Currently. N-methyl-N'-nitroguanidine (MNG) is being considered by the U.S. Air Force Armament Laboratory for use in explosive formulations. A mammalian toxicity profile has been performed which includes the analysis of chemical impurities and an assessment of the potential for the metabolism of MNG to 1-methyl-3-nitro-1-nitrosoguanidine (MNNG). Potential in situ gastric conversion of MNG to MNNG is a toxicological concern because MNNG is both mutagenic and carcinogenic. The compound was also evaluated in several bioassays to assess its potential genotoxic activity. The acute oral toxicity was determined in male and female Fischer 344 rats administered a single dose of MNG in corn oil. The maximum suspension of MNG that could be delivered, 1 mg MNG/kg body weight, produced no signs of toxic stress during the 14-day observation period. The primary eye and skin irritation potential of MNG was determined in female New Zealand white rabbits using the Draize technique. MNG produced no irritation to intact skin but did produce mild conjunctival irritation. The response of a single guinea pig to the dermal sensitization evaluation indicated that MNG is a weak sensitizer. The results of three genetic tests indicated that MNG does not interact with genetic material. Gastric contents and feces from treated animals showed no evidence of conversion of MNG to MNNG.
AmesB.N.McCannJ.YamasakiE. (1975). “Methods for detecting carcinogens and mutagens with the Salmonella/mammalian microsome mutagenicity test.”Mutat. Res. 31:347–367.
2.
BrownL.D.WheelerC.R.KorteD.W. (1988). Oral Toxicity of Nitroguanidine in Male and Female Rats. Letterman Army Institute of Research, LAIR Report No. 264, Presidio of San Francisco, San Francisco, CA.
3.
CampbellK.I.GeorgeE.L.HaleL.L.StaraJ.F. (1975). “Dermal irritancy of metal compounds.”Arch. Environ. Health30:168–170.
4.
DraizeJ.H.WoodwardG.CalveryH.O. (1944). “Methods for the study of irritation and toxicity of substances applied to the skin and mucous membranes.”J. Pharm. Exp. Therap. 32:377–390.
5.
EndoH.TakahashiK.AoyagiH. (1974). “Screening of compounds structurally and functionally related to N-methyl-N'-nitro-N-nitrosoguanidine, a gastric carcinogen”. GANN Monog Cane. Res. 65:45–54.
6.
EndoH.TakahashiK.KonoshitaN.UtsunomiyaT.BabaT. (1975). “An approach to the detection of possible etiologic factors in human gastric cancer.”GANN Monog. Cane. Res. 17:17–29.
7.
HiattG.F.S.SanoS.K.KorteD.W. (1986). Primary Eye Irritation Potential of Nitroguanidine in Rabbits. Letterman Army Institute of Research, AD-A164675, Presidio of San Francisco, San Francisco, CA.
8.
HiattG.F.S.SanoS.K.WheelerC.R.KorteD.W. (1988a). Acute Oral Toxicity of Nitroguanidine in Mice. Letterman Army Institute of Research, LAIR Report No. 265, Presidio of San Francisco, San Francisco, CA.
9.
HiattG.F.S.MorganE.W.KorteD.W. (1988b). Sensitization Potential of Guanidine Nitrate in Guinea Pigs. Letterman Army Institute of Research, AD-A198496, Presidio of San Francisco, San Francisco, CA.
10.
HillM.J.HanksworthG., (1973). “Bacteria, nitrosamines and cancer of the stomach.”Br. J. Cancer28:562–567.
11.
HortonJ.R.MacEwenJ.D.VernotE.H.HallA. (1981). Comparisons of Skin Sensitization Methods: Landsteiner, Maguire and Guinea Pig Maximization, AFAMRL-TR-81-131 (AD-AI10633), Aerospace Medical Research Laboratory, Wright-Patterson Air Force Base, OH.
12.
HseA.W.SebastianSan J.R.PerdueS.W.SchenleyR.L.WatersM.D. (1987). “Multiple-endpoint mutagenesis with Chinese Hamster Ovary (CHO) cells: Evaluation with eight carcinogenic and non-carcinogenic compounds.”Mol. Toxicol. 1:217–234.
13.
IshidateM. (1988). Data Book of Chromosomal Aberration Test In Vitro. Elsevier, Amsterdam. p. 277.
14.
KinkeadE.R.BungerS.K.RimmelE.G.FlemmingC.D.WallH.G.GrabauJ.H. (1991). “Effects of a 13-wcek chloropentafluorobenzene inhalation exposure of Fischer 344 rats and B6C3F1 mice.”Tox. and Ind. Health. 7(4): 309–318.
15.
KinkeadE.R.WolfeR.E.BungerS.K.LeahyH.F. (1992). “The acute toxicity of a low-temperature hydraulic fluid.”Am. Ind. Hyg. Assoc. J. 53(3): 163–168.
16.
KlaassenC.D.DoullJ. (1980). “Evaluation of safety: Toxicologic evaluation.” In: Casarett and Doull's Toxicology, The Basic Science of Poison (DoullJ.D.KlaassenC.D.AmdurM.D., eds.). 2nd Edition, MacMillan Publishing Co., Inc., New York.
17.
KobayashiY.KuboH.KinoshitaT. (1987). “Post-column derivatization system for the fluorometric determination of guanidine compounds with ninhydrtn by reversed-phase ion-pair high-performance liquid chromatography.”J. Chromatogr. 400:113–121.
18.
Le TellierY.C.BausermanJ.W.KorteD.W. (1988). Primary Dermal Irritation Potential of Guanidine Nitrate in Rabbits. Letterman Army Institute of Research, AD-A198495, Presidio of San Francisco, San Francisco, CA.
19.
MaguireH.C. (1973). “The bioassay of contact allergens in the guinea pig.”J. Soc. Cosmet. Chem. 24:151–162.
20.
McKayA.F.WrightG.F. (1947). “Preparation and properties of N-methyl-N-nitroso-N'-nitroguanidine.”J. Am. Chem. Soc. 69:3028–3030.
21.
MaronD.AmesB.N., (1983). “Revised methods for the Salmonella mutagenicity test.”Mutat. Res. 113:173–215.
22.
MirvishS.S. (1975). “Formation of N-nitroso compounds: Chemistry, kinetics, and in vivo occurrence.”Toxicol. Appl. Pharmacol. 31:325–351.
23.
MorganE.W.SanoS.K.KorteD.W. (1986a). Primary Dermal Irritation Potential of Nitroguanidine in Rabbits. Letterman Army Institute of Research, LAIR Report No. 220, Presidio of San Francisco, San Francisco, CA.
24.
MorganE.W.BausermanJ.W.KorteD.W. (1986b). Primary Eye Irritation of Guanidine Nitrate in Male Rabbits. Letterman Army Institute of Research, AD-A166449, Presidio of San Francisco, San Francisco, CA.
25.
MullenL.MorganE.W.LewisC.M.WheelerC.R.KorteD.W. (1988). Acute Oral Toxicity of Guanidine Nitrate in Rats. Letterman Army Institute of Research, AD-A196954, Presidio of San Francisco, San Francisco, CA.
26.
NagaoM.YahagT.NakadateM.KawachiT.SugimuraT. (1975). “Mutagenic or DNA-modifying activities of N-alkyl-N'-nitro-N-nitrosoguanidine.”Jap. J. Genet. 50:403–408.
27.
PatrickM.ACadyH.H. (1990). Development of the phase diagram of the methylnitroguanidine/ammonium nitrate system. Los Alamos National Laboratory, Los Alamos, NM. August Interim Report No. AFATL-TR-90-78. Eglin AFB, FL: Munitions Division, Air Force Armament Laboratory.
28.
SanderJ.SchweinsbergF. (1972). “Wechselbeziehungen zwischen nitrat, nitrit und kanzerogenen N-nitrosoverbindungen.”Zbl. Bakt. Hyg. B. 156:299–340.
29.
SanoS.K.KorteD.W. (1988). Acute Dermal Toxicity of Guanidine Nitrate in Male and Female Rabbits. Letterman Army Institute of Research, AD-A198494, Presidio of San Francisco, San Francisco, CA.
30.
U.S. Department Of Health And Human Services. (1985). “Guide for the Care and Use of Laboratory Animals (Publication #86–23).”National Institutes of Health, Bethesda, MD.
31.
BurgerWeis J.H.WilliamsG.M. (1980). “Chemical Carcinogens.” In: Casarett and Doull's Toxicology, The Basic Science of Poisons (DoullJ.D.KlaassenC.D.AmdurM.D., eds.). 2nd Edition, MacMillan Publishing Co., Inc., New York. pp. 89–91.
