid uterus weights of the animals of test groups 1, 2 and 3 (15; 50 or 150 mg/kg bw/d) were not influenced by the test substance. The differences between these groups and the control group revealed no dose-dependency and were assessed to be without biological relevance. They reflect the normal degree of variation for rats of the strain used for this study and have to be assessed in association with the fortuitous fluctuations in the mean number of live fetuses/dam in this study - Gross pathological findings:
- no effects observed
- Neuropathological findings:
- not examined
- Histopathological findings: non-neoplastic:
- not examined
- Histopathological findings: neoplastic:
- not examined
Maternal developmental toxicity
- Number of abortions:
- not specified
- Pre- and post-implantation loss:
- no effects observed
- Total litter losses by resorption:
- no effects observed
- Early or late resorptions:
- not specified
- Dead fetuses:
- not specified
- Changes in pregnancy duration:
- not specified
- Changes in number of pregnant:
- not specified
- Details on maternal toxic effects:
- The conception rate reached 96% in test groups 0, 2 and 3 (0; 50 and 150 mg/kg bw/d) and 100% in test group 1 (15 mg/kg bw/d). There were no test substance-related and/or biologically relevant differences among the test groups in the conception rate, in the mean number of corpora lutea and implantation sites or in the values calculated for the pre- and the postimplantation losses as well as the number of resorptions and viable fetuses. All observed differences are considered to reflect the normal range of fluctuations for animals of this strain and age
Effect levels (maternal animals)
open allclose all
- Dose descriptor:
- NOAEL
- Remarks:
- maternal toxicity
- Effect level:
- 15 mg/kg bw/day
- Basis for effect level:
- body weight and weight gain
- clinical biochemistry
- haematology
- Dose descriptor:
- NOAEL
- Remarks:
- developmental toxicity
- Effect level:
- 150 mg/kg bw/day
- Basis for effect level:
- other: highest concentration tested
Results (fetuses)
- Fetal body weight changes:
- no effects observed
- Reduction in number of live offspring:
- not specified
- Changes in sex ratio:
- no effects observed
- Changes in litter size and weights:
- not specified
- Changes in postnatal survival:
- not examined
- External malformations:
- effects observed, non-treatment-related
- Description (incidence and severity):
- External malformations were recorded for one fetus each in the mid- and high-dose group (50 and 150 mg/kg bw/d). Both fetuses concerned had multiple malformations. The domed head mirrored the hydrocephaly found in this fetus and is therefore no independent finding. Cleft palates are present in the historical control data at a comparable incidence, thus these, findings were considered to be spontaneous in nature and without a relation to dosing. In the treated groups, the total incidences of external malformation were not significantly different from the control group.
- Skeletal malformations:
- effects observed, non-treatment-related
- Description (incidence and severity):
- One skeletal malformation was noted in one fetus each of test groups 0 and 1 (0 and 15 mg/kg bw/d). Neither statistically significant differences between the test groups nor a dose-response relationship were observed. Based on the rate of affected fetuses per litter, the incidence of skeletal malformations was comparable to the historical control data. No association to the treatment is assumed.
For all test groups, skeletal variations of different bone structures were observed, with or without effects on corresponding cartilages. The observed skeletal variations were related to several parts of fetal skeletons and appeared without a relation to the dose. Based on the rate of affected fetuses per litter, the incidence of skeletal variations was comparable to the historical control data - Visceral malformations:
- effects observed, treatment-related
- Description (incidence and severity):
- The examination of the soft tissues revealed soft tissue malformations in one litter each of test groups 2 and 3 (50 and 150 mg/kg bw/d). Some of these soft tissue malformations are present in the historical control data at comparable incidences and on the whole no specific malformation pattern was obvious. Thus, these individual cases were not considered to be related to the treatment. Malformation incidences showed no statistically significant differences between the test groups and the control.
Three soft tissue variations, i.e. short innominate, uni- or bilateral dilation of the renal pelvis and dilated cerebral ventricle, were detected. These findings were observed in 3 to 4 fetuses of 3 litters in each group including the controls and showed no dose-response relationship. No association to the treatment is assumed. - Description (incidence and severity):
- No statistically significant or biological relevant change of the mean placental weights
Effect levels (fetuses)
- Dose descriptor:
- NOAEL
- Effect level:
- 150 mg/kg bw/day
- Basis for effect level:
- other: highest concentration tested
Fetal abnormalities
- Abnormalities:
- not specified
Overall developmental toxicity
- Developmental effects observed:
- not specified
Any other information on results incl. tables
Examinations of the Fetuses
Total external malformations |
|
Test group 0 0 mg/kg bw/d |
Test group 1 15 mg/kg bw/d |
Test group 2 50 mg/kg bw/d |
Test group 3 150 mg/kg bw/d |
Litter Fetuses |
N N |
24 229 |
25 224 |
24 201 |
24 206 |
Fetal incidence |
N |
0.0 |
0.0 |
1(0.5%) |
1(0.5%) |
Litter incidence |
N |
0.0 |
0.0 |
1(4.2%) |
1(4.2%) |
Affectd fetuses/litter |
Mean % |
0.0 |
0.0 |
0.5 |
0.4 |
|
|
|
|
|
|
Total fetal soft tissue malformation |
|
Test group 0 0 mg/kg bw/d |
Test group 1 15 mg/kg bw/d |
Test group 2 50 mg/kg bw/d |
Test group 3 150 mg/kg bw/d |
Litter Fetuses |
N N |
24 109 |
25 105 |
24 95 |
24 98 |
Fetal incidence |
N |
0.0 |
0.0 |
1(2.1%) |
1(1.0%) |
Litter incidence |
N |
0.0 |
0.0 |
1(4.2%) |
1(4.2%) |
Affectd fetuses/litter |
Mean % |
0.0 |
0.0 |
2.1 |
0.8 |
|
|
|
|
|
|
Total soft tissue variations |
|
Test group 0 0 mg/kg bw/d |
Test group 1 15 mg/kg bw/d |
Test group 2 50 mg/kg bw/d |
Test group 3 150 mg/kg bw/d |
Litter Fetuses |
N N |
24 109 |
25 105 |
24 95 |
24 98 |
Fetal incidence |
N |
3 (2.8%) |
4 (3.8%) |
4(4.2%) |
4 (4.1%) |
Litter incidence |
N |
3 (2.8%) |
3 (12%) |
3 (13%) |
3 (13%) |
Affectd fetuses/litter |
Mean % |
2.7 |
3.3 |
2.1 |
0.8 |
|
|
|
|
|
|
Total skeletal malformations |
|
Test group 0 0 mg/kg bw/d |
Test group 1 15 mg/kg bw/d |
Test group 2 50 mg/kg bw/d |
Test group 3 150 mg/kg bw/d |
Litter Fetuses |
N N |
24 120 |
25 119 |
24 106 |
24 108 |
Fetal incidence |
N |
1 (0.8%) |
1 (0.8%) |
0.0 |
0.0 |
Litter incidence |
N |
1 (4.2%) |
1 (4.0%) |
0.0 |
0.0 |
Affectd fetuses/litter |
Mean % |
0.8 |
0.8 |
0.0 |
0.0 |
|
|
|
|
|
|
Total skeletal variations |
|
Test group 0 0 mg/kg bw/d |
Test group 1 15 mg/kg bw/d |
Test group 2 50 mg/kg bw/d |
Test group 3 150 mg/kg bw/d |
Litter Fetuses |
N N |
24 120 |
25 119 |
24 106 |
24 108 |
Fetal incidence |
N |
120 (100%) |
119 (100%) |
106 (100%) |
108 (100%) |
Litter incidence |
N |
24 (100%) |
25 (100%) |
24 (100%) |
24 (100%) |
Affectd fetuses/litter |
Mean % |
100.0 |
100.0 |
100.0 |
100.0 |
Total fetal malfromations |
|
Test group 0 0 mg/kg bw/d |
Test group 1 15 mg/kg bw/d |
Test group 2 50 mg/kg bw/d |
Test group 3 150 mg/kg bw/d |
Litter Fetuses |
N N |
24 229 |
25 224 |
24 201 |
24 206 |
Fetal incidence |
N |
1 (0.4%) |
1 (0.4%) |
2 (1.0%) |
1 (0.5%) |
Litter incidence |
N |
1 (4.2%) |
1 (4.0%) |
1 (4.2%) |
1 (4.2%) |
Affectd fetuses/litter |
Mean % |
0.5 |
0.4 |
1.0 |
0.4 |
Total fetal variations |
|
Test group 0 0 mg/kg bw/d |
Test group 1 15 mg/kg bw/d |
Test group 2 50 mg/kg bw/d |
Test group 3 150 mg/kg bw/d |
Litter Fetuses |
N N |
24 229 |
25 224 |
24 201 |
24 206 |
Fetal incidence |
N |
123 (54%) |
123 (55%) |
110 (55%) |
112 (54%) |
Litter incidence |
N |
24 (100%) |
25 (100%) |
24 (100%) |
24 (100%) |
Affectd fetuses/litter |
Mean % |
53.7 |
55.1 |
54.7 |
53.7 |
mg/kg bw/d = milligram per kilogram body weight per day; N = mumber; % = per cent
Applicant's summary and conclusion
- Conclusions:
- The no observed adverse effect level (NOAEL) for maternal toxicity is 15 mg/kg bw/d based on clinical pathological effects at dose levels of 50 mg/kg bw/d and above, as well as additional clinical findings and a temporarily reduced body weight gain at a dose level of 150 mg/kg bw/d. The no observed adverse effect level (NOAEL) for prenatal developmental toxicity is 150 mg/kg bw/d, the highest tested dose.
- Executive summary:
In this GLP-compliant study performed according to OECD TG 414, the test substance was administered to pregnant Wistar rats daily by stomach tube from implantation to one day prior to expected day of parturition (GD 6 -19). There were no test substance-related effects on the dams concerning mortality, food consumption, gross and corrected (net) body weights, gestational parameters, uterine and placental weights, as well as necropsy observations up to and including a dose of 150 mg/kg bw/day. One individual high-dose dam (No. 88) showed distinct clinical signs of maternal toxicity such as abdominal position; convulsion, twitching and hypersensitivity after treatment on just one occasion during the treatment (GD 7). Although this is only one case, a relation of these findings to the treatment cannot be excluded. Some mid- and high-dose dams showed transient salivation for a few minutes immediately after each treatment, which was likely to be induced by the unpleasant taste of the test substance or by local irritation of the upper digestive tract. It is not considered to be a sign of systemic toxicity. Salivation was not observed after treatment with the low doses. Body weight gain of the high-dose rats was significantly reduced (by 63%) at initiation of treatment (GD 6-8) but recovered afterwards. This temporary, significant reduction is considered to be related to the test compound although it hat no dramatic impact on the average body weight gain throughout the entire treatment phase (GD 6-19). The increase of the red blood cell counts, the hemoglobin as well as the hematocrit values in the dams on GD 20 beginning in the 50 mg/kg bw/d dose group was an indication of hemo-concentration, most probably because of stress. This assumption was confirmed by the increase of the total white blood cell counts, which was due to higher lymphocyte counts, in the rats of the 150 mg/kg bw/d dose group. Correspondingly, the increase of the urea as well as of the cholesterol values in the dams beginning in the 50 mg/kg bw/d dose group can be interpreted as a consequence of stress accompanied by an increased protein metabolism. Additionally, the latter effect can be partly explained by an increased bone metabolism, which was also expressed by increased inorganic phosphate and calcium blood levels in the rats beginning in the 50 mg/kg bw/d dose group. A slight affection of the liver cells in the dams of the 150 mg/kg bw/d dose group was indicated by the increase of the ALT activity. Fetal examinations revealed no influence of the test compound on sex distribution of the fetuses and fetal body weights. The test substance had no direct and specific effect on fetal morphological structures.
In conclusion, the no observed adverse effect level (NOAEL) for maternal toxicity is 15 mg/kg bw/d based on clinical pathological effects at dose levels of 50 mg/kg bw/d and above, as well as additional clinical findings and a temporarily reduced body weight gain at a dose level of 150 mg/kg bw/d. The no observed adverse effect level (NOAEL) for prenatal developmental toxicity is 150 mg/kg bw/d, the highest tested dose.
Information on Registered Substances comes from registration dossiers which have been assigned a registration number. The assignment of a registration number does however not guarantee that the information in the dossier is correct or that the dossier is compliant with Regulation (EC) No 1907/2006 (the REACH Regulation). This information has not been reviewed or verified by the Agency or any other authority. The content is subject to change without prior notice.
Reproduction or further distribution of this information may be subject to copyright protection. Use of the information without obtaining the permission from the owner(s) of the respective information might violate the rights of the owner.

EU Privacy Disclaimer
This website uses cookies to ensure you get the best experience on our websites.