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o-Toluidine

April 15, 2024

o-Toluidine (ortho-toluidine) is an organic compound with the chemical formula CH3C6H4NH2. It is the most important of the three isomeric toluidines. It is a colorless liquid although commercial samples are often yellowish. It is a precursor to the herbicides metolachlor and acetochlor.[2]

o-Toluidine
Names
Preferred IUPAC name
2-Methylaniline[1]
Other names
o-Methylaniline
o-Toluidine
1-Amino-2-methylbenzene
2-Aminotoluene, 2-Toluamine
Identifiers
  • 95-53-4 Y
ChEBI
  • CHEBI:66892 Y
ChEMBL
  • ChEMBL1381 Y
ChemSpider
  • 13854136 Y
ECHA InfoCard 100.002.209
KEGG
  • C14403 Y
  • 7242
UNII
  • B635MZ0ZLU N
  • DTXSID1026164
Properties
C7H9N
Molar mass 107.156 g·mol−1
Appearance Colorless liquid
Odor Aromatic, aniline-like odor
Density 1.004 g/cm3
Melting point −23.68 °C (−10.62 °F; 249.47 K)
Boiling point 200 to 202 °C (392 to 396 °F; 473 to 475 K)
0.19 g/100 ml at 20 °C
Vapor pressure 0.307531 mmHg (25 °C)
1.56987
Viscosity 4.4335 (20 °C)
Hazards
Occupational safety and health (OHS/OSH):
Main hazards
 Flammable, moderately toxic
GHS labelling:
Danger
H301, H302, H319, H331, H350, H400
P201, P202, P261, P264, P270, P271, P273, P280, P281, P301+P310, P304+P340, P305+P351+P338, P308+P313, P311, P321, P330, P337+P313, P391, P403+P233, P405, P501
NFPA 704 (fire diamond)
Health 3: Short exposure could cause serious temporary or residual injury. E.g. chlorine gasFlammability 2: Must be moderately heated or exposed to relatively high ambient temperature before ignition can occur. Flash point between 38 and 93 °C (100 and 200 °F). E.g. diesel fuelInstability 0: Normally stable, even under fire exposure conditions, and is not reactive with water. E.g. liquid nitrogenSpecial hazards (white): no code
3
2
0
Flash point 85 °C (185 °F; 358 K)
481.67 °C (899.01 °F; 754.82 K)
Lethal dose or concentration (LD, LC):
900 mg/kg (rat, oral)
323 mg/kg (rabbit, oral)
Related compounds
Related compounds
 Toluidine
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).

Synthesis and reactions edit

o-Toluidine is produced industrially by nitration of toluene to give a mixture of nitrotoluenes, favoring the ortho isomer. This mixture is separated by distillation. 2-Nitrotoluene is hydrogenated to give o-toluidine.[2]

The conversion of o-toluidine to the diazonium salt gives access to the 2-bromo, 2-cyano-, and 2-chlorotoluene derivatives.[3][4][5] N-acetylation is also demonstrated.[6]

Safety edit

The LD50 (oral, rats) is 670 mg/kg.[2]

Binding of hemoglobin edit

o-Nitrosotoluene, a metabolite of o-toluidine, converts hemoglobin to methemoglobin, resulting in methemoglobinemia.[7][8][ISBN missing][9]


o-Nitrosotoluene is suspected of causing bladder cancer in rats.[10][11][12] Nitrosotoluene exposure has been researched in a number of different degrees in animals.[13][14][15][16]

Carcinogenicity edit

In the U.S., o-toluidine was first listed in the Third Annual Report on Carcinogens as 'reasonably anticipated to be a human carcinogen' in 1983, based on sufficient evidence from studies in experimental animals. The Report on Carcinogens (RoC) is a U.S. congressionally-mandated, science-based public health report that identifies agents, substances, mixtures, or exposures in the environment that pose a hazard to people residing in the United States[17] Since then, other cancer related studies have been published and the listing of o-toluidine was changed to 'known to be a human carcinogen'. o-toluidine was especially linked to bladder cancer. This was done 31 years later in the (2014).[14] The International Agency for Research on Cancer (IARC) has classified o-toluidine as 'carcinogenic to humans (group 1)'.[18]

Metabolism edit

o-Toluidine is absorbed through inhalation and dermal contact as well as from the gastrointestinal tract.[19][13][20][21]

The metabolism of o-toluidine involves many competing activating and deactivating pathways, including N-acetylation, N-oxidation, and N-hydroxylation, and ring oxidation.[22] 4-Hydroxylation and N-acetylation of toluidine are the major metabolic pathways in rats. The primary metabolism of o-toluidine takes place in the endoplasmic reticulum. Exposure to o-toluidine enhances the microsomal activity of aryl hydrocarbon hydroxylase (particularly in the kidney), NADPH-cytochrome c reductase and the content of cytochrome P-450. Cytochrome P450–mediated N-hydroxylation to N-hydroxy-o-toluidine, a carcinogenic metabolite, occurs in the liver. N-Hydroxy-o-toluidine can be either metabolized to o-nitrosotoluene or conjugated with glucuronic acid or sulfate and transported to the urinary bladder via the blood. Once in the bladder, N-hydroxy-o-toluidine can be released from the conjugates in an acidic urine environment to either react directly with DNA or be bio-activated via sulfation or acetylation by cytosolic sulfotransferases or N-acetyltransferases (presumably NAT1).[14] The postulated activated form (based on comparison with other aromatic amines), N-acetoxy-o-toluidine, is a reactive ester that forms electrophilic arylnitrenium ions that can bind to DNA.[22][23][10] Other activation pathways (ring-oxidation pathways) for aromatic amines include peroxidase-catalyzed reactions that form reactive metabolites (quinone-imines formed from nonconjugated phenolic metabolites) in the bladder. These metabolites can produce reactive oxygen species, resulting in oxidative cellular damage and compensatory cell proliferation. Support for this mechanism comes from studies of oxidative DNA damage induced by o-toluidine metabolites in cultured human cells (HL-60), calf thymus DNA, and DNA fragments from key genes thought to be involved in carcinogenesis (the c-Ha-ras oncogene and the p53 tumor-suppressor gene).[24][25] Also supporting this mechanism are observations of o-toluidine-induced DNA damage (strand breaks) in cultured human bladder cells and bladder cells from rats and mice exposed in vivo to o-toluidine.[26][27]

 
Figure 1: Metabolism of o-(methyl-14C)-toluidine hydrochloride in the rat.

Excretion edit

The main excretion pathway is through the urine where up to one-third of the administered compound was recovered unchanged. Major metabolites are 4-amino-m-cresol and to a lesser extent, N-acetyl-4-amino-m-cresol,[20] azoxytoluene, o-nitrosotoluene, N-acetyl-o-toluidine, N-acetyl-o-aminobenzyl alcohol, anthranilic acid, N-acetyl-anthranilic acid, 2-amino-m-cresol, p-hydroxy-o-toluidine. Conjugates that were formed were predominated by sulfate conjugates over glucuronide conjugates by a ratio of 6:1.

Related metabolic pathways edit

Prilocaine, an amino amide-type local anesthetic, yields o-toluidine when metabolized by carboxylesterase enzymes.[28] Large prilocaine doses can cause methemoglobinemia due to oxidation of hemoglobin by o-toluidine.[29]

References edit

  1. ^ Nomenclature of Organic Chemistry: IUPAC Recommendations and Preferred Names 2013 (Blue Book). Cambridge: The Royal Society of Chemistry. 2014. p. 669. doi:10.1039/9781849733069-FP001. ISBN 978-0-85404-182-4. The names 'toluidine', 'anisidine', and 'phenetidine' for which o-, m-, and p- have been used to distinguish isomers, and 'xylidine' for which numerical locants, such as 2,3-, have been used, are no longer recommended, nor are the corresponding prefixes 'toluidine', 'anisidino', 'phenetidine', and 'xylidino'.
  2. ^ a b c Bowers, Joseph S. "Toluidines". Ullmann's Encyclopedia of Industrial Chemistry. Weinheim: Wiley-VCH. doi:10.1002/14356007.a27_159. ISBN 978-3527306732.
  3. ^ H. T. Clarke; R. R. Read (1925). "o-Tolunitrile and p-Tolunitrile". Org. Synth. 4: 69. doi:10.15227/orgsyn.004.0069.
  4. ^ L. A. Bigelow (1929). "o-Bromotoluene". Org. Synth. 9: 22. doi:10.15227/orgsyn.009.0022.
  5. ^ C. S. Marvel; S. M. McElvain (1923). "o-Chlorotoluene and p-Chlorotoluene". Org. Synth. 3: 33. doi:10.15227/orgsyn.003.0033.
  6. ^ Rolf Huisgen; Klaus Bast (1962). "Indazole". Org. Synth. 42: 69. doi:10.15227/orgsyn.042.0069.
  7. ^ Hazardous Substances Data Bank (HSDB, online database). National Toxicology Information Program. National Library of Medicine, Bethesda, MD: U.S. Department of Health and Human Services. 1997.
  8. ^ Clayton, G. D.; Clayton, F. E., eds. (1981). Patty's Industrial Hygiene and Toxicology. Vol. 2A (3rd rev. ed.). New York: John Wiley & Sons.
  9. ^ Birnier, G.; Neumann, H. (1988). "Biomonitoring of aromatic amines. II: Haemoglobin binding of some monocyclic aromatic amines". Arch. Toxicol. 62 (2–3): 110–115. doi:10.1007/BF00570128. PMID 3196145. S2CID 33391149.
  10. ^ a b English, J. C.; Bhat, V. S.; Ball, G. L.; C. J., McLellan (2012). "Establishing a total allowable concentration of o-toluidine in drinking water incorporating early lifestage exposure and susceptibility". Regul. Toxicol. Pharmacol. 64 (2): 269–284. doi:10.1016/j.yrtph.2012.08.011. PMID 22940434.
  11. ^ Eyer, P. (1983). "The Red Cell as a Sensitive Target for Activated Toxic Arylamines". Toxicology in the Use, Misuse, and Abuse of Food, Drugs, and Chemicals. Archives of Toxicology. Vol. 6. pp. 3–12. doi:10.1007/978-3-642-69083-9_1. ISBN 978-3-540-12392-7. PMID 6578736. {{cite book}}: |journal= ignored (help)
  12. ^ Hecht, S. S.; El-Bayoumy, K.; Rivenson, A.; Fiala, E. (1983). "Bioassay for carcinogenicity of 1,2-dimethyl-4-nitrosobiphenyl, o-nitrosotoluene, nitrosobenzene and the corresponding amines in Syrian golden hamsters". Cancer Lett. 20 (3): 349–354. doi:10.1016/0304-3835(83)90034-4. PMID 6627231.
  13. ^ a b Hiles, R. C.; Abdo, K. M. (1990). "5. ortho-Toluidine". In Buhler, D. R.; Reed, D. J. (eds.). Nitrogen and Phosphorus Solvents (2nd ed.). Elsevier. pp. 202–207.
  14. ^ a b c "o-Toluidine" (PDF). Report on Carcinogens (13th ed.). US National Institute of Health.
  15. ^ Gregg, N.; et al. (1998). o-Toluidine. World Health Organization. pp. 5–22. ISBN 92-4-153007-3. (NLM classification: QV 235.)
  16. ^ Rubino, G. F.; Scansetti, G.; Piolatto, G.; Fira, E. (1982). "The carcinogenic effect of aromatic amines: An epidemiological study on the role of o-toluidine and 4,4′-methylenebis(2-methylaniline) in inducing bladder cancer in man". Env. Res. 27 (2): 241–254. Bibcode:1982ER.....27..241R. doi:10.1016/0013-9351(82)90079-2. PMID 7084156.
  17. ^ Burwell, S. M. (2014). Report on Carcinogens (13th ed.).
  18. ^ IARC Monographs. Retrieved 2016-06-13. {{cite book}}: |website= ignored (help)
  19. ^ Cheever, K.; Richards, D.; Plotnick, H. (1980). "Metabolism of o-, m- and p-toluidine in the adult male rat". Toxicol. Appl. Pharmacol. 56 (3): 361–369. doi:10.1016/0041-008x(80)90069-1. PMID 7222020.
  20. ^ a b Son, O. S.; Everett, D. W.; Fiala, E. S. (1980). "Metabolism of o-[methyl-14C]toluidine in the F344 rat". Xenobiotica. 10 (7–8): 457–468. doi:10.3109/00498258009033781. PMID 7445517.
  21. ^ Brock, W. J.; Hundley, S. G.; Lieder, P. H. (1990). "Hepatic macromolecular binding and tissue distribution of ortho- and para-toluidine in rats". Toxicol. Lett. 54 (2–3): 317–325. doi:10.1016/0378-4274(90)90199-v. PMID 1701932.
  22. ^ a b Riedel, K.; Scherer, G.; Engl, J.; Hagedorn, H. W.; Tricker, A. R. (2006). "Determination of three carcinogenic aromatic amines in urine of smokers and nonsmokers". J. Anal. Toxicol. 30 (3): 187–195. doi:10.1093/jat/30.3.187. PMID 16803653.
  23. ^ Kadlubar, F. F.; Badawi, A. F. (1995). "Genetic susceptibility and carcinogen-DNA adduct formation in human urinary bladder carcinogenesis". Toxicol. Lett. 82–83: 627–632. doi:10.1016/0378-4274(95)03507-9. PMID 8597119.
  24. ^ Ohkuma, Y. Y.; Hiraku, S.; Oikawa, S.; Yamashita, N.; Murata, M.; Kawanishi, S. (1999). "Distinct mechanisms of oxidative DNA damage by two metabolites of carcinogenic o-toluidine". Arch. Biochem. Biophys. 372 (1): 97–106. doi:10.1006/abbi.1999.1461. PMID 10562421.
  25. ^ Watanabe, C; Egami, T; Midorikawa, K.; Hiraku, Y.; Oikawa, S.; Kawanishi, S; Murata, M. (2010). "DNA damage and estrogenic activity induced by the environmental pollutant 2-nitrotoluene and its metabolite". Environ. Health Prev. Med. 15 (5): 319–326. doi:10.1007/s12199-010-0146-1. PMC 2921039. PMID 21432561.
  26. ^ Robbiano, L.; Carrozzino, R.; Bacigalupo, M.; Corbu, C.; Brambilla, G. (2002). "Correlation between induction of DNA fragmentation in urinary bladder cells from rats and humans and tissue-specific carcinogenic activity". Toxicology. 179 (1–2): 115–128. doi:10.1016/s0300-483x(02)00354-2. PMID 12204548.
  27. ^ Sekihashi, K.; Yamamoto, A.; Matsumura, Y.; Ueno, S.; Watanabe-Akanuma, M.; Kassie, F; Knasmuller, S.; Tsuda, S.; Sasaki, Y. F. (2002). "Comparative investigation of multiple organs of mice and rats in the comet assay". Mutat. Res. 517 (1–2): 53–75. doi:10.1016/s1383-5718(02)00034-7. PMID 12034309.
  28. ^ Ryota Higuchi; Tatsuki Fukami; Miki Nakajima; Tsuyoshi Yokoi (2013). "Prilocaine- and Lidocaine-Induced Methemoglobinemia Is Caused by Human Carboxylesterase-, CYP2E1-, and CYP3A4-Mediated Metabolic Activation". Drug Metab. Dispos. 41 (6): 1220–1230. doi:10.1124/dmd.113.051714. PMID 23530020. S2CID 9741909.
  29. ^ Medetalibeyoğlu A.; Koç E.S.; Beyaz O.; Edizer A. (2020). "Prilocaine-Induced Methemoglobinemia". Case Rep. Acute Med. 3 (2): 25-28. doi:10.1159/000508403.

April 15, 2024
toluidine, ortho, toluidine, organic, compound, with, chemical, formula, ch3c6h4nh2, most, important, three, isomeric, toluidines, colorless, liquid, although, commercial, samples, often, yellowish, precursor, herbicides, metolachlor, acetochlor, namespreferre. o Toluidine ortho toluidine is an organic compound with the chemical formula CH3C6H4NH2 It is the most important of the three isomeric toluidines It is a colorless liquid although commercial samples are often yellowish It is a precursor to the herbicides metolachlor and acetochlor 2 o Toluidine NamesPreferred IUPAC name 2 Methylaniline 1 Other names o Methylanilineo Toluidine1 Amino 2 methylbenzene2 Aminotoluene 2 ToluamineIdentifiersCAS Number 95 53 4 YChEBI CHEBI 66892 YChEMBL ChEMBL1381 YChemSpider 13854136 YECHA InfoCard 100 002 209KEGG C14403 YPubChem CID 7242UNII B635MZ0ZLU NCompTox Dashboard EPA DTXSID1026164PropertiesChemical formula C 7H 9NMolar mass 107 156 g mol 1Appearance Colorless liquidOdor Aromatic aniline like odorDensity 1 004 g cm3Melting point 23 68 C 10 62 F 249 47 K Boiling point 200 to 202 C 392 to 396 F 473 to 475 K Solubility in water 0 19 g 100 ml at 20 CVapor pressure 0 307531 mmHg 25 C Refractive index nD 1 56987Viscosity 4 4335 20 C HazardsOccupational safety and health OHS OSH Main hazards Flammable moderately toxicGHS labelling PictogramsSignal word DangerHazard statements H301 H302 H319 H331 H350 H400Precautionary statements P201 P202 P261 P264 P270 P271 P273 P280 P281 P301 P310 P304 P340 P305 P351 P338 P308 P313 P311 P321 P330 P337 P313 P391 P403 P233 P405 P501NFPA 704 fire diamond 320Flash point 85 C 185 F 358 K Autoignitiontemperature 481 67 C 899 01 F 754 82 K Lethal dose or concentration LD LC LD50 median dose 900 mg kg rat oral 323 mg kg rabbit oral Related compoundsRelated compounds ToluidineExcept where otherwise noted data are given for materials in their standard state at 25 C 77 F 100 kPa Infobox references Contents 1 Synthesis and reactions 2 Safety 2 1 Binding of hemoglobin 2 2 Carcinogenicity 2 3 Metabolism 2 4 Excretion 2 5 Related metabolic pathways 3 ReferencesSynthesis and reactions edito Toluidine is produced industrially by nitration of toluene to give a mixture of nitrotoluenes favoring the ortho isomer This mixture is separated by distillation 2 Nitrotoluene is hydrogenated to give o toluidine 2 The conversion of o toluidine to the diazonium salt gives access to the 2 bromo 2 cyano and 2 chlorotoluene derivatives 3 4 5 N acetylation is also demonstrated 6 Safety editThe LD50 oral rats is 670 mg kg 2 Binding of hemoglobin edit o Nitrosotoluene a metabolite of o toluidine converts hemoglobin to methemoglobin resulting in methemoglobinemia 7 8 ISBN missing 9 o Nitrosotoluene is suspected of causing bladder cancer in rats 10 11 12 Nitrosotoluene exposure has been researched in a number of different degrees in animals 13 14 15 16 Carcinogenicity edit In the U S o toluidine was first listed in the Third Annual Report on Carcinogens as reasonably anticipated to be a human carcinogen in 1983 based on sufficient evidence from studies in experimental animals The Report on Carcinogens RoC is a U S congressionally mandated science based public health report that identifies agents substances mixtures or exposures in the environment that pose a hazard to people residing in the United States 17 Since then other cancer related studies have been published and the listing of o toluidine was changed to known to be a human carcinogen o toluidine was especially linked to bladder cancer This was done 31 years later in the Thirteenth Report on Carcinogens 2014 14 The International Agency for Research on Cancer IARC has classified o toluidine as carcinogenic to humans group 1 18 Metabolism edit o Toluidine is absorbed through inhalation and dermal contact as well as from the gastrointestinal tract 19 13 20 21 The metabolism of o toluidine involves many competing activating and deactivating pathways including N acetylation N oxidation and N hydroxylation and ring oxidation 22 4 Hydroxylation and N acetylation of toluidine are the major metabolic pathways in rats The primary metabolism of o toluidine takes place in the endoplasmic reticulum Exposure to o toluidine enhances the microsomal activity of aryl hydrocarbon hydroxylase particularly in the kidney NADPH cytochrome c reductase and the content of cytochrome P 450 Cytochrome P450 mediated N hydroxylation to N hydroxy o toluidine a carcinogenic metabolite occurs in the liver N Hydroxy o toluidine can be either metabolized to o nitrosotoluene or conjugated with glucuronic acid or sulfate and transported to the urinary bladder via the blood Once in the bladder N hydroxy o toluidine can be released from the conjugates in an acidic urine environment to either react directly with DNA or be bio activated via sulfation or acetylation by cytosolic sulfotransferases or N acetyltransferases presumably NAT1 14 The postulated activated form based on comparison with other aromatic amines N acetoxy o toluidine is a reactive ester that forms electrophilic arylnitrenium ions that can bind to DNA 22 23 10 Other activation pathways ring oxidation pathways for aromatic amines include peroxidase catalyzed reactions that form reactive metabolites quinone imines formed from nonconjugated phenolic metabolites in the bladder These metabolites can produce reactive oxygen species resulting in oxidative cellular damage and compensatory cell proliferation Support for this mechanism comes from studies of oxidative DNA damage induced by o toluidine metabolites in cultured human cells HL 60 calf thymus DNA and DNA fragments from key genes thought to be involved in carcinogenesis the c Ha ras oncogene and the p53 tumor suppressor gene 24 25 Also supporting this mechanism are observations of o toluidine induced DNA damage strand breaks in cultured human bladder cells and bladder cells from rats and mice exposed in vivo to o toluidine 26 27 nbsp Figure 1 Metabolism of o methyl 14C toluidine hydrochloride in the rat Excretion edit The main excretion pathway is through the urine where up to one third of the administered compound was recovered unchanged Major metabolites are 4 amino m cresol and to a lesser extent N acetyl 4 amino m cresol 20 azoxytoluene o nitrosotoluene N acetyl o toluidine N acetyl o aminobenzyl alcohol anthranilic acid N acetyl anthranilic acid 2 amino m cresol p hydroxy o toluidine Conjugates that were formed were predominated by sulfate conjugates over glucuronide conjugates by a ratio of 6 1 Related metabolic pathways edit Prilocaine an amino amide type local anesthetic yields o toluidine when metabolized by carboxylesterase enzymes 28 Large prilocaine doses can cause methemoglobinemia due to oxidation of hemoglobin by o toluidine 29 References edit Nomenclature of Organic Chemistry IUPAC Recommendations and Preferred Names 2013 Blue Book Cambridge The Royal Society of Chemistry 2014 p 669 doi 10 1039 9781849733069 FP001 ISBN 978 0 85404 182 4 The names toluidine anisidine and phenetidine for which o m and p have been used to distinguish isomers and xylidine for which numerical locants such as 2 3 have been used are no longer recommended nor are the corresponding prefixes toluidine anisidino phenetidine and xylidino a b c Bowers Joseph S Toluidines Ullmann s Encyclopedia of Industrial Chemistry Weinheim Wiley VCH doi 10 1002 14356007 a27 159 ISBN 978 3527306732 H T Clarke R R Read 1925 o Tolunitrile and p Tolunitrile Org Synth 4 69 doi 10 15227 orgsyn 004 0069 L A Bigelow 1929 o Bromotoluene Org Synth 9 22 doi 10 15227 orgsyn 009 0022 C S Marvel S M McElvain 1923 o Chlorotoluene and p Chlorotoluene Org Synth 3 33 doi 10 15227 orgsyn 003 0033 Rolf Huisgen Klaus Bast 1962 Indazole Org Synth 42 69 doi 10 15227 orgsyn 042 0069 Hazardous Substances Data Bank HSDB online database National Toxicology Information Program National Library of Medicine Bethesda MD U S Department of Health and Human Services 1997 Clayton G D Clayton F E eds 1981 Patty s Industrial Hygiene and Toxicology Vol 2A 3rd rev ed New York John Wiley amp Sons Birnier G Neumann H 1988 Biomonitoring of aromatic amines II Haemoglobin binding of some monocyclic aromatic amines Arch Toxicol 62 2 3 110 115 doi 10 1007 BF00570128 PMID 3196145 S2CID 33391149 a b English J C Bhat V S Ball G L C J McLellan 2012 Establishing a total allowable concentration of o toluidine in drinking water incorporating early lifestage exposure and susceptibility Regul Toxicol Pharmacol 64 2 269 284 doi 10 1016 j yrtph 2012 08 011 PMID 22940434 Eyer P 1983 The Red Cell as a Sensitive Target for Activated Toxic Arylamines Toxicology in the Use Misuse and Abuse of Food Drugs and Chemicals Archives of Toxicology Vol 6 pp 3 12 doi 10 1007 978 3 642 69083 9 1 ISBN 978 3 540 12392 7 PMID 6578736 a href Template Cite book html title Template Cite book cite book a journal ignored help Hecht S S El Bayoumy K Rivenson A Fiala E 1983 Bioassay for carcinogenicity of 1 2 dimethyl 4 nitrosobiphenyl o nitrosotoluene nitrosobenzene and the corresponding amines in Syrian golden hamsters Cancer Lett 20 3 349 354 doi 10 1016 0304 3835 83 90034 4 PMID 6627231 a b Hiles R C Abdo K M 1990 5 ortho Toluidine In Buhler D R Reed D J eds Nitrogen and Phosphorus Solvents 2nd ed Elsevier pp 202 207 a b c o Toluidine PDF Report on Carcinogens 13th ed US National Institute of Health Gregg N et al 1998 o Toluidine World Health Organization pp 5 22 ISBN 92 4 153007 3 NLM classification QV 235 Rubino G F Scansetti G Piolatto G Fira E 1982 The carcinogenic effect of aromatic amines An epidemiological study on the role of o toluidine and 4 4 methylenebis 2 methylaniline in inducing bladder cancer in man Env Res 27 2 241 254 Bibcode 1982ER 27 241R doi 10 1016 0013 9351 82 90079 2 PMID 7084156 Burwell S M 2014 Report on Carcinogens 13th ed IARC Monographs Retrieved 2016 06 13 a href Template Cite book html title Template Cite book cite book a website ignored help Cheever K Richards D Plotnick H 1980 Metabolism of o m and p toluidine in the adult male rat Toxicol Appl Pharmacol 56 3 361 369 doi 10 1016 0041 008x 80 90069 1 PMID 7222020 a b Son O S Everett D W Fiala E S 1980 Metabolism of o methyl 14C toluidine in the F344 rat Xenobiotica 10 7 8 457 468 doi 10 3109 00498258009033781 PMID 7445517 Brock W J Hundley S G Lieder P H 1990 Hepatic macromolecular binding and tissue distribution of ortho and para toluidine in rats Toxicol Lett 54 2 3 317 325 doi 10 1016 0378 4274 90 90199 v PMID 1701932 a b Riedel K Scherer G Engl J Hagedorn H W Tricker A R 2006 Determination of three carcinogenic aromatic amines in urine of smokers and nonsmokers J Anal Toxicol 30 3 187 195 doi 10 1093 jat 30 3 187 PMID 16803653 Kadlubar F F Badawi A F 1995 Genetic susceptibility and carcinogen DNA adduct formation in human urinary bladder carcinogenesis Toxicol Lett 82 83 627 632 doi 10 1016 0378 4274 95 03507 9 PMID 8597119 Ohkuma Y Y Hiraku S Oikawa S Yamashita N Murata M Kawanishi S 1999 Distinct mechanisms of oxidative DNA damage by two metabolites of carcinogenic o toluidine Arch Biochem Biophys 372 1 97 106 doi 10 1006 abbi 1999 1461 PMID 10562421 Watanabe C Egami T Midorikawa K Hiraku Y Oikawa S Kawanishi S Murata M 2010 DNA damage and estrogenic activity induced by the environmental pollutant 2 nitrotoluene and its metabolite Environ Health Prev Med 15 5 319 326 doi 10 1007 s12199 010 0146 1 PMC 2921039 PMID 21432561 Robbiano L Carrozzino R Bacigalupo M Corbu C Brambilla G 2002 Correlation between induction of DNA fragmentation in urinary bladder cells from rats and humans and tissue specific carcinogenic activity Toxicology 179 1 2 115 128 doi 10 1016 s0300 483x 02 00354 2 PMID 12204548 Sekihashi K Yamamoto A Matsumura Y Ueno S Watanabe Akanuma M Kassie F Knasmuller S Tsuda S Sasaki Y F 2002 Comparative investigation of multiple organs of mice and rats in the comet assay Mutat Res 517 1 2 53 75 doi 10 1016 s1383 5718 02 00034 7 PMID 12034309 Ryota Higuchi Tatsuki Fukami Miki Nakajima Tsuyoshi Yokoi 2013 Prilocaine and Lidocaine Induced Methemoglobinemia Is Caused by Human Carboxylesterase CYP2E1 and CYP3A4 Mediated Metabolic Activation Drug Metab Dispos 41 6 1220 1230 doi 10 1124 dmd 113 051714 PMID 23530020 S2CID 9741909 Medetalibeyoglu A Koc E S Beyaz O Edizer A 2020 Prilocaine Induced Methemoglobinemia Case Rep Acute Med 3 2 25 28 doi 10 1159 000508403 Retrieved from https en wikipedia org w index php title O Toluidine amp oldid 1195638930, wikipedia, wiki, book, books, library,

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