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EC number: 800-003-4 | CAS number: 1415316-96-9
- 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
Specific investigations: other studies
Administrative data
- Endpoint:
- mechanistic studies
- Type of information:
- experimental study
- Adequacy of study:
- supporting study
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: Well-documented mechanistic investigation which meets basic scientific principles
Data source
Referenceopen allclose all
- Reference Type:
- publication
- Title:
- Diethanolamine Induces Hepatic Choline Deficiency in Mice
- Author:
- Lehman-McKeeman, L.D. et al.
- Year:
- 2 002
- Bibliographic source:
- Toxicological sciences 67, 39-45 (2002)
- Reference Type:
- publication
- Title:
- TOXICOLOGICAL HIGHLIGHT Choline Deficiency Associated with Diethanolamine Carcinogenicity
- Author:
- Newberne, P.M.
- Year:
- 2 002
- Bibliographic source:
- Toxicological Sciences 67, 1-3
Materials and methods
Test guideline
- Qualifier:
- no guideline followed
- Principles of method if other than guideline:
- A subacute screening study on effects of dermally administered DEA on choline (Cho) and metabolites (phosphocholine (PCho); glycerophosphocholine (GCP); phosphatidylcholine (PC); s-adenosylmethionine (SAM); s-adenosylhomocysteine (SAH) was examined in groups of 6 – 8 male mice of two different strains.
- GLP compliance:
- not specified
- Type of method:
- in vivo
- Endpoint addressed:
- carcinogenicity
Test material
- Reference substance name:
- 2,2'-iminodiethanol
- EC Number:
- 203-868-0
- EC Name:
- 2,2'-iminodiethanol
- Cas Number:
- 111-42-2
- Molecular formula:
- C4H11NO2
- IUPAC Name:
- 2,2'-iminodiethanol
- Details on test material:
- DEA (99% purity) was obtained ftom Aldrich Chemical Co. (Milwaukee, WI) . Absolute ethanol (Aaper Alcohol and Chemical Co., Shelbyville, KY) was used to prepare 95% ethanol used as the vehicle in these studies. Betaine (HCl salt) was obtained from Aldrich, SAM and SAH were obtained from Sigma Chemical Co. (St. Louis, MO), and all standards for choline analyses were as described by Fornfict el al. (1989) .
Constituent 1
Test animals
- Species:
- mouse
- Strain:
- other: B6C3F1 and C57BL6
- Sex:
- male
- Details on test animals or test system and environmental conditions:
- Male B6C3F1 mice, approximately 5 weeks of age at receipt, mice were housed in a temperature- and humidity-controlled environment and acclimated for approximately 1 week prior to study initiation. Unless otherwise noted, were allowed rodent chow (Purina 5001 ; Ralston-Purina. St. Louis, MO) and water ad libitum throughout the study. Dietary concentrations of choline and methionine in the Purina diet were 0.2 and 0.4%, respectively, whereas the fat composition was approximately 5%.
The same holds true for the male C57BL/6 mice.
DIETARY CHOLINE DEFICIENCY
Male B6C3F1 and C57BL6 mice (approximately 6-weeks old at study initiadon) were allowed ad libitum exposure to a control or choline-devoid diet (Dyets, Bethlehem, PA) for a period of 2 weeks (n = 8/group). The control diet contained 0.25% choline (as choline bitartrate) and the methionine content in the control and choline-devoid diets was 0.6% . At the end of the 2-week exposure period, livers were rapidly removed under anesthesia, immediately flash-frozen in liquid N, and stored at -80°C pending analysis of choline metabolites. In a separate group of mice (n - 4/group), blood was collected for clinical chemistry analyses, and livers were weighed and fixed in 10% neutral buffered formalin for histopathological assessment.
Administration / exposure
- Route of administration:
- dermal
- Vehicle:
- ethanol
- Details on exposure:
- For dosing, the backs of all mice were shaved, and the dosing solutions (1.8 ml/kg) were applied to a region approximately 2 cm2 (from the mid-back to the interscapular region) using a pipette . All mice, including the untreated controls, were shaved on an as-needed basis during the study period . At the end of the dosing or recovery period, livers were harvested as described above and analyzed for choline metabolites.
To evaluate potential strain differences in the response to DEA, male C57BL/6 mice, also about 6-weeks-old at study initiation, were dosed with 0 or 160 mg, DEA/kg for a similar 4-week period. The untreated and ethanol-treated control groups were also used in this study. - Analytical verification of doses or concentrations:
- not specified
- Duration of treatment / exposure:
- 4 weeks
- Frequency of treatment:
- 5 days/week
Doses / concentrations
- Remarks:
- Doses / Concentrations:
10, 20, 40, 80 and 160 mg/kg
Basis:
- No. of animals per sex per dose:
- 6
- Control animals:
- yes, concurrent vehicle
- Details on study design:
- Male B6C3F1 mice (approximately 6-weeks old at study initiation) were housed individually and dosed dermally with DEA dissolved in 95% ethanol at 0, 10, 20, 40, 80, or 160 mg/kg (n = 6/group) for a period of 4 weeks (5 days/week). These dosages were selected to include those shown to be carcinogenic (40, 80, and 160 mg/kg/day; NTP, 1999). There were 2 control groups for this study including untreated and ethanol treated mice. A separate group of mice was dosed with the ethanol vehicle or 160 mg DEA/kg/day for 4 weeks (5 days/week) and then allowed a 2-week recovery prior to necropsy . For dosing, the backs of all mice were shaved, and the dosing solutions (1.8 ml/kg) were applied to a region approximately 2 cm2 (from the mid-back to the interscapular region) using a pipette . All mice, including the untreated controls, were shaved on an as-needed basis during the study period . At the end of the dosing or recovery period, livers were harvested as described above and analyzed for choline metabolites.
To evaluate potential strain differences in the response to DEA, male C57BL/6 mice, also about 6-weeks-old at study initiation, were dosed with 0 or 160 mg, DEA/kg for a similar 4 -week period. The untreated and ethanol-treated control groups were also used in this study.
Examinations
- Examinations:
- Analysis of hepatic choline metabolites
Results and discussion
- Details on results:
- After dermal treatment of B6C3F1 mice with DEA at 0, 10, 20, 40, 80, 160 mg/kg bw/day for 4 weeks, PCho was most sensitive to DEA treatment, decreasing at ≥20 mg/kg bw/day. GPC, choline, and PC also decreased in a dose-dependent manner. At ≥80 mg/kg bw/day, SAM levels decreased, while SAH levels increased in liver. The no-observed effect level (NOEL) for DEA induced changes was 10 mg/kg bw/day. Choline metabolites, SAM and SAH returned to control levels in mice allowed a 2-week recovery period. No fatty change was observed in the liver of DEA treated mice in a manner similar to dietary choline deficiency. In C57BL/6 mice, DEA treatment also decreased PCho concentrations, without affecting hepatic SAM levels. Dermal application of 95% ethanol for 4 weeks alone decreased hepatic betaine levels, suggesting that the use of ethanol as a vehicle for dermal application of DEA may exacerbate or confound the biochemical actions of DEA.
Any other information on results incl. tables
Effect of dietary choline deficiency on hepatic choline metabolites
Parameter |
Control |
Choline-devoid |
Body weight (g) |
24.8±0.4 |
24.9±0.6 |
Liver/BW (%) |
5.1±0.1 |
4.8±0.1 |
PCho (nmol/g liver) |
1146±100 |
297±53 |
GPC (nmol/g liver) |
615±83 |
460±27 |
Cho (nmol/g liver) |
139±4 |
95±18 |
PC (umol/g liver) |
16.6±1.6 |
15.2±0.6 |
SAM (nmol/g liver) |
69.2±4.2 |
56.8±3.3 |
SAH (nmol/g liver) |
31.8±2.3 |
41.1±2.4 |
Effect of DEA Treatment on Hepatic Choline Metabolites
|
DEA (mg/kg/day) |
||||||
Parameter |
0 |
10 |
20 |
40 |
80 |
160 |
160-R |
Body weight (g) |
26.6±0.8 |
25.9±0.4 |
26.6±0.1 |
25.8±0.4 |
26.1±0.4 |
27.1±0.6 |
25.8±0.8 |
Liver/BW (%) |
5.6±0.1 |
5.6±0.1 |
5.7±0.1 |
5.5±0.1 |
5.5±0.1 |
6.2±0.1 |
5.5±0.1 |
PCho (nmol/g liver) |
1220±44 |
1192±77 |
994±78 |
959±70 |
831±52 |
615±37 |
1224±114 |
GPC (nmol/g liver) |
372±34 |
463±34 |
303±32 |
275±14 |
281±23 |
193±20 |
318±38 |
Cho (nmol/g liver) |
155±14 |
137±12 |
152±11 |
126±7 |
94±14 |
106±13 |
180±21 |
PC (umol/g liver) |
19.6±1.0 |
17.7±1.0 |
17.0±0.4 |
18.0±1.0 |
17.4±0.8 |
16.8±0.4 |
17.7±0.7 |
SAM (nmol/g liver) |
83.9±1.1 |
84.1±4.1 |
84.7±3.9 |
82.1±7.2 |
65.1±6.4 |
53.3±4.3 |
84.9±1.0 |
SAH (nmol/g liver) |
48.1±1.9 |
52.2±6.2 |
49.1±1.8 |
52.6±1.4 |
61.8±4.4 |
58.5±2.7 |
46.1±4.2 |
Applicant's summary and conclusion
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.
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