Final report of the safety assessment of urea

International Journal of Toxicology

Volumn 24, Issue SUPPL. 3, 2005, Pages 1-56

  Andersen, F Alan ^a  

^a Cosmetic Ingredient Review ^*  (United States)

Author keywords

[No Author keywords available]

Indexed keywords

BUFFER; COSMETIC; DNA; FAT; HUMECTANT; METHYLNITROSOUREA; OIL; PESTICIDE; UREA DERIVATIVE;

ANTIMICROBIAL ACTIVITY; BRAIN REGION; CAUDATE NUCLEUS; CONCENTRATION RESPONSE; CORPUS CALLOSUM; DAIRY PRODUCT; DERMIS; DESQUAMATION; DOG; FOOD AND DRUG ADMINISTRATION; FRONTAL LOBE; GENOTOXICITY; GESTATIONAL AGE; HALF LIFE TIME; HIPPOCAMPUS; HUMAN; HYPOTHALAMUS; LIVER; MATERNAL MORBIDITY; MATERNAL MORTALITY; MUSCLE; NONHUMAN; NUDE MOUSE; PONS; PROTEIN METABOLISM; RABBIT; REVIEW; SECOND TRIMESTER PREGNANCY; SKIN; SKIN PERMEABILITY; SURFACE PROPERTY; SWINE; THALAMUS; TOXICITY; TOXICITY TESTING; TOXICOKINETICS; WHITE MATTER;

ANIMALIA; BACTERIA (MICROORGANISMS); CANIS FAMILIARIS; MAMMALIA; MUS MUSCULUS; ORYCTOLAGUS CUNICULUS; SUS SCROFA;

EID: 27544452056     PISSN: 10915818     EISSN: 1092874X     Source Type: Journal    
DOI: 10.1080/10915810500257097     Document Type: Review

References (229)

1. Abramovich, D. R., B. Heaton, and K. R. Page. 1974. Transfer of labeled urea, creatinine and electrolytes between liquor amnia and the fetoplacental unit in midpregnancy. Eur. J. Obstet. Gynecol. Reprod. Biol. 4:143-146.
2. Ackermann, C., and G. L. Flynn. 1987. Ether-water partitioning and permeability through nude mouse skin in vitro. Part 1. Urea, thiourea, glycerol and glucose. Int. J. Pharm. 36:61-66.
3. Agner, T. 1992. An experimental study of irritant effects of urea in different vehicles. Acta Derm. Venereol. 177:44-46.
4. Aleksandrov, V. A., and F. K. Dzhioev. 1977. Inhibition of the embryotoxic and teratogenic effects of methylurea and sodium nitrite by various substances. Bull. Exp. Biol. Med. (USSR) 83:88-90.
5. Auclair, F., M. Besnard, C. Dupont, and J. Wepierre. 1991. Importance of blood flow to the local distribution of drugs after percutaneous absorption in the bipediculated dorsal flap of the hairless rat. Skin Pharmacol. 4:1-8.
6. Babar, A., R. D. Bhandari, and F. M. Plakogiannis. 1991. In vitro release studies of chlorpheniramine maleate from topical bases using cellulose membrane and hairless mouse skin. Drug Dev. Ind. Pharm. 17:2145-156.
7. Balestri, P. L., P. Rindi, and M. Biagini. 1971. Chronic Urea intoxication in dogs. Experientia 27:811-812.
8. Barber, E. D., N. M. Teetsel, K. F. Kolberg, and D. Guest. 1992. A comparative study of the rates of in vitro percutaneous absorption of eight chemicals using rat and human skin. Fundam. Appl. Toxicol. 19:493-497.
9. Battaglia, F. C., P. D. Bruns, R. E. Behrman, A. E. Seeds, and A. E. Hellegers. 1964. Comparison of permeability of different layers of the primate placenta to D-arabinose and urea. Am. J. Physiol. 207:500-502.
10. Bensinger, T. A., L. Mahmood, M. E. Conrad, and P. R. McCurdy. 1972. The effect of oral Urea administration on red cell survival in sickle cell disease. Am. J. Med. Sci. 264:283-287.
11. Bentley, M. V., E. R. Kedor, R. F. Vianna, and J. H. Collett. 1997. Influence of lecithin and urea on the in vitro permeation of hydrocortisone acetate through skin from hairless mouse. Int. J. Pharm. 146:255-262.
12. Bettinger, J., M. Gloor, and W. Gehring. 1994. Influence of a pretreatment with emulsions on the dehydration of the skin by surfactant. Int. J. Cosmet. Sci. 16:53-60.
13. Bettinger, J., and H. I. Maibach. 1997. SC water-binding capacity: Influence of emulsions with and without urea. Cosmet. Toiletries 112:49-53.
14. Beverley, D. W., and D. Wheeler. 1986. High plasma urea concentrations in collodion babies. Arch. Dis. Child 61:696-698.
15. Bissonnette, J. M., J. Z. Cronan, L. L. Richards, and W. K. Wickham. 1979. Placental transfer of water and nonelectrolytes during a single circulatory passage. Am. J. Physiol. 236:C47-C52.
16. Blake, D. A., L. S. Burnett, B. C. Miyasaki, H. A. Lim, and T. M. King. 1976a. Comparative effects of hyperosmolar urea administered by intra-amniotic, intravenous and intraperitioneal routes in rhesus monkeys. Am. J. Obstet. Gynecol. 124:239-244.
17. Blake, D. A., L. S. Burnett, B. C. Miyasaki, J. A. Longstreth, and T. M. King. 1976b. Pharmacokinetics of intra-amniotically administered hyperosmolar urea in rhesus monkeys. Am. J. Obstet. Gynecol. 124:245-250.
18. Bourne, G. R., and H. E. Barber. 1972. The pharmacokinetics of inulin and urea: A comparison of the dose eliminated from a compartmental model and that eliminated in urine. J. Pharm. Pharmacol. 24:532-537.
19. Brightman, M. W., M. Hori, S. I. Rapoport, T. S. Reese, and E. Westergaard. 1973. Osmotic opening of tight junctions in cerebral endothelium. J. Comp. Neurol. 152:317-326.
20. Bronaugh, R. L., and R. F. Stewart. 1985. Methods for in vitro percutaneous absorption studies V. Permeation through damaged skin. J. Pharm. Sci. 74:1062-1066.
21. Bronaugh, R. L., R. F. Stewart, E. R. Congdon, and A. L. Giles. 1982a. Methods for in vitro percutaneous absorption studies. I. Comparison with in vivo results. Toxicol. Appl. Pharmacol. 62:474-480.
22. Bronaugh, R. L., R. F. Stewart, and E. R. Congdon. 1982b. Methods for in vitro percutaneous absorption studies. II. Animal models for human skin. Toxicol. Appl. Pharmacol. 62:481-488.
23. Bronaugh, R. L., R. F. Stewart, and E. R. Congdon. 1983. Differences in permeability of rat skin related to sex and body site. J. Soc. Cosmet. Chem. 34:127-135.
24. Budavari S, ed. 1989. The Merck Index. An encyclopedia of chemicals, drugs, and biologicals, 11th ed., 9789 Rahaway, NJ: Merck & Co.
25. Button, C., J. P. Joubert, and B. P. Maartens. 1982. Absence of urea toxicity in young pigs. J. S. Afr. Vet. Assoc. 53:67-68.
26. Challier, J. C., M. Guerre-Millo, M. Nandakumaran, L. Gerbaut, and P. D'Athis. 1985. Clearance of compounds of different molecular size in the human placenta in vitro. Biol. Neonate 48:143-148.
27. Chang, C., and H. J. Li. 1974. Urea perturbation and the reversibility of nucleohistone conformation. Nucleic Acids Res. 1:945-958.
28. Charlton, J. E, I. R. Schwab, and R. Stuchell. 1996. Topical urea as a treatment for non-infectious keratopathy. Acta Ophthalmol. Scand. 74:391-394.
29. Chaurasia, L. C., and J. S. Rathore. 1976. Induction of meiotic anomalies in allium cepa L. by urea. Indian J. Exp. Biol. 14:522-523.
30. Chaurasia, O. P., and S. P. Sinha. 1987. Effects of urea on mitotic chromosomes of mice and onion. Cytologia 52:877-882.
31. Chessells, M., D. W. Hawker, and D. W. Connell. 1992. Influence of solubility in lipid on bioconcentration of hydrophobic compounds. Ecotoxicol. Environ. Safety 23:260-273.
32. Chi, S. C., E. S. Park, and H. Kim. 1995. Effect of penetration enhances on flurbiprofen permeation through rat skin. Int. J. Pharm. 126:267-274.
33. Clarys, P., B. Gabard, and A. O. Barel. 1999. A qualitative estimate of the influence of halcinonide concentration and urea on the reservoir formation in the stratum corneum. Skin Pharacol. Appl. Skin Physiol. 12:85-89.
34. Committee of Revision of the United States Pharmacopeial Convention. 1995. The United States Pharmacopeia, 23rd ed., 1617-1618, 2114. Rockville, MD: United States Pharmacopeial Convention.
35. Conner, E. A., D. A. Blake, T. H. Parmley, L. S. Burnett, and T. M. King. 1976. Efficacy of various locally applied chemicals as contragestational agents in rats. Contraception 13:571-582.
36. 2
37. 2
38. Cramers, M., and J. Thormann. 1981. Skin reactions to a urea-containing cream. Contact Dermatitis 7:189-191.
39. Dancis, J., S. Kammerman, V. Jansen, H. Schneider, and M. Levitz. 1981. Transfer of urea, sodium and chloride across the perfused human placenta. Am. J. Obstet. Gynecol. 141:677-681.
40. Danopoulos, E. D., G. A. Chilaris, I. E. Danopoulou, and S. B. Liaricos. 1975. Urea in the treatment of epibulbar malignancies. Br. J. Ophthalmol. 59:282-287.
41. Danopoulos, E. D., and I. E. Danopoulou. 1974a. Regression of liver cancer with oral urea. Lancet 1:132.
42. Danopoulos, E. D., and I. E. Danopoulou. 1974b. Urea treatment of skin malignancies. Lancet 1:115-118.
43. Danopoulos, E. D., and I. E. Danopoulou. 1979. Effects of urea treatment in combination with curettage in extensive periopthalmic malignancies. Opthalmologica 179:52-61.
44. Danopoulos, E. D., and I. E. Danopoulou. 1981. Eleven years experience of oral urea in liver malignancies. Clin. Oncol. 7:281-289.
45. Danopoulos, E. D., I. E. Danopoulou, S. B. Liarikos, and K. M. Merkuris. 1979. Effects of urea treatment of malignancies of the conjunctiva and cornea. Opthalmologica 178:198-203.
46. Davis, B. M., R. K. Miller, R. L. Brent, and T. R.Koszalda. 1978. Materno-fetal transport of creatine in the rat. Biol. Neonate 33:43-54.
47. Decaux, G., P. Mols, P. Cauchi, and F. Delwiche. 1985. Use of urea for treatment of water retention in hypoatremic cirrhosis with ascites resistant to diuretics. BMJ 290:1782-1783.
48. 2Available for review. Director, Cosmetic Ingredient Review, 1101 17th Street, N.W., Suite 310, Washington, DC 20036, USA.
49. Deutz, N. E., M. J. Bruins, and P. B. Soeters. 1998. Infusion of soy and casein protein meals affects interorgan amino acid metabolism and urea kinetics differently in pigs. J. Nutr. 128:2435-2445.
50. Dierickx, P. J. 1989. Cytotoxicity testing of 114 compounds by the determination of the protein content in HEP G2 cell cultures. Toxicol. In Vitro 3:189-194.
51. Eknoyan, G., S. J. Wacksman, H. I. Glueck, and J. J. Will. 1969. Platelet function in renal failure. New Engl. J. Med. 280:677-681.
52. Elfbaum, S. G., and M. A. Wolfram. 1970. Effect of dimethyl sulfoxide and other reagents upon mechanical properties of stratum corneum strips. J. Soc. Cosmet. Chem. 21:129-140.
53. El-Sourady, H. A., F. S. Habib, and S. I. Mohamed. 1986. Influence of certain additives on the diffusion rate of aspirin, salicylamide and phenacetin through the rat's ileum. Drug Dev. Ind. Pharm. 12:889-898.
54. European Economic Community (EEC). 1999. EEC Cosmetics Directive 76/768/EEC, as amended Annexes I-VII. Brussels: EEC.
55. Faber, J. J., and F. M. Hart. 1967. Transfer of charged and uncharged molecules in the placenta of the rabbit. Am. J. Physiol. 213:890-894.
56. Fair, R. H., and R. J. Krum. 1979. Double blind irritation study of a new stabilized base hydrocortisone cream. Curr. Ther. Res. Clin. Exp. 26:611-614.
57. Food and Drug Administration (FDA). 1984. Cosmetic product formulation and frequency of use data. FDA database. Washington, DC: FDA.
58. FDA. 1994. OTC Drug Review Ingredient Status Report (September 1, 1994). Washington, DC: FDA.
59. FDA. 2001. Frequency of use of cosmetic ingredients. FDA database. Washington, DC: FDA.
60. Feldmann, R. J., and H. I. Maibach. 1974. Percutaneous penetration of hydrocortisone with urea. Arch Dermatol. 109:58-59.
61. Fleischman, R. W., J. R. Baker, M. Hagopian, and G. C. Wade. 1980. Carcinogenesis bioassay of acetamide, hexanamide, adipamide, urea and P-tolyurea in mice and rats. J. Environ. Pathol. Toxicol. 3:149-170.
62. Franz, T. J. 1978. The finite dose technique as a valid in vitro model for the study of percutaneous absorption in man. Curr. Prob. Dermatol. 7:58-68.
63. Fredriksson, T., and T. Gip. 1975. Urea creams in the treatment of dry skin and hand dermatitis. Int. J. Dermatol. 14:442-444.
64. Fredriksson, T., and M. Lundberg. 1985. Blind controlled comparison between new cream (12+12), its vehicle, and salicylic acid in petrolatum on psoriatic plaques. Curr. Ther. Res. 37:805-809.
65. Garberg, P., E. Akerblom, and G. Bolcsfoldi. 1988. Evaluation of a genotoxicity test measuring DNA-strand breaks in mouse lymphoma cells by alkaline unwinding and hydroxyapatite elution. Mutat. Res. 203:155-176.
66. Gennaro, A. R. ed. 1990. Remington's pharmaceutical science, 18th ed., 931-932, 1170-1171. Easton, PA: Mack Publishing Co.
67. Gibson, J. A., N. J. Park, G. E. Sladen, and A. M. Dawson. 1976. The role of the colon in urea metabolism in man. Clin. Sci. Mol. Med. 50:51-59.
68. Gip, L., and M. Lundberg. 1985. Double blind controlled trial of a new antipsoriatic cream containing urea and sodium chloride. Curr. Ther. Res. 37:797-804.
69. Glinos, A. D., G. N. Bardi, K. C. Dermitzaki, S. A. Perez, and M. J. Talieri. 1983. Cytokinetic and cytotoxic effects of urea on HELA cells in suspension cultures. J Natl. Cancer Inst. 71:1211-1219.
70. Godwin, D. A., M. R. Player, J. W. Sowell, and B. B. Michniak. 1998. Synthesis and investigation of urea compounds as transdermal penetration enhancers. Int. J. Pharm. 167:165-175.
71. Gol'dfarb, D. M., and S. A. Sergeeva. 1968. Genetic transformation of phage T4RIIB-638 with deoxyribonucleic acid of phage T4R+. Part 2. Effect of denaturing agents and actinomycin (aurantin) on the transforming activity of DNA of phage T4R+. Sov. Genet. 4:73-79.
72. Gollhausen, R., and A. M. Kligman. 1985. Effects of pressure on contact dermatitis. Am. J. Ind. Med. 8:323-328.
73. Gordon, C. J. 1989. Thermoregulatory responses in mice following acute administration of principal nitrogenous excretory substances. Pharmacol. Biochem. Behav. 31:699-703.
74. Gordon, E. L., T. S. Nguyen, A. C. Ngai, and H. R. Winn. 1995. Differential effects of alcohols on intracerebral arterioles. Ethanol alone causes vasoconstriction. J. Cerebral Blood Flow Metab. 15:532-538.
75. Gordon, R. S. Jr, R. H. Thompson, D. Thrasher, and J. W. Benson Jr. 1976. Genesis of the sweat: Plasma urea concentration gradient. J. Invest. Dermatol. 66:218-221.
76. Gournay, A., R. Navarro, J. Mathieu, and M. Riviere. 1995. Water retention of treated stratum corneum measured by a coupling method: Thermal desorption-mass spectrometry. Int. J. Cosmet. Sci. 17:165-172.
77. Grant, J., ed. 1972. Hackh's chemical dictionary, 4th ed., 702-703. New York, NY:McGraw-Hill Book Co.
78. Grasselli, J. G., ed. 1973. Atlas of spectral data and physical constants for organic compounds. Cleveland, OH: CRC Press.
79. Gregoire, A. T., and A. E. Rakoff. 1963. Urea content of the female rabbit genital tract fluids. J. Reprod. Fertil. 169:467-469.
80. Gregory, M. C., and J. R. Robinson. 1965. Effects of urea upon the water and ionic content of liver slices. J. Physiol. (Lond.) 177:122-132.
81. Grogl, M., B. G. Schuster, W. Y. Ellis, and J. D. Berman. 1999. Successful topical treatment of murine cutaneous leishmaniasis with a combination of paromomycin (Aminosidine) and gentamicin. J. Parasitol. 85:354-359.
82. Grollman, E. F., and A. Grollman. 1959. Toxicity of Urea and its role in the pathogenesis of uremia. J. Clin. Invest. 38:749-754.
83. Guerrier, C. J., and D. I. Porter. 1983. An open assessment of 0.1% dithranol in a 17% urea base ('Psoradrate' 0.1%) in the treatment of psoriasis of children. Curr. Med. Res. Opin. 8:446-450.
84. Hakim, A. A., and N. Lifson. 1964.Urea transport across dog intestinal mucosa in vitro. Am. J. Physiol. 206:1315-1320.
85. Han, S. K., Y. H. Jun, Y. J. Rho, S. C. Hong, and Y. M. Kim. 1991. Percutaneous absorption-enhancing activity of urea derivatives. Arch. Pharm. Res. 14:12-18.
86. Haning, R. V., and B. M. Peckham. 1985. Evaluation of intra-amniotic administration of 120 gm urea with 5 mg of prostaglandin F2alpha for midtrimester termination of pregnancy between 20 and 24 weeks gestation. Am. J. Obstet. Gynecol. 151:92-96.
87. Harper, A. M., and R. A. Bell. 1963. The failure of intravenous urea to alter the blood flow through the cerebral cortex. J. Neurol. Neurosurg. Psychiat. 26:69-70.
88. Hayes, S., A. Gordon, I. Sadowski, and C. Hayes. 1984. RK bacterial test for independently measuring chemical toxicity and mutagenicity: Short-term forward selection assay. Mutat. Res. 130:97-106.
89. l5N-tracer technique. J. Pediatr. Gastroenterol. Nutr. 3:709-712.
90. Heinz, K. A., D. J. Glofcheski, J. R. Lepock, and J. Kruuv. 1990. Mechanism of freeze-thaw damage to liver alcohol dehydrogenate and protection by cryoprotectants and amino acids. Cryobiology 27:521-538.
91. Hellgren, L., and K. Larsson. 1974. On the effect of urea on human epidermis. Dermatologica 149:289-293.
92. Hewitt, S., and T. E. Nicholas. 1983. Urea metabolism in isolated perfused lungs of the laboratory rat and of a desert rodent, Notomys alexis. Comp. Biochem. Physiol. 74A:467-469.
93. 2
94. Hisanaga, H., H. Iioka, I. Moriyama, K. Nabuchi, K. Morimoto, and M. Ichij. 1991. The mechanism of human placental urea transport: A study using placental brush border (microvillous) membrane vesicles. Asia Oceania J. Obstet. Gynaecol. 17:67-72.
95. Horii, I., Y. Nakayama, M. Obata, and H. Tagami. 1989. Stratum corneum hydration and amino acid content in xerotic skin. Br. J. Dermatol. 121:587-592.
96. Houpt, T. R. 1963. Urea utilization by rabbits fed a low-protein ration. Am. J. Physiol. 205:1144-1150.
97. Hui, X., R. C. Wester, P. S. Magee, and H. I. Maibach. 1995. Partitioning of chemicals from water into powdered human stratum corneum (callus): A model study. In Vitro Toxicol. 8:159-167.
98. Hutchinson, D. L., W. T. Kelly, E. A. Friedman, and A. A. Plentl. 1962. The distribution and metabolism of carbon-labeled urea in pregnant primates. J. Clin. Invest. 41:1745-1753.
99. Inoue, K., and F. Masuda. 1976. Effects of detergents on mouse fetuses. J. Food Hyg. Soc. Japan 17:158-169.
100. Ishidate, M., and S. Odashima. 1977. Chromosome tests with 134 compounds on Chinese hamster cells in vitro: A screening for chemical carcinogens. Mutat. Res. 48:337-354.
101. Ishidate, M., and K. Yoshikawa. 1980. Chromosome abberation tests with Chinese hamster cells in vitro with and without metabolic activation: A comparative study on mutagens and carcinogens. Arch. Toxicol. Suppl. 4:41-44.
102. Ishidate, M., T. Sofuni, and K. Yoshikawa. 1981. Chromosomal aberration tests in virro as a primary screening tool for environmental mutagens and/or carcinogens. Gann. Monogr. Cancer. Res. 27:95-108.
103. Ishikura, T., T. Nagai, Y. Sakai, T. Shishikura, H. Ebisawa, and Y. Machida. 1987. Enhanced percutaneous absorption of ionizable water-soluable drugs. Drug Des. Deliv. 1:285-295.
104. 14C]urea by the in vivo choroid plexus-cerebrospinal fluid-brain system: Identification of sites of molecular sieving. J. Physiol. 275:167-176.
105. Johnson, A. J., J. W. Rebuck, and B. F. Knoll. 1970. The effect of autogenous urine on leukocyte defenses in man. II. The response to varied concentrations of saline, urea, and urine. Invest. Urol. 8:224-230.
106. Johnson, W. J., W. W. Hagge, R. D. Wagoner, R. P. Dinapoli, and J. W. Rosevear. 1972. Effects of Urea loading in patients with far-advanced renal failure. Mayo Clinic Proc. 47:21-29.
107. Joshi, C. D., C. D. Knight, and L. D. Mueller. 1996. Genetics of larval urea tolerance in Drosophila melanogaster. Heredity 77:33-39.
108. Kalhan, S. C., K. Y. Tserng, C. Gilfillan, and L. J. Dierker. 1982. Metabolism of urea and glucose in normal and diabetic pregnancy. Metabolism 31:824-833.
109. Kalhan, S. C., K. Y. Tserng, C. Gilfillan, and L. J. Dierker. 1993. Rates of urea synthesis in the human newborn: Effect of maternal diabetes and small size for gestational age. Pediatr. Res. 34:801-804.
110. Kanikkannan, N., S. B. Jayaswal, and J. Singh. 1994. Transdermal delivery of indornethacin: II. Effect of penetration enhances on the in vitro percutaneous absorption from patch formations. Pharmazie 49:619-620.
111. Kaplan, B., Z. Wang, O. Siddhom, T. K. Henthorn, and S. K. Mujais. 1999. Evaluation of urea kinetics utilizing stable isotope urea and pharmacokinetic modeling. Artif. Organs 23:44-50.
112. Kappen, L. S., and I. H. Goldberg. 1979. Mechanism of the effect of organic solvents and other protein denaturant on neocarzinosation activity. Biochemistry 18:5647-5653.
113. Kim, C. K., J. J. Kim, S. C. Chi, and C. K. Shim. 1993. Effect of fatty acids and urea on the penetration of ketoprofen through rat skin. Int. J. Pharm. 99:109-118.
114. Kornegay, E. T., V. Mosanghini, and R. D. Snee. 1970. Urea and amino acid supplementation of swine diets. J. Nutr. 100:330-340.
115. Kozak, W., and W. T. Dobrzanski. 1970. Activity of some agents in the lysogenic induction in corynebacterium diphtheria strain no. 25. Bull. Acad. Pol. Sci. Ser. Sci. Biol. 18:445-450.
116. Krochmal, L., C. T. Wang, B. Patel, and B. S. Rogers. 1989. Topical corticosteroid compounding: Effects on physicochemical stability and skin penetration rate. J. Am. Acad. Dermatol. 21:979-984.
117. Lashmar, U. T., J. Hadgraft, and N. Thomas. 1989. Topical application of penetration enhances to the skin of nude mice: A histopathological study. J. Pharm. Pharmacol. 41:118-122.
118. Lata, A., C. Gowri, S. C. Dhar, J. D. Gibeault, and M. Chvapil. 1988. Effect of topically applied beta-aminopropionitrile on granuloma tissue biochemistry. Proc. Soc. Exp. Biol. Med. 187:442-447.
119. Lee, C., E. A. Stahlberg, and G. Fitzgerald. 1995. The chemical structure of urea in water. Abst. Amer. Chem. Soc. 210(1-2):ENVR 57.
120. Lemiere, C., J. L. Malo, and L. Garbe-Galanti. 1996. Bronchial irritation syndrome following inhalation of Urea histological and immuno-histochemical evaluation. Rev. Mal. Resp. 13:595-597.
121. Lewis, R. J. Sr., ed. 1993a. Hawley's condensed chemical dictionary, 12th ed. 1203-1204. New York: Van Nostrand Reinhold Co.
122. Lewis, R. J., Sr., ed. 1993b. Hazardous chemicals desk reference, 3rd ed. 1303. New York: Van Nostrand Reinhold Co.
123. Lewis, R. J., Sr., ed. 2000. Sax's dangerous properties of industrial materials, 10th ed., New York: John Wiley & Sons.
124. Lippold, B. C., and D. Hackemüller. 1990. Influence of skin moisturizers on drug penetration in vivo. Int. J. Pharm. 61:205-211.
125. Loden, M. 1996. Urea containing moisturizers influence barrier properties of normal skin. Arch. Dermatol. Res. 288:103-107.
126. Loden, M., A. C., Andersson, and M. Lindberg. 1999. Improvement in skin barrier function in patients with atopic dermatitis after treatment with a moisturizing cream. Br. J. Dermatol. 140:264-267.
127. Loden, M., P. Boström, and M. Kneczke. 1995. Distribution and keratolytic effect of salicylic acid and urea in human skin. Skin Pharmacol. 8:173-178.
128. Long, C. L., M. Jeevanandam, and J. M. Kinney. 1978. Metabolism and recycling urea in man. Am. J. Clin. Nutr. 31:1367-1382.
129. Lu, M. Y., S. Lee, and G. S. Rao. 1992. Percutaneous absorption enhancement of leuprolide. Pharm. Res. 9:1575-1579.
130. Luck, J. M., and E. T. Engle. 1929. The permeability of the placenta of the rat to glycine, alanine and urea. Am. J. Physiol. 88:230-236.
131. Luduena, R. F., M. C. Roach, P. P. Trcka, M. L. Mallevais, and T. Macrae. 1987. The effect of 2-(4-methyl-1-piperazinylmethyl) acrylophenone dihydrochloride on the alkylation of tubulin. Arch. Biochem. Biophys. 255:453-459.
132. MacKenzie, E. T., J. McCulloch, M. O'Keane, J. D. Pickard, and A. M. Harper. 1976. Cerebral circulation and norepinephrine: Relevance of the blood-brain barrier. Am. J. Physiol. 231:483-488.
133. Maddock, A. L., and C. Westenfelder. 1996. Urea induces the heat shock response in human neuroblastoma cells. J. Am. Soc. Nephrol. 7:275-282.
134. Main, K. B., T. Medwick, L. C. Bailey, and J. H. Shinkai. 1987. Quantitative analysis of hydroxyurea and urea by proton nuclear magnetic resonance (NMR) spectroscopy. Pharm. Res. 4:412-415.
135. Mann, A. M., T. Masui, F. J. Chlapowski, T. Okamura, C. D. Borgeson, and S. M. Cohen. 1991. In vitro transformation of rat bladder epithelium by 2-amino-4-(5-nitro-2-furyl)thiazole. Carcinogenesis 12:417-422.
136. Michel, M., L. Germain, P. M. Bélanger, and F. A. Auger. 1995. Functional evaluation of anchored skin equivalent in vitro: Percutaneous absorption studies and lipid analysis. Pharm. Res. 12:455-458.
137. Ministry of Health, Labor, and Welfare (MHLW). 2000. Pharmaceutical and Medical Safety Bureau Notification No. 990. Ministry of Health, Labor and Welfare, Pharmaceutical and Medical Safety Bureau, Inspection and Guidance Divison, 2-2, 1-chrome, Kasumigaseki, Chiyoda-ku, Tokyo 100-8045, Japan.
138. Moran, B. J., and A. A. Jackson. 1990a. 15N-urea metabolism in the functioning human colon: Luminal hydrolysis and mucosa permeability. Gut 31:454-457.
139. l5N-labelled urea in the functioning and defunctioned human colon. Clin. Sci. (Colch.) 79:253-258.
140. Nascimento, D. C., and M. Sakate. 1996. Antagonism produced by hypertonic nutrient solutions on the depressive effect of carbofuran on isolated guinea pig atria. Pharmacol. Res. 33:251-254.
141. Nash, D. P. 1971. Urea cream for dry skin. J. Am. Pod. Assoc. 61:382-384.
142. National Academy of Sciences (NAS). 1996. Food Chemicals Codex, 4th ed., Washington, DC: National Academy Press.
143. Nielsen, P. E., Y. Matsuoka, and B. J. Norden. 1985. Stepwise unfolding of chromatin by urea. A flow linear dichroism and photoaffinity labeling study. Eur. J. Biochem. 147:65-68.
144. Nikitakis, J. M., and G. N. McEwen, Jr. eds. 1990a. CTFA compendium of cosmetic ingredient composition-specifications. Washington, DC: CTFA.
145. Nikitakis, J. M., and G. N. McEwen, Jr. eds. 1990b. CTFA Compendium of cosmetic ingredient composition-descriptions I and II. Washington, DC: CTFA.
146. Nishihata, T., J. H. Rytting, A. Kamada, K. Matsumoto, and K. Takahashi. 1990. Combined effect of alcohol and urea on the in vitro transport of indomethacin across rat dorsal skin. J. Pharm. Sci. 79:487-489.
147. Nook, T. H. 1987. In vivo measurement of the keratolytic effect of salicylic acid in three ointment formulations. Br. J. Dermatol. 117:243-245.
148. Ochsenfahrt, H., and D. Winne. 1973. The contribution of solvent drag to the intestinal absorption of tritiated water and urea from the jejunum of the rat. Naunyn-Schmiedeberg's Arch. Pharmacol. 279:133-152.
149. Odeh, Y., Z. Wang, T. I. Ruo, T. Wang, M. C. Fredericksen, P. A. Pospisil, and A. J. Atkinson. 1993. Simultaneous analysis of inulin and 15N2-urea kinetics in humans. Clin. Pharmacol. Ther. 53:419-425.
150. Ogiso, T., M. Iwaki, and T. Paku. 1995. Effect of various enhances on transdermal penetration of indomethacin and urea, and relationship between penetration parameters and enhancement factors. J. Pharm. Sci. 84:482-488.
151. Ohshima, T., H. Yoshikawa, K. Takada, and S. Muranishi. 1984. Enhancing effect of absorption promoters on percutaneous absorption of a model dye (6-carboxyfluorescein) as poorly absorbable drugs. I Comparison of plasma levels after addition of various absorption promoters in rat. J. Pharm. Dyn. 7:648-655.
152. Okumura, K., I. P. Lee, and R. L. Dixon. 1975. Permeability of selected drugs and chemicals across the blood-testis barrier of the rat. J. Pharmacol. Exp. Ther. 194:89-95.
153. Oppenheim, J. J., and W. N. Fishbein. 1965. Induction of chromosome breaks in cultured normal human leukocytes by potassium arsenate, hydroxyurea and related compounds. Cancer Res. 25:980-985.
154. Pankova, N. V., and N. N. Sokolov. 1974. Determination of subchromatids in the structural organization of chromosomes in frog lymphocytes treated with urea. Sov. Genet. 10:305-308.
155. Parikh, N. H., A. Babar, and F. M. Plakogiannis. 1986. Medicament release from ointment bases. Part 2. Testosterone: In vitro release and effects of additives on its release. Drug Dev. Ind. Pharm. 12:2493-2509.
156. Pearson, P., S. Lew, F. Abramson, and J. Bosch. 1994. Measurement of kinetic parameters for urea in end-stage renal disease patients using a two-compartment model. J. Am. Soc. Nephrol. 4:1869-1873.
157. Peck, K. D., A. H. Ghanem, and W. I. Higuchi. 1995. The effect of temperature upon the permeation of polar and ionic solutes through human epidermal membrane. J. Pharm. Sci. 84:975-982.
158. Peck, K. D., J. Hsu, S. K. Li, A. H. Ghanem, and W. I. Higuchi. 1998. Flux enhancement effects of ionic surfactant upon passive and eletroosmotic trandsdermal transport. J. Pharm. Sci. 87:1161-1169.
159. Petersen, R. V., M. S. Kislalioglu, W. Liang, S. Fang, M. Enam, and S. Dickman. 1986. Athymic nude mouse grafted with human skin as a model for evaluating the safety and effectiveness of radiolabeled cosmetic ingredients. J. Soc. Cosmet. Chem. 37:249-265.
160. Phelps, A. W., E. O. Dillingham, and J. Autian. 1983. The influence of urea and cell-surface protein on the behavior of nontumorigenic and chemically transformed cells. J. Toxicol. Environ. Health 11:783-797.
161. Pickard, J. D., F. Durity, F. A. Welsh, T. W. Langfitt, A. M. Harper, and E. T. MacKenzie. 1977. Osmotic opening of the blood-brain barrier: value in pharmacological studies on the cerebral circulation. Brain Res. 122:170-176.
162. l5N-urea on the effects of a low protein diet and malnutrition on urea metabolism in children. Clin. Sci. 43:17P.
163. Pollay, M. 1975a. Effect of hypertonic solutions on the blood-brain barrier. Neurology 25:852-856.
164. Pollay, M. 1975b. Evaluation of altered blood-brain barrier permeability to amino acids. Res. Commun. Chem. Pathol. Pharmacol. 10:763-766.
165. Přiborsky, J., K. Takayama, and T. Nagai. 1998. Influence of acute uraemia on percutaneous absorption of nonsteroidal anti-inflammatory drugs. Acta Univ. Palacki Olomuc Fac. Med. 141:35-38.
166. Raab, W. P. 1990. Uses of urea in cosmetology. Cosmet. Toiletries 105:97-98, 100-102.
167. Rahman, M. S., A. Babar, N. K. Patel, and F. M. Plakogiannis. 1990. Medicament release from ointment bases. Part 5. Naproxen in vitro release and in vivo percutaneous absorption in rabbits. Drug Dev. Ind. Pharm. 16:651-672.
168. Rao, V. U., and A. N. Misra. 1994. Enhancement of iontophoretic permeation of insulin across human cadaver skin. Pharmazie 49:538-539.
169. Rao, V. U., and A. N. Misra. 1995. Comparative evaluation of the effect of penetration enhancers on passive diffusion and iontophoretic transport of insulin. Indian Drugs 32:437-441.
170. 14C]ureapharmacokinetics. Am. J. Physiol. 242:R339-R348.
171. Rapoport, S. I., M. Hori, and I. Klatzo. 1972. Testing of a hypothesis for osmotic opening of the blood-brain barrier. Am. J. Physiol. 223:323-331.
172. Registry of Toxic Effects of Chemical Substances (RTECS). 1999. Urea entry. RTECS database. Bethesda, MD: National Library of Medicine.
173. Regoeczi, E., L. Irons, A. Koj, and A. S. McFarlane. 1965. Isotopic studies of urea metabolism in rabbits. Biochem. J. 95:521-532.
174. Reske, G., and H. Bauer. 1973. Influence of environment on the photooxidation of tryptophan with the hydrocarbon 3,4-benzopyrene in aqueous solutions of soap, caffeine, and urea. Z. Naturforsch (C) 28:390-396.
175. Roopnarinesingh, S. 1975. Termination of hypertensive pregnancies with intraamniotic revert. West Indian Med. J. 24:164-168.
176. Rose, C., and A. B. Mandal. 1996. The interaction of sodium dodecyl sulfate and urea with catfish collagen solutions in acetate buffer: hydrodynamic and thermodynamic studies. Int. J. Biol. Macromol. 18:41-53.
177. l5N-labelled glycine and urea. Contrib. Nephrol. 6:141-152.
178. 2+ channels. Mol. Cell Endocrinol. 70:273-290.
179. Schneider, W., K. Schumacher, and R. Gross. 1969. The influence of urea on energy metabolism of human blood platelet. Thromb. Diath. Haemorrh, 22:208-209.
180. Schubert, I., and R. Rieger. 1976. Effects of pre- and simultaneous treatment with urea on the induction of chromatid aberrations in vicia faba. Experientia 32:854-855.
181. 15N from orally administered urea in lactating pony mares. Arch. Anim. Nutr. Berlin 41:457-463.
182. Serup, J. 1992. A double-blind comparison of two creams containing urea as the active ingredient. Assessment of efficacy and side-effects by non-invasive techniques and a clinical scoring scheme. Acta Derm. Venereol. Suppl. 177:34-43.
183. Shannon, I. L., and J. R. Prigmore. 1961. Effects of Urea dosage on Urea correlations in human parotic fluid and blood serum. Arch. Oral Biol. 5:161-167.
184. Shaya, S. Y., C. W. Smith, and J. G. Heathcote. 1978. Percutaneous electrophoresis of amino acids and urea. Med. Biol. Eng. Comput. 16:126-134.
185. Shear, M. J., and J. Leiter. 1941. Studies in carcinogenesis. XVI. Production of subcutaneous tumors in mice by miscellaneous polycylcic compounds. J. Natl. Cancer Inst. 2:241-258.
186. Shimizu, H., Y. Suzuki, N. Takemura, S. Goto, and H. Matsushita. 1985. The results of microbial mutation test for forty-three industrial chemicals. Jpn. J. Ind. Health 27:400-419.
187. Sindhvananda, J., P. Gritiyarangsan, P. Rungrairatanaroij, and P. Kullavanijaya. 1993. Hygroscopicity and water-holding capacity of moisturizing agents: single-application in vivo study. J. Soc. Cosmet. Chem. 44:279-288.
188. Sobhon, P., P. Thungkasemvathana, and N. Tanphaichitr. 1981. Electron microscopic studies of rat sperm heads treated with urea, dithiothreitol and micrococcal nucleate. Anat. Rec. 201:225-235.
189. 14C]glucose analogues by rabbit brain. Neuropathol. Appl. Neurobiol. 2:53-61.
190. Szász, I., and G. Gárdos. 1970. The effect of urea and related compounds on the morphology and energy metabolism of erythrocytes. Acta Biochim. Biophys. Acad. Sci. Hung. 5:309-311.
191. Sznitowska, M., S. Janicki, and T. Gos. 1996. Effect of sorption promoters on percutaneous permeation of a model zwitterion-baclofen. Int. J. Pharm. 137:125-132.
192. Takahashi, K., T. Suzuki, H. Sakano, and N. Mizuno. 1995. Effect of vehicles on diclofenac permeation across excised rat skin. Biol. Pharm. Bull. 18:571-575.
193. Takeuchi, K., T. Ohuchi, H. Harada, and S. Okabe. 1995 Irritant and protective action of urea-urease ammonia in rat gastric mucosa. Different effects of ammonia and ammonium ion. Dig. Dis. Sci. 40:274-281.
194. Teramoto, S., M. Kaneda, H. Aoyama, and Y. Shirasu. 1981. Correlation between molecular structure of N-alkylureas and N-alkylthioureas and their teratogenic properties. Teratology 23:335-342.
195. Theodore, J., E. D. Robin, R. Gaudio, and J. Acevedo. 1975. Transaveolar transport of large polar solutes (sucrose, insulin and dextran). Am. J. Physiol. 229:989-996.
196. Thornburg, K. L., and J. J. Faber. 1977. Transfer of hydrophillic molecules by placenta and yolk sac of the guinea pig. Am. J. Physiol. 233:C111-C124.
197. +, carbohydrate and amino acid metabolism in weanling mice: NaCl induces insulin secretion and hypoglycemia. Metab. Brain Dis. 1:129-146.
198. 2
199. Topham, J. C. 1980. Do induced sperm-head abnormalities in mice specifically identify mammalian mutagens rather than carcinogens? Mutat. Res. 74:379-387.
200. Treffet, P., and B. Gabard. 1995. Stratum corneum dynamic function measurements after moisturizer or irritant application. Arch. Dermatol. Res. 287:474-479.
201. Treheme, J. E. 1956. The permeability of skin to some non-electrolytes. J. Physiol. 133:171-180.
202. Troshev, K., I. Kozarev, and D. Markov. 1990. Regulation of traumatic skin wound healing by influencing the process in the neighboring zone of the wound. Acta Chir. Plast. 32:152-163.
203. Ts'o, P. O. P., G. K. Helmkamp, and C. Sander. 1962. Interactions of nucleoside and related compounds with nucleic acids as indicated by the change of helix-coil transition temperature. Proc. Natl. Acad. Sci. U.S.A 48:686-697.
204. 15N]urea in plasma and application to urea metabolism study. Anal. Chem. 54:489-491.
205. Umeda, M., K. Noda, and T. Ono. 1980. Inhibition of metabolic cooperation in Chinese hamster cells by various chemicals including tumor promoters. Jpn. J. Cancer Res. 71:614-620.
206. United States Pharmacopeial Convention, Inc. 1995. The United States Pharmacopeia, Vol. 23, and the National Formulary, Vol. 18. Taunton, MA: Rand McNally.
207. United States Pharmacopeial Convention, Inc. 2000. The United States Pharmacopeia, Vol. 24, and the National Formulary, Vol. 19. Taunton, MA: Rand McNally.
208. Valenta, C., and S. Wedenig. 1997. Effects of penetration enhances on the in vitro percutaneous absorption of progesterone. J. Pharm. Pharmacol. 49:955-959.
209. Valentovic, M., and K. Bachmann. 1980. Effects of urea on hexobarbital and antipyrine disposition in rats. Pharmacology 21:167-174.
210. Van Duzee, B. F. 1975. Thermal analysis of human stratum corneum. J. Invest. Dermatol. 65:404-408.
211. Van Duzee, B. F. 1978. The influence of water content, chemical treatment and temperature on the rheological properties of stratum corneum. J. Invest. Dermatol. 71:140-144.
212. Varcoe, R., D. Halliday, E. R. Carson, P. Richards, and A. S. Tavill. 1975. Efficiency of utilization of urea nitrogen for albumin synthesis by chronically uremia and normal man. Clin. Sci. Mol. Med. 48:379-390.
213. Wahlberg, J. E., and G. Swanbeck. 1973. The effect of urea and lactic acid on the percutaneous absorption of hydrocortisone. Acta Derm. Venereol. 53:207-210.
214. Walser, M., and L. J. Bodenlos. 1959. Urea metabolism in man. J. Clin. Invest. 38:1617-1626.
215. Wangenheim, J., and G. Bolcsfoldi. 1988. Mouse lymphoma L5178Y thymidine kinase locus assay of 50 compounds. Mutagenesis 3:193-205.
216. Wardle, E. N. 1970. A study of the effects of possible toxic metabolites of uremia on red cell metabolism. Acta Haematol. 43:129-143.
217. Weinberg, P. C., and M. K. Shepard. 1973. Intraamniotic urea for induction of mid-trimester abortion. Obstet. Gynecol. 41:451-454.
218. Wenninger, J. A., R. C. Canterbery, and G. N. McEwen, Jr., eds. 2000. International cosmetic ingredient dictionary and handbook. 8th ed., vol. 2, 1547-1548. Washington, DC: CTFA.
219. Wilkinson, J., and R. Moore, eds. 1982. Harry's cosmeticology, 7th ed. New York: Chemical Publishing.
220. Wohlrab, W. 1984. The influence of urea on the penetration kinetics of topically applied corticosteroids. Acta Derm. Venereol. 64:233-238.
221. 15N-urea. Am. J. Physiol. 240:E428-E434.
222. Wolfe, R. R., R. D. Goodenough, M. H. Wolfe, G. T. Royle, and E. R. Nadel. 1982. Isotopic analysis of leucine and urea metabolism in exercising humans. J. Appl. Physiol. 52:458-466.
223. Wolpert, E., S. F. Phillips, and W. H. J. Summerskill. 1971. Transport of Urea and ammonia production in the human colon. Lancet. 2:1387-1390.
224. Wrong, O. M., and A. Vince. 1984. Urea and ammonia metabolism in the human large intestine. Proc. Nutr. Soc. 43:77-86.
225. Wrong, O. M., A. J. Vince, and J. C. Waterlow. 1982. In: Colon and nutrition, eds. H. Kasper, and H. Goebell, 133-137. Lancaster: MTP Press.
226. Yarnell, P. R., R. L. Bell, P. Ng, and W. T. Gormley. 1972. Plasma urea kinetics in urea infusion. Clin. Pharmacol. Ther. 13:558-562.
227. Yuasa, H., N. Soga, Y. Kimura, and J. Watanabe. 1997. Effect of aging on the intestinal transport of hydrophillic drugs in the rat small intestine. Biol. Pharm. Bull. 20:1188-1192.
228. Zhai, H., P. Willard, and H. I. Maibach. 1998. Evaluating skin-protective materials against contact irritants and allergens. An in vivo screening human model. Contact Dermatitis 38:155-158.
229. Zhurkov, V. S. 1975. Investigation of the mutagenic activity of drug preparations and food additives in a culture of human lymphocytes. Sov. Genet. 11:528-530.