{"operation":"document","citation":"03-0107","title":"Molecular Probes, Inc. — Hazardous Materials Safety Interpretation","source_type":"guidance","agency":"Pipeline and Hazardous Materials Safety Administration","status":"guidance","official":true,"published_on":"2004-04-15","effective_on":null,"summary":"03-0107 response to Molecular Probes, Inc. concerning 173.133.","machine_formats":{"json":"https://regulus.evalyn.ai/document/phmsa-interpretation-03-0107.json","markdown":"https://regulus.evalyn.ai/document/phmsa-interpretation-03-0107.md"},"app_url":"https://regulus.evalyn.ai/document/phmsa-interpretation-03-0107","source_url":"https://www.phmsa.dot.gov/sites/phmsa.dot.gov/files/legacy/interpretations/Interpretation%20Files/2003/030107.pdf","body":"<<<PAGE 1>>>\n\nU.S. Department\nof Transportation\n400 Seventh St., S.W.\nResearch and\nAPR 15 2004\nWashington, D.C. 20590\nspecial Programs\nAdministratior\nMr. Bruce H. Bale\nMolecular Probes, Inc.\nRegulatory/Safety Manager\nReference No. 03-0107\n4849 Pitchford Avenue\nEugene, OR 97402-9165\nDear Mr. Bale:\nThis is in response to your letter and telephone conversation with a member of my staff asking\nnoW to properly classity and describe three fluorescent reagents under the Hazardous Material\nRegulations (HMR; 49 CFR Parts 171-180). You describe the reagents as three naturall\noccurring toxins, phalloidin, phallacidin, and bungarotoxin covalently bonded to fluorescent\nmolecules. Your company offers each product for transportation by aircraft as a dangerous good\nin excepted quantities and would like to described them as a \"Toxic solid, organic, n.o.s., 6.1\n(poisonous), UN 2811, PG I or PG II.\" Your questions are paraphrased and answered below in\nthe order provided.\nQ1.\nFrom our review of the published data on the toxins, it is our opinion that our solid\nfluorescent conjugates of these toxins would be appropriately assigned to Packing Group\nI or Packing Group II. Which is correct?\nAl. As provided in § 173.22, it is the shipper's responsibility to properly classify a hazardous\nmaterial. This Ottice does not perform that function. However, based on the information\nand toxicity data you provided, it is this Office's opinion that the classification for this\nmaterial is, at a minimum, Class 6.1, Packing Group II.\nQ2. If the appropriate assignment for the material is Packing Group I, it is our opinion that\nthese reagents would not constitute an inhalation hazard in transport. Is that correct?\nA2:\ninhalation hazard, under the HMR.\nIt is this Office's opinion that the reagents do not meet the criteria in §173.133(a) for an\nI hope this information is helpful.\nSincerely,\nHitte a mished\nHattie L. Mitchell, Chief\nOffice of Hazardous Materials Standards\nRegulatory Review and Reinvention\n173.133\n030107\n\n<<<PAGE 2>>>\n\nEdmonson\n$172,101\n8113,133\nPackinda for aup\nMolecular\nProbes\n(541) 465-8300 • Fax (541) 344-6504 • www.probes.com\n4849 Pitchford Ave. • Eugene, OR 97402-9165\n03-0107\nApril 17, 2003\nEdward T. Mazzullo\nUS Department of Transportation\nResearch and Special Program Administration\nOffice of Hazardous Materials Standards.-\nDHM-10\n400 7th St., S.W.\nWashington, DC 20590-0001\nDear Mr. Mazzullo,\nThis morning I spoke with Dr. George Cushmac at the Office of Hazardous Materials\nTechnology and he recommended that I submit my questions to your office to obtain a written\ninterpretation.\nUnder the Research and Development exemption of TSCA, our company manufactures\nextremely small quantity, high-purity fluorescent reagents for biochemical research. We sell and\ndistribute approximately 2,500 products worldwide under International Air Transport\nRegulations (IATA).\nA few of these products, the focus of this letter, are fluorescent conjugates of three naturally\noccurring toxins, phalloidin, phallacidin, and bungarotoxin. Essentially, we covalently bond\ntoxin scent enaecule to the ers to The tiesultin quaint reta singful presence of toparent\nFor safety purposes, we conservatively assume that these reagents are toxic.\n\"dangerous goods in excepted quantities.\" We would like to ship these materials as Toxic solids,\nWe sell these products as solids in 1 mg units. We are experienced in safely shipping by air\norganic, n.o.s., UN2811, 6.1. To do that, we need to assign the appropriate Packing Group for\nthese reagents and there is no specific health hazard data available for them. There is\ntoxicological data in the open literature for the toxins. In our conversation today, Dr. Cushmac\nexplained that correlations are made from such data to distinguish between the Packing Groups.\nFrom our review of the published data on the toxins, it is our opinion that our solid\nfluorescent conjugates of these toxins would be appropriately assigned to:\n\n<<<PAGE 3>>>\n\nPacking Group I, or\nPacking Group II\n1. Which group is correct?\n.!::\nAlso, if the appropriate assignment is Packing Group I, iț is our opinion that these reagents\nwould not constitute an inhalation häzard in transport. * di\n2. Is that correct?\nI am including copies of the references on published health hazard assessments for each of the\nthree toxins. These references were obtained from the Registry of Toxic Effects of Chemical\nSubstances published by the National Institutes of Occupational Safety and Health.\nyou require any further information.\ngo epine ay it alone made ate to coar me demy offe a 541-05 39 i7\n.:0\nThank you.\nSincerely,\nBruce H. Bale\nRegulatory/Safety Manager\nEncl.\n; 6;\n401.\ni eh\n:\n...\n\n<<<PAGE 4>>>\n\n**..*\n*\n*\n*\n*\nRTE C S (R)\n*\n*\n* Supplied by : MDI Information Systems,, Inc.\n*\n* Provided by : Canadian Centre for Occupational Health and Safety\n*****\n* *\n2002)\n**********Issue: 2002-4 (November,\n***\nCHEMICAL IDENTIFICATION ***\nRTECS NUMBER\nCHEMICAL NAME\n:\n: EI6100500\nCAS REGISTRY NUMBER\nBungarotoxin\nDATA\nLAST UPDATED\n37209-28-2\nCOMPOUND DESCRIPTOR\nITEMS CITED\n199703\n1\n: Natural Product:\n*** HEALTH HAZARD DATA:***\n** ACUTE TOXICITY DATA **\nROUTE OF EXPOSURE\nTYPE OF TEST\n: LD50 - Lethal dose, 50 percent kill\nSPECIES OBSERVED\nIntraperitoneal\nDOSE/DURATION\nRodent - mouse\nTOXIC EFFECTS\n:\n: 100 ug/kg\nREFERENCE :\nDetails of toxic effects not reported other than lethal dose value\nOX3 OBW, UK)\nTOXIA6 Toxicon.\nv.1-\n(Pergamon Bress Itd., Headington Hill Hall, Oxford\nVolume (issue)/page/year: 10,227,1972\n3**\nEND OF RECORD***\n::\n::. ::\n\n<<<PAGE 5>>>\n\n**-*\n*\n*\n* *\n*\n*\n*\n*\n* *\n-RTE C S(R)\n•:\n* Supplied by : MDL Information Systems, Inc.\n* Provided by : Canadian Centre for Occupational Health and Safety\n*\n* * *\n******\n* Issue: 2002-4. (November,\n2002)\n*** CHEMICAL IDENTIFICATION ***\nRTECS NUMBER\nCHEMICAL NAME :\n: GT8943000\nvalyl-ery thro-3-hydroxy-D-alpha-asparty1-I-cysteiny1-cis-4-hydroxy-L-\ncyclic(L-Alanyl-2-mercapto-L-tryptophyl-4,5-dihydroxy-L-leucyl-L-\nprolyl) cyclic (2-6) -sulfide\nCAS REGISTRY NUMBER\n: 26645-35-2\nLAST UPDATED\nBEILSTEIN REFERENCE NO. : 0604129\nMOLECULAR FORMULA\nMOLECULAR WEIGHT\n: C37-H50-N8-013-S\nSYNONYMS/ TRADE NAMES :\n* Phallacidin\n*** HEALTH HAZARD DATA ***\n** ACUTE TOXICITY DATA **\nTYPE OF TEST\nSPECIES OBSERVED\nROUTE OF EXPOSURE\n: ID50 = Lethal dose, 50 percent kill\nDOSE/DURATION\nRodent - mouse\n: 2 mg/kg\nREFERENCE :\nDetails of toxic effects hot reported other than lethal dose value\n2000 Corporate Blvd., NW, Boca\nCRBCAI CRC Critical Reviews in Biochemistry.\nFL 33431)\n(CRC Press,\nVolume (issue) /page/year: 5,185, 1978\nROUTE OF EXPOSURE\nTYPE OF TEST\n: ID50 - Lethal dose,\n50 percent kill\nDOSE/DURATION\nSPECIES OBSERVED\n: Rodent - mouse\nUnreported\nTOXIC EFFECTS\n2500 ug/kg\nDetails of\nnot reported other than lethal dose value\nREFERENCE\nArzneimittel-Forschüng. Drug Research.\n(Editio Cantor\n1951- Volume (issue) /page/year: 22, 2142, 1972.\nVerlag, Postfach 1255,\nW-7960 Aulendorf,\n•***\n: END OF RECORD. ***\n\n<<<PAGE 6>>>\n\n* * *\n* *\nR I ECS (R)\n* Supplied by : MDI Information Systems, Inc.\n* Provided by : Canadian: Centre for Occupational Health and Safety\n*\n*\n*\n*\n2002)\n***** Issue : 2002-4 (November,\n*** CHEMICAL IDENFIFICATION ***\nRTECS NUMBER\n: SE9800000\nCHEMICAL NAME :\nCAS REGISTRY NUMBER\nPhalloidin\nOTHER CAS REGISTRY NOS. : 63-24-1\n: 17466-45-4\nBEILSTEIN REFERENCE NO. : 4347460\nLAST UPDATED\nDATA ITEMS CITED\n: 200003\nMOLECULAR FORMULA\n10\nMOLECULAR WEIGHT\n788:97\nC35-H48-N8-011-S\nCOMPOUND DESCRIPTOR\nMutagen\nSYNONYMS/ TRADE NAMES :\nNatüral Product\n* Phalloidine\n*** FEALTH HAZARD DATA ***\n** ACUTE TOXICIIY DATA **\nTYPE OF TEST\nROUTE OF EXPOSURE\n: Intraperitoneal\n: LDIo - Lowest published lethal dose\nSPECIES OBSERVED\n: Rodent - rat\nDOSE/DURATION\nTOXIC EFFECTS\n: 1 ng/kg\nDetails of toxic effects not reported other than lethal dose value\nA42\nREFERENCE :\nTOXIA6 Toxicon.\n(Pergamon Press Itd., Headington Hill Hall, Oxford\n0X3 OBW, UK)\nv.1-\n1962- \"Volume (issue) /page/year: 10, 357,1972\nTYPE OF TEST\n: ID50 - Lethal dose, 50 percent kill\nROUTE OF EXPOSURE\nSPECIES OBSERVED\nRodent\nInt raperitoneal\nDOSE/DURATION\n- mouse\nTOXIC EFFECTS\n2 mg/kg\nREFERENCE\nDetails of\ntoxic effects not\nreported other than lethal dose value\nSoc., 10 Shattuck St., Boston, MA\nNEJMAG New England Journal of Medicine.\n02115)\nV: 198-\n(Massachusetts Medical\n1928-\nVolume (issue)/page/year: 269/223,1963\nTYPE OF TEST\nROUTE OF EXPOSURE\nIntravenous\nLDLO - Lowest\npublished lethal dose\nDOSE/DURATION\nSPECIES OBSERVED\n6600 ug/kg\nRodent - mouse\nSAL:\n24.\n:\n\n<<<PAGE 7>>>\n\n2920:\nTOXIC EFFECTS :\nLiver\nBehavioral\n- fatty liver degeneration\n- muscle weakness\nREFERENCE :\nund Pharmakologie.\nAEPPAE\nNaunyn-Schmiedeberg's Archiv fuer Experimentelle Pathologie\nPublisher information, see NACC. Volume issue) /page/year:\nV.110-253; 1925-66.\n190,406, 1938\nROUTE OF EXPOSURE\n: LD50 - Lethal. dose, 50 percent kill\nDOSE/DURATION\nSPECIES OBSERVED\n: Unreported\nRodent - mouse\n: 2 ma/kg\nREFERENCE :\nDetails of toxic effects not reported other than lethal dose value\nVerlag, Postfach 1255,\nARZNAD Arzneimittel-Forschung. Drug Research.\nW-7960 Aulendorf, Fed. Rep. Ger.)\n(Editio Cantor\nv.I-\n1951 - Volume (issue) /page/year! 22, 2142,1972\nTYPE OF TEST\n: ID. - Lethal dose\nROUTE OF EXPOSURE\nSPECIES OBSERVED\n: Intravenous\nDOSE/DURATION\n: Mammal - dog\nTOXIC EFFECTS\n>10 mg/kg*\nREFERENCE :\nDetails of toxic effects not reported other than lethal dose value\nARTON Archives of Toxicology.\n3, D-1000 Berlin 33, Fed. Rep::.\nGer.)\n(Springer-Verlag, Heidelberger P1.\nVolume (issue) /page/year: 48,61,1981\nv.32-\n1974-\nROUTE OF EXPOSURE\nTYPE OF TEST\n: LDL04- Lowest published lethal dose\nSPECIES OBSERVED\n: Mammal - species unspecified\nOral\"\nDOSE/DURATION\nTOXIC EFFECTS\n: 1000 ug/kg\nREFERENCE :\nDetails of toxic effects not reported other than lethal dose value\npublisher information, see JTCTDW.\nCOXAO Clinical Toxicology.\n(New York, NY) V.1-18, 1968-81. For\n17,45,1980\nVolume (issue) /page/year:\n** OTHER MULTIPLE DOSE TOXICITY DATA **\nTYPE OF TEST\n: IDEo - Lowest published toxic dose\nSPECIES OBSERVED\nROUTE OF EXPOSURE\nIntraperitoneal\nDOSE/DURATION\n: Rodent - rat\nTOXIC EFFECTS\n:\n2500 ug/kg/5D-I\nREFERENCE :\nLiver - other\n•changes\nGastroenterology,\nJOGAET\nJournal of Gastroenterology. (Japanese Society of\n104 Japan)\nv.29-1994-\nGinza Orient BLDG,\nVolume (issue) /page/year: 29,172,1994\n9-13 Ginza 8, Chuo-ku, Tokyo\nTYPE OF TEST\nROUTE OF EXPOSURE\nTOLO - Lowest published toxic dosE\nDOSE/DURATION\nSPECIES OBSERVED\n: Intraperitoneal\n3500 ug/kg/7D-I\n\n<<<PAGE 8>>>\n\nTOXIC EFFECTS :\nLiver - jaundice, cholestatic\nLiver - changes in liver,\nLiver - other changes\nREFERENCE :\nweight\n:.:\nDuluth, MN 55802)\nGASTAB\nGastroenterology. (Academic Press,\n1943- Völume (issue) /page/year: 75,450,1978\nInc., 1 E. First St.,\n** MUTATION DAIA **\nTYPE OF TEST\nTEST SYSTEM\n: Morphological transformațion\n: 1 umol/I\nRodent - rat Liver\nREFERENCE :\nDOSE/DURATION\n153:\nFor publisher information,\nCYTZAM Cytobiologie.\n(Stuttgart, Fed. Rep: Ger.)\n•see EJCBDN.\nVolume (issue) /page/year:\nV.1-18, 1969-79.\n17,73,1978\nTEST SYSTEM\nTYPE OF TEST\n: DNA, inhibition\nREFERENCE\nDOSE/DURATION\n• Rodent - rat; Liver :\n100- nmol/L\nTOXIA6\n:\n0x3 OBW, UK)\nToxicon.\nv.1-\n(Pergamon Press Ltd., Headington Hill Hall, Oxford\n1962- Volume (issue) /page/year: 25,1265, 1987\nL*** END OF RECORD:***\nWar\n:: cha\n62\nRAP:","truncated":false,"body_characters":11260}