Dicyclohexylcarbodiimide

206.33

206.33

610662

208-704-1

0T1427205E

57182|53373|30022

2811

DTXSID1023817

Crystalline mass|White crystals|Colorless crystalline solid

29252000

24.7

4.7

White to pale yellow Waxy Solid or Crystalline Mass

1.325

34.5 °C

154-156 °C

190 °F

1.567

Solubility in water: reaction.methylene chloride: 0.1 g/mL, clear, colorless

Store at RT.

3.39X10-3 mm Hg at 25 deg C (est)

LD50 orally in Rabbit: 1110 mg/kg LD50 dermal Rat 71 mg/kg

Heavy sweet odor

Set point = 29-30 °C|Incompatible with acids and oxidizers; emits toxic fumes when combusted|Hydroxyl radical reaction rate constant = 2.0X10-11 cu cm/molecule-sec at 25 °C (est)

May be sensitive to moisture.

Amines, Phosphines, and Pyridines

N,N'-DICYCLOHEXYLCARBODIIMIDE is an amine. This compound is incompatible with acids and oxidizing agents. It reacts with water. (NTP, 1992)

Corrosive to tissue

Ⅱ

6.1

UN 2922 8/PG 2

3

23/24/25-34-40-43-41-36/38-21-24-22-62-37/38-10-61-26-38-20/22

26-36/37/39-45-41-24-37/39-24/25-36-16-53-28

FF2160000

T,Xn,T+

Stable, but moisture sensitive. Combustible. Incompatible with strong oxidizing agents. Avoid exposure to air or moisture.

P260-P280-P301 + P312 + P330-P305 + P351 + P338 + P310

H302 + H312-H315-H317-H318-H335-H336-H351-H373

SRP: The most favorable course of action is to use an alternative chemical product with less inherent propensity for occupational harm/injury/toxicity or environmental contamination. Recycle any unused portion of the material for its approved use or return it to the manufacturer or supplier. Ultimate disposal of the chemical must consider: the material's impact on air quality; potential migration in soil or water; effects on animal and plant life; and conformance with environmental and public health regulations.

This chemical is probably combustible. (NTP, 1992)

|Danger|H302: Harmful if swallowed [Warning Acute toxicity, oral]|P261, P264, P270, P272, P280, P301+P312, P302+P352, P305+P351+P338, P310, P312, P321, P322, P330, P333+P313, P361, P363, P405, and P501|H302 (100%): Harmful if swallowed [Warning Acute toxicity, oral]|P260, P261, P264, P270, P271, P272, P280, P284, P301+P312, P301+P330+P331, P302+P352, P303+P361+P353, P304+P340, P305+P351+P338, P310, P312, P320, P321, P322, P330, P333+P313, P361, P363, P403+P233, P405, and P501|Aggregated GHS information provided by 359 companies from 9 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.|P260, P261, P264, P270, P271, P272, P280, P284, P301+P312, P302+P352, P304+P340, P305+P351+P338, P309+P311, P310, P320, P321, P330, P332+P313, P333+P313, P362, P363, P403+P233, P405, and P501

Fires involving this material can be controlled with a dry chemical, carbon dioxide or Halon extinguisher. (NTP, 1992)

Excerpt from ERG Guide 154 [Substances - Toxic and/or Corrosive (Non-Combustible)]: As an immediate precautionary measure, isolate spill or leak area in all directions for at least 50 meters (150 feet) for liquids and at least 25 meters (75 feet) for solids. SPILL: Increase, in the downwind direction, as necessary, the isolation distance shown above. FIRE: If tank, rail car or tank truck is involved in a fire, ISOLATE for 800 meters (1/2 mile) in all directions; also, consider initial evacuation for 800 meters (1/2 mile) in all directions. (ERG, 2016)

SMALL SPILLS AND LEAKAGE: Should a spill occur while you are handling this chemical, FIRST REMOVE ALL SOURCES OF IGNITION, then you should dampen the solid spill material with 60-70% ethanol and transfer the dampened material to a suitable container. Use absorbent paper dampened with 60-70% ethanol to pick up any remaining material. Seal the absorbent paper, and any of your clothes, which may be contaminated, in a vapor-tight plastic bag for eventual disposal. Solvent wash all contaminated surfaces with 60-70% ethanol followed by washing with a soap and water solution. Do not reenter the contaminated area until the Safety Officer (or other responsible person) has verified that the area has been properly cleaned. STORAGE PRECAUTIONS: You should keep this material in a tightly closed container under an inert atmosphere, and store it at refrigerated temperatures. (NTP, 1992)

MINIMUM PROTECTIVE CLOTHING: If Tyvek-type disposable protective clothing is not worn during handling of this chemical, wear disposable Tyvek-type sleeves taped to your gloves. RECOMMENDED RESPIRATOR: Where the neat test chemical is weighed and diluted, wear a NIOSH-approved half face respirator equipped with an organic vapor/acid gas cartridge (specific for organic vapors, HCl, acid gas and SO2) with a dust/mist filter. Splash proof safety goggles should be worn while handling this chemical. Alternatively, a full face respirator, equipped as above, may be used to provide simultaneous eye and respiratory protection. (NTP, 1992)

LD50 Rat oral 400 mg/kg|LC50 Rat inhalation 159 mg/cu m/6 hr|LD50 Rat intraperitoneal 10 mg/kg|LD50 Mouse intraperitoneal >800 mg/kg|For more Non-Human Toxicity Values (Complete) data for Dicyclohexylcarbodiimide (6 total), please visit the HSDB record page.

Groups of 15 female p53 Haploinsufficient mice were dermally administered 0, 0.75, 1.5, 3, 6, or 12 mg dicyclohexylcarbodiimide/kg body weight in ethanol, 5 days per week for up to 27 weeks. Dosing of the 6 and 12 mg/kg groups was discontinued after 11 and 8 days, respectively, because of the severity of skin lesions at the site of application. Twelve animals died or were sacrificed moribund prior to the end of the study: three from the 3 mg/kg group, one from the 6 mg/kg group, and eight from the 12 mg/kg group. Mean body weights of dosed groups of mice were similar to those of the vehicle controls. No neoplasms were attributed to administration of dicyclohexylcarbodiimide. At the site of application, the incidences of focal epidermal hyperplasia were significantly increased in 1.5, 3, and 12 mg/kg mice, the incidences of focal chronic active inflammation of the dermis were increased in groups administered 3 or 12 mg/kg, and the incidences of focal ulcer and focal chronic active inflammation of the subcutaneous tissue were increased in the 12 mg/kg group.|Groups of 10 female Tg.AC hemizygous mice were dermally administered 0, 0.75, 1.5, 3, 6, or 12 mg dicyclohexylcarbodiimide/kg body weight in ethanol, 5 days per week for up to 20 weeks. Due to the severity of skin lesions observed in 12 mg/kg animals, the application of dicyclohexylcarbodiimide was discontinued after eight dermal applications in this group. There were no deaths considered related to dicyclohexylcarbodiimide administration, although 13 animals died or were sacrificed moribund prior to the end of the study: three each from the vehicle control and 0.75 mg/kg groups, four from the 3 mg/kg group, two from the 6 mg/kg group, and one from the 12 mg/kg group. Overall, the survival was within the range known for the Tg.AC hemizygous mouse. Mean body weights of dosed groups of mice were similar to those of the vehicle controls. At the site of application, the incidences of squamous cell papilloma were increased in a dose-related manner. The incidences of chronic active inflammation of the dermis and epidermal hyperplasia were significantly increased in mice administered 3 or 6 mg/kg.|Groups of 10 male and 10 female B6C3F1 mice were dermally administered 0, 1.5, 3, 6, 12, or 24 mg dicyclohexylcarbodiimide/kg body weight in ethanol, 5 days per week for 13 weeks. All 24 mg/kg male and female mice died or were found moribund and sacrificed prior to day 16. Final mean body weights of 6 and 12 mg/kg males and mean body weight gains of 6 and 12 mg/kg males and females were significantly less than those of the vehicle controls. The predominant clinical pathology changes suggest a secondary, treatment-related inflammatory leukogram and minimal decreased erythron of chronic inflammation that would be consistent with necrosis and chronic active inflammation of the skin. Dermal administration of dicyclohexylcarbodiimide significantly decreased the weight of the epididymis in 6 and 12 mg/kg males and significantly decreased epididymal spermatozoal motility in 6 mg/kg males. Significantly increased incidences of skin lesions at the site of application included epidermal hyperplasia in all dosed groups except those administered 24 mg/kg, chronic active inflammation in all dosed groups except 1.5 mg/kg females, and epidermal necrosis in 24 mg/kg males and females.|Groups of 10 male and 10 female F344/N core study rats were dermally administered 0, 0.75, 1.5, 3, 6, or 12 mg dicyclohexylcarbodiimide/kg body weight in ethanol, 5 days per week for 13 weeks; groups of 10 male and 10 female clinical pathology study rats were administered the same doses for 22 days. All 12 mg/kg male and female core study rats died or were found moribund and sacrificed prior to day 45. Final mean body weight and body weight gain of 6 mg/kg males were significantly less than those of the vehicle controls. The predominant clinical pathology changes suggest a secondary, treatment-related inflammatory leukogram and minimal decreased erythron of chronic inflammation that would be consistent with necrosis and chronic active inflammation of the skin. Significantly increased incidences of skin lesions at the site of application included epidermal hyperplasia in 3 mg/kg or greater males and 1.5 mg/kg or greater females, chronic active inflammation in 6 and 12 mg/kg males and 1.5 mg/kg or greater females, and epidermal necrosis in 12 mg/kg males. The incidences and severities of epidermal hyperplasia increased in a dose-related manner in both sexes of rats.|For more National Toxicology Program Studies (Complete) data for Dicyclohexylcarbodiimide (6 total), please visit the HSDB record page.

Dicyclohexylcarbodiimide's production and use in industry as a stabilizing agent, coupling agent, condensing agent and widespread use during protein synthesis in the recombinant DNA industry and in the synthesis of polypeptides in the chemical and pharmaceutical industries(1) may result in its release to the environment through various waste streams(SRC).

TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 3X10+4(SRC), determined from a structure estimation method(2), indicates that dicyclohexylcarbodiimide is expected to have slight mobility in soil(SRC). However, dicyclohexylcarbodiimide reacts with water(3); in moist soils, dicyclohexylcarbodiimide can react (hydrate) to form dicyclohexylurea which has an estimated Koc of about 100(2) indicating high mobility in soil(1) for this degradation product(SRC). Volatilization of dicyclohexylcarbodiimide from moist soil surfaces is not expected to be an important fate process since the compound reacts with water(SRC). A 0-1% of theoretical BOD using activated sludge in the Japanese MITI test(4) suggests that biodegradation is not an important environmental fate process in soil(SRC).|AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 3X10+4(SRC), determined from a structure estimation method(2), indicates that dicyclohexylcarbodiimide is expected to adsorb to suspended solids and sediment(SRC). However, dicyclohexylcarbodiimide reacts with water to form dicyclohexylurea(3). Therefore, adsorption to sediment and volatilization from water are not expected to be an important fate processes(SRC). According to a classification scheme(4), measured BCF values of <0.2 to <2.2 for carp (Carprinus carpio)(5) suggests bioconcentration in aquatic organisms is low(SRC). A 0-1% of theoretical BOD using activated sludge in the Japanese MITI test(5) suggests that biodegradation is not an important environmental fate process(SRC).|ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), dicyclohexylcarbodiimide, which has an estimated vapor pressure of 3.39X10-3 mm Hg at 25 °C(SRC), determined from a fragment constant method(2), is expected to exist solely as a vapor in the ambient atmosphere. Vapor-phase dicyclohexylcarbodiimide is degraded in the atmosphere by reaction with photochemically-produced hydroxyl radicals(SRC); the half-life for this reaction in air is estimated to be 19 hours(SRC), calculated from its rate constant of 4.4X10-11 cu cm/molecule-sec at 25 °C(SRC) that was derived using a structure estimation method(2). Dicyclohexylcarbodiimide is moisture sensitive and reacts with water(3); therefore, removal from air may occur through contact with water vapor or precipitation(SRC).

The rate constant for the vapor-phase reaction of dicyclohexylcarbodiimide with photochemically-produced hydroxyl radicals has been estimated as 4.4X10-11 cu cm/molecule-sec at 25 °C(SRC) using a structure estimation method(1). This corresponds to an atmospheric half-life of about 19 hours at an atmospheric concentration of 5X10+5 hydroxyl radicals per cu cm(1). Dicyclohexylcarbodiimide is reported to be moisture sensitive and it reacts with water(2); dicyclohexylcarbodiimide hydrates in water to form dicyclohexylurea.

Dicyclohexylcarbodiimide BCF values of <0.2 to <2.2 were measured for carp (Carprinus carpio) exposed to 0.1 mg/L and 1 mg/L dicyclohexylcarbodiimide over a 6 week exposure period(1). According to a classification scheme(2), these BCF values suggests bioconcentration in aquatic organisms is low(SRC). Since dicyclohexylcarbodiimide reacts with water(3), bioconcentration in aquatic organisms is not expected to be an important fate process(SRC).

Using a structure estimation method based on molecular connectivity indices(1), the Koc of dicyclohexylcarbodiimide can be estimated to be 3X10+4(SRC). According to a classification scheme(2), this estimated Koc value suggests that dicyclohexylcarbodiimide is expected to have slight mobility in soil. Dicyclohexylcarbodiimide reacts with water(3); in moist soils, dicyclohexylcarbodiimide can react (hydrate) to form dicyclohexylurea which has an estimated Koc of about 100(1) indicating high mobility in soil(2).

Dicyclohexylcarbodiimide reacts with water(1); therefore, volatilization from water or moist soil is not expected to be an important fate process(SRC). Dicyclohexylcarbodiimide has an estimated vapor pressure of 3.39X10-3 mm Hg at 25 °C(SRC), determined from a fragment constant method(2). Although this vapor pressure suggests little or no environmental importance of volatilization from dry soil(SRC), dicyclohexylcarbodiimide has a heavy sweet odor and presents a vapor-inhalation risk to humans(1); therefore, some volatization from dry surfaces may occur(SRC).

NIOSH (NOES Survey 1981-1983) has statistically estimated that 28 workers (0 of these were female) were potentially exposed to dicyclohexylcarbodiimide in the US(1). Occupational exposure to dicyclohexylcarbodiimide may occur primarily through dermal contact with this compound at workplaces where dicyclohexylcarbodiimide is produced or used, but exposure through inhalation of vapor can also occur(SRC). Human exposure to dicyclohexylcarbodiimide could occur during handling of the compound that occurs during the synthesis of peptides and other compounds in the chemical, pharmaceutical, and recombinant DNA industries(2). Occupational contact dermatitis to dicyclohexylcarbodiimide has been reported in research laboratory workers since the late 1950s(2); occupational exposure through inhalation of vapors can also occur(2).

The molecular mechanism of the electroneutral organic cation/H+ antiporter in renal brush border membrane vesicles was studied utilizing the prototypic organic cation N1-methylnicotinamide. The hydrophobic carbodiimide, N,N'-dicyclohexylcarbodiimide (DCCD), inactivated organic cation transport irreversibly with an IC50 of 2.6 microM at pH 7.5 and 40 nM at pH 6.0. On the other hand, the hydrophilic reagents, 1-ethyl-3-[3-(dimethylamino)-propyl]carbodiimide and N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline, did not affect organic cation transport. Substrate did not affect the rate of the DCCD inactivation which followed pseudo-first-order-kinetics. A double logarithmic plot of the apparent rate constants vs. the DCCD concentration gave a straight line with a slope of 0.8. The data are consistent with a simple bimolecular reaction mechanism and imply that one molecule of DCCD inactivates one carboxylate group per active transport unit and that the carboxylate group is critical for transport.|The hydrophobic carbodiimide dicyclohexylcarbodiimide (DCCD) has been shown to inhibit the catalytic (C) subunit of adenosine cyclic 3',5'-phosphate dependent protein kinase (EC 2.7.1.3) in a time-dependent, irreversible manner. The rate of inactivation was first order and showed saturation kinetics with an apparent Ki of 60 microM. Magnesium adenosine 5'-triphosphate (MgATP) was capable of protecting against this inhibition, whereas neither a synthetic peptide substrate nor histone afforded protection. Mg alone afforded some protection. When the catalytic subunit was aggregated with the regulatory subunit in the holoenzyme complex, no inhibition was observed. The inhibition was enhanced at low pH, suggesting that a carboxylic acid group was the target for interaction with DCCD. On the basis of the protection studies, it is most likely that this carboxylic acid group is associated with the MgATP binding site, perhaps serving as a ligand for the metal. Efforts to identify the site that was modified by DCCD included (1) modification with [14C]DCCD, (2) modification by DCCD in the presence of [3H]aniline, and (3) modification with DCCD and [14C]glycine ethyl ester. In no case was radioactivity incorporated into the protein, suggesting that the irreversible inhibition was due to an intramolecular cross-link between a reactive carboxylic acid group and a nearby amino group. Differential peptide mapping identified a single peptide that was consistently lost as a consequence of DCCD inhibition. This peptide (residues 166-189) contained four carboxylic acid residues as well as an internal Lys.|Dicyclohexylcarbodiimide (DCCD) specifically inhibits the F1F0-H+-ATP synthase complex of Escherichia coli by covalently modifying a proteolipid subunit that is embedded in the membrane. Multiple copies of the DCCD-reactive protein, also known as subunit c, are found in the F1F0 complex. ...|A spontaneous mutant of Methanothermobacter thermautotrophicus resistant toward the ATP-synthase inhibitor N,N'-dicyclohexylcarbodiimide (DCCD) was isolated. DCCD normally inhibits methanogenic electron-transport-driven ATP synthesis, however, the DCCD-resistant strain exhibited methanogenesis in the presence of 300 micromol/L DCCD. Total ATP synthesis was shown to be higher in the mutant strain, both in the presence and absence of DCCD. These results suggested a modification in the ATP-synthesizing system of the mutant strain. Using Blue Native PAGE combined with MALDI TOF/TOF mass spectrometry, increased concentrations of both the A(1) and A(o) subcomplexes of the A(1)A(o)-type synthase were identified in the mutant strain. However, no alterations were found in the structural genes (atp) for the A(1)A(o) ATP synthase. The results imply that DCCD resistance is a consequence of increased A(1)A(o) ATP synthase expression, and suggest that genes involved in regulating synthase expression are responsible for DCCD resistance.

SYMPTOMS: Symptoms of exposure to this compound may include skin irritation and sensitization, severe eye irritation, irritation of the mucous membranes and upper respiratory tract, and subsequent allergic reactions. It can cause severe destruction of tissue, depending on the intensity and duration of exposure. ACUTE/CHRONIC HAZARDS: This compound is highly toxic by inhalation. It is an irritant of the skin, mucous membranes and upper respiratory tract, and is a severe irritant of the eyes. It can be corrosive to tissues if exposure is in high concentrations or over extended periods of time. When heated to decomposition it emits toxic fumes of carbon monoxide, carbon dioxide, and NOx. (NTP, 1992)

EYES: First check the victim for contact lenses and remove if present. Flush victim's eyes with water or normal saline solution for 20 to 30 minutes while simultaneously calling a hospital or poison control center. Do not put any ointments, oils, or medication in the victim's eyes without specific instructions from a physician. IMMEDIATELY transport the victim after flushing eyes to a hospital even if no symptoms (such as redness or irritation) develop. SKIN: IMMEDIATELY flood affected skin with water while removing and isolating all contaminated clothing. Gently wash all affected skin areas thoroughly with soap and water. IMMEDIATELY call a hospital or poison control center even if no symptoms (such as redness or irritation) develop. IMMEDIATELY transport the victim to a hospital for treatment after washing the affected areas. INHALATION: IMMEDIATELY leave the contaminated area; take deep breaths of fresh air. If symptoms (such as wheezing, coughing, shortness of breath, or burning in the mouth, throat, or chest) develop, call a physician and be prepared to transport the victim to a hospital. Provide proper respiratory protection to rescuers entering an unknown atmosphere. Whenever possible, Self-Contained Breathing Apparatus (SCBA) should be used; if not available, use a level of protection greater than or equal to that advised under Protective Clothing. INGESTION: DO NOT INDUCE VOMITING. Corrosive chemicals will destroy the membranes of the mouth, throat, and esophagus and, in addition, have a high risk of being aspirated into the victim's lungs during vomiting which increases the medical problems. If the victim is conscious and not convulsing, give 1 or 2 glasses of water to dilute the chemical and IMMEDIATELY call a hospital or poison control center. IMMEDIATELY transport the victim to a hospital. If the victim is convulsing or unconscious, do not give anything by mouth, ensure that the victim's airway is open and lay the victim on his/her side with the head lower than the body. DO NOT INDUCE VOMITING. Transport the victim IMMEDIATELY to a hospital. (NTP, 1992)

/SRP:/ Immediate first aid: Ensure that adequate decontamination has been carried out. If patient is not breathing, start artificial respiration, preferably with a demand-valve resuscitator, bag-valve-mask device, or pocket mask, as trained. Perform CPR as necessary. Immediately flush contaminated eyes with gently flowing water. Do not induce vomiting. If vomiting occurs, lean patient forward or place on left side (head-down position, if possible) to maintain an open airway and prevent aspiration. Keep patient quiet and maintain normal body temperature. Obtain medical attention. /Irritating materials/|/SRP:/ Basic Treatment: Establish a patent airway (oropharyngeal or nasopharyngeal airway, if needed). Suction if necessary. Encourage patient to take deep breaths. Watch for signs of respiratory insufficiency and assist ventilations if necessary. Administer oxygen by nonrebreather mask at 10 to 15 L/min. Monitor for pulmonary edema and treat if necessary ... . Monitor for shock and treat if necessary ... . Anticipate seizures and treat if necessary ... . For eye contamination, flush eyes immediately with water. Irrigate each eye continuously with 0.9% saline (NS) during transport ... . Do not use emetics. For ingestion, rinse mouth and administer 5 mL/kg up to 200 mL of water for dilution if the patient can swallow, has a strong gag reflex, and does not drool ... . /Irritating materials/|/SRP:/ Advanced treatment: Consider orotracheal or nasotracheal intubation for airway control in the patient who is unconscious, has severe pulmonary edema, or is in severe respiratory distress. Early intubation at the first sign of upper airway obstruction may be necessary. Positive-pressure ventilation techniques with a bag valve mask device may be beneficial. Consider drug therapy for pulmonary edema ... . Monitor cardiac rhythm and treat arrhythmias if necessary ... . Start IV administration of D5W /SRP: "To keep open", minimal flow rate/. Use 0.9% saline (NS) or lactated Ringer's if signs of hypovolemia are present. For hypotension with signs of hypovolemia, administer fluid cautiously. Watch for signs of fluid overload ... .Treat seizures with diazepam or lorazepam ... Use proparacaine hydrochloride to assist eye irrigation ... . /Irritating materials/

/CASE REPORTS/ Allergic contact dermatitis occurring in a 25 years old female biochemist was found to be due to occupational handling of dicyclohexylcarbodiimide (DCC). This was confirmed by patch testing. Though DCC is widely used in peptide chemistry as completing reagent, only a few publications report occupational allergic contact dermatitis.|/CASE REPORTS/ /Investigators/ report a case of a female laboratory worker in the chemical industry who acquired contact allergy to dicyclohexylcarbodiimide and N-hydroxyphthalimide. Both substances are used in the chemical synthesis of peptides. So far there have only been a few reports concerning contact allergy to these substances.|/CASE REPORTS/ Dicyclohexylcarbodiimide is a commonly used coupling agent found in protein synthesis. It is a potent allergic sensitizer found especially in the emerging industries involved in recombinant DNA synthesis. Chemists who work in research and development of this industry are especially at risk of development of contact dermatitis, unless they are careful and avoid skin contact. This report describes two chemists with allergic contact dermatitis from repeated contact with this compound in their work as research and development chemists. An appropriate concentration for patch testing is suggested.|/OTHER TOXICITY INFORMATION/ Dicyclohexylcarbodiimide (DCC) and diisopropylcarbodiimide (DIC) are two commonly used coupling reagents in protein synthesis resulting in exposure of individuals in chemical and pharmaceutical industries as well as research laboratories involved in protein synthesis and recombinant DNA techniques. The objectives of these studies were to determine the irritation and sensitizing potential of these two compounds when applied topically to...

DCCD

Cyclohexanamine, N,N'-methanetetraylbis-: ACTIVE