Mallinckrodt Baker  -- UREA  57-13-6
Fisher - Urea, Pearls 57-13-6
Fisher - Urea 57-13-6
Fisher - Urea, Reagent ACS 57-13-6
Fisher - Urea, p.a. 57-13-6

UREA

 CAS Nr 57-13-6

The following information was generated from the
Hazardous Substances Databank (HSDB),
a database of the National Library of Medicine's TOXNET system
(http://toxnet.nlm.nih.gov) on September 7, 2002.

Query: Records containing  the word nr 
Singular and plural forms were searched.

Information added from ChemIDplus:
 Chemid Name: urea [57-13-6] 
 ( carbamide, varioform ii, urevert, ureophil, ureaphil, pseudourea, mocovina,
isourea, carbonyldiamine, carbonyl diamide, carbamimidic acid )
urea ( carbamide, varioform ii, urevert, ureophil, pseudourea, mocovina, isourea,
carbonyldiamine, carbonyl diamide, carbamimidic acid )
cas Chemid Name:  [41427-34-3] 

Registry Numbers:
  57-13-6   57-13-6   41427-34-3


1
NAME: UREA

RN: 57-13-6


HUMAN HEALTH EFFECTS:


HUMAN TOXICITY EXCERPTS:
      ADVERSE REACTIONS INCLUDE HEADACHE, NAUSEA, VOMITING, SYNCOPE,
      DISORIENTATION, TRANSIENT CONFUSION, & ELECTROLYTE DEPLETION
      (HYPONATREMIA & HYPOKALEMIA). [GENNARO. REMINGTON'S PHARM SCI 17TH ED
      1985 p 935]**PEER REVIEWED**

      BECAUSE THE EYE IS PERMEABLE TO UREA, REBOUND ELEVATION IN INTRAOCULAR
      PRESSURE & VITREOUS VOL MAY OCCUR AFTER OCULAR HYPOTENSIVE EFFECT HAS
      TERMINATED (ABOUT 8 TO 12 HR AFTER ADMIN). [American Medical Association,
      AMA Department of Drugs, AMA Drug Evaluations. 3rd ed. Littleton,
      Massachusetts: PSG Publishing Co., Inc., 1977. 936]**PEER REVIEWED**

      THE SYSTEMIC TOXICITY OF UREA IS SIMILAR TO THAT OF MANNITOL. UREA IS
      IRRITATING TO TISSUES; IT CAUSES PAIN AT SITE OF INFUSION & NECROSIS
      MAY RESULT IF EXTRAVASATION OCCURS. SUPERFICIAL & DEEP THROMBOSIS MAY
      RESULT IF UREA IS INFUSED IN VEINS OF LOWER EXTREMITIES. [American Medical
      Association, AMA Department of Drugs, AMA Drug Evaluations. 3rd ed.
      Littleton, Massachusetts: PSG Publishing Co., Inc., 1977. 936]**PEER
      REVIEWED**

HUMAN TOXICITY VALUES:
      Human, skin 22 mg/3 days intermittent, toxic effects: mild irritation
      [NIOSH; Current Awareness Listing (1985)]**PEER REVIEWED**

SKIN, EYE AND RESPIRATORY IRRITATIONS:
      Urea causes redness and irritation of skin and eyes. [Environment Canada;
      Tech Info for Problem Spills: Urea p.2 (1985)]**PEER REVIEWED**

DRUG WARNINGS:
      UREA SHOULD NOT BE USED IN PATIENTS WITH SEVERELY IMPAIRED RENAL FUNCTION.
      [American Medical Association, AMA Department of Drugs, AMA Drug
      Evaluations. 3rd ed. Littleton, Massachusetts: PSG Publishing Co., Inc.,
      1977. 936]**PEER REVIEWED**

      UREA IS OFTEN RECONSTITUTED WITH INVERT SUGAR SOLN. INVERT SUGAR CONTAINS
      FRUCTOSE, WHICH CAN CAUSE SEVERE REACTION (HYPOGLYCEMIA, NAUSEA, VOMITING,
      TREMORS, COMA, & CONVULSIONS) IN PATIENTS WITH HEREDITARY FRUCTOSE
      INTOLERANCE (ALDOLASE DEFICIENCY). [American Medical Association, AMA
      Department of Drugs, AMA Drug Evaluations. 3rd ed. Littleton,
      Massachusetts: PSG Publishing Co., Inc., 1977. 936]**PEER REVIEWED**

PROBABLE ROUTES OF HUMAN EXPOSURE:
      Occupational exposure to urea occurs through dermal contact and inhalation
      of dust, especially to workers applying urea fertilizers(1). [(1)
      Parmeggiani L; Encyl Occup Health & Safety 3rd ed. Geneva,
      Switzerland: International Labour Office p. 846-8 (1983)]**PEER REVIEWED**

      The National Occupational Hazard Survey conducted by NIOSH estimated that
      855,894 workers may be exposed to urea; 7% from actual observed use, 31%
      from observed use of a tradename product known to contain this chemical,
      and 62% from observed use of a product in some type of general use which
      leads NIOSH to suspect that this chemical may be contained in the product.
      [NIOSH National Hazard Exposure Survey (1972-1974)]**PEER REVIEWED**

      NIOSH (NOES Survey 1981-1983) has statistically estimated that 661,00
      workers are potentially exposed to urea in the USA(1). NIOSH (NOHS Survey
      1972-1974) has statistically estimated that 855,894 workers are
      potentially exposed to urea in the USA(2). [(1) NIOSH; National
      Occupational Exposure Survey (NOES) (1983) (2) NIOSH; National
      Occupational Hazard Survey (NOHS) (1974)]**PEER REVIEWED**

MINIMUM FATAL DOSE LEVEL:
      In ruminants unaccustomed to urea, ingestion of 0.3-0.5 g urea/kg may be
      toxic ... The toxic dose of urea in (presumably unaccustomed) cattle is
      0.45 g/kg (50 g total dose) but that animals can ingest more urea than
      this if the dose is increased gradually. [Booth, N.H., L.E. McDonald
      (eds.). Veterinary Pharmacology and Therapeutics. 5th ed. Ames, Iowa: Iowa
      State University Press, 1982. 1029]**PEER REVIEWED**


EMERGENCY MEDICAL TREATMENT:


EMERGENCY MEDICAL TREATMENT:
     
EMT COPYRIGHT DISCLAIMER:
Portions of the POISINDEX(R) database are provided here for general reference. 
THE COMPLETE POISINDEX(R) DATABASE, AVAILABLE FROM MICROMEDEX, SHOULD BE       
CONSULTED FOR ASSISTANCE IN THE DIAGNOSIS OR TREATMENT OF SPECIFIC CASES.      
Copyright 1974-1998  Micromedex, Inc. Denver, Colorado.  All Rights Reserved.  
Any duplication, replication or redistribution of all or part of the           
POISINDEX(R) database is a violation of Micromedex' copyrights and is strictly 
prohibited.<p>The following Overview, *** UREA ***,    is relevant for this HSDB
record chemical.
LIFE SUPPORT:

  o   This overview assumes that basic life support measures
      have been instituted.                          
CLINICAL EFFECTS:

  SUMMARY OF EXPOSURE
   0.2.1.1 ACUTE EXPOSURE
     o   WITH POISONING/EXPOSURE
      1.  Urea is considered a mild to moderate intoxicant and a
          mild irritant.  Exposure causes erythema of eyes and
          skin.  Urea's systemic toxicity is similar to that of
          mannitol.
     o   WITH THERAPEUTIC USE
      1.  Adverse effects include nausea, vomiting, dizziness,
          disorientation, drowsiness, diuresis, hyponatremia,
          hypokalemia, and confusion.  Urea's systemic toxicity
          is similar to that of mannitol.
     o   ANIMAL STUDIES - In sheep and cattle, clinical effects
         included pronounced muscle fasciculations, trembling,
         grinding teeth, dysrhythmias, ataxia, lateral
         recumbency, anuria, dry mouth, frothy salivation,
         dyspnea, bloating, abdominal pain,  regurgitation,
         hyperesthesia, mydriasis and convulsions.  The primary
         cause of  death was respiratory arrest.  Laboratory
         examination showed increased glucose,  ammonia and urea
         levels.
  HEENT
   0.2.4.1 ACUTE EXPOSURE
     o   WITH POISONING/EXPOSURE
      1.  Eye damage is expected only when concentrations are
          high or duration of exposure is extended .  Rebound
          increases in intraocular pressure  have been seen.
  CARDIOVASCULAR
   0.2.5.1 ACUTE EXPOSURE
     o   WITH THERAPEUTIC USE
      1.  Therapeutic administration of intravenous solutions
          may cause a fall in blood pressure.
  RESPIRATORY
   0.2.6.1 ACUTE EXPOSURE
     o   WITH POISONING/EXPOSURE
      1.  Human data not found.
     o   ANIMAL STUDIES have shown dyspnea and respiratory
         arrest.
  NEUROLOGIC
   0.2.7.1 ACUTE EXPOSURE
     o   WITH THERAPEUTIC USE
      1.  Therapeutic administration of intravenous solution has
          caused intracranial hemorrhage, headache and
          confusion.
     o   ANIMAL STUDIES - Animals have developed trembling,
         fasciculations, hyperreflexia, convulsions, ataxia, and
         lethargy.
  GASTROINTESTINAL
   0.2.8.1 ACUTE EXPOSURE
     o   WITH THERAPEUTIC USE
      1.  Nausea and vomiting have been seen with both oral and
          intravenous administration.
     o   ANIMAL STUDIES - Grinding teeth, dry mouth, bloating,
         and regurgitation were observed in animals.
  GENITOURINARY
   0.2.10.1 ACUTE EXPOSURE
     o   WITH THERAPEUTIC USE
      1.  High urea levels will produce diuresis and should not
          be used in patients with severely impaired renal
          function.
  HEMATOLOGIC
   0.2.13.1 ACUTE EXPOSURE
     o   WITH THERAPEUTIC USE
      1.  Thrombosis and leukocytosis are possible.  Rapid
          intravenous administration may cause hemolysis.
  DERMATOLOGIC
   0.2.14.1 ACUTE EXPOSURE
     o   WITH POISONING/EXPOSURE
      1.  Is a mild skin irritant.
  MUSCULOSKELETAL
   0.2.15.1 ACUTE EXPOSURE
     o   WITH THERAPEUTIC USE
      1.  Urea is irritating to tissues.  Extravasation may lead
          to pain and necrosis.
  METABOLISM
   0.2.17.1 ACUTE EXPOSURE
     o   WITH THERAPEUTIC USE
      1.  An intolerance to carbohydrates may develop with high
          urea levels.
  REPRODUCTIVE HAZARDS
    o   Intraplacental and intrauterine administration of urea
        to humans has produced abortions.
  CARCINOGENICITY
   0.2.21.2 HUMAN OVERVIEW
     o   Carcinogenicity data are questionable.  Both negative
         and positive studies have been reported.
  GENOTOXICITY
    o   Human mutation data have been reported.
LABORATORY:

  o   Follow blood urea nitrogen (BUN) to detect urea increases.
  o   When diuresis is extensive, follow fluids and
      electrolytes.                                          
TREATMENT OVERVIEW:

  ORAL EXPOSURE
    o   Urea is not highly toxic, and extensive decontamination
        and treatment is seldom necessary.  Gastric
        decontamination is not indicated in high concentrations
        due to possible strong irritant effects.  Gastric
        decontamination may be of value with high volumes of
        lower concentrations.  Activated charcoal has not been
        tested.
    o   Urea is effectively eliminated by the kidney.  If normal
        renal function exists, diuresis will ensue.  Patients
        should have adequate hydration.  If diuresis is
        extensive, monitor electrolytes.
  INHALATION EXPOSURE
    o   INHALATION:  Move patient to fresh air.  Monitor for
        respiratory distress.  If cough or difficulty breathing
        develops, evaluate for respiratory tract irritation,
        bronchitis, or pneumonitis.  Administer oxygen and
        assist ventilation as required.  Treat bronchospasm with
        beta2  agonist and corticosteroid aerosols.
    o   Urea would be a mild to moderate irritant if inhaled in
        an aerosol.  After the exposure has been terminated,
        patients should be evaluated for respiratory distress.
        Dyspnea and respiratory failure has been seen in
        poisoned animals, respiratory support should be
        available in severe cases.
  EYE EXPOSURE
    o   DECONTAMINATION:  Irrigate exposed eyes with copious
        amounts of tepid water for at least 15 minutes.  If
        irritation, pain, swelling, lacrimation, or photophobia
        persist, the patient should be seen in a health care
        facility.
    o   Urea may be mild to moderately irritating to the eye.
        Most exposures may be handled by irrigation and
        observation for prolonged pain or erythema (not
        expected).
     1.  HIGH CONCENTRATIONS - or prolonged exposures may
         produce more significant irritation and should be seen
         by an ophthalmologist for evaluation.
  DERMAL EXPOSURE
    o   DECONTAMINATION:  Remove contaminated clothing and wash
        exposed  area thoroughly with soap and water.  A
        physician may need to  examine the area if irritation or
        pain persists.                     
RANGE OF TOXICITY:

  o   IRRITATION -
   1.  SUMMARY - As with all irritants, concentration is not the
       only factor which affects the extent of tissue damage.
       The concentrations below should only be used as a rough
       guide, and each patient examined individually.
   2.  INHALATION - Concentrations under 50% are not likely to
       cause tissue damage.
   3.  SKIN/MUCOUS MEMBRANES - 25% to 50% concentrations did not
       produce toxicity in the ear.
   4.  INJECTION - SQ injection of a 6% to 30% solution did not
       produce toxicity.  Injection of a 58% solution in the
       uterus produced necrosis, 10% injected in the cervix did
       not.                                   

ANTIDOTE AND EMERGENCY TREATMENT:
      This should involve the use of weak acid as a chemical antidote,
      demulcents and stimulants. ... Recommended 2.5-5 l of 5% acetic acid as an
      effective antidote to urea poisoning in cattle. ... /It was/ also shown
      that weak acids such as acetic and propionic acid offer some protection
      against the harmful effects of urea. Drenching with acetic acid those
      animals showing signs of intoxication does not lower their blood ammonia
      concentration within 120 minutes ... . However, administration of 2 mol of
      acetic acid per mol of urea at 15 minutes, and 1 mol per mol 180 minutes
      after giving 0.44 g/kg body weight of urea ... resulted in the survival of
      28 of 29 pregnant cows ... . Emptying the rumen of fistulated cattle
      showing clinical signs of poisoning results in a rapid fall in their blood
      ammonia concentration and recovery within one to two hours ... .
      [Humphreys, D.J. Veterinary Toxicology. 3rd ed. London, England: Bailliere
      Tindell, 1988. 18]**PEER REVIEWED**

      In animals that are not too ill, the cold water acetic acid treatment may
      work. the adult cow is given 19-38 liters cold water and 3.8 liters 5%
      acetic acid (or vinegar) orally. This treatment limits absorption of
      ammonia from the rumen by diluting the rumen contents and slowing the rate
      of hydrolysis of urea by decreasing rumen pH and temperature. The
      treatment also promotes urine flow that, if maintained by fluid therapy,
      may assure recovery from urea toxicosis. Gaseous or fluid bloat should be
      relieved before pumping water into the rumen. [Booth, N.H., L.E. McDonald
      (eds.). Veterinary Pharmacology and Therapeutics. 5th ed. Ames, Iowa: Iowa
      State University Press, 1982. 1033]**PEER REVIEWED**

      This involves chemical examination of the suspect fertilizer, feed or
      rumen contents. In most cases of urea poisoning the ammonial level in the
      rumen contents will be greater than 80 mg/100 ml (47 mmol/l) and may be as
      high as 200 mg/100 ml (117 mmol/l). It should be remembered that rumen
      contents should be examined quickly after death or kept frozen until they
      can be analysed. The reason for this is that microbial decomposition can
      produce ammonia and thus lead to misleading results. The possible uneven
      distribution of the causal agent in feed and rumen contents must be borne
      in mind when collecting samples for chemical examination. Blood and serum
      ammonia nitrogen concentrations between 2 and 4 mg/100 ml (1.17 and 2.35
      mmol/l) or greater which are associated with urea poisoning may also have
      diagnostic applications. [Humphreys, D.J. Veterinary Toxicology. 3rd ed.
      London, England: Bailliere Tindell, 1988. 18]**PEER REVIEWED**


ANIMAL TOXICITY STUDIES:


NON-HUMAN TOXICITY EXCERPTS:
      INTRAVITREAL INJECTION OF 0.2 ML OF 10 MOLAR /SOLN INTO VITREOUS HUMOR OF/
      RABBITS HAS CAUSED INFLAMMATION, CHORIORETINITIS, &amp; DEGENERATION OF
      RETINA. [Grant, W.M. Toxicology of the Eye. 3rd ed. Springfield, IL:
      Charles C. Thomas Publisher, 1986. 965]**PEER REVIEWED**

      UREA MIXED WITH SOYA MEAL IS PARTICULARLY DANGEROUS, AS UREASE IN LATTER
      LEADS TO FORMATION OF AMMONIA ... POISONING OF CATTLE MAY ALSO BE CAUSED
      BY UREA AS FERTILIZER &amp; SPREAD UNEVENLY ON PASTURE [Clarke, E.G., and
      M. L. Clarke. Veterinary Toxicology. Baltimore, Maryland: The Williams and
      Wilkins Company, 1975. 30]**PEER REVIEWED**

      LAMBS GIVEN 2 G/KG OF UREA DIED IN 90-200 MIN. ADULT SHEEP GIVEN SAME DOSE
      EXHIBITED ALMOST CONTINUOUS CONVULSIONS AFTER 165 MIN ... SHEEP CAN
      CONSUME UP TO 100 G OF UREA A DAY PROVIDED THAT CONCN OF UREA IN RATION
      DOES NOT EXCEED 6% ... LIVER DYSFUNCTION INCR SUSCEPTIBILITY TO POISONING.
      [Clarke, E.G., and M. L. Clarke. Veterinary Toxicology. Baltimore,
      Maryland: The Williams and Wilkins Company, 1975. 30]**PEER REVIEWED**

      ... ORAL ADMIN OF 50 G OF UREA KILLED 4 OUT OF 5 GOATS WITHIN 30 MIN, 450
      G GIVEN BY MOUTH KILLED 7 PONIES OUT OF 8 ... [Clarke, E.G., and M. L.
      Clarke. Veterinary Toxicology. Baltimore, Maryland: The Williams and
      Wilkins Company, 1975. 30]**PEER REVIEWED**

      TOXIC DOSE IN CATTLE GIVEN UREA FOR FIRST TIME IS VARIOUSLY CONSIDERED TO
      BE 0.45 G/KG ... OR TOTAL OF 100-200 G ... SLOWLY INCR UREA CONTENT OF
      FEED, MATURE BULLOCKS CAN DIGEST AS MUCH AS 400 G A DAY WITHOUT ILL
      EFFECT. AS LITTLE AS 50 G MAY CAUSE POISONING IN CATTLE NOT ACCUSTOMED TO
      IT ... . [Clarke, E.G., and M. L. Clarke. Veterinary Toxicology.
      Baltimore, Maryland: The Williams and Wilkins Company, 1975. 30]**PEER
      REVIEWED**

      Urea was tested for mutagenicity in the Salmonella/microsome preincubation
      assay using the standard protocol approved by the National Toxicology
      Program. Urea was tested at doses of 0.10, 0.33, 1.0, 3.3, and 10 mg/plate
      in as many as 5 Salmonella typhimurium strains (TA1535, TA1537, TA97,
      TA98, and TA100) in the presence and absence of rat or hamster liver S-9.
      Urea was negative in these tests and the highest ineffective dose tested
      in any Salmonella typhimurium strain was 10 mg/plate. [Mortelmans K et al;
      Environ Mutagen 8:1-119 (1986)]**PEER REVIEWED**

      Single doses of 16 g/kg body weight and 10% of urea in the feed has been
      reported to have no apparent effect on ten week old piglets ... . Although
      the highest level made the feed unpalatable, incorporation of 0.4, 0.6 or
      1.0 g of urea per kg body weight into the ration of 18 month old pigs
      weighing 120-140 kg also failed to produce intoxication ... . [Humphreys,
      D.J. Veterinary Toxicology. 3rd ed. London, England: Bailliere Tindell,
      1988. 17]**PEER REVIEWED**

      Administration of 450 g of urea, which caused the death of seven of eight
      ponies, resulted in an increase in blood urea, ammonia,
      alphaketoglutarate, glucose and pyruvate concentrations. The sequence and
      nature of the changes produced suggested that inhibition of
      alphaketoglutarate decarboxylation may be the primary site of ammonia
      intoxication. [Humphreys, D.J. Veterinary Toxicology. 3rd ed. London,
      England: Bailliere Tindell, 1988. 17]**PEER REVIEWED**

      Urea poisoning has been reported in sheep which drank a 21% solution used
      as a fertilizer for cotton ... and in those consuming treated rations ...
      . Sheep grazing pastures low in protein are particularly susceptible to
      urea poisoning ... . The short term feeding of protein concentrates before
      giving urea supplements can increase sheep's tolerance to urea ... .
      Experimental administration of 0.5 g/kg of urea has been shown to cause
      intoxication in the heaviest, while 0.8 g/kg resulted in poisoning in all
      the treated sheep ... . Urea poisoning in sheep is associated with an
      elevated blood ammonia concentration, increased erythrocyte counts and
      packed cell volume values, and decreased leucocyte counts ... . Detailed
      clinical biochemical studies on experimental urea poisoned sheep have been
      reported ... . The blood ammonia concentration of the fetus in fatally
      poisoned sheep is lower than that of the dam at death, and the ammonia
      concentrations in their livers, kidneys, spleen and muscles are similarly
      different. [Humphreys, D.J. Veterinary Toxicology. 3rd ed. London,
      England: Bailliere Tindell, 1988. 17]**PEER REVIEWED**

      On rabbit eyes saturated urea solution causes loss of epithelium from the
      cornea after five minutes contact, and produces moderate grayness of the
      stroma, with subsequent slow regeneration of the epithelium. A rabbit's
      cornea can return to normal in several weeks after exposure for an hour to
      40% urea solution. [Grant, W.M. Toxicology of the Eye. 3rd ed.
      Springfield, IL: Charles C. Thomas Publisher, 1986. 965]**PEER REVIEWED**

      Intravenous urea in monkeys has not damaged the ciliary epithelium,
      supporting a belief that reduction of intraocular pressure in glaucomatous
      patients is accomplished by an osmotic, rather than a toxic mechanism.
      However, intracarotid injection of concentrated urea in monkeys has done
      dramatic damage to the retina and the ciliary body. Retinal pigment
      epithelial cells are affected and blood-retina barrier broken down. The
      blood-aqueous barrier is broken down secondary to changes in the
      capillaries and selective damage to the ciliary body epithelium.
      Intraocular pressure is strikingly reduced and the aqueous outflow system
      rapidly shows swelling of the connective tissue of the inner wall of
      Schlemm's canal, and then edema of the trabecular meshwork. However, in
      several weeks there is general return to normal, except for failure of
      pigmented ciliary epithelium to regenerate. [Grant, W.M. Toxicology of the
      Eye. 3rd ed. Springfield, IL: Charles C. Thomas Publisher, 1986.
      965]**PEER REVIEWED**

      Serine-specific reagents, anticholinesterase organophosphorus compounds
      like VX provoke, in the micromolar range, digitalis-like ventricular
      arrhythmias of non-cholinergic origin in rodent hearts. The sensitivities
      of the two rat cardiac sodium + or - potassium ATPase isoforms (alpha 1
      and alpha 2) to VX (0.1-100 uM) were measured in sarcolemma vesicles. At 1
      microM VX, the inhibition of the total activity averaged 18% but never
      exceeded 75% with 100 uM. When the alpha 2 isoform activity was inhibited
      by 0.1 uM ouabain, alpha 1 was 35% inhibited by 1 uM VX, i.e. a 16 + or -
      4% inhibition of the total activity. The cardiac alpha 1 being related to
      the digitalis-induced toxicity, its selective inhibition by a micromolar
      dose of VX fully accounts for the cardiotoxicity of VX. Inasmuch as VX had
      no effect on the rat kidney alpha 1, differentially inactivated the
      cardiac isozymes and specifically reacted with serine residues, the
      putative binding-site(s) of the organophosphorus compound on the sodium +
      or - potassium ATPase molecules has been indicated.  [Robineau P et al;
      FEBS Lett 281 (1-2): 145-8 (1991)]**PEER REVIEWED**

      Accidental urea intoxication resulted in the death of 17 of 29 suckler
      cows within six hours after the contamination of their drinking water with
      urea fertiliser. The other cows showed no lasting ill effects and neither
      their three-month-old calves nor the stock bull were affected. The urea
      concentration in the water was 86 mmol/litre, and the concentrations of
      ammonia nitrogen in the rumen fluid of two of the cows which were examined
      after death were 1825 and 957 mg/litre.  [Caldow GL, Wain EB; Vet Rec 128
      (21): 489-91 (1991)]**PEER REVIEWED**

NON-HUMAN TOXICITY VALUES:
      LD100 Sheep 500 mg/l; mean survival time: 165 minutes [Edjtehad; M et al;
      Canadian J Comp Med 64 (1): 63-68 (1978) as cited in Environment Canada;
      Tech Info for Problem Spills: Urea p.46 (1985)]**PEER REVIEWED**

      LD50 Sheep acute oral 28.5 g/100 kg [Booth, N.H., L.E. McDonald (eds.).
      Veterinary Pharmacology and Therapeutics. 5th ed. Ames, Iowa: Iowa State
      University Press, 1982. 1029]**PEER REVIEWED**


METABOLISM/PHARMACOKINETICS:


ABSORPTION, DISTRIBUTION & EXCRETION:
      SOME SMALL, WATER SOL, BUT NONIONIZABLE COMPD SUCH AS UREA READILY
      TRAVERSE MAMMALIAN MEMBRANES, PROBABLY ALONG WITH WATER, BY WAY OF THE
      PORES. THIS FILTRATION PROCESS IS PARTICULARLY RAPID BETWEEN CAPILLARIES
      &amp; EXTRACELLULAR FLUID. [Hayes, W. J., Jr. Toxicology of Pesticides
      Baltimore: Williams &amp; Wilkins, 1975. 130]**PEER REVIEWED**

      ... UREA ... PENETRATES OTHER CELLS RAPIDLY, ENTERS THE BRAIN ONLY VERY
      SLOWLY ... [LaDu, B.N., H.G. Mandel, and E.L. Way. Fundamentals of Drug
      Metabolism and Disposition. Baltimore: Williams and Wilkins, 1971.
      51]**PEER REVIEWED**

      ... DISTRIBUTED APPROX IN TOTAL BODY WATER ... HAVE BEEN USED FOR
      MEASUREMENT OF TOTAL BODY WATER. [LaDu, B.N., H.G. Mandel, and E.L. Way.
      Fundamentals of Drug Metabolism and Disposition. Baltimore: Williams and
      Wilkins, 1971. 53]**PEER REVIEWED**

      EXCRETION OF UREA DURING SWEATING IN MAN: 1.84 SWEAT/PLASMA RATIO WITH PKA
      @ 13.8. /FROM TABLE/ [LaDu, B.N., H.G. Mandel, and E.L. Way. Fundamentals
      of Drug Metabolism and Disposition. Baltimore: Williams and Wilkins, 1971.
      143]**PEER REVIEWED**

      Regional variations in the absorption of benzoic acid, cortisone, urea,
      and water in sections obtained from the back and abdominal skin of male
      and female Osborne-Mendel rats were determined using in vitro diffusion
      cell techniques. Skin permeability constants and lag times were determined
      for the substances. Benzoic acid was absorbed from a petrolatum vehicle,
      and the other compounds were applied to the skin samples in an aqueous
      solution. Differences in absorption were compared with skin thickness
      measurements. The mechanism of sex related permeability differences was
      studied in castrated rats with subsequent permeability and histological
      examination of the skin. Results showed a sex related difference in
      variation of absorption in the back and abdominal skin of both sexes. In
      general, female back skin was approximately twice as permeable as male
      back skin. Abdominal skin, particularly in the male rat, was more
      permeable than back skin. The male rat back stratum corneum was
      approximately twice as thick as that of the female, correlating with the
      observed permeability differences. Similar stratum corneum thicknesses
      were observed in the abdominal skin from both sexes. The back skin of
      castrated males was similar in permeability and thickness to that of the
      females. [Bronaugh RL et al; J Soc Cosmet Chem 34: 127-35 (1983)]**PEER
      REVIEWED**

      The maternal and newborn renal function in 84 normal pregnant women
      delivering at term was investigated. There was no difference between
      maternal and newborn plasma concentrations of urea (3.9 + or - 1.0 vs. 3.9
      + or - 1.2 mmol/l) and creatinine (65.8 + or - 13.3 vs. 65.3 + or - 11.6
      mumols/l). Newborn urea with maternal urea concentrations (p = 0.0001),
      and newborn creatinine with maternal creatinine concentrations (p =
      0.0001). [Lao TT et al; Gynecol Obstet Invest 28 (2): 70-2 (1989)]**PEER
      REVIEWED**

MECHANISM OF ACTION:
      ... The primary mechanism of ammonia toxicosis appears to be inhibition of
      the citric acid cycle. There is an increase in anaerobic glycolysis, blood
      glucose, and blood lactate ... . Acidosis is manifested. The exact means
      by which ammonia blocks the citric acid cycle is not known. It is
      postulated that ammonia saturation of the glutamine-synthesizing system
      causes a backing-up in the citrate cycle, a decrease in its intermediates,
      and a decrease in energy production and cellular respiration, which leads
      to convulsions ... . The decrease of citrate cycle intermediates is
      postulated to result from reamination of pyruvic, ketoglutaric, and
      oxaloacetic acids. [Booth, N.H., L.E. McDonald (eds.). Veterinary
      Pharmacology and Therapeutics. 5th ed. Ames, Iowa: Iowa State University
      Press, 1982. 1031]**PEER REVIEWED**

INTERACTIONS:
      A case of sudden collapse after the intra-amniotic injection of 5 mg
      dinoprostone (Prostaglandin E2) and 40 g urea for pregnancy termination in
      a 36 yr old woman after the diagnosis of fetal Down's syndrome is
      reported. Within one minute of injection of a test dose of one mg of
      dinoprostone, the patient collapsed. Intravenous injections of 100 mg
      hydrocortisone and 10 mg chlorpheniramine maleate were administered and
      the patient was given oxygen by a face mask. Within 10 minutes blood
      pressure had returned to 110/68 mm Hg, and after a further 15 minutes
      pulse rate was normal. [Cameron IT, Baird DT; Lancet 2: 1046-7
      (1984)]**PEER REVIEWED**

      TREATMENT OF GUINEA PIGS WITH UREA INCR THE EFFECT OF THEIR SUBSEQUENT
      SENSITIZATION WITH EPOXY RESIN (EGK-19) OR K2CR207. UREA TREATMENT INCR
      PERCENTAGE OF ANIMALS SENSITIZED BY EPOXY RESINS FROM 50-87%. UREA ALONE
      DID NOT SENSITIZE SKIN. [ZIGLER F, ROETER A; DERMATOL VENEROL (SOFIA) 18
      (1): 25-28 (1979)]**PEER REVIEWED**

      The hemolytic action on human red blood cells (RBC) and the aggregations
      of human and rat red blood cells in the presence of sodium alginate were
      studied. Sodium alginate had no hemolytic action on human red blood cells.
      Human and rat red blood cells showed a marked aggregation by sodium
      alginate in a neutral medium. Sodium alginates having larger molecular
      weights showed more pronounced activities for aggregation of red blood
      cells as compared with those having smaller molecular weights, and the
      aggregation of red blood cells increased with an increase in the
      concentration of sodium alginate. The aggregation was inhibited by urea,
      suggesting the aggregation of red blood cells is caused by hydrogen
      bonding. When sodium alginate was added to human or rat blood rouleaux
      formation of red blood cells covered with fibrin net was observed in the
      coagulation cruor (blood clot). [Daigo K et al; Yakugaku Zasshi 102 (6):
      573-578 (1982)]**PEER REVIEWED**

      Osmotic diuretics (mannitol, urea) decrease the effect on serum lithium
      level; significant increase in lithium excretion. /Lithium-drug
      interactions; from table/ [Ellenhorn, M.J. and D.G. Barceloux. Medical
      Toxicology - Diagnosis and Treatment of Human Poisoning. New York, NY:
      Elsevier Science Publishing Co., Inc. 1988. 1043]**PEER REVIEWED**


PHARMACOLOGY:


THERAPEUTIC USES:
      Dermatologic Agents; Diuretics, Osmotic [National Library of Medicine's
      Medical Subject Headings online file (MeSH, 1999)]**QC REVIEWED**

      UREA IS /USED LESS COMMONLY THAN OTHER OSMOTIC AGENTS/ FOR THE SHORT-TERM
      REDUCTION OF INTRAOCULAR PRESSURE &amp; VITREOUS VOL ... IN ANGLE-CLOSURE
      GLAUCOMA .. PRIOR TO SURGERY ... IN CHRONIC GLAUCOMA ... PRE- AND
      POSTOPERATIVE TREATMENT. [American Medical Association. AMA Drug
      Evaluations Annual 1991. Chicago, IL: American Medical Association, 1991.
      1825]**PEER REVIEWED**

      DOSE--USUAL, IV INFUSION, 100 MG TO 1 G/KG DAILY, AS 30% SOLN IN DEXTROSE
      INJECTION @ RATE NOT EXCEEDING 4 ML/MIN. [GENNARO. REMINGTON'S PHARM SCI
      17TH ED 1985 p 935]**PEER REVIEWED**

      USED TOPICALLY IN THE TREATMENT OF PSORIASIS, ICHTHYOSIS, ATOPIC
      DERMATITIS, AND OTHER DRY, SCALY CONDITIONS. [GENNARO. REMINGTON'S PHARM
      SCI 17TH ED 1985 p 785]**PEER REVIEWED**

      Experimental: A study was made in which 57 symmetrically affected
      psoriatic patients applied to their lesions on opposite sides either 0.1%
      dithranol (anthralin) /urea cream (Psordrate 0.1%) or 0.1% beta-methasone
      valerate (Betnovate). After six weeks the dithranol/ urea cream proved to
      be more effective. [Ferguson A, Maden CJ; Br J Clin Prac 36: 60-67
      (1982)]**PEER REVIEWED**

      The efficacy of oral urea in producing a sufficiently high osmotic
      diuresis was studied in 7 patients with the syndrome of inappropriate
      secretion of antidiuretic hormone. In all patients, urea corrected the
      hyponatremia despite a normal fluid intake. Five patients were controlled
      with a dose of 30 g daily. The patients who needed 30 g drank up to 2
      liters of fluid daily, while those who needed 60 g drank up to 3
      liters/day. No major side effects were noted, even after treatment periods
      of up to 270 days. It was concluded that urea is a safe and efficacious
      treatment of the syndrome of inappropriate secretion of antidiuretic
      hormone. [Decaux G, Genette F; Br Med 283: 1081-1083 (1981)]**PEER
      REVIEWED**

      Experimental: Use of urea kinetics in the estimation of protein balance of
      nutritionally unstable renal failure patients, and for optimal management
      of nutrition therapy. [Bennett N; Nutr Support Serv 4: 21-25 (1984)]**PEER
      REVIEWED**

      Experimental: A number of studies evaluating an osmotic cervical dilator
      consisting of polyvinyl foam saturated with magnesium sulfate in women
      undergoing mid trimester abortion with intra-amniotic hyperosmolar urea
      plus prostaglandin F2A were completed. Comparisons with women receiving no
      pre-treatment with a laminaria tent or with one laminaria indicate that
      their use appears to shorten injection-abortion intervals, particularly in
      parous women, and reduce risk of endometritis and cervical laceration
      compared to women not receiving any type of device. The data suggests that
      two osmotic dilators may be more effective than one. Also, magnesium
      toxicity does not appear to be a substantial risk with their use. [Atienza
      MF et al; Contraception 30 (3): 215-223 (1984)]**PEER REVIEWED**

      EXPTL: REPORTED HELPFUL IN TREATING SICKLE-CELL CRISIS [Hawley, G.G. The
      Condensed Chemical Dictionary. 9th ed. New York: Van Nostrand Reinhold
      Co., 1977.  905]**PEER REVIEWED**

      In patients with squamous cell carcinoma of palpebral and bulbar
      conjunctiva, repeated applications of urea powder have been made to
      eradicate the malignant growth. [Grant, W.M. Toxicology of the Eye. 3rd
      ed. Springfield, IL: Charles C. Thomas Publisher, 1986. 965]**PEER
      REVIEWED**

      A sterile preparation of urea (UREAPHIL) is available that may be
      reconstituted for intravenous use. When administered in this manner, the
      solution contains 30% urea and either 5 or 10% dextrose or invert sugar
      (equal parts of dextrose and fructose). Intravenous doses of 1 to 1.5 g of
      urea per kilogram of body weight are optimal in preparation for
      neurosurgical procedures or for reduction of intraocular pressure. On a
      molar basis urea is less effective as a diuretic than is mannitol, since
      approximately 50% of the compound is reabsorbed from the tubular fluid.
      [Gilman, A.G., T.W. Rall, A.S. Nies and P. Taylor (eds.). Goodman and
      Gilman's The Pharmacological Basis of Therapeutics. 8th ed. New York, NY.
      Pergamon Press, 1990. 715]**PEER REVIEWED**

      UREA HAS BEEN USED AS AN INSECT (MOSQUITO) REPELLENT. [HILL JA ET AL; MOSQ
      NEWS 39 (2): 307-310 (1979)]**QC REVIEWED**

DRUG WARNINGS:
      UREA SHOULD NOT BE USED IN PATIENTS WITH SEVERELY IMPAIRED RENAL FUNCTION.
      [American Medical Association, AMA Department of Drugs, AMA Drug
      Evaluations. 3rd ed. Littleton, Massachusetts: PSG Publishing Co., Inc.,
      1977. 936]**PEER REVIEWED**

      UREA IS OFTEN RECONSTITUTED WITH INVERT SUGAR SOLN. INVERT SUGAR CONTAINS
      FRUCTOSE, WHICH CAN CAUSE SEVERE REACTION (HYPOGLYCEMIA, NAUSEA, VOMITING,
      TREMORS, COMA, &amp; CONVULSIONS) IN PATIENTS WITH HEREDITARY FRUCTOSE
      INTOLERANCE (ALDOLASE DEFICIENCY). [American Medical Association, AMA
      Department of Drugs, AMA Drug Evaluations. 3rd ed. Littleton,
      Massachusetts: PSG Publishing Co., Inc., 1977. 936]**PEER REVIEWED**

INTERACTIONS:
      A case of sudden collapse after the intra-amniotic injection of 5 mg
      dinoprostone (Prostaglandin E2) and 40 g urea for pregnancy termination in
      a 36 yr old woman after the diagnosis of fetal Down's syndrome is
      reported. Within one minute of injection of a test dose of one mg of
      dinoprostone, the patient collapsed. Intravenous injections of 100 mg
      hydrocortisone and 10 mg chlorpheniramine maleate were administered and
      the patient was given oxygen by a face mask. Within 10 minutes blood
      pressure had returned to 110/68 mm Hg, and after a further 15 minutes
      pulse rate was normal. [Cameron IT, Baird DT; Lancet 2: 1046-7
      (1984)]**PEER REVIEWED**

      TREATMENT OF GUINEA PIGS WITH UREA INCR THE EFFECT OF THEIR SUBSEQUENT
      SENSITIZATION WITH EPOXY RESIN (EGK-19) OR K2CR207. UREA TREATMENT INCR
      PERCENTAGE OF ANIMALS SENSITIZED BY EPOXY RESINS FROM 50-87%. UREA ALONE
      DID NOT SENSITIZE SKIN. [ZIGLER F, ROETER A; DERMATOL VENEROL (SOFIA) 18
      (1): 25-28 (1979)]**PEER REVIEWED**

      The hemolytic action on human red blood cells (RBC) and the aggregations
      of human and rat red blood cells in the presence of sodium alginate were
      studied. Sodium alginate had no hemolytic action on human red blood cells.
      Human and rat red blood cells showed a marked aggregation by sodium
      alginate in a neutral medium. Sodium alginates having larger molecular
      weights showed more pronounced activities for aggregation of red blood
      cells as compared with those having smaller molecular weights, and the
      aggregation of red blood cells increased with an increase in the
      concentration of sodium alginate. The aggregation was inhibited by urea,
      suggesting the aggregation of red blood cells is caused by hydrogen
      bonding. When sodium alginate was added to human or rat blood rouleaux
      formation of red blood cells covered with fibrin net was observed in the
      coagulation cruor (blood clot). [Daigo K et al; Yakugaku Zasshi 102 (6):
      573-578 (1982)]**PEER REVIEWED**

      Osmotic diuretics (mannitol, urea) decrease the effect on serum lithium
      level; significant increase in lithium excretion. /Lithium-drug
      interactions; from table/ [Ellenhorn, M.J. and D.G. Barceloux. Medical
      Toxicology - Diagnosis and Treatment of Human Poisoning. New York, NY:
      Elsevier Science Publishing Co., Inc. 1988. 1043]**PEER REVIEWED**

MINIMUM FATAL DOSE LEVEL:
      In ruminants unaccustomed to urea, ingestion of 0.3-0.5 g urea/kg may be
      toxic ... The toxic dose of urea in (presumably unaccustomed) cattle is
      0.45 g/kg (50 g total dose) but that animals can ingest more urea than
      this if the dose is increased gradually. [Booth, N.H., L.E. McDonald
      (eds.). Veterinary Pharmacology and Therapeutics. 5th ed. Ames, Iowa: Iowa
      State University Press, 1982. 1029]**PEER REVIEWED**


ENVIRONMENTAL FATE & EXPOSURE:


ENVIRONMENTAL FATE/EXPOSURE SUMMARY:
      Urea occurs naturally in urine and animal waste and can be formed
      naturally in the environment through protein metabolism. It is
      artificially released to the environment through direct application to
      soil as a nitrogen-release fertilizer. If released to the atmosphere, urea
      will degrade rapidly in the vapor-phase by reaction with photochemically
      produced hydroxyl radicals (half-life of 9.6 hr). If released to soil,
      urea is hydrolyzed to ammonium through soil urease activity (the basis of
      its use as a fertilizer). The rate of hydrolysis can be fast (24 hr);
      however, a number a variables (such as increasing the pellet size of the
      fertilizer) can decrease the degradation rate from days to weeks. If
      released to water, urea can degrade readily through biotic hydrolysis as
      demonstrated by various screening studies. The presence of
      naturally-occurring phytoplankton increases the degradation rate because
      phytoplankton use urea as a nitrogen source and because urea is decomposed
      by phytoplankton photosynthesis. In phytoplankton-rich waters, degradation
      occurs much faster in sunlight than in the dark. Abiotic hydrolysis of
      urea occurs very slowly in relation to biotic hydrolysis. Occupational
      exposure to urea occurs through dermal contact and inhalation of dust,
      especially to workers applying urea fertilizers. (SRC) **PEER REVIEWED**

PROBABLE ROUTES OF HUMAN EXPOSURE:
      Occupational exposure to urea occurs through dermal contact and inhalation
      of dust, especially to workers applying urea fertilizers(1). [(1)
      Parmeggiani L; Encyl Occup Health &amp; Safety 3rd ed. Geneva,
      Switzerland: International Labour Office p. 846-8 (1983)]**PEER REVIEWED**

      The National Occupational Hazard Survey conducted by NIOSH estimated that
      855,894 workers may be exposed to urea; 7% from actual observed use, 31%
      from observed use of a tradename product known to contain this chemical,
      and 62% from observed use of a product in some type of general use which
      leads NIOSH to suspect that this chemical may be contained in the product.
      [NIOSH National Hazard Exposure Survey (1972-1974)]**PEER REVIEWED**

      NIOSH (NOES Survey 1981-1983) has statistically estimated that 661,00
      workers are potentially exposed to urea in the USA(1). NIOSH (NOHS Survey
      1972-1974) has statistically estimated that 855,894 workers are
      potentially exposed to urea in the USA(2). [(1) NIOSH; National
      Occupational Exposure Survey (NOES) (1983) (2) NIOSH; National
      Occupational Hazard Survey (NOHS) (1974)]**PEER REVIEWED**

NATURAL POLLUTION SOURCES:
      Urea is a natural product of nitrogen and protein metabolism(1,3); it
      occurs in urine(2) and animal waste(3). Urea can be formed in natural
      waters as a result of protein decomposition(3). [(1) Windholz M; The Merck
      Index 10th ed. Rahway, NJ: Merck &amp; Co p. 1410 (1983) (2) Mavrovic I,
      Shirley AR Jr; Kirk-Othmer Encycl Chem Technol 3rd ed, NY: John Wiley
      &amp; Sons Inc 23: 548 (1983) (3) Brockett OD; Water Res 11: 317-21
      (1977)]**PEER REVIEWED**

ARTIFICIAL POLLUTION SOURCES:
      In its primary use, urea is released to the environment through direct
      application to soil as a nitrogen-release fertilizer(1). Small amounts of
      urea can be released in wastewater effluents from manufacturing and use
      sites(1). [(1) Mavrovic I, Shirley AR Jr; Kirk-Othmer Encycl Chem Technol
      3rd ed. NY: John Wiley &amp; Sons Inc 23: 548-75 (1983)]**PEER REVIEWED**

ENVIRONMENTAL FATE:
      Terrestial Fate: A forest fertilization study led to the conclusion that
      application rates less than 224 kg/ha (200 lb N2/acre) were ineffective in
      supplying nitrogen. Urea applications above this threshold brought about
      increases in soil nitrogen, pH, absorbed ammonia, and cation exchange
      capacity, the latter especially in surface and litter material. Addition
      of urea appeared to have adverse effects on the uptake of phosphorus.
      [Baker J; Some Effects of Urea Fertilization on Soil Characteristics and
      Tissue Mineral Content in Overstocked Western Hemlock Stands. Canadian
      Forestry Service Report No. BC-X-39 (1970) as cited in Environment Canada;
      Tech Info for Problem Spills: Urea p.47 (1985)]**PEER REVIEWED**

      Terrestrial Fate: Urea fertilizer was applied to a pasture and the runoffs
      were measured. Maximum concn of runoff was attained for ammonia nitrogen 3
      weeks after application and for nitrate nitrogen 1 week after application.
      In the runoff, ammonia-nitrogen was only 0.3% of that applied, nitrogen
      nitrate was 1.0%, and total nitrogen was 7.1% of that applied. It was
      concluded that most of the applied urea will not run off. [Sharpley AN et
      al; Water, Air and Soil Pollution 14 (3): 425-430 (1983) as cited in
      Environment Canada; Tech Info for Problem Spills: Urea p.47 (1985)]**PEER
      REVIEWED**

      Terrestrial and Aquatic Fate: If the soil surface is saturated with
      moisture at the time of the spill, as might be the case after a rainfall,
      the spilled /urea/ may run off into the surface water. ... Upon reaching
      the groundwater table, the contaminant will continue to move, now in the
      direction of groundwater flow. A contaminated plume will be produced, with
      diffusion and dispersion serving to reduce the acid concn. [Environment
      Canada; Tech Info for Problem Spills: Urea p.37 (1985)]**PEER REVIEWED**

      Terrestrial Fate: When solid urea is spilled, only a limited groundwater
      contamination hazard exists if the soil is dry and if no precipitation
      falls prior to cleanup. ... Concentrated solutions of /urea/ can
      infiltrate the soil. Some interaction between urea and the soil will
      occur. However, much of the urea exchanged ions will migrate downward
      /SRP: as well as lateral/ through the soil. [Environment Canada; Tech Info
      for Problem Spills: Urea p.37 (1985)]**PEER REVIEWED**

      TERRESTRIAL FATE: Various field and laboratory studies have demonstrated
      that urea degrades rapidly in most soils(1-3). In general, urea is rapidly
      hydrolyzed to ammonium through soil urease activity(1). In various soils,
      the hydrolysis may near completion within 24 hrs(2); however, the rate of
      hydrolysis can be much slower depending upon soil type, moisture content,
      and urea formulation(1). For example, increasing the pellet size of urea
      fertilitizers can decrease the urea decomposition rate from days to
      weeks(1). Soil adsorption studies have demonstrated that urea adsorbs very
      weakly to soil(4); therefore, leaching is possible(SRC). Ultimate urea
      degradation produces ammonia and CO2 as volatile products(5). [(1) Malhi
      SS, Nyborg M; Plant Soil 51: 177-86 (1979) (2) Sankhayan SD, Shukla UC;
      Geoderma 16: 171-8 (1976) (3) Scheunert I et al; Chemosphere 16: 1031-41
      (1987) (4) Hance RJ; Weed Res 5: 98-107 (1965) (5) Mavrovic I, Shirley AR
      Jr; Kirk-Othmer Encycl Chem Technol 3rd ed. NY: John Wiley &amp; Sons Inc
      23: 548 (1983)]**PEER REVIEWED**

      AQUATIC FATE: Biodegradation is expected to be the major fate process in
      the aquatic ecosystem. Various screening studies have demonstrated that
      urea can biodegrade readily(1-5) with the release of CO2 and ammonia. The
      rate of biodegradation generally decreases with decreasing
      temperatures(4); under cold winter-like conditions, biodegradation may be
      relatively slow (0-6% per day)(4). The presence of naturally-occurring
      phytoplankton increases the degradation rate(2,5) because phytoplankton
      use urea as a nitrogen source(2) and because urea is decomposed by
      phytoplankton photosynthesis(5); in phytoplankton-rich waters, degradation
      occurs much faster in sunlight than in the dark(5). Abiotic hydrolysis of
      urea occurs very slowly in relation to biotic hydrolysis(6); abiotic
      hydrolysis yields ammonium carbamate which decomposes to form CO2 and
      ammonia(6); the enzyme urease catalyzes urea hydrolysis(6).
      Volatilization, bioconcentration and adsorption to sediment are not
      expected to be important fate processes(SRC). [(1) Freitag D et al;
      Chemosphere 14: 1589-616 (1985) (2) Remsen CC; Ecology 53: 921-6 (1972)
      (3) Scheunert I et al; Chemosphere 16: 1031-41 (1987) (4) Evans WH et al;
      Water Res 7: 975-85 (1973) (5) Mitamura O, Saijo Y; Marine Biology 58:
      147-152 (1980) (6) Stiff MJ, Gardiner DK; Water Treat Exam 22: 259-68
      (1973)]**PEER REVIEWED**

      ATMOSPHERIC FATE: Based upon a vapor pressure of 1.2X10-5 mm Hg at 25 deg
      C(1), urea can exist in both the vapor and particulate-phases in the
      ambient atmosphere, although the vapor-phase can be expected to
      dominate(2,SRC). It will degrade rapidly in the vapor-phase by reaction
      with photochemically produced hydroxyl radicals with an estimated
      half-life of 9.6 hr(3,SRC). Particulate-phase urea and aerosols released
      to air during spray applications of urea fertilizers will be removed from
      air physically by dry and wet deposition(SRC). [(1) Jones AH; J Chem Eng
      Data 5: 196-200 (1960) (2) Bidleman TF; Environ Sci Technol 22: 361-7
      (1988) (3) Atkinson R; Environ Toxicol Chem 7: 435-42 (1988)]**PEER
      REVIEWED**

ENVIRONMENTAL BIODEGRADATION:
      Waste water treatment: degradation rate by psychrophilic bacteria: at 20
      deg C: maximum: 11.6 mg/l/hr with an average of 10.9 mg/l/hr; at 2 deg C:
      maximum: 4.0 mg/l/hr with an average of 3.2 mg/l/hr. [Verschueren, K.
      Handbook of Environmental Data of Organic Chemicals. 2nd ed. New York, NY:
      Van Nostrand Reinhold Co., 1983. 1178]**PEER REVIEWED**

      At 100 mg/l, no inhibition of NH3 oxidation by Nitrosomonas sp /was
      observed/. [Verschueren, K. Handbook of Environmental Data of Organic
      Chemicals. 2nd ed. New York, NY: Van Nostrand Reinhold Co., 1983.
      1178]**PEER REVIEWED**

      /Urea concentrations/ from 1 to 15 mg/l for up to 14 days in river water
      at   <  8 deg C exhibited negligible degradation; the same concentrations
      at 4 to 6 days in river water a 20 deg C exhibited complete degradation.
      /Data derived from table/ [Evans WH, Patterson S; Water Res 7: 975-985
      (1973) as cited in Environment Canada; Tech Info for Problem Spills: Urea
      p.48 (1985)]**PEER REVIEWED**

      Using an activated sludge seed, a CO2 evolution of 85.9% was measured over
      a 5-day incubation period(1). At the relatively high concns of 20-100 ppm,
      5-day theoretical BODs of 0% were measured in freshwater and synthetic
      seawater to which a raw wastewater seed was added(2). In a river die-away,
      1.05-2.20% of added urea hydrolyzed after 10-days while only 0.35%
      hydrolyzed in sterile controls(3). Urea was completely biodegraded in
      aerobic biodegradation studies using activated sludge and a 14-day
      incubation period(4). In degradation studies using estuary and coastal
      waters from Georgia, avg urea degradation rates of 6.2 to 19.6 nmoles/L-hr
      were observed(5); phytoplankton in the waters were responsible for the
      major urea decomposition(5). In a 5-day CO2 evolution study using a
      suspended soil inocula, CO2 evolution was 70.1% in anaerobic conditions
      and 66.3% in aerobic conditions(6). [(1) Freitag D et al; Chemosphere 14:
      1589-616 (1985) (2) Takemoto S et al; Suishitsu Odaku Kenkyu 4: 80-90
      (1981) (3) Atkinson R; Water Treat Exam 20: 193-203 (1971) (4) Ebisuno T
      et al; Seitai Kagaku 7: 27-34 (1984) (5) Remsen CC; Ecology 53: 921-6
      (1972) (6) Scheunert I et al; Chemosphere 16: 1031-41 (1987)]**PEER
      REVIEWED**

      The degradation of urea was examined in a river die-away study using
      various river waters and various test conditions(1); the degradation rate
      increased with increasing temperatures; at 20 deg C, degradation was
      general complete within 6-14 days of incubation while in some waters at
      lower temperatures (4-12 deg C) little or no degradation occurred in 10-14
      days(1); below 8 deg C (simulating winter conditions), a maximum daily
      degradation of 3-6% was observed during the first 7 days of incubation(1);
      depending upon the source of the water, degradation under aerobic
      conditions varied from slightly faster to more than twice as fast as
      compared to anaerobic conditions(1). In 4-day CO2 evolution tests using
      waters collected from three regions of the Pacific Ocean, CO2 evolution
      was observed to occur much faster in sunlight than in dark controls (the
      ratio of light to light+dark was 61.6-86.4%)(2); the reason for the
      accelerated rate in sunlight is that urea is actively decomposed by
      photosynthesis of phytoplankton that occur in seawater(2). [(1) Evans WH
      et al; Water Res 7: 975-85 (1973) (2) Mitamura O, Saijo Y; Marine Biology
      58: 147-152 (1980)]**PEER REVIEWED**

ENVIRONMENTAL ABIOTIC DEGRADATION:
      The rate constant for the vapor-phase reaction of urea with
      photochemically produced hydroxyl radicals has been estimated to be
      4X10-11 cu cm/molecule-sec at 25 deg C which corresponds to an atmospheric
      half-life of about 9.6 hr at an atmospheric concn of 5X10+5 hydroxyl
      radicals per cu cm(1,SRC). The rate constant for the reaction between
      photochemically produced hydroxyl radicals in water and urea is reported
      to be 7.9X10+5 L/mole-sec(2); assuming that the conc of hydroxyl radicals
      in brightly sunlit natural water is 1X10-17 M(3), the half-life would be
      in excess of 3000 yrs of continuous (24 hr/day) sunlight(SRC). In one
      photodegradation study using a silica gel adsorbent(4), only 0.2% of
      applied urea photomineralized after a 17-hr irradiation with a UV lamp
      (  > 290 nm). [(1) Atkinson R; Environ Toxicol Chem 7: 435-42 (1988) (2)
      Buxton GV et al; J Phys Chem Ref Data 17: 727 (1988) (3) Mill T et al; Sci
      207: 886-7 (1980) (4) Freitag D et al; Chemosphere 14: 1589-616
      (1985)]**PEER REVIEWED**

      In aqueous solution, urea is in equilibrium with ammonia and isocyanate
      ions(1); in the absence of microorganisms, urea hydrolyzes very slowly to
      yield ammonium carbamate which decomposes to form ammonia and carbon
      dioxide(2). The hydrolysis is catalyzed by increasing temperatures,
      increasing alkalinity, and especially, by the presence of the enzyme
      urease(1); in hydrolysis studies where urease was artificially added to
      aqueous urea solutions, 20 to 50% of initial urea hydrolyzed in 3 hr at
      respective temperatures of 2 to 10 deg C(1); at 0 deg C (with added
      urease), hydrolysis ranged from 25 to 100% after 24 hr at respective pHs
      of 6.4 to 8.4(1). At 5 deg C in demineralized/distilled water, only 0.35%
      of added urea hydrolyzed during a 10-day test period(3). [(1) Stiff MJ,
      Gardiner DK; Water Treat Exam 22: 259-68 (1973) (2) Mavrovic I, Shirley AR
      Jr; Kirk-Othmer Encycl Chem Technol 3rd ed. NY: John Wiley &amp; Sons Inc
      23: 548 (1983) (3) Atkinson R; Water Treat Exam 20: 193-203 (1971)]**PEER
      REVIEWED**

ENVIRONMENTAL BIOCONCENTRATION:
      In 6 to 72 hr bioaccumulation studies using carp (Cyprinus carpio) and a
      static flow system, the concn of urea was found to be equally distributed
      in all organs and in the water at all time periods(1); thus, the BCF would
      be only 1(SRC). In 3-day static-system tests using golden ide fish
      (Leuciscus idus melanotus), the BCF of urea was less then 10(2). [(1)
      Gluth G et al; Comp Biochem Physiol 81C: 273-7 (1985) (2) Freitag D et al;
      Chemosphere 14: 1589-616 (1985)]**PEER REVIEWED**

SOIL ADSORPTION/MOBILITY:
      Urea is essentially non-volatile. [Environment Canada; Tech Info for
      Problem Spills: Urea p.21 (1985)]**PEER REVIEWED**

      The adsorption of urea was measured in six different British soils with
      organic carbon contents ranging from 1.76 to 36.5%(1); no adsorption was
      measurable in five of the soils(1); in the sixth soil (36.5% organic
      carbon), a KOC of 8 can be determined from the measured Freundlich
      isotherm(1,SRC); according to a suggested classification scheme(2), a Koc
      value of 8 indicates high mobility in soil(SRC). It has been reported that
      urea can adsorb to humic acids through a free-radical addition interaction
      to form a complex(3). [(1) Hance RJ; Weed Res 5: 98-107 (1965) (2) Swann
      RL et al; Res Rev 85: 23 (1983) (3) Choudhry GG; Toxicol Environ Chem 6:
      127-71 (1983)]**PEER REVIEWED**

VOLATILIZATION FROM WATER/SOIL:
      Based upon a measured water solubility of 5.45X10+5 mg/L(1) and an
      extrapolated vapor pressure of 1.2X10-5 mm Hg at 25 deg C(2,SRC), the
      Henry's Law constant for urea can be estimated to be 1.74X10-12 atm cu
      m/mole(SRC); a Henry's Law constant of this magnitude indicates that urea
      is essentially non-volatile from environmental waters(3,SRC). [(1)
      Yalkowsky SH; Arizona Database of Aqueous Solubilities. Univ of AZ,
      College of Pharmacy (1989) (2) Jones AH; J Chem Eng Data 5: 196-200 (1960)
      (3) Lyman WJ et al; Handbook of Chemical Property Estimation Methods
      Washington, DC: Amer Chem Soc pp. 15-15 to 15-29 (1990)]**PEER REVIEWED**

ENVIRONMENTAL WATER CONCENTRATIONS:
      SURFACE WATER: Urea concns in surface waters off the continental shelf
      between Panama and Callao, Peru varied from 0.54-5.00 ug/L(1); along the
      continental shelf of the northeast US between Cape Cod and Cape May, urea
      concn varied from a low of 0.25 ug/L (in a deep water sample) to a high of
      11.20 ug/L in New York Harbor(1). In monitoring conducted in Mar 1971,
      urea concns ranged from 36 to 535 ug/L in the Savannah-Wilmington-Ogeechee
      estuaries and adjacent coastal waters in Georgia(2). The following urea
      concns were detected in water samples collected from three regions of the
      Pacific Ocean(3): 0.85-1.43 ug/L (Sagami Bay, Japan), 0.19-0.51 ug/L
      (northwestern Pacific central waters), and 0.17-0.40 ug/L (subarctic
      Pacific waters)(3). [(1) Remsen CC; Limnol Oceanogr 16: 732-40 (1971) (2)
      Remsen CC; Ecology 53: 921-6 (1972) (3) Mitamura O, Saijo Y; Marine
      Biology 58: 147-152 (1980)]**PEER REVIEWED**

EFFLUENT CONCENTRATIONS:
      Contents of domestic sewage: 2-6 mg/L; domestic sewer effluent: 0.020
      mg/L; primary domestic sewage plant effluent: 0.016-0.043 mg/L
      [Verschueren, K. Handbook of Environmental Data of Organic Chemicals. 2nd
      ed. New York, NY: Van Nostrand Reinhold Co., 1983. 1178]**PEER REVIEWED**


ENVIRONMENTAL STANDARDS & REGULATIONS:


FIFRA REQUIREMENTS:
      Residues of urea are exempted from the requirement of a tolerance when
      used as a stabilizer or inhibitor in accordance with good agricultural
      practices as inert (or occasionally active) ingredients in pesticide
      formulations applied to growing crops or to raw agricultural commodities
      after harvest. [40 CFR 180.1001(c) (7/1/91)]**PEER REVIEWED**

      Urea is exempted from the requirement of a tolerance when used as a
      adjuvant/intensifier for herbicides in accordance with good agricultural
      practice as inert (or occasionally active) ingredients in pesticide
      formulations applied to growing crops only. [40 CFR 180.1001(d)
      (7/1/91)]**PEER REVIEWED**

      Urea is exempted from the requirement of a tolerance when used as a
      stabilizer or inhibitor in accordance with good agricultural practice as
      inert (or occasionally active) ingredients in pesticide formulations
      applied to animals. [40 CFR 180.1001(e) (7/1/91)]**PEER REVIEWED**

      As the federal pesticide law FIFRA directs, EPA is conducting a
      comprehensive review of older pesticides to consider their health and
      environmental effects and make decisions about their future use. Under
      this pesticide reregistration program, EPA examines health and safety data
      for pesticide active ingredients initially registered before November 1,
      1984, and determines whether they are eligible for reregistration. In
      addition, all pesticides must meet the new safety standard of the Food
      Quality Protection Act of 1996. Pesticides for which EPA had not issued
      Registration Standards prior to the effective date of FIFRA, as amended in
      1988, were divided into three lists based upon their potential for human
      exposure and other factors, with List B containing pesticides of greater
      concern and List D pesticides of less concern. Urea is found on List D.
      Case No: 4096; Pesticide type: antimicrobial; Case Status: No products
      containing the pesticide are actively registered ... The case /is
      characterized/ as "cancelled." Under FIFRA, pesticide producers may
      voluntarily cancel their registered products. EPA also may cancel
      pesticide registrations if registrants fail to pay required fees or
      make/meet certain reregistration commitments, or if EPA reaches findings
      of unreasonable adverse effects.; Active ingredient (AI): Urea; AI Status:
      The active ingredient is no longer contained in any registered pesticide
      products ... "cancelled." [USEPA/OPP; Status of Pesticides in
      Registration, Reregistration and Special Review p.343 (Spring, 1998) EPA
      738-R-98-002]**QC REVIEWED**

FDA REQUIREMENTS:
      Substance added directly to human food affirmed as generally recognized as
      safe (GRAS). [21 CFR 184.1923 (4/1/91)]**PEER REVIEWED**

ALLOWABLE TOLERANCES:
      Residues of urea are exempted from the requirement of a tolerance when
      used as a stabilizer or inhibitor in accordance with good agricultural
      practices as inert (or occasionally active) ingredients in pesticide
      formulations applied to growing crops or to raw agricultural commodities
      after harvest. [40 CFR 180.1001(c) (7/1/91)]**PEER REVIEWED**

      Urea is exempted from the requirement of a tolerance when used as a
      adjuvant/intensifier for herbicides in accordance with good agricultural
      practice as inert (or occasionally active) ingredients in pesticide
      formulations applied to growing crops only. [40 CFR 180.1001(d)
      (7/1/91)]**PEER REVIEWED**

      Urea is exempted from the requirement of a tolerance when used as a
      stabilizer or inhibitor in accordance with good agricultural practice as
      inert (or occasionally active) ingredients in pesticide formulations
      applied to animals. [40 CFR 180.1001(e) (7/1/91)]**PEER REVIEWED**


CHEMICAL/PHYSICAL PROPERTIES:


MOLECULAR FORMULA:
      C-H4-N2-O [Budavari, S. (ed.). The Merck Index - Encyclopedia of
      Chemicals, Drugs and Biologicals. Rahway, NJ: Merck and Co., Inc., 1989.
      1553]**PEER REVIEWED**

MOLECULAR WEIGHT:
      60.06 [Budavari, S. (ed.). The Merck Index - Encyclopedia of Chemicals,
      Drugs and Biologicals. Rahway, NJ: Merck and Co., Inc., 1989. 1553]**PEER
      REVIEWED**

COLOR/FORM:
      WHITE CRYSTALS [Sax, N.I. Dangerous Properties of Industrial Materials.
      6th ed. New York, NY: Van Nostrand Reinhold, 1984. 2713]**PEER REVIEWED**

      TETRAGONAL PRISMS [Budavari, S. (ed.). The Merck Index - Encyclopedia of
      Chemicals, Drugs and Biologicals. Rahway, NJ: Merck and Co., Inc., 1989.
      1553]**PEER REVIEWED**

      COLORLESS TO WHITE, PRISMATIC CRYSTALS OR WHITE CRYSTALLINE POWDER [Osol,
      A. and J.E. Hoover, et al. (eds.). Remington's Pharmaceutical Sciences.
      15th ed. Easton, Pennsylvania: Mack Publishing Co., 1975. 864]**PEER
      REVIEWED**

ODOR:
      ALMOST ODORLESS; MAY GRADUALLY DEVELOP SLIGHT ODOR OF AMMONIA, ESP IN
      PRESENCE OF MOISTURE [Osol, A. and J.E. Hoover, et al. (eds.). Remington's
      Pharmaceutical Sciences. 15th ed. Easton, Pennsylvania: Mack Publishing
      Co., 1975. 864]**PEER REVIEWED**

TASTE:
      COOLING, SALINE TASTE [Osol, A. and J.E. Hoover, et al. (eds.).
      Remington's Pharmaceutical Sciences. 15th ed. Easton, Pennsylvania: Mack
      Publishing Co., 1975. 864]**PEER REVIEWED**

      Detection by taste of urea in water is as follows: 1.20 x 10-1 m/l (purity
      not specified); Taste values of chemically pure urea: 2.51 x 10-1
      moles/liter, 3.16 x 10-1 moles/liter, 3.98 x 10-1 moles/liter, 3.63 x 10-1
      moles/liter, 5.01 x 10-1 moles/liter. [ASTM; Compilation of Odor and Taste
      Threshold Values Data p.162 (1978)]**PEER REVIEWED**

MELTING POINT:
      132.70 deg C [Budavari, S. (ed.). The Merck Index - Encyclopedia of
      Chemicals, Drugs and Biologicals. Rahway, NJ: Merck and Co., Inc., 1989.
      1553]**PEER REVIEWED**

DENSITY/SPECIFIC GRAVITY:
      1.3230 @ 20 DEG C/4 DEG C [Lide, D.R. (ed). CRC Handbook of Chemistry and
      Physics. 72nd ed. Boca Raton, FL: CRC Press, 1991-1992.,p. 3-509]**PEER
      REVIEWED**

DISSOCIATION CONSTANTS:
      PKA: 0.1 @ 21 DEG C [Osol, A. and J.E. Hoover, et al. (eds.). Remington's
      Pharmaceutical Sciences. 15th ed. Easton, Pennsylvania: Mack Publishing
      Co., 1975. 864]**PEER REVIEWED**

OCTANOL/WATER PARTITION COEFFICIENT:
      log Kow = -2.11 [Hansch, C., Leo, A., D. Hoekman. Exploring QSAR -
      Hydrophobic, Electronic, and Steric Constants. Washington, DC: American
      Chemical Society., 1995. 3]**QC REVIEWED**

PH:
      7.2 (10% solution) [Environment Canada; Tech Info for Problem Spills: Urea
      p.4 (1985)]**PEER REVIEWED**

SOLUBILITIES:
      1 G DISSOLVES IN 1 ML WATER, 10 ML 95% ALC, 6 ML METHANOL, 1 ML BOILING
      95% ALC, 20 ML ABS ALC, 2 ML GLYCEROL; ALMOST INSOL IN CHLOROFORM, ETHER;
      SOL IN CONCN HCL [Budavari, S. (ed.). The Merck Index - Encyclopedia of
      Chemicals, Drugs and Biologicals. Rahway, NJ: Merck and Co., Inc., 1989.
      1553]**PEER REVIEWED**

      INSOL IN BENZENE; SOL IN ACETIC ACID [Weast, R.C. (ed.). Handbook of
      Chemistry and Physics. 60th ed. Boca Raton, Florida: CRC Press Inc.,
      1979.,p. C-536]**PEER REVIEWED**

      Sol in pyrimidine [Lide, D.R. (ed). CRC Handbook of Chemistry and Physics.
      72nd ed. Boca Raton, FL: CRC Press, 1991-1992.,p. 3-509]**PEER REVIEWED**

SPECTRAL PROPERTIES:
      MAX ABSORPTION (SODIUM HYDROXIDE): BELOW 220 NM; SADTLER REF NUMBER: 447
      (IR, PRISM) [Weast, R.C. (ed.). Handbook of Chemistry and Physics. 60th
      ed. Boca Raton, Florida: CRC Press Inc., 1979.,p. C-536]**PEER REVIEWED**

      IR: 123 (Sadtler Research Laboratories IR Grating Collection) [Weast, R.C.
      and M.J. Astle. CRC Handbook of Data on Organic Compounds. Volumes I and
      II. Boca Raton, FL: CRC Press Inc. 1985.,p. V2 415]**PEER REVIEWED**

      UV: 1-3 (Organic Electronic Spectral Data, Phillips et al, John Wiley
      &amp; Sons, New York) [Weast, R.C. and M.J. Astle. CRC Handbook of Data on
      Organic Compounds. Volumes I and II. Boca Raton, FL: CRC Press Inc.
      1985.,p. V2 415]**PEER REVIEWED**

      NMR: 16982 (Sadtler Research Laboratories Spectral Collection) [Weast,
      R.C. and M.J. Astle. CRC Handbook of Data on Organic Compounds. Volumes I
      and II. Boca Raton, FL: CRC Press Inc. 1985.,p. V2 415]**PEER REVIEWED**

      MASS: 7 (Aldermaston, Eight Peak Index of Mass Spectra, UK) [Weast, R.C.
      and M.J. Astle. CRC Handbook of Data on Organic Compounds. Volumes I and
      II. Boca Raton, FL: CRC Press Inc. 1985.,p. V2 415]**PEER REVIEWED**

VISCOSITY:
      1.78 mPas 46% solution at 20 deg C; 1.81 mPas at 137 deg C; 1.90 mPas
      (saturated solution at 20 deg C) [Environment Canada; Tech Info for
      Problem Spills: Urea p.3 (1985)]**PEER REVIEWED**

OTHER CHEMICAL/PHYSICAL PROPERTIES:
      ON FURTHER HEATING IT DECOMP TO BIURET, NH3, CYANURIC ACID; PH OF 10%
      WATER SOLN: 7.2; DENSITY OF WATER SOLN (WT/WT): 1.027 @ 10%; 1.054 @ 20%;
      1.145 @ 50% [Budavari, S. (ed.). The Merck Index - Encyclopedia of
      Chemicals, Drugs and Biologicals. Rahway, NJ: Merck and Co., Inc., 1989.
      1553]**PEER REVIEWED**

      ON STANDING OR ON HEATING, DECOMP INTO NH3 AND CO2 [Osol, A. and J.E.
      Hoover, et al. (eds.). Remington's Pharmaceutical Sciences. 15th ed.
      Easton, Pennsylvania: Mack Publishing Co., 1975. 864]**PEER REVIEWED**

      Ionization potential: 9 ev [Environment Canada; Tech Info for Problem
      Spills: Urea p.4 (1985)]**PEER REVIEWED**

      Latent heat of fusion: 15.1 kJ/mole (at melting point) [Environment
      Canada; Tech Info for Problem Spills: Urea p.4 (1985)]**PEER REVIEWED**

      Latent heat of sublimation: 87.9 kJ/mole at 25 deg C [Environment Canada;
      Tech Info for Problem Spills: Urea p.4 (1985)]**PEER REVIEWED**

      Heat of formation: -333.7 kJ/mole at 25 deg C [Environment Canada; Tech
      Info for Problem Spills: Urea p.4 (1985)]**PEER REVIEWED**

      Decomposition temperature 135 deg C [Environment Canada; Tech Info for
      Problem Spills: Urea p.3 (1985)]**PEER REVIEWED**

      Boiling point: urea decomposes before boiling. [Environment Canada; Tech
      Info for Problem Spills: Urea p.1 (1985)]**PEER REVIEWED**

      The possibility of improving the dissolution of chlorthalidone (Hygroton)
      via solid dispersion techniques was investigated by means of phase
      diagrams. Physical mixtures and melts of various compositions of
      chlorthalidone and urea were prepared. Substantial increases in
      dissolution rate were found for molten discs and compressed molten discs
      with a chlorthalidone concn of 35% w/w, as compared to physical mixtures.
      Urea generally enhanced dissolution in all forms. Thermodynamic parameters
      of the interaction between chlorthalidone and urea are also reported.
      [Bloch DW et al; Drugs Made Ger 25: 231-235 (1982)]**PEER REVIEWED**

      The effect of urea (1), thiourea (2), niacinamide (3), succinamide (4),
      succinimide sodium (5), saccharin sodium (6), caffeine citrate (7), ...
      caffeine (8) on the solubility of hydrochlorothiazide and chlorothiazide
      in water was studied with the exception of (4), all of the tested
      compounds increased the solubility of both diuretics. Solubility in (5),
      (6), (7), and (8) was better than in (1), (2), or (3). ... [Ammar HO et
      al; Pharm Ind 43 (3): 292-295 (1981)]**PEER REVIEWED**

      1.73 kPa at 20 deg C; 5.33 kPa at 40 deg C (saturated solutions in water)
      [Environment Canada; Tech Info for Problem Spills: Urea p.4 (1985)]**PEER
      REVIEWED**

      Henry's Law constant: 1.74X10-12 atm cu m/mole (est) [SRC;; Lyman WJ et
      al; Handbook of Chemical Property Estimation Methods Washington, DC: Amer
      Chem Soc pp. 15-15 to 15-29 (1990)]**PEER REVIEWED**


CHEMICAL SAFETY & HANDLING:


SKIN, EYE AND RESPIRATORY IRRITATIONS:
      Urea causes redness and irritation of skin and eyes. [Environment Canada;
      Tech Info for Problem Spills: Urea p.2 (1985)]**PEER REVIEWED**

FIRE POTENTIAL:
      NONCOMBUSTIBLE [Sax, N.I. and R.J. Lewis, Sr. (eds.). Hawley's Condensed
      Chemical Dictionary. 11th ed. New York: Van Nostrand Reinhold Co., 1987.
      1209]**PEER REVIEWED**

HAZARDOUS REACTIVITIES & INCOMPATIBILITIES:
      REACTS VIOLENTLY WITH GALLIUM PERCHLORATE. [Sax, N.I. Dangerous Properties
      of Industrial Materials. 5th ed. New York: Van Nostrand Rheinhold, 1979.
      467]**PEER REVIEWED**

      ... Urea ... /is/ excreted in human urine, react /s/ with chlorine to form
      chloramines. [Seiler, H.G., H. Sigel and A. Sigel (eds.). Handbook on the
      Toxicity of Inorganic Compounds. New York, NY: Marcel Dekker, Inc. 1988.
      229]**PEER REVIEWED**

HAZARDOUS DECOMPOSITION:
      When heated to decomposition it emits toxic fumes of nitrogen oxides.
      [Sax, N.I. Dangerous Properties of Industrial Materials. 6th ed. New York,
      NY: Van Nostrand Reinhold, 1984. 2713]**PEER REVIEWED**

PREVENTIVE MEASURES:
      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. **PEER REVIEWED**

CLEANUP METHODS:
      Water Spill: Contain by damming, water diversion or natural barriers.
      Remove and treat contaminated liquids. Absorb small amounts of liquid
      spill with natural or synthetic sorbents, shovel into containers and
      cover. [Environment Canada; Tech Info for Problem Spills: Urea p.2
      (1985)]**PEER REVIEWED**

      If urea is spilled in solid form, shovel material into containers and
      cover. Construct barriers to contain solutions or divert to impermeable
      holding area. Remove material by manual or mechanical means. [Environment
      Canada; Tech Info for Problem Spills: Urea p.1 (1985)]**PEER REVIEWED**

DISPOSAL METHODS:
      Urea is a waste chemical stream constituent which may be subjected to
      ultimate disposal by controlled incineration. Incinerator is equipped with
      a scrubber or thermal unit to reduce nitrogen oxide emissions. [USEPA;
      Engineering Handbook for Hazardous Waste Incineration p.2-10 (1981) EPA
      68-03-3025]**PEER REVIEWED**

      The following wastewater treatment technology has been investigated for
      urea: Concentration process: Biological treatment. [USEPA; Management of
      Hazardous Waste Leachate, EPA Contract No.68-03-2766 p.E-36 (1982)]**PEER
      REVIEWED**


OCCUPATIONAL EXPOSURE STANDARDS:


OTHER OCCUPATIONAL PERMISSIBLE LEVELS:
      Workplace Environmental Exposure Level (WEEL): 8-hr Time-weighted Average
      (TWA) 10 mg/cu m. [American Industrial Hygiene Association. The AIHA 1999
      Emergency Response Planning Guidelines and Workplace Environmental
      Exposure Level Guides Handbook.American Industrial Hygiene Association.
      Fairfax, VA 1999. 41]**QC REVIEWED**


MANUFACTURING/USE INFORMATION:


MAJOR USES:
      The active ingredient is no longer contained in any registered pesticide
      products ... "cancelled." [USEPA/OPP; Status of Pesticides in
      Registration, Reregistration and Special Review p.343 (Spring, 1998) EPA
      738-R-98-002]**QC REVIEWED**

      MFR OF RESINS &amp; PLASTICS; CONDENSED WITH MALONIC ESTER TO FORM
      BARBITURIC ACID; CELLULOSE SOFTENER; IN AMMONIATED DENTIFRICES. [Budavari,
      S. (ed.). The Merck Index - Encyclopedia of Chemicals, Drugs and
      Biologicals. Rahway, NJ: Merck and Co., Inc., 1989. 1553]**PEER REVIEWED**

      CHEMICAL INTERMEDIATE; STABILIZER IN EXPLOSIVES; IN MEDICINE (DIURETIC);
      SEPARATION OF HYDROCARBONS; SULFAMIC ACID PRODUCTION; FLAMEPROOFING
      AGENTS. [Sax, N.I. and R.J. Lewis, Sr. (eds.). Hawley's Condensed Chemical
      Dictionary. 11th ed. New York: Van Nostrand Reinhold Co., 1987.
      1209]**PEER REVIEWED**

      LIQUID &amp; OTHER FERTILIZER APPLICATIONS; LIVESTOCK NUTRIENT; MONOMER
      FOR UREA-FORMALDEHYDE RESINS; CHEMICAL INTERMEDIATE FOR MELAMINE
      [SRI]**PEER REVIEWED**

      Incorporation of high concentrations of urea   >  300 g/l in a print paste
      greatly accelerates the fixation of low molecular weight dyes on wool.
      [Kirk-Othmer Encyclopedia of Chemical Technology. 3rd ed., Volumes 1-26.
      New York, NY: John Wiley and Sons, 1978-1984.,p. V24 612 (1984)]**PEER
      REVIEWED**

      UREA HAS BEEN USED AS AN INSECT (MOSQUITO) REPELLENT. [HILL JA ET AL; MOSQ
      NEWS 39 (2): 307-310 (1979)]**QC REVIEWED**

      45% urea solutions are used in dentifrices [Kirk-Othmer Encyclopedia of
      Chemical Technology. 3rd ed., Volumes 1-26. New York, NY: John Wiley and
      Sons, 1978-1984.,p. V7 522 (1979)]**PEER REVIEWED**

      Urea is dehydrated and condensed to produce melamine [Kirk-Othmer
      Encyclopedia of Chemical Technology. 3rd ed., Volumes 1-26. New York, NY:
      John Wiley and Sons, 1978-1984.,p. V7 303 (1979)]**PEER REVIEWED**

      Urea is a decomposition inhibitor for ammonium perchlorate [Kirk-Othmer
      Encyclopedia of Chemical Technology. 3rd ed., Volumes 1-26. New York, NY:
      John Wiley and Sons, 1978-1984.,p. V5 650 (1979)]**PEER REVIEWED**

      Urea is reacted with alcohols to form alkylcarbamates [Kirk-Othmer
      Encyclopedia of Chemical Technology. 3rd ed., Volumes 1-26. New York, NY:
      John Wiley and Sons, 1978-1984.,p. V4 475 (1978)]**PEER REVIEWED**

      Urea is a building block for amino resins [Kirk-Othmer Encyclopedia of
      Chemical Technology. 3rd ed., Volumes 1-26. New York, NY: John Wiley and
      Sons, 1978-1984.,p. V2 442 (1978)]**PEER REVIEWED**

      Urea is reacted with fatty acids from coconut oil to produce amides in 90%
      yields [Kirk-Othmer Encyclopedia of Chemical Technology. 3rd ed., Volumes
      1-26. New York, NY: John Wiley and Sons, 1978-1984.,p. V2 253
      (1978)]**PEER REVIEWED**

      Urea is used with zinc formaldehyde sulfoxylate to remove permanent hair
      dye [Kirk-Othmer Encyclopedia of Chemical Technology. 3rd ed., Volumes
      1-26. New York, NY: John Wiley and Sons, 1978-1984.,p. V12 109
      (1980)]**PEER REVIEWED**

      Urea is reacted with alpha-diketones or dialdehydes to form hydantoins
      [Kirk-Othmer Encyclopedia of Chemical Technology. 3rd ed., Volumes 1-26.
      New York, NY: John Wiley and Sons, 1978-1984.,p. V12 702 (1980)]**PEER
      REVIEWED**

      Urea is used to partially reverse the methylolamine chain reaction in glue
      gellation processes [Kirk-Othmer Encyclopedia of Chemical Technology. 3rd
      ed., Volumes 1-26. New York, NY: John Wiley and Sons, 1978-1984.,p. V11
      913 (1980)]**PEER REVIEWED**

      Urea and phosphoric acid mixtures impart flame resistance to cotton
      fabrics [Kirk-Othmer Encyclopedia of Chemical Technology. 3rd ed., Volumes
      1-26. New York, NY: John Wiley and Sons, 1978-1984.,p. V10 421
      (1980)]**PEER REVIEWED**

      Concentrated urea solutions are used to promote the rate of reaction
      between reactive dyes and wools [Kirk-Othmer Encyclopedia of Chemical
      Technology. 3rd ed., Volumes 1-26. New York, NY: John Wiley and Sons,
      1978-1984.,p. V8 387 (1979)]**PEER REVIEWED**

      Urea is used as a moisture resistant paper additive [Kirk-Othmer
      Encyclopedia of Chemical Technology. 3rd ed., Volumes 1-26. New York, NY:
      John Wiley and Sons, 1978-1984.,p. V16 791 (1981)]**PEER REVIEWED**

      Ammonolysis of urea and ammonium thiocyanate produces guanidine
      [Kirk-Othmer Encyclopedia of Chemical Technology. 3rd ed., Volumes 1-26.
      New York, NY: John Wiley and Sons, 1978-1984.,p. S 519 (1984)]**PEER
      REVIEWED**

      Urea is used as a deicing compound on airport runways [Kirk-Othmer
      Encyclopedia of Chemical Technology. 3rd ed., Volumes 1-26. New York, NY:
      John Wiley and Sons, 1978-1984.,p. V21 219 (1983)]**PEER REVIEWED**

      Formulation and fermentation aid in yeast-raised bakery products,
      alcoholic beverages, and gelatin products. [21 CFR 184.1923
      (4/1/91)]**PEER REVIEWED**

      Urea and other organic and inorganic sources of nitrogen such as biuret
      and ammonium phosphate are added to ruminant rations as a source of
      nonprotein nitrogen. However, urea is the most widely used. It is also
      used as a fertilizer and a substitute for salts in melting of snow and ice
      in residential areas. [Booth, N.H., L.E. McDonald (eds.). Veterinary
      Pharmacology and Therapeutics. 5th ed. Ames, Iowa: Iowa State University
      Press, 1982. 1029]**PEER REVIEWED**

      MEDICATION **QC REVIEWED**

MANUFACTURERS:
      Agricultural Minerals Corp, Hq, 5100 E Skelly Drive, Suite 800, Tulsa, OK
      74135-6549, (918) 660-0050, (800) 523-9083; Production site: Blytheville,
      AK 72319; Verdigris, OK 74015 [SRI. 1992 Directory of Chemical
      Producers-United States of America. Menlo Park, CA: SRI International,
      1992. 1045]**PEER REVIEWED**

      Air Products and Chemicals, Inc, Hq, 7201 Hamilton Blvd, Allentown, PA
      18195-1501, (215) 481-4911; Chemicals Group (800) 345-3148; Industrial
      Chemicals Division; Production site: Pace, FL 32571 [SRI. 1992 Directory
      of Chemical Producers-United States of America. Menlo Park, CA: SRI
      International, 1992. 1045]**PEER REVIEWED**

      American Cyanamid Company, Hq, One Cyanamid Plaza, Wayne, NJ 07470, (201)
      831-2000; Chemical Products Division; Production site: Fortier Plant,
      Avondale, LA 70094 [SRI. 1992 Directory of Chemical Producers-United
      States of America. Menlo Park, CA: SRI International, 1992. 1045]**PEER
      REVIEWED**

      Arcadian Corp, Hq, 6750 Poplar Avenue, Suite 600, Memphis, TN 38138-7419,
      (901) 758-5200; Production sites: Augusta, GA 30903; Clinton, IA 52732;
      Geismar, LA 70734; Lake Charles, LA 70602; La Platte, NE 68005; Memphis,
      TN 38127 [SRI. 1992 Directory of Chemical Producers-United States of
      America. Menlo Park, CA: SRI International, 1992. 1045]**PEER REVIEWED**

      Borden Chemicals and Plastics Partnership, Hq, Highway 73, Geismar, LA
      70734, (504) 387-5101; Production site: Geismar, LA 70734 [SRI. 1992
      Directory of Chemical Producers-United States of America. Menlo Park, CA:
      SRI International, 1992. 1045]**PEER REVIEWED**

      BP America, Inc, Hq, 200 Public Sq, Cleveland, OH 44114-2375, (216)
      586-4141; Subsidiary: BP Chemicals America, Inc; Production site: Lima, OH
      45802 [SRI. 1992 Directory of Chemical Producers-United States of America.
      Menlo Park, CA: SRI International, 1992. 1046]**PEER REVIEWED**

      CF Industries, Inc, Hq, Salem Lake Dr, Long Grove, IL 60047, (312)
      438-9500; Production site: Donaldsonville, LA 70346 [SRI. 1992 Directory
      of Chemical Producers-United States of America. Menlo Park, CA: SRI
      International, 1992. 1046]**PEER REVIEWED**

      Chevron Corporation, Hq, 225 Bush St, San Francisco, CA 94104, (415)
      894-7700; Subsidiarie: Chevron Chemical Company; Chevron Fertilizer
      Division, 6001 Bolinger Canyon Rd, San Ramon, CA 94583-0947; Production
      site: St Helens, OR 97051 [SRI. 1992 Directory of Chemical
      Producers-United States of America. Menlo Park, CA: SRI International,
      1992. 1046]**PEER REVIEWED**

      The Coastal Corp, Hq, Coastal Tower, 9 Greenway Plaza, Houston, TX
      77046-0995, (713) 877-1400; Subsidiary: Coastal Chem, Inc; Productions
      site: Cheyeme, WY 82003 [SRI. 1992 Directory of Chemical Producers-United
      States of America. Menlo Park, CA: SRI International, 1992. 1046]**PEER
      REVIEWED**

      Cominco American Inc, Hq, 601 West Riverside, Spokane, WA 99201, (509)
      747-6111; Cominco Fertilizers Division; Production site: Borger, TX 79008
      [SRI. 1992 Directory of Chemical Producers-United States of America. Menlo
      Park, CA: SRI International, 1992. 1046]**PEER REVIEWED**

      Farmland Industries, Inc, Hq, 3315 North Oak Trafficway, PO Box 7305,
      Kansas City, MO 64116, (816) 459-6000; Production sites: Beatrice, NE
      68310; Dodge City, KS 67801; Enid, OK 73702; Lawrence, KS 66044 [SRI. 1992
      Directory of Chemical Producers-United States of America. Menlo Park, CA:
      SRI International, 1992. 1046]**PEER REVIEWED**

      Freeport-McMoRan Resource Partners, Hq, 1615 Poydras, New Orleans, LA
      70112, (504) 582-4000; Agrico Chemical Co, PO Box 60031; New Orleans, LA
      70160; Production site: Donaldsonville, LA 70346 [SRI. 1992 Directory of
      Chemical Producers-United States of America. Menlo Park, CA: SRI
      International, 1992. 1046]**PEER REVIEWED**

      Inspiration Resources Corporation, Hq; Subsidiary: Terra International,
      Inc, Terra Centre, 600 Fourth St, Sioux City, IA 51101, (712) 277-1340;
      Production site: Sergeant Bluff, IA 51054 [SRI. 1992 Directory of Chemical
      Producers-United States of America. Menlo Park, CA: SRI International,
      1992. 1046]**PEER REVIEWED**

      La Roche Holdings Inc, Hq, La Roche Industries, Inc, Perimeter 400 Center,
      1100 Johnson Ferry Rd NE, Atlanta, GA 30342, (404) 851-0300; Production
      site: Cherokee, AL 35616 [SRI. 1992 Directory of Chemical Producers-United
      States of America. Menlo Park, CA: SRI International, 1992. 1046]**PEER
      REVIEWED**

      Mississippi Chemical Corporation, Hq, PO Box 388, Yazoo City, MS 39194,
      (601) 746-4131; Production site: Yazoo City, MS 39194 [SRI. 1992 Directory
      of Chemical Producers-United States of America. Menlo Park, CA: SRI
      International, 1992. 1046]**PEER REVIEWED**

      Nitrogen Products, Inc, Hq, PO Box 825, Helena, AR 72342, (501) 338-9111;
      Production site: Helena, AR 72342 [SRI. 1992 Directory of Chemical
      Producers-United States of America. Menlo Park, CA: SRI International,
      1992. 1046]**PEER REVIEWED**

      Triad Chemical, Hq, PO Box 388, Yazoo City, MS 39194, (601) 746-4131;
      Production site: Donaldsonville, LA 70346 [SRI. 1992 Directory of Chemical
      Producers-United States of America. Menlo Park, CA: SRI International,
      1992. 1046]**PEER REVIEWED**

      Unocal Corp, Hq, 1201 West Fifth St, PO Box 7600, Los Angeles, CA 90051,
      (213) 977-7600; Unocal Minerals and Chemicals Division; Agricultural
      Products Group; Production site: Kenai, AK 99611 [SRI. 1992 Directory of
      Chemical Producers-United States of America. Menlo Park, CA: SRI
      International, 1992. 1046]**PEER REVIEWED**

      The Vigoro Corporation, Hq, 225 N Michigan Ave, Suite 2416, Chicago, IL
      60601, (312) 819-2020; Phoenix Chemical Company, 11675 Highway 20 West, PO
      Box 229, East Dubuque, IL 61025-0229; Production site: East Dubuque, IL
      61025-0229 [SRI. 1992 Directory of Chemical Producers-United States of
      America. Menlo Park, CA: SRI International, 1992. 1046]**PEER REVIEWED**

      Willard Feed and Grain, Hq, Route 2, Box 41, Celina, TX 75009, (214)
      382-2367; Wil-Gro Fertilizer, Inc, division, Pryor, OK 74362 [SRI. 1992
      Directory of Chemical Producers-United States of America. Menlo Park, CA:
      SRI International, 1992. 1046]**PEER REVIEWED**

      Columbia Nitrogen Corporatin, Hq, PO Box 1483, Augusta, GA 30903, (404)
      823-4300 [United States International Trade Commission. Synthetic Organic
      Chemicals-United States Production and Sales, 1989. USITC Publication
      2338, 1990. Washington, DC:United States International Trade Commission,
      1990.,p. 14-10]**PEER REVIEWED**

      Mississippi Chemical Corporation, Hq, PO Box 388, Yazoo City, MS 39194,
      (601) 746-4131 [United States International Trade Commission. Synthetic
      Organic Chemicals-United States Production and Sales, 1989. USITC
      Publication 2338, 1990. Washington, DC:United States International Trade
      Commission, 1990.,p. 14-10]**PEER REVIEWED**

      Olin Corporation, Hq, 120 Long Ridge Road, Stanford, CT 06904, (203)
      354-2000 [United States International Trade Commission. Synthetic Organic
      Chemicals-United States Production and Sales, 1989. USITC Publication
      2338, 1990. Washington, DC:United States International Trade Commission,
      1990.,p. 14-10]**PEER REVIEWED**

      JR Simplot Company, Hq, PO Box 912, Pocatello, ID 83204, (208) 336-2110
      [United States International Trade Commission. Synthetic Organic
      Chemicals-United States Production and Sales, 1989. USITC Publication
      2338, 1990. Washington, DC:United States International Trade Commission,
      1990.,p. 14-10]**PEER REVIEWED**

      Triad Chemical, Hq, PO box 310, Donaldsonville, LA 70346, (504) 473-9231
      [United States International Trade Commission. Synthetic Organic
      Chemicals-United States Production and Sales, 1989. USITC Publication
      2338, 1990. Washington, DC:United States International Trade Commission,
      1990.,p. 14-10]**PEER REVIEWED**

      Tennessee Valley Authority, Hq, Muscle Shoals, AL 35660, (205) 386-3521;
      Division of Developmental Production [United States International Trade
      Commission. Synthetic Organic Chemicals-United States Production and
      Sales, 1989. USITC Publication 2338, 1990. Washington, DC:United States
      International Trade Commission, 1990.,p. 14-10]**PEER REVIEWED**

      Union Oil Company of California, 1201 W Fifth Street, Los Angeles, Ca
      90017, (213) 977-5131 [United States International Trade Commission.
      Synthetic Organic Chemicals-United States Production and Sales, 1989.
      USITC Publication 2338, 1990. Washington, DC:United States International
      Trade Commission, 1990.,p. 14-10]**PEER REVIEWED**

METHODS OF MANUFACTURING:
      DEHYDRATION OF AMMONIUM CARBONATE WHICH IS SYNTHESIZED FROM AMMONIA AND
      CARBON DIOXIDE. [SRI]**PEER REVIEWED**

      ... FROM AMMONIA, CARBON MONOXIDE &amp; SULFUR IN METHANOL. [Budavari, S.
      (ed.). The Merck Index - Encyclopedia of Chemicals, Drugs and Biologicals.
      Rahway, NJ: Merck and Co., Inc., 1989. 1553]**PEER REVIEWED**

      LIQ AMMONIA &amp; LIQ CARBON DIOXIDE @ 1750-3000 PSI &amp; 160-200 DEG C
      REACT TO FORM AMMONIUM CARBAMATE, NH4CO2NH2, WHICH DECOMP @ LOWER PRESSURE
      (ABOUT 80 PSI) TO UREA &amp; WATER. METHOD OF PURIFICATION:
      CRYSTALLIZATION. [Sax, N.I. and R.J. Lewis, Sr. (eds.). Hawley's Condensed
      Chemical Dictionary. 11th ed. New York: Van Nostrand Reinhold Co., 1987.
      1209]**PEER REVIEWED**

GENERAL MANUFACTURING INFORMATION:
      OCCURS IN URINE &amp; OTHER BODY FLUIDS. FIRST ORG CMPD TO BE SYNTHESIZED
      ... [Sax, N.I. and R.J. Lewis, Sr. (eds.). Hawley's Condensed Chemical
      Dictionary. 11th ed. New York: Van Nostrand Reinhold Co., 1987.
      1209]**PEER REVIEWED**

      PURE UREA SHOULD NOT GIVE THE BIURET REACTION UNLESS HEATED ABOVE MELTING
      POINT. IN PRACTICE ALL REAGENT GRADE UREA GIVES POSITIVE BIURET REACTION.
      [Budavari, S. (ed.). The Merck Index - Encyclopedia of Chemicals, Drugs
      and Biologicals. Rahway, NJ: Merck and Co., Inc., 1989. 1553]**PEER
      REVIEWED**

 &nb