Diphenylguanidine

211.26

211.26

1875653

203-002-1

6MRZ85RNHQ

0467

3272

3077

DTXSID3025178

Monoclinic needles (crystalized from alcohol and toluene)|White powder

29252000

50.4

2.4

Pale Cream Powder

1.19 g/cm³

150 °C

170 °C

170°C

1.6000 (estimate)

H2O: slightly soluble ;soluble in alcohol, chloroform, hot benzene, hot toluene, and dilute mineral acids

Store below +30°C.

Vapour pressure, kPa at 20°C: 0.17

LD50 oral in rabbit: 250mg/kg

Slight odor

BItter taste

Aq soln is strongly alkaline

Henry's Law constant = 7.1X10-12 atm-cu m/mol at 25 °C /Estimated/

pKa = 10.12 (conjugate acid)

Decomposes above 170 °C|Hydroxyl radical reaction rate constant = 8.5X10-11 cu cm/molec-sec at 25 °C /Estimated/

Sensitive to moisture. Aqueous solutions are strongly alkaline. Insoluble in water.

Amines, Phosphines, and Pyridines

1,3-DIPHENYLGUANIDINE behaves as an amine. Amines are chemical bases. They neutralize acids to form salts plus water. These acid-base reactions are exothermic. The amount of heat that is evolved per mole of amine in a neutralization is largely independent of the strength of the amine as a base. Amines may be incompatible with isocyanates, halogenated organics, peroxides, phenols (acidic), epoxides, anhydrides, and acid halides. Flammable gaseous hydrogen is generated by amines in combination with strong reducing agents, such as hydrides. This chemical is incompatible with strong oxidizers. (NTP, 1992)

III

9

UN 3077 9/PG 3

2

22-36/37/38-51/53-62-25

26-36/37/39-61-45

MF0875000

Xn,N,T

Separated from food and feedstuffs.

Stable. Combustible. Incompatible with strong oxidizing agents. Moisture sensitive.

P261-P273-P281-P301 + P310-P305 + P351 + P338

H301-H315-H319-H335-H361f-H411

SRP: The most favorable course of action is to use an alternative chemical product with less inherent propensity for occupational exposure 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, aquatic, and plant life; and conformance with environmental and public health regulations.

DHHS/NTP; NTP Technical Report on Toxicity Studies of 1.3-Diphenylguanidine Administered in Feed to F344/N Rats and B6C3F1 Mice. Toxicity Rpt Series No. 42 NIH Publication No. 95-3993 (1995)|The U.S. high production volume (HPV) chemicals are those which are manufactured in or imported into the United States in amounts equal to or greater than one million pounds per year. Robust Summaries include health effects, ecotoxicity data, and environmental fate information for selected chemicals. EPA/Office of Pollution Prevention and Toxics; High Production Volume (HPV) Challenge Program's Robust Summaries and Test Plans. Available from: http://www.epa.gov/chemrtk/viewsrch.htm on 1,3-Diphenylguanidine as of November 3, 2004.

This chemical is combustible. (NTP, 1992)|Combustible.

|Warning|H302: Harmful if swallowed [Warning Acute toxicity, oral]|P201, P202, P261, P264, P270, P271, P273, P280, P281, P301+P312, P302+P352, P304+P340, P305+P351+P338, P308+P313, P312, P321, P330, P332+P313, P337+P313, P362, P391, P403+P233, P405, and P501|Danger|H301 (32.13%): Toxic if swallowed [Danger Acute toxicity, oral]|P201, P202, P261, P264, P270, P271, P273, P280, P281, P301+P310, P301+P312, P302+P352, P304+P340, P305+P351+P338, P308+P313, P312, P321, P330, P332+P313, P337+P313, P362, P391, P403+P233, P405, and P501|Aggregated GHS information provided by 554 companies from 20 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.|H301: Toxic if swallowed [Danger Acute toxicity, oral]|P201, P202, P261, P264, P270, P271, P280, P281, P301+P310, P304+P340, P305+P351+P338, P308+P313, P312, P321, P330, P337+P313, P403+P233, P405, and P501|P201, P202, P264, P270, P281, P301+P310, P305+P351+P338, P308+P313, P321, P330, P337+P313, P405, and P501

Fires involving this material can be controlled with a dry chemical, carbon dioxide or Halon extinguisher. A water spray may also be used. (NTP, 1992)|In case of fire in the surroundings, use appropriate extinguishing media.

Excerpt from ERG Guide 171 [Substances (Low to Moderate Hazard)]: 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 store this chemical under ambient temperatures, and protect it from moisture and oxidizers. (NTP, 1992)

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. (NTP, 1992)

SRP: The scientific literature for the use of contact lenses in industry is conflicting. The benefit or detrimental effects of wearing contact lenses depend not only upon the substance, but also on factors including the form of the substance, characteristics and duration of the exposure, the uses of other eye protection equipment, and the hygiene of the lenses. However, there may be individual substances whose irritating or corrosive properties are such that the wearing of contact lenses would be harmful to the eye. In those specific cases, contact lenses should not be worn. In any event, the usual eye protection equipment should be worn even when contact lenses are in place.

1,3-diphenylguanidine is irritating to the eye and non-irritating to the skin.

Personal protection: P2 filter respirator for harmful particles. Do NOT wash away into sewer. Do NOT let this chemical enter the environment. Sweep spilled substance into covered containers. If appropriate, moisten first to prevent dusting.

Separated from food and feedstuffs.

No indication can be given about the rate at which a harmful concentration of this substance in the air is reached on evaporation at 20 °C.

The substance is mildly irritating to the eyes.

Animal tests show that this substance possibly causes toxic effects upon human reproduction.

NO open flames.

PREVENT DISPERSION OF DUST!

Use local exhaust.

Protective gloves.

Wear safety goggles.

A mathematical design to study combined toxic effects of rubber ingredients thiram and Diphenylguanidine derivative revealed only mild toxicity.

LD50 Rat oral 375 mg/kg|LD50 Rat ip 75 mg/kg|LD50 Mouse oral 150 mg/kg|LD50 Mouse ip 25 mg/kg

N,N'-Diphenylguanidine's production and use as a rubber accelerator and primary standard for acids(1) may result in its release to the environment through various waste streams.

TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 5,900(SRC), determined from a structure estimation method(2), indicates that N,N'-diphenylguanidine is expected to be immobile in soil(SRC). Volatilization of N,N'-diphenylguanidine from moist soil surfaces is not expected to be an important fate process(SRC) given an estimated Henry's Law constant of 7.1X10-12 atm-cu m/mole(SRC), using a fragment constant estimation method(3). N,N'-Diphenylguanidine is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 8.4X10-6 mm Hg(SRC), determined from a fragment constant method(4). N,N'-diphenylguanidine reached 0% of its theoretical BOD in 2 weeks using an activated sludge and the Japanese MITI test(5), indicating that biodegradation in soil is not an important environmental fate process(SRC).|AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 5,900(SRC), determined from a structure estimation method(2), indicates that N,N'-diphenylguanidine is expected to adsorb to suspended solids and sediment(SRC). The pKa of N,N'-diphenylguanidine is 10.12(3), indicating that this compound will primarily exist in cation form in the environment and cations generally adsorb more strongly to suspended solids and sediment than their neutral counterparts(4). N,N'-Diphenylguanidine will exist almost entirely as a cation at pH values of 5 to 9 and therefore volatilization from water surfaces is not expected to be an important fate process. According to a classification scheme(5), BCFs of <2 and <20(6) suggest the potential for bioconcentration in aquatic organisms is low(SRC). Biodegradation rates of 18% and 9% in river water and sea water, respectively, after a 3-day cultivation period(7), indicates that biodegradation in water may not be an important environmental fate process(SRC).|ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), N,N'-diphenylguanidine, which has an estimated vapor pressure 8.4X10-6 mm Hg at 25 °C(SRC), determined from a fragment constant method(2), will exist in both the vapor and particulate phases. Vapor-phase N,N'-diphenylguanidine 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 4.5 hours(SRC), calculated from its rate constant of 8.5X10-11 cu cm/molecule-sec at 25 °C(SRC) that was derived using a structure estimation method(3). Particulate-phase N,N'-diphenylguanidine may be removed from the air by wet and dry deposition(SRC).

The rate constant for the vapor-phase reaction of N,N'-diphenylguanidine with photochemically-produced hydroxyl radicals has been estimated as 8.5X10-11 cu cm/molecule-sec at 25 °C(SRC) using a structure estimation method(1). This corresponds to an atmospheric half-life of about 4.5 hours at an atmospheric concentration of 5X10+5 hydroxyl radicals per cu cm(1). N,N'-Diphenylguanidine is not expected to undergo hydrolysis in the environment due to the lack of hydrolyzable functional groups(2).

19.95|BCFs of <2 and <20 were measured for N,N'-diphenylguanidine(SRC) using orange-red killifish (Oryzias latipes) which were exposed over a 6-week period(1). According to a classification scheme(2), these BCFs suggest the potential for bioconcentration in aquatic organisms is low(SRC).

Using a structure estimation method based on molecular connectivity indices(1), the Koc for N,N'-diphenylguanidine can be estimated to be 5,900(SRC). According to a classification scheme(2), this estimated Koc value suggests that N,N'-diphenylguanidine is expected to be immobile in soil. The pKa of N,N'-diphenylguanidine is 10.12(3), indicating that this compound will primarily exist in the protonated form in the environment and cations generally adsorb more strongly to organic carbon and clay than their neutral counterparts(4).

The Henry's Law constant for N,N'-diphenylguanidine is estimated as 7.1X10-12 atm-cu m/mole(SRC) using a fragment constant estimation method(1). This Henry's Law constant indicates that N,N'-diphenylguanidine is expected to be essentially nonvolatile from water surfaces(2). A pKa of 10.12(3) indicates N,N'-diphenylguanidine will exist almost entirely in the ionized form at pH values of 5 to 9 and therefore volatilization from water surfaces is not expected to be an important fate process. The compound's pKa(3) also indicates that volatilization from moist soil surfaces may not occur(SRC). N,N'-Diphenylguanidine is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 8.4X10-6 mm Hg(SRC), determined from a fragment constant method(4).

NIOSH (NOES Survey 1981-1983) has statistically estimated that 28,146 workers (4,339 of these are female) are potentially exposed to N,N'-diphenylguanidine in the US(1). Occupational exposure to N,N'-diphenylguanidine may occur through inhalation of dusts and dermal contact with this compound at workplaces where N,N'-diphenylguanidine is produced or used(SRC).

Diphenylguanidine is approved for use within allergenic epicutaneous patch tests which are indicated for use as an aid in the diagnosis of allergic contact dermatitis (ACD) in persons 6 years of age and older.

A chronic experiment with rabbits established that diphenylguanidine after entering the blood is absorbed by all body tissues with its predominant location in the kidneys and liver.|/1,3-Diphenylguanidine/ (DPG) is rapidly absorbed and distributed throughout the body tissues: 30 min after administration of 100 mg DPG/kg bw, the substance was found in the blood; in an hour it was discovered in all the visceral organs; after 24 hours, it was found in the urine. DPG excretion with the urine had ceased on the day 6.|Major organ and tissue volumes were sampled for radioactive content at various time points following iv administration of a 15.15-umol/kg (14C)-/n,n'-diphenylguanidine/ (DPG) dose. Initially the highest concentration (% total dose/g tissue) of DPG-derived radioactivity was observed in liver followed by kidney and lung. The peak concentration in liver was reached in 45 min after administration whereas the DPG-derived radioactivity in other tissues with the possible exception of testes and adipose tissues showed a decline. The concentration of DPG-derived radioactivity in liver was higher than in other tissues at every time point examined. At 24 hr post-exposure the concentration of DPG in liver was 5-10 times higher than in most other tissues. Interestingly, the brain and most lean tissues contained similar concentrations of DPG-derived radioactivity at comparable time points.|The distribution of radioactivity in rat tissues at various time points following a single iv dose of (14C)-DPG of 15.15 umol/kg is presented. DPG-derived radioactivity was readily cleared from all tissues so that within 24 hr after exposure the total tissue burden was approximately 10-fold lower than that observed at the earliest time point, 15 min.|For more Absorption, Distribution and Excretion (Complete) data for N,N'-DIPHENYLGUANIDINE (9 total), please visit the HSDB record page.

/Following a single iv dose of 15.5 umol/kg (14C)-DPG to rats/ ... the nature of the (14C)-DPG derived radioactivity excreted in urine and bile was examined by direct HPLC analysis. Bile contained only small amounts of parent compound at all time points examined. Most of the radioactivity in bile (95%) was in the form of a major metabolite (Peak II) of DPG with traces of another metabolite (Peak I). The major metabolite (Peak II) excreted in bile was resistant to hydrolysis by arylsulfatase, by strong acid, or by strong base. However, incubation of this metabolite with b-glucuronidase resulted in near complete hydrolysis to yield metabolite V. It is believe that this metabolite (Peak II) is in the form of a glucuronide, the position of glucuronidation has not been determined.|/Following a single iv dose of 15.5 umol/kg (14C)-DPG to rats/ ... DPG-derived radioactivity excreted in feces was primarily (94%) in the form of metabolite V. Therefore, it appears that the glucuronide present in bile (Peak II) was subsequently hydrolysed in the intestine, most probably by intestinal flora, to release metabolite V which accounted for most of the radioactivity excreted in feces. HPLC analysis of urine indicated that around 28% of the radioactivity excreted in urine was in the form of parent compound. The major metabolite (Peak II) in urine accounted for approximately 37% of the total radioactivity. Treatment of this metabolite with b -glucuronidase resulted in its hydrolysis t o yield metabolite V.|/Following a single iv dose of 15.5 umol/kg (14C)-DPG to rats/ ... Comparison of excretion in bile versus feces indicates that as much as 30% of the total dose is reabsorbed from the intestine after excretion in bile. Since most of this material is metabolite V, reabsorption from the intestine and reconjugation may account for most of the metabolite II excreted in urine. Two other metabolites were detected in urine. Metabolite III which eluted from the column shortly after peak II accounted for approximately 32% of the radioactivity while the unconjugated metabolite V accounted only for 3% of the radioactivity.|/Following a single iv dose of 15.5 umol/kg (14C)-DPG to rats/ ... radioactivity extracted from lung, skin, and adipose tissue at the 45-min and 2-hr time points was present only in the form of the parent compound. The radioactivity extracted from other tissues at the 24-hr time point was insufficient for accurate metabolite determination.|The enzymic C-oxygenation of N,N'-diphenylguanidine (DPG) to N-(4-hydroxyphenyl)-N'-phenylguanidine (4HPG)... is reported. ...Rat and rabbit liver homogenates (9000 g supernatant and microsomes) were used as enzyme source. The enzymic oxygenations were both O2 and NADPH dependent. NADPH could not be replaced by hydrogen peroxide.

Total clearance followed a single component exponential decay with a half-life of approximately 9.6 hr.

SYMPTOMS: Symptoms of exposure to this compound may include irritation of the skin, eyes, mucous membranes and respiratory tract. Other symptoms include tearing, reddening and swelling of the skin and eyes; skin sensitization (with possible blistering) and dermatitis. Inhalation may result in runny nose, dry throat, sneezing, coughing and chest discomfort. Ingestion may result in nausea, vomiting and diarrhea. Conjunctivitis may occur. Eye contact may also cause punctuate corneal epithelial defects and edema of the lids and conjunctiva. ACUTE/CHRONIC HAZARDS: This compound is toxic by ingestion. It is harmful if inhaled or absorbed through the skin. It is a severe eye irritant. It is also an irritant of the skin, eyes, mucous membranes and respiratory tract. When heated to decomposition it emits toxic fumes of carbon monoxide, carbon dioxide, nitrogen oxides and organic amines. (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. If symptoms such as redness or irritation develop, IMMEDIATELY call a physician and be prepared to transport the victim to a hospital for treatment. 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. 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. Be prepared to transport the victim to a hospital if advised by a physician. 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. IMMEDIATELY transport the victim to a hospital. (NTP, 1992)

Fresh air, rest.

Rinse skin with plenty of water or shower.

First rinse with plenty of water for several minutes (remove contact lenses if easily possible), then refer for medical attention.

Basic treatment: Establish a patent airway. Suction if necessary. Watch for signs of respiratory insufficiency and assist ventilations if needed. 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 normal saline 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 ... . Cover skin burns with dry sterile dressings after decontamination ... . /Poison A and B/|Advanced treatment: Consider orotracheal or nasotracheal intubation for airway control in the patient who is unconscious, has severe pulmonary edema, or is in respiratory arrest. Positive pressure ventilation techniques with a bag valve mask device may be beneficial. Monitor cardiac rhythm and treat arrhythmias as necessary ... . Start an IV with D5W /SRP: "To keep open", minimal flow rate/. Use lactated Ringer's if signs of hypovolemia are present. Watch for signs of fluid overload. Consider drug therapy for pulmonary edema ... . For hypotension with signs of hypovolemia, administer fluid cautiously. Watch for signs of fluid overload ... . Treat seizures with diazepam (Valium) ... . Use proparacaine hydrochloride to assist eye irrigation ... . /Poison A and B/

/SIGNS AND SYMPTOMS/ Occupational accidental exposure of workers to /n,n'-diphenylguanidine/ (DPG) can cause burning of the eyelids, reddening of the eyes, a bitter taste in the mouth and a painful sensation in the esophagus; flabbiness of the gums and a reduction in the acidity of the gastric juice, tending to achylia, were also reported.|/HUMAN EXPOSURE STUDIES/ /Investigators/ ... found that Spanish agricultural workers with a contact dermatitis had a significantly higher sensitization to 1,3-diphenylguanidine than a contact dermatitis control group working in another profession (11.76% versus 5.32%). The authors attributed this to possible cross-reactions with pesticides, as some of these substances (e.g. Cyprex) are guanidine derivatives and others (e.g. the cyanamides) possess a similar chemical structure.|/HUMAN EXPOSURE STUDIES/ Patch testing of 49 human volunteers with 70 % /n,n'-diphenylguanidine/ (DPG) in petrolatum produced no positive reactions following initial application; 19 of the 49 subjects displayed positive reactions during subsequent exposures. Two subjects displayed positive reactions upon rechallenge 2 weeks later.|/SIGNS AND SYMPTOMS/ Occupational allergic dermatosis was observed in rubber workers and was caused by rubber additives such as diphenylguanidine.|/SIGNS AND SYMPTOMS/ Workers (29-58 years old) occupationally exposed for 3-15 years to /n,n'-diphenylguanidine/ DPG were /examined/; 30 % of the examined subjects different complaints were reported, mostly gastritis, cholangitis, cholecystitis, neurological disturbances and dermatitis; beside these symptoms in some patients bronchial asthma, rhinitis, neuropathy, polyathritis, hypertonia and lithiasis were diagnosed and the liver function was disturbed: changes in the protein metabolism and increased bilirubin levels.

1,3-diphenylguanidine

The substance can be absorbed into the body by inhalation and by ingestion.

Redness. Pain.

Recycling|Guanidine, N,N'-diphenyl-: ACTIVE|Promoted lettuce seed germination.|The expected production volume of 1,3-Diphenylguanidine in year 2000 is 2400 tonnes/year in Europe, 2400 tonnes/year in the USA, an amount of 5300 tonnes/year for Asia and 11100 tonnes per year for the world.

A THIN LAYER CHROMATOGRAPHIC METHOD WAS DEVELOPED FOR DETERMINING DIPHENYLGUANIDINE IN URINE, BLOOD AND TISSUES OF INTERNAL ORGANS OF HUMANS AND ANIMALS.