| Revision as of 05:34, 17 February 2012 editBeetstra (talk | contribs)Edit filter managers, Administrators172,031 edits Saving copy of the {{chembox}} taken from revid 456624497 of page Alpha-Naphthylthiourea for the Chem/Drugbox validation project (updated: 'KEGG', 'CASNo'). |
Latest revision as of 12:29, 25 September 2024 edit BD2412 (talk | contribs)Autopatrolled, IP block exemptions, Administrators2,454,469 editsm →Effects on animals: Clean up spacing around commas and other punctuation fixes, replaced: ,P → , P, ,V → , VTag: AWB |
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{{ambox | text = This page contains a copy of the infobox ({{tl|chembox}}) taken from revid of page ] with values updated to verified values.}} |
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| verifiedrevid = 399498755 |
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| verifiedrevid = 477319544 |
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|Name=α-Naphthylthiourea |
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| Name=α-Naphthylthiourea |
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|ImageFile=Alpha-naphthylthioureum.png |
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| ImageFile=1-(naphthalen-1-yl)thiourea 200.svg |
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|IUPACName=naphthalen-1-ylthiourea |
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| IUPACName=Naphthalen-1-ylthiourea |
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|OtherNames= |
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| OtherNames=ANTU<br>1-(1-Naphthyl)-2-thiourea<br>1-(1-Naphthyl)thiourea<br>1-Naphthylthiourea<br>α-Naphthylthiocarbamide<br>1-(Naphthalen-1-yl)thiourea<br>Dirax<br>Anturat<br>Rattrack<br>Smeesana<br>Alrato |
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|Section1={{Chembox Identifiers |
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|Section1={{Chembox Identifiers |
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| Abbreviations=ANTU |
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| Abbreviations=ANTU |
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| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}} |
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| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}} |
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| ChemSpiderID = 643492 |
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| ChemSpiderID = 643492 |
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| InChI = 1/C11H10N2S/c12-11(14)13-10-7-3-5-8-4-1-2-6-9(8)10/h1-7H,(H3,12,13,14) |
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| InChI = 1/C11H10N2S/c12-11(14)13-10-7-3-5-8-4-1-2-6-9(8)10/h1-7H,(H3,12,13,14) |
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| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}} |
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| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}} |
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| StdInChIKey = PIVQQUNOTICCSA-UHFFFAOYSA-N |
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| StdInChIKey = PIVQQUNOTICCSA-UHFFFAOYSA-N |
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| CASNo_Ref = {{cascite|correct|??}} |
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| CASNo_Ref = {{cascite|correct|CAS}} |
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| CASNo = <!-- blanked - oldvalue: 86-88-4 --> |
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| CASNo=86-88-4 |
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| UNII_Ref = {{fdacite|correct|FDA}} |
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| PubChem=736366 |
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| UNII = UKY0H6XJ4J |
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| PubChem=736366 |
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| KEGG_Ref = {{keggcite|changed|kegg}} |
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| KEGG_Ref = {{keggcite|changed|kegg}} |
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| KEGG = <!-- blanked - oldvalue: C19136 --> |
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| KEGG = C19136 |
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| SMILES=C1=CC=C2C(=C1)C=CC=C2NC(=S)N |
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| SMILES=C1=CC=C2C(=C1)C=CC=C2NC(=S)N |
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|Section2={{Chembox Properties |
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|Section2={{Chembox Properties |
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| C=11 | H=10 | N=2 | S=1 |
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| Formula=C<sub>11</sub>H<sub>10</sub>N<sub>2</sub>S |
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| Appearance=White solid,<ref name=PGCH/> crystallizes in prisms from alcohol<ref name="O'Neil, M.J. 2001. p. 122">O'Neil, M.J. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. 13th Edition, Whitehouse Station, NJ: Merck and Co., Inc., 2001., p. 122</ref> Colorless, solid. White.<ref name="Mackison, F. W. 1981. p. 1-2">Mackison, F. W., R. S. Stricoff, and L. J. Partridge, Jr. (eds.). NIOSH/OSHA - Occupational Health Guidelines for Chemical Hazards. DHHS(NIOSH) Publication No. 81-123 (3 VOLS). Washington, DC: U.S. Government Printing Office, Jan. 1981., p. 1-2</ref> White, crystalline or gray powder.<ref name="ReferenceA">NIOSH. NIOSH Pocket Guide to Chemical Hazards & Other Databases. U.S. Department of Health & Human Services, Public Health Service, Center for Disease Control & Prevention. DHHS (NIOSH) Publication No. 2001-145 (CD-ROM) August 2001</ref> |
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| MolarMass=202.28 g/mol |
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| MeltingPtC= 197.8 |
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| BoilingPt= Decomposes |
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| Solubility=600 mg/L |
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| SolubleOther = 2.43 g/100mL (acetone) <br>8.6 g/100mL (triethylene glycol) <ref name="O'Neil, M.J. 2001. p. 122">O'Neil, M.J. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. 13th Edition, Whitehouse Station, NJ: Merck and Co., Inc., 2001., p. 122</ref> |
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| Solvent = other solvents |
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| VaporPressure = 6.6x10<sup>−6</sup> mmHg <ref name="epa.gov">US EPA; Estimation Program Interface (EPI) Suite. Ver.3.11. June 10, 2003. Available from, as of Mar 3, 2004: http://www.epa.gov/oppt/exposure/pubs/episuitedl.htm</ref> |
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| LogP =1.65 <ref>Govers H et al; Chemosphere 15: 383-93 (1986)</ref> |
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| HenryConstant = 8.51x10<sup>−9</sup> atm-cu m/mol <ref name="epa.gov">US EPA; Estimation Program Interface (EPI) Suite. Ver.3.11. June 10, 2003. Available from, as of Mar 3, 2004: http://www.epa.gov/oppt/exposure/pubs/episuitedl.htm</ref> |
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|Section3={{Chembox Hazards |
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|Section3={{Chembox Hazards |
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| MainHazards=Toxic |
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| MainHazards=Toxic |
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| FlashPt=noncombustible<ref name=PGCH/> |
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| NFPA-H = 4 |
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| NFPA-R = 0 |
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| NFPA-F = 1 |
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| NFPA-S = |
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| PEL = TWA 0.3 mg/m<sup>3</sup><ref name=PGCH>{{PGCH|0037}}</ref> |
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| IDLH = 100 mg/m<sup>3</sup><ref name=PGCH/> |
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| REL = TWA 0.3 mg/m<sup>3</sup><ref name=PGCH/> |
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| LD50 = 0.38 mg/kg (dog, oral)<br/>6 mg/kg (rat, oral)<br/>4250 mg/kg (monkey, oral)<br/>5 mg/kg (mouse, oral)<ref>{{IDLH|86884|ANTU}}</ref> |
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| Odor = Odorless<ref></ref> |
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| Taste = Bitter taste<ref>[US EPA; Estimation Program Interface (EPI) Suite. Ver.3.11. June 10, 2003. Available from, as of Mar 3, 2004: http://www.epa.gov/oppt/exposure/pubs/episuitedl.htm</ref> |
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| Other = Stable on exposure to air and to sunlight.<ref></ref> |
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'''α-Naphthylthiourea''' ('''ANTU''') is an ] with the formula C<sub>10</sub>H<sub>7</sub>NHC(S)NH<sub>2</sub>. This a white, crystalline powder although commercial samples may be off-white.<ref name="Mackison, F. W. 1981. p. 1-2">Mackison, F. W., R. S. Stricoff, and L. J. Partridge, Jr. (eds.). NIOSH/OSHA - Occupational Health Guidelines for Chemical Hazards. DHHS(NIOSH) Publication No. 81-123 (3 VOLS). Washington, DC: U.S. Government Printing Office, Jan. 1981., p. 1-2</ref><ref name="O'Neil, M.J. 2001. p. 122">O'Neil, M.J. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. 13th Edition, Whitehouse Station, NJ: Merck and Co., Inc., 2001., p. 122</ref><ref name="ReferenceA">NIOSH. NIOSH Pocket Guide to Chemical Hazards & Other Databases. U.S. Department of Health & Human Services, Public Health Service, Center for Disease Control & Prevention. DHHS (NIOSH) Publication No. 2001-145 (CD-ROM) August 2001</ref> It is used as a ] and as such is fairly toxic. Naphthylthiourea is available as 10% active baits in suitable protein- or carbohydrate-rich materials and as a 20% tracking powder.<ref>IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Man. Geneva: World Health Organization, International Agency for Research on Cancer, 1972-PRESENT. (Multivolume work). p. V30 348 (1983)</ref> |
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==Synthesis== |
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Like other ]s, ANTU can be prepared by several routes. The usual method is the reaction of ] hydrochloride with ]:<ref>Kirk-Othmer Encyclopedia of Chemical Technology. 4th ed. Volumes 1: New York, NY. John Wiley and Sons, 1991-Present., p. V16 987 (1995)</ref> |
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:Cl + NH<sub>4</sub>SCN → C<sub>10</sub>H<sub>7</sub>NHC(S)NH<sub>2</sub> + NH<sub>3</sub> + HCl |
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It is produced from the reaction of ] with ]. |
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:C<sub>10</sub>H<sub>7</sub>NCS + NH<sub>3</sub> → C<sub>10</sub>H<sub>7</sub>NHC(S)NH<sub>2</sub> |
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==Mechanism of action== |
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ANTU is specifically toxic in lung cells due to its conversion to a short-lived active metabolite to which it is converted in the liver, not ANTU acting directly. This damage is focused on the ] of pulmonary capillaries and venules, it will lead to the formation of irreversible gaps in the endothelium of pulmonary vessels. This damage can lead to pulmonary edema. |
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In ANTU poisoning plasma, carbon and ] escape through a gap in the thick part of the pulmonary capillary into the interstitial tissues of the lung<ref>Cunningham, A. L., and J. V. Hurley. "Alpha‐naphthyl‐thiourea‐induced pulmonary oedema in the rat: A topographical and electron‐microscope study."The Journal of Pathology 106.1 (1972): 25-35.</ref> |
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==Toxicity== |
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Alpha-Naphthylthiourea is toxic to inhalation, ingestion, or skin contact, although the intoxication may be delayed. According to the U.S. ] (NIOSH), the recommended workplace airborne exposure limit is 0.3 mg/m<sup>3</sup> averaged over a 10-hour workshift. Exposure to 100 mg/m<sup>3</sup> is immediately dangerous to life and health. The lethal dose in humans is approximately 4 g/kg.<ref name=NJ>Hazardous substance fact sheet- alpha Naphthylthiourea. (2001). In N. J. d. o. h. a. s. services (Ed.).http://nj.gov/health/eoh/rtkweb/documents/fs/0051.pdf (accessed 01-04-14)</ref> |
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It is classified as an ] in the United States as defined in Section 302 of the U.S. ] (42 U.S.C. 11002), and is subject to strict reporting requirements by facilities which produce, store, or use it in significant quantities.<ref name="gov-right-know">{{Cite web | publisher = ] | title = 40 C.F.R.: Appendix A to Part 355—The List of Extremely Hazardous Substances and Their Threshold Planning Quantities | url = http://edocket.access.gpo.gov/cfr_2008/julqtr/pdf/40cfr355AppA.pdf | edition = July 1, 2008 | access-date = October 29, 2011 | archive-url = https://web.archive.org/web/20120225051612/http://edocket.access.gpo.gov/cfr_2008/julqtr/pdf/40cfr355AppA.pdf | archive-date = February 25, 2012 | url-status = dead }}</ref> |
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===Effects on animals=== |
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An oral dose of 3 mg per kilogram of body weight causes the death of 50% of the rats exposed ({{LD50}}), showing a very high selectivity when compared for example to monkeys ( 4000 mg per kilogram of body weight).<ref>Klaassen, C.D. (ed). Casarett and Doull's Toxicology. The Basic Science of Poisons. 6th ed. New York, NY: McGraw-Hill, 2001., p. 801</ref> However other studies have shown a much higher efficacy for dogs (a {{LD50}} of 0.38 mg/kg).<ref>Lewis, R.J. Sax's Dangerous Properties of Industrial Materials. 9th ed. Volumes 1-3. New York, NY: Van Nostrand Reinhold, 1996., p. 260</ref> |
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The mortality of rats caused by 5 mg/kg of ANTU is reduced when ], ], ], or ] are administered simultaneously with ANTU.<ref>Hayes, W.J., Jr., E.R. Laws, Jr., (eds.). Handbook of Pesticide Toxicology. Volume 3. Classes of Pesticides. New York, NY: Academic Press, Inc., 1991., p. 1289</ref> ], ] and ] all protect against the lung damage by ANTU (although the results are diverse). This indicates that ]s are responsible for this type of lung injury. Given ] over two days does not block the ANTU damage when ]s are decreased or when administered acutely. ] may generate the free radicals since ] blocked as well the ANTU damage.<ref>Marin D et al; Acta Physiol Scand 548: 119-25 (1986)</ref> |
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{| class="wikitable" |
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|+ Toxicity of alpha-Naphthyl thiourea in different animals |
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! Organism !! Test type !! Route !! Reported dose |
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| Cat<ref name=PSEBM>Proceedings of the Society for Experimental Biology and Medicine. Vol. 62, Pg. 22, 1946.</ref> || LD50|| oral || 500 mg/kg |
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| Chicken<ref name=PSEBM/> || LD50|| intraperitoneal|| 2500 mg/kg |
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| Chicken<ref name=PSEBM/>|| LD50|| oral|| 4250 mg/kg |
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| Chicken<ref>Chemistry of Pesticides, Melnikov, N.N., New York, Springer-Verlag New York, Inc., 1971Vol. -, Pg. 238, 1971.</ref>|| LD50|| unreported|| 700 mg/kg |
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| Dog<ref name=PSEBM/>|| LD50|| intraperitoneal || 16 mg/kg |
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| Dog<ref>Pesticide Chemicals Official Compendium, Association of the American Pesticide Control Officials, Inc., 1966. Vol. -, Pg. 57, 1966.</ref>|| LD50|| oral|| 0.38 mg/kg |
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| Guinea pig<ref name=PSEBM/>|| LD50|| intraperitoneal|| 350 mg/kg |
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| Man<ref>Poisoning; Toxicology, Symptoms, Treatments, 2nd ed., Arena, J.M., Springfield, IL, C.C. Thomas,1970Vol. 2, Pg. 73, 1970.</ref>|| LDLo|| unreported|| 588 mg/kg |
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| Monkey<ref name=PSEBM/>|| LD50|| intraperitoneal|| 175 mg/kg |
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| Monkey<ref>Wirksubstanzen der Pflanzenschutz und Schadlingsbekampfungsmittel, Perkow, W., Berlin, Verlag Paul Parey, 1971-1976Vol. -, Pg. -, 1971/1976.</ref>|| LD50|| oral|| 4250 mg/kg |
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| Monkey<ref name="Bollettino Chimico Farmaceutico 1958">Bollettino Chimico Farmaceutico. Vol. 97, Pg. 289, 1958.</ref>|| LD50|| unreported|| 2000 mg/kg |
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| Mouse<ref>National Technical Information Service. Vol. AD277-689</ref>|| LD50|| intraperitoneal|| 10 mg/kg |
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| Mouse<ref name="Yakkyoku. Pharmacy 1977">Yakkyoku. Pharmacy. Vol. 28, Pg. 329, 1977.</ref>|| LD50|| oral|| 5 mg/kg |
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| Pig<ref name="Yakkyoku. Pharmacy 1977"/>|| LDLo|| oral|| 50 mg/kg |
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| Rabbit<ref name="Bollettino Chimico Farmaceutico 1958"/>|| LD50|| unreported || 200 mg/kg |
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| Rat<ref>Journal of Pharmacology and Experimental Therapeutics. Vol. 97, Pg. 432, 1949.</ref>|| LD50|| intraperitoneal|| 2.47 mg/ kg |
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| Rat<ref>Quarterly Bulletin--Association of Food and Drug Officials of the United States. Vol. 16, Pg. 47,1952.</ref>|| LD50|| oral|| 6 mg/kg |
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ANTU causes local gastric irritation in animals and when it is absorbed, it increases permeability of the lung capillaries in all animals. The symptoms that the animals present after absorption of alpha-naphthyl thiourea are first weakness, ], weak pulse and subnormal temperatures. Afterwards, they have the following symptoms: vomiting, hypersalivation, coughing and severe ]. In the most cases a pale, mottled liver and damaged kidneys are found in animals which have ingested ANTU. |
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Animals with an empty stomach readily vomit after ingestion of this substance. However, when there is food in the stomach of the animals the stimulation to vomit decreases, so more quantities may be absorbed. It has been found that ANTU may cause death in some animals within 2–4 hours of ingestion, while animals that survive 12 hours may recover from the poison.<ref name="merckmanuals.com">Merk veterinary manual. (2012) http://www.merckmanuals.com/vet/toxicology/rodenticide_poisoning/antu_%CE%B1-naphthylthiourea.html (accessed 01-04-14)</ref> |
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In a long-term, ANTU may cause pulmonary edema and ] in certain animals, such as rats. Mice treated with alpha-naphthyl thiourea with a dose of 10 mg/kg developed pulmonary edema which was maximal after 3 hours and was resolved by 12 hours. 35 mg/kg of ANTU was caused death to 60% of the animals. It also increases the blood sugar levels in rats.<ref name=NJ/> Dogs and pigs are occasionally poisoned with this compound while ]s are resistant.<ref name="merckmanuals.com"/> But when the exposure of this compound in dogs is quite long they may have gastric irritation and respiratory difficulties. Death can then be followed within 6–48 hours depending on the quantity of ANTU ingested. |
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==Metabolism== |
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α-Naphthylthiourea is metabolized by rat liver and lung ]s to α-naphthylurea (ANU), which is essentially nontoxic to rats with an ({{LD50}} > 800 mg/kg). Conversion of ANTU to ANU requires ]. ] inhibits the reaction.<ref name=Boyd>Boyd, M. R., and Robert A. Neal. "Studies on the mechanism of toxicity and of development of tolerance to the pulmonary toxin, alpha-naphthylthiourea (ANTU)." Drug Metabolism and Disposition 4.4 (1976): 314-322.</ref> There are some evidence of ] being responsible for the bioactivation of ANTU. Therefore, the toxicity of ANTU cannot be explained with the activity of ANU. There are subproducts of this reaction which play an important role in toxicity: atomic sulfur and a metabolic reactive containing the carbon carbonyl of ANTU.<ref name=Lee>Lee, Philip W., Thomas Arnau, and Robert A. Neal. "Metabolism of α-naphthylthiourea by rat liver and rat lung microsomes." Toxicology and Applied Pharmacology 53.1 (1980): 164-173.</ref> |
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The loss of cytochrome P-450 and ] activity seen on incubation of liver microsomes with ANTU is likely the result of the covalent binding of atomic sulfur to cytochrome P-450. The available evidence suggests that the pulmonary toxicity of ANTU results, at least in part, from the covalent binding of a cytochrome P-450 monooxygenase catalyzed metabolite of ANTU to pulmonary macromolecules. This metabolite is most likely atomic sulfur or alternatively, the one containing the carbonyl carbon of ANTU. However, it is possible that the binding of both metabolites may be responsible for the lung toxicity.<ref name=Lee/> |
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==History== |
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ANTU was developed to combat infestation of rats in the US city of ], where the increase in population had overwhelmed the sanitation services, causing huge rat-infested garbage piles. Baltimore was also the scene of the discovery of ANTU. In 1942 Curt Richter discovered that phenyl thiourea was lethal, yet tasteless to domesticated rats. This was interesting because a rat's defense against toxins is primarily its sense of taste. However, when Richter started testing the compound in wild rats, it was not equally tasteless for them, but had a bitter taste; Richter's lab screened over 200 thiourea compounds to find one equally tasteless and toxic to wild rats. This led to the discovery of ANTU.{{citation needed|date=August 2022}} |
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Next Richter set out to test the compound on a large scale. He determined rats will not cross streets and therefore city blocks were used as test areas. Local ]s volunteered to distribute the poison. When the first tests returned large amounts of dead rats, the tests were extended to a 200-block area with poor housing. The ANTU field trials soon expanded and in 1943 Richter was asked to lead citywide rat control campaign and received funding to replace the Scouts with adult baiters and trappers. Through a joint effort of the city and volunteers about 8400 city blocks were cleaned from May 1943 to mid-1946. After the war ANTU became available to the public, being advertised as a miracle rat killer for households. Richter had however advised against the use of ANTU at a small scale, as rats get a 30-day tolerance for ANTU after a non-lethal dose and become able to detect the chemical. As the rat population returned, the popularity of ANTU decreased. It became clear that more than poisoning alone was needed to get rid of rats. The city of Baltimore soon returned to an environmental approach in rat control and ANTU disappeared from the market after a few years.<ref>Keiner, Christine. "Wartime rat control, rodent ecology, and the rise and fall of chemical rodenticides." ''Endeavour'' 29.3 (2005): 119-125</ref> |
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==References== |
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{{reflist}} |
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{{rodenticides}} |
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{{DEFAULTSORT:Naphthylthiourea, alpha-}} |
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