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EC number: 208-704-1 | CAS number: 538-75-0
- 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: dermal
Administrative data
- Endpoint:
- short-term repeated dose toxicity: dermal
- Type of information:
- experimental study
- Adequacy of study:
- weight of evidence
- Study period:
- June 29, 1994 - July 15, 1994
- Reliability:
- 3 (not reliable)
- Rationale for reliability incl. deficiencies:
- significant methodological deficiencies
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 2 007
- Report date:
- 2007
Materials and methods
Test guideline
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 410 (Repeated Dose Dermal Toxicity: 21/28-Day Study)
- Deviations:
- yes
- Remarks:
- Treatment 5 days per week for 16 days. No haemathology or biochemistry analysis.
- GLP compliance:
- yes
- Limit test:
- no
Test material
- Reference substance name:
- Dicyclohexylcarbodiimide
- EC Number:
- 208-704-1
- EC Name:
- Dicyclohexylcarbodiimide
- Cas Number:
- 538-75-0
- Molecular formula:
- C13H22N2
- IUPAC Name:
- N,N'-dicyclohexylcarbodiimide
Constituent 1
- Specific details on test material used for the study:
- SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: Aldrich Chemical Company (Milwaukee, WI), lot 00929TZ
- Purity: 99.5% (determined by GC)
STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: at room temperature, under a nitrogen head space, protected from light
- Stability under test conditions: Periodic analyses of the bulk chemical were performed by the study laboratories during the studies using GC: no degradation of the bulk chemical was detected.
FORM AS APPLIED IN THE TEST (if different from that of starting material)
Dose formulations were prepared by mixing dicyclohexylcarbodiimide and anhydrous ethanol to give the required concentration.
Test animals
- Species:
- mouse
- Strain:
- B6C3F1
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Taconic Laboratory Animals and Services (Germantown, NY).
- Age at study initiation: 8 weeks
- Weight at study initiation: males 25.9 -28.1 g; females 19.9 - 21.3 g
- Fasting period before study: not specified
- Housing: individually housed
- Diet: ad libitum, NIH-07 open formula pelleted diet (Zeigler Brothers, Inc., Gardners, PA),
- Water: ad libitum, tap water (Washington Suburban Sanitary Commission Potomac Plant)
- Acclimation period: 20 days
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22.22 ± 0.16 ºC
- Humidity (%): 35-65%
- Air changes (per hr): at least 10 changes per hour
- Photoperiod (hrs dark / hrs light): 12 hours light/12 hours dark
Administration / exposure
- Type of coverage:
- not specified
- Vehicle:
- ethanol
- Details on exposure:
- TEST SITE
- Area of exposure: clipped dorsal skin, from the posterior of the scapulae to the base of the tail
- % coverage: not specified
- Type of wrap if used: not specified.
REMOVAL OF TEST SUBSTANCE: not specified
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0, 0.2, 0.6, 1.7, 5, or 15 mg/animal in 0.1 ml ethanol
- Concentration (if solution): 0, 2, 6, 17, 50, or 150 mg dicyclohexylcarbodiimide per ml of ethanol. 0.6 mg/animal approximately corresponded to 24 mg/kg body weight.
- For solids, paste formed: no, test substance was diluted in anhydrous ethanol to give the required concentration
VEHICLE
- Vehicle (if other than water): anhydrous ethanol
- Amount(s) applied (volume or weight with unit): 0.1 ml
- Lot/batch no. (if required): not specified
- Purity: greater than 99.9 %
PREPARATION OF DOSING SOLUTIONS
- A weighed amount of dicyclohexylcarbodiimide was dissolved in absolute ethanol to prepare the highest dose concentration formulation; lower dose formulations were prepared by diluting aliquots of this preparation with absolute ethanol. Dose formulations were prepared twice. The dose formulations were stored in sealed vials under a headspace of inert gas for up to 28 days at room temperature. Stability studies of 0.38, 2, and 7 mg/ml dose formulations of lot 00929TZ were conducted by the study laboratory using GC. Stability was confirmed for up to 35 days for dose formulations stored at room temperature in sealed containers under a nitrogen headspace and for up to 3 hours when exposed to light and air at room temperature. - Analytical verification of doses or concentrations:
- yes
- Details on analytical verification of doses or concentrations:
- Dose formulations were prepared twice during the study and were analyzed once by GC . All five dose formulations were within 10% of the target concentrations.
- Duration of treatment / exposure:
- 16 days
- Frequency of treatment:
- 5 days per week
Doses / concentrationsopen allclose all
- Dose / conc.:
- 0 other: mg / animal
- Remarks:
- control group
- Dose / conc.:
- 0.2 other: mg / animal
- Dose / conc.:
- 0.6 other: mg / animal
- Remarks:
- ca. 24 mg/kg bw
- Dose / conc.:
- 1.7 other: mg / animal
- Dose / conc.:
- 5 other: mg / animal
- Dose / conc.:
- 15 other: mg / animal
- No. of animals per sex per dose:
- 5 males and 5 females per dose
- Control animals:
- yes, concurrent vehicle
- Details on study design:
- - Rationale for animal assignment: animals were distributed randomly into groups of approximately equal initial mean body weights.
Examinations
- Observations and examinations performed and frequency:
- CAGE SIDE OBSERVATIONS: Yes
- Time schedule: twice daily
DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: clinical findings (including dermal irritation) were recorded initially, on day 8 and at the end of the studies.
BODY WEIGHT: Yes
- Time schedule for examinations: animals were weighed initially, on day 8 and at the end of the studies
FOOD CONSUMPTION: No data
FOOD EFFICIENCY: No data
WATER CONSUMPTION: No data
OPHTHALMOSCOPIC EXAMINATION: No data
HAEMATOLOGY: No data
CLINICAL CHEMISTRY: No data
URINALYSIS: No data
NEUROBEHAVIOURAL EXAMINATION: No data - Sacrifice and pathology:
- GROSS PATHOLOGY: Yes
Necropsies were performed on all animals. Organs weighed were the adrenal gland, heart, right kidney, liver, lung, right testis, and thymus.
HISTOPATHOLOGY: Yes
Histopathology was performed on vehicle control, 0.2, 0.6 and 1.7 mg/animal mice. In addition to gross lesions and tissue masses, the following tissues were examined: brain, kidney, liver, lung, skin, and spinal cord. - Statistics:
- Organ and body weight data, which historically have approximately normal distributions, were analyzed with the parametric multiple comparison procedures of Dunnett (1955) and Williams (1971, 1972).
Results and discussion
Results of examinations
- Clinical signs:
- effects observed, treatment-related
- Description (incidence and severity):
- Clinical signs of toxicity at doses of 0.6 mg or greater.
- Dermal irritation:
- effects observed, treatment-related
- Description (incidence and severity):
- Skin irritation at the site of application in all dosed groups.
- Mortality:
- mortality observed, treatment-related
- Description (incidence):
- One 0.6 mg female mouse and all mice in the 1.7, 5, and 15 mg groups died before the end of the study.
- Body weight and weight changes:
- effects observed, treatment-related
- Description (incidence and severity):
- Final mean body weights of the 0.6 mg groups were significantly less than those of the vehicle controls, and animals in these groups generally lost weight during the study.
- Food consumption and compound intake (if feeding study):
- not specified
- Food efficiency:
- not examined
- Water consumption and compound intake (if drinking water study):
- not examined
- Ophthalmological findings:
- not examined
- Haematological findings:
- not examined
- Clinical biochemistry findings:
- not examined
- Urinalysis findings:
- not examined
- Behaviour (functional findings):
- no effects observed
- Immunological findings:
- not examined
- Organ weight findings including organ / body weight ratios:
- effects observed, treatment-related
- Description (incidence and severity):
- Heart weights of 0.6 mg groups of mice were significantly greater than those of the vehicle controls; thymus weights in these groups were significantly less than those of the vehicle controls.
- Gross pathological findings:
- no effects observed
- Neuropathological findings:
- not examined
- Histopathological findings: non-neoplastic:
- effects observed, treatment-related
- Description (incidence and severity):
- Histopathologic examination of mice dosed with 1.7 mg dicyclohexylcarbodiimide or less revealed lesions of the skin at the site of application including epidermal hyperplasia, epidermal necrosis, and acute or chronic active dermal inflammation (data not shown).
- Histopathological findings: neoplastic:
- no effects observed
- Other effects:
- no effects observed
- Details on results:
- At a dose of 0.6 mg or greater, clinical signs of toxicity appeared. Final mean body weights were significantly lower than the control, heart weights were significantly greater and thymus weights were significantly lower.
Effect levels
- Key result
- Dose descriptor:
- NOAEL
- Effect level:
- 0.2 other: mg/animal
- Based on:
- act. ingr.
- Sex:
- male/female
- Basis for effect level:
- clinical signs
- mortality
- Remarks on result:
- other: ca. 8 mg/kg bw
Target system / organ toxicity
- Key result
- Critical effects observed:
- no
Any other information on results incl. tables
Table 1. Survival and body weights of B6C3F1 mice.
Dose mg/animal |
Survival |
Mean body weight |
Final weight Relative to controls (%) |
||
Initial |
Final |
Change |
|||
MALE |
|||||
0 |
5/5 |
27.0 ± 1.1 |
28.8 ± 1.1 |
1.8 ± 0.0 |
|
0.2 |
5/5 |
26.7 ± 0.7 |
28.3 ± 0.5 |
1.6 ± 0.3 |
98 |
0.6 |
5/5 |
27.0 ± 0.5 |
26.0 ± 0.5* |
-1.0 ± 0.4 * |
90 |
1.7 |
0/5 |
26.5 ± 0.6 |
- |
- |
|
5 |
0/5 |
26.6 ± 0.7 |
- |
- |
|
15 |
0/5 |
26.5 ± 0.7 |
- |
- |
|
FEMALE |
|||||
0 |
5/5 |
20.6 ± 0.6 |
24.0 ± 0.5 |
3.4 ± 0.3 |
|
0.2 |
5/5 |
20.4 ± 0.5 |
23.9 ± 0.4 |
3.5 ± 0.4 |
100 |
0.6 |
4/5 |
20.8 ± 0.7 |
21.3 ± 0.8 * |
-0.1 ± 0.5* |
89 |
1.7 |
0/5 |
21.0 ± 0.3 |
- |
- |
|
5 |
0/5 |
20.8 ± 0.3 |
- |
- |
|
15 |
0/5 |
20.6 ± 0.6 |
- |
- |
|
* Significantly different from the vehicle control group by Dunnett’s or Williams’ test
Applicant's summary and conclusion
- Conclusions:
- The NOAEL for the test substance was 0.2 mg/animal (ca. 8 mg/kg bw) in male and females mice after 16 days of dermal exposure.
- Executive summary:
Groups of five male and five female mice were dermally treated with 0.1 ml ethanol containing 0, 0.2, 0.6, 1.7, 5 or 15 mg dicyclohexylcarbodiimide, 5 days per week (16 days of dosing). The control animals were treated with the vehcicle only (ethanol). One 0.6 mg female mouse and all mice in the 1.7, 5, and 15 mg groups died before the end of the study. Final mean body weights of the 0.6 mg groups were significantly less than those of the vehicle controls, and animals in these groups generally lost weight during the study. Clinical findings included skin irritation at the site of application in all dosed groups and clinical signs of toxicity at doses of 0.6 mg or greater. Heart weights of 0.6 mg groups of mice were significantly greater than those of the vehicle controls; thymus weights in these groups were significantly less than those of the vehicle controls. Histopathologic examination of mice dosed with 1.7 mg dicyclohexylcarbodiimide or less revealed lesions of the skin at the site of application including epidermal hyperplasia, epidermal necrosis, and acute or chronic active dermal inflammation. Based on these results, the NOAEL for the test substance was 0.2 mg/animal (ca. 8 mg/kg bw) in male and females mice after 16 days of dermal exposure.
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