Mammalian Toxicity of 1,3-Dichloropropene

  • William T. Stott
  • B. Bhaskar Gollapudi
  • K. S. Rao
Part of the Reviews of Environmental Contamination and Toxicology book series (RECT, volume 168)


1,3-Dichloropropene (DCP) has primarily been employed for the control of parasitic nematodes for preplanting control of parasitic plant nematodes in numerous food and nonfood crops including deciduous fruit and nuts, vines, strawberries, field crops, vegetables, tobacco, tree nurseries, and numerous other specialty crops. Soil fumigant formulations have historically varied in DCP content from 50% to 97% purity as approximately equal amounts of cis- and trans-isomers to the more recent purified cis-only formulations. An acid scavenger, historically epichlorohydrin (Epi) or, more recently, epoxidized soybean oil (ESO), has been added to the final formulation at a concentration of l%–2%. In addition, DCP may be mixed with a variable amount of a disease control agent such as methylisothiocyanate or chloropicrin. Formulated DCP is typically injected into the soil where it subsequently dissolves into the film of water that surrounds soil particles and which harbors the targeted organism, parasitic nematodes. DCP in the soil is lost via chemical hydrolysis in water, metabolism by soil biotica, and volatilization. Half-lives in soil and water in the absence of volatilization typically range from 2 to 13 d, dependent upon temperature and microbial load (WHO 1993). Efficacy is thus dictated not only by target organism sensitivity but also by a number of physicochemical properties of DCP and soil and atmospheric conditions.


Oral Gavage National Toxicology Program Soil Fumigant Genotoxicity Assay Toxicol Environ Health 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Berenblum I (1978) Established principles and unresolved problems in carcinogenesis. J Natl Cancer Inst 35:949.Google Scholar
  2. Breslin WJ, Kirk HD, Streeter CM, Quast JF, Szabo JR (1989) 1,3-Dichloropropene: two-generation inhalation reproduction study in Fischer 344 rats. Fundam Appl Toxicol 12:129–143.PubMedCrossRefGoogle Scholar
  3. Brouwer EJ, Evelo CTA, Verplanke AJW, van Welie RTH, Wolff FA (1991) Biological effect monitoring of occupational expolsure to 1,3-dichloropropene: effects on liver and reanl function and on glutathione conjugation. Br J Ind Med 48:167–172.PubMedGoogle Scholar
  4. Bruckner JV, MacKenzie WF, Ramanathan R, Muralidhara S, Kim HJ, Dallas CE (1989) Oral toxicity of 1,2-dichloropropene: acute, short-term and long-term studies in rats. Fundam Appl Toxicol 12:713–730.PubMedCrossRefGoogle Scholar
  5. Butterworth BE, Slaga TJ, Farland W, McClain M (1991) Chemically Induced Cell Proliferation: Implications for Risk Assessment. Wiley-Liss, New York.Google Scholar
  6. Climie I, Hutson D, Morrison B, Stoydin G (1979) Glutathione conjugation in the detoxi-cation of (Z)-l,3-dichloropropene (a component of the nematocide D-D) in the rat. Xenobiotica 9:149–156.PubMedCrossRefGoogle Scholar
  7. Creedy C, Brooks T, Dean B, Hutson D, Wright A (1984) The protective action of glutathione on the microbial mutagenicity of the Z- and E-isomers of 1,3-dichloropro-pene. Chem-Biol Interact 50:39–48.PubMedCrossRefGoogle Scholar
  8. Dean BJ, Brooks TM, Hodson-Walker G, Hutson DH (1985) Genetic toxicology testing of industrial chemicals. Mutat Res 153:57–77.PubMedGoogle Scholar
  9. De Lorenzo F, Degtinnocenti S, Ruocco A, Silengo L, Cortese R (1977) Mutagenicity of pesticides containing 1,3-dichloropropene. Cancer Res 37:1915–1917.PubMedGoogle Scholar
  10. Dietz F, Hermann E, Ramsey J (1984a) The pharmacokinetics of l4C-1,3-dichloropro-peneichloropropene in rats and mice following oral administration. Toxicologist 4: A585.Google Scholar
  11. Dietz F, Dittenber D, Kirk H, Ramsey J (1984b) Non-protein sulfhydryl content and macromolecular binding in rats and mice following administration of 1,3-dichloropro-peneichloropropene. Toxicologist 4:A586.Google Scholar
  12. Di Nucci A, Imbriani M, Ghittori S, Baldi C, Locatelli C, Manzo L, Capodaglio E (1988) 1,2-Dichloropropene-induced liver toxicity. Clinical data and preliminary studies in rats. The target organ and the toxic process. Arch Toxicol 12(suppl):370–374.CrossRefGoogle Scholar
  13. Eder E, Henschler D, Neudecker T (1982a) Mutagenic properties of allylic and α,β-unsaturated compounds: Consideration of alkylating mechanisms. Xenobiotica 12: 831–848.PubMedCrossRefGoogle Scholar
  14. Eder E, Neudecker T, Lutz D, Henschler D (1982b) Correlation of alkylating and mutagenic activities of allyl and allylic compounds: standard alkylation test vs. kinetic investigation. Chem-Biol Interact 38:303–315.PubMedCrossRefGoogle Scholar
  15. Elia MC, Storer RD, McKelvey TW, Kraynak AR, Barnum JE, Harmon LS, DeLuca JG, Nichols WW (1994) Rapid DNA degradation in primary rat hepatocytes treated with diverse cytotoxic chemicals: analysis by pulsed field gel electrophoresis and implications for alkaline elution assay. Environ Mol Mutagen 24:181–191.PubMedCrossRefGoogle Scholar
  16. Eustis SL, Boorman GA, Harada T, Popp JA (1990) Liver. In: Boorman GA, Eustis SL, Elwll MR, Montgomery CA Jr, Mckenzie WF, (eds) Pathology of Fischer Rat. Reference and Atlas. Academic Press, San Diego, pp 71–94.Google Scholar
  17. Fisher GD, Kilgore WW (1988a) Mercapturic acid excretion by rats following inhalation exposure to 1,3-dichloropropene. Fundam Appl Toxicol 11:300–307.PubMedCrossRefGoogle Scholar
  18. Fisher GD, Kilgore WW (1988b) Tissue levels of glutathione following acute inhalation of 1,3-dichloropropene. J Toxicol Environ Health 23:171–182.PubMedCrossRefGoogle Scholar
  19. Fisher GD, Kilgore WW (1989) Pharmacokinetics of S-[3-chloroprop-2-enyl]glutathione in rats following acute inhalation exposure to 1,3-dichloropropene. Xenobiotica 19: 269–278.PubMedCrossRefGoogle Scholar
  20. Flessel P, Goldsmith J, Kahn E, Wesolwski J, Maddy K, Peoples S (1978) Acute and possible long-term effects of 1,3-dichloropropene—California. MMWR (Morb Mortal Week Rep) 27:50–55.Google Scholar
  21. Ghia M, Robbiano L, Allavena A, Martelli A, Brambilla G (1993) Genotoxic activity of 1,3-dichloropropene in a battery of in vivo short-term tests. Toxicol Appl Pharmacol 120:120–125.PubMedCrossRefGoogle Scholar
  22. Gollapudi BB, Cieszlak FS, Day SJ, Carney EW (1998) Dominant lethal test with rats exposed to 1,3-dichloropropene by inhalation. Environ Mol Mutagen 32:351–359.PubMedCrossRefGoogle Scholar
  23. Gosselin R, Hodge H, Smith R, Gleason M (1976) Clinical Toxicology of Commercial Products, 4th Ed. Williams & Wilkins, Baltimore, pp 119–121.Google Scholar
  24. Hanley TR, John-Greene J, Young JT, Calhoun LL, Rao KS (1987) Evaluation of the effects of inhalation exposure to 1,3-dichloropropene on fetal development in rats and rabbits. Fundam Appl Toxicol 8:562–570.PubMedCrossRefGoogle Scholar
  25. Haut KT, Stebbins KE, Johnson KE, Shabrang SN, Stott WT (1996) Subchronic toxicity of ingested 1,3-dichloropropene in rats and mice. Fundam Appl Toxicol 32:224–232.PubMedCrossRefGoogle Scholar
  26. Hernandez AF, Martin-Rubi JC, Ballesteros JL, Oliver M, Pia A, Villanueva E (1994) Clinical and pathological findings in fatal 1,3-dichloropropene intoxication. Hum Exp Toxicol 13:303–306.PubMedCrossRefGoogle Scholar
  27. Hutson DH, Moss JA, Pickering BA (1971) Components of the soil fumigant D-D* and their metabolites in the rat. Food Cosmet Toxicol 9:677–680.PubMedCrossRefGoogle Scholar
  28. Kevekordes S, Gebel T, Pav K, Edenharder R, Dunkelberg H (1996) Genotoxicity of selected pesticides in the mouse bone marrow micronucleus test and in the sister-chromatid exchange test with human lymphocytes in vitro. Toxicol Lett 89:35–42.PubMedCrossRefGoogle Scholar
  29. Kezic S, Monster AC, Verplanke JW, de Wolff FA (1996) Dermal absorption of cis-1,3-dichloropropene vapour: human experimental exposure. Hum Exp Toxicol 15: 396–399.PubMedCrossRefGoogle Scholar
  30. Kitchin KT, Brown JL (1994) Dose-response relationship for rat liver DNA damage caused by 49 rodent carcinogens. Toxicology 88:31–49.PubMedCrossRefGoogle Scholar
  31. Linnett SL, Clark DG, Blair D, Cassidy SL (1988) Effects of subchronic inhalation of D-D(l,3-dichloropropene/l,2-dichloropropane) on reproduction in male and female rats. Fundam Appl Toxicol 10:214–223.PubMedCrossRefGoogle Scholar
  32. Lock EA (1988) Studies on the mechanism of nephrotoxicity and nephrocarcinogenicity of halogenated alkenes. Crit Rev Toxicol 19:23–42.PubMedCrossRefGoogle Scholar
  33. Lomax LG, Stott WT, Johnson KA, Calhoun LL, Yano BL, Quast JF (1989) The chronic toxicity and oncogenicity of inhaled technical grade 1,3-dichloropropene in rats and mice. Fundam Appl Toxicol 12:418–431.PubMedCrossRefGoogle Scholar
  34. Loveday KS, Lugo MH, Resnick MA, Anderson BE, Zeiger E (1989) Chromosome aberration and sister chromatid exchange tests in Chinese hamster ovary cells in vitro: II. Results with 20 chemicals. Environ Mol Mutagen 3:60–94.CrossRefGoogle Scholar
  35. Markovitz A, Crosby WH (1984) Chemical carcinogenesis. A soil fumigant, 1,3-dichloropropene, as possible cause of hematologic malignancies. Arch Intern Med 144: 1409–1411.PubMedCrossRefGoogle Scholar
  36. Martelli A, Allavena A, Ghia M, Robbiano L, Brambilla G (1993) Cytotoxic and geno-toxic activity of 1,3-dichlororporpene in cultured mammalian cells. Toxicol Appl Pharmacol 120:114–119.PubMedCrossRefGoogle Scholar
  37. Meulenbelt J, de Vries I (1997) Acute work-related poisoning by pesticides in the Netherlands: a one year follow-up study. Przegl Lek 54:665–669.PubMedGoogle Scholar
  38. Miyaoka T, Yamashita E, Hasegawa T, Akiyama M, Tsuda S, Shirasu Y (1990) Mechanism of 1,3-dichloropropene-induced hepatotoxicity in mice. J Pestic Sci 15:419–425.CrossRefGoogle Scholar
  39. Myhr BC, Caspary WJ (1991) Chemical mutagenesis at the thymidine kinase locus in L5178Y mouse lymphoma cells: results for 31 coded compounds in the National Toxicology Program. Environ Mol Mutagen 18:51–83.PubMedCrossRefGoogle Scholar
  40. Nater JP, Goskens VHJ (1976) Occupational dermatosis due to a soil fumigant. Contact Dermatitis 2:227–229.PubMedCrossRefGoogle Scholar
  41. Neudecker T, Henschler D (1986) Mutagenicity of chloroolefins in the Salmonella/mammalian microsome test. III. Metabolic activation of the allylic chloropropenes allyl chloride, 1,3-dichloropropene, 2,3-dichloro-l-propene, 1,2,3-trichloropropene, 1,1,2,3-tetrachloro-2-propene and hexachloropropene by S9 mix via two different metabolic pathways. Mutat Res 170:1–9.PubMedCrossRefGoogle Scholar
  42. Neudecker T, Stefani A, Henschler D (1977) In vitro mutagenicity of soil nematocide 1,3-dichloropropene. Experientia (Basel) 33:1084–1085.CrossRefGoogle Scholar
  43. Neudecker T, Lutz D, Eder E, Henschler D (1980) Structure-activity relationship in halogen and alkyl substituted allyl and allylic compounds: correlation of alkating and mutagenic properties. Biochem Pharmacol 29:2611–2617.PubMedCrossRefGoogle Scholar
  44. NTP (National Toxicology Program) (1985) Carcinogenesis studies of TELONE II in F344/N rats and B6C3F1 mice (gavage studies). Technical Rep 269, National Toxicology Program, Washington, DC.Google Scholar
  45. Onkenhout W, Mulder PPJ, Boogaard PJ, Buijs W, Vermeulen PE (1986) Identification and quantitative determination of mercapturic acids formed from Z-and E-1,3-dichloropropene by the rat, using gas chromatography with three different detection techniques. Arch Toxicol 59:235–241.PubMedCrossRefGoogle Scholar
  46. Osterloh JD, Feldman BJ (1993) Urinary protein markers in pesticide applicators during a chlorinated hydrocarbon exposure. Environ Res 63:171–181.PubMedCrossRefGoogle Scholar
  47. Osterloh JD, Xiwen H (1990) Effects of 1,3-dichloropropene on the kidney of Fisher 344 rats after pretreatment with diethylmaleate, buthionine sulfoximine, and amino-oxyacetic acid. J Toxicol Environ Health 28:247–255.Google Scholar
  48. Osterloh J, Letz G, Pond S, Becker C (1983) An assessment of the potential testicular toxicity of 10 pesticides using the mouse-sperm morphology assay. Mutat Res 116: 407–415.PubMedCrossRefGoogle Scholar
  49. Osterloh JD, Cohen BS, Popendorf W, Pond SM (1984) Urinary excretion of the N-acetyl cysteine conjugate of cis-1,3-dichloropropene by exposed individuals. Arch Environ Health 39:271–275.PubMedGoogle Scholar
  50. Osterloh JD, Wang R, Schneider F, Maddy K (1989) Biological monitoring of dichloro-propene: air concentrations, urinary metabolite and renal enzyme excretion. Arch Environ Health 44:207–213.PubMedCrossRefGoogle Scholar
  51. Parker CM, Coate WB, Voelker RW (1982) Subchronic inhalation toxicity of 1,3-di-chloropropene/1,2-dichloropropane (D-D) in mice and rats. J Toxicol Environ Health 9:899–910.PubMedCrossRefGoogle Scholar
  52. Sasaki YF, Imanishi H, Matsumoto K, Watanabe M, Watanabe K (1988) 1,3-Dichloro-propene: in vitro cytogenetics test. Institute of Environmental Toxicology, Kodaira, Tokyo.Google Scholar
  53. Schneider M, Quistad GB, Casida JE (1998a) 1,3-Dichloropropene epoxides: intermediates in bioactivation of the promutagen 1,3-dichloropropene. Chem Res Toxicol 11: 1137–1144.PubMedCrossRefGoogle Scholar
  54. Schneider M, Quistad G, Casida JE (1998b) N2,7-bis(l-hydroxy-2-oxopropyl)-2’-deoxy-guanosine: identical noncyclic adducts with 1,3-dichloropropene epoxides and meth-ylglyoxal. Chem Res Toxicol 11:1536–1542.PubMedCrossRefGoogle Scholar
  55. Shelby MD, Erexson GL, Hook GJ, Tice RR (1993) Evaluation of a three-exposure mouse bone marrow micronucleus protocol: results with 49 chemicals. Environ Mol Mutagen 21:160–179.PubMedCrossRefGoogle Scholar
  56. Shirasu Y, Moriya M, Tequka H, Teramoto S, Ohata T, Inoue T (1981) Mutagenicity Screening Studies on Pesticides. In, Environmental Mutagens and Carcinogens: Proc Third International Conference on Environmental Mutagens, Tokyo, Mishima, and Kyoto, September 21–27, pp 331–335.Google Scholar
  57. Stebbins KE, Quast JF, Haut KT, Stott WT (1999) Subchronic and chronic toxicity of ingested 1,3-dichloropropene in dogs. Regul Pharmacol Toxicol 30:233–243.CrossRefGoogle Scholar
  58. Stebbins KE, Johnson KA, Jeffries TK, Redmond JM, Haut KT, Shabrang SN, Stott WT (2000) Chronic toxicity and oncogenicity studies of ingested 1,3-dichloropropene in rats and mice. Regul Pharmacol Toxicol (in press).Google Scholar
  59. Stolzenberg SJ, Hine CH (1980) Mutagenicity of 2-and 3-carbon halogenated compounds in the Salmonella/mammalian-microsome test. Environ Mutagen 2:59–66.PubMedCrossRefGoogle Scholar
  60. Stott WT, Kastl PL (1986) Inhalation pharmacokinetics of technical grade 1,3-dichloro-propene in rats. Toxicol Appl Pharmacol 85:332–341.PubMedCrossRefGoogle Scholar
  61. Stott WT, Young JT, Calhoun LL, Battjes JE (1988) Subchronic toxicity of inhaled technical-grade 1,3-dichloropropene in rats and mice. Fundam Appl Toxicol 11:207–220.PubMedCrossRefGoogle Scholar
  62. Stott WT, Waechter JM, Quast JT (1990) Letter to the editor. Arch Environ Health 45: 250–253.PubMedGoogle Scholar
  63. Stott WT, Mendrala AL, Redmond JM, Nwosu AF, Lomax LG (1992) Mechanism of 1,3-dichloropropene (1,3-D) induced toxicity in urinary bladder epithelium of mice. Toxicologist 12:A415.Google Scholar
  64. Stott WT, Gollapudi BB, Clements CM, Linscombe VA, Dittenber DA, Lick SJ, Johnson KA (1997) 1,3-Dichloropropene: mechanism of tumorigenicity studies in Male B6C3F1 and Fischer 344 rats. Dow Chemical Company, Midland, MI.Google Scholar
  65. Stott WT, Gilbert JR, McGuirk RJ, Brzak KA, Alexander LM, Dryzga MD, Mendrala AL, Bartels MJ (1998) Bioavailability and pharmacokinetics of microencapsulated 1,3-dichloropropene in rats. Toxicol Sci 41:21–28.PubMedCrossRefGoogle Scholar
  66. Sudo S, Kimura Y, Yamamoto K, Ichihara S (1979) The mutagenicity test on 1,3-dichloropropene in bacteria test system. Dow Chemical Company, Midland, MI.Google Scholar
  67. Talcott R, King J (1984) Mutagenic impurities in 1,3-dichloropropene preparations. J Natl Cancer Inst 72:1113–1116.PubMedGoogle Scholar
  68. Torkelson TR (1994) Halogenated aliphatic hydrocarbons containing chlorine, bromine, and iodine. In: Clayton GD, Clayton FE (eds) Patty’s Industrial Hygiene and Toxicology, 4th Ed., Vol. 2, Part E. Wiley, New York, pp 4007–4251.Google Scholar
  69. Torkelson T, Oyen F (1977) The toxicity of 1,3-dichloropropene as determined by repeated exposure of laboratory animals. Am Ind Hyg Assoc J 38:217–223.PubMedCrossRefGoogle Scholar
  70. Valencia R, Mason JM, Woodruff RC, Zimmering S (1985) Chemical mutagenesis testing in Drosophila. III. Results of 48 coded compounds tested for the national toxicology program. Environ Mutagen 7:325–348.PubMedCrossRefGoogle Scholar
  71. Van Duuren BL, Goldschmidt BM, Loewengart G, Smith AC, Melchionne S, Seidman I, Roth D (1979) Carcinogenicity of halogenated olefinic and aliphatic hydrocarbons in mice. J Natl Cancer Inst 63:1433–1439.PubMedGoogle Scholar
  72. van Sittert NJ, Veenstra GE, Dumas EP, Tordoir EF (1991) Letter to the editor. Br J Med 48:646–648.Google Scholar
  73. van Welie RTH, van Duyn P, Brouwer DH, van Hemmen JJ, Brouwer EJ, Vermeulen NPE (1991) Inhalation exposure to 1,3-dichloropropene in the Dutch flower-bulb culture. Part II. Biological monitoring by measurement of urinary excretion of two mer-capturic acid metabolites. Arch Environ Contam Toxicol 20:6–12.PubMedCrossRefGoogle Scholar
  74. Venable JR, McClimans CD, Flake RE, Dimick DB (1980) A fertility study of male employees engaged in the manufacture of glycerine. J Occup Med 22:87–91.PubMedCrossRefGoogle Scholar
  75. Verplanke AJW, Bloemen L, Brouwer EJ, Van Sittert NJ, Boogaard PJ, De Wolff FA (1995) Monitoring of occupational exposure to cis-1,3-dichloropropene and effects on liver and kidney, Part 2. Effects on liver and kidney. Universiteit van Amsterdam, Netherlands.Google Scholar
  76. von der Hude W, Scheutwinkel M, Gramlich U, Fibler B, Basier A (1987) Genotoxicity of three-carbon compounds evaluated in the SCE test in vitro. Environ Mutagen 9: 401–410.PubMedCrossRefGoogle Scholar
  77. von der Hude W, Behm C, Grtler R, Basier A (1988) Evaluation of the SOS chromotest. Mutat Res 203:81–94.PubMedGoogle Scholar
  78. Vos RME, van Welie RTH, Peters WHM, Evelo CTA, Boogaards JJP, Vermeulen NPE, van Bladeren PJ (1991) Genetic deficiency of human class mu glutathione S-transfer-ase isoenzymes in relation to the urinary excretion of the mercapturic acids of Z- and E-l,3-dichloropropene. Arch Toxicol 65:95–99.PubMedCrossRefGoogle Scholar
  79. Waechter JM, Brzak KA, McCarty LP, LaPack MA, Brownson PJ (1992) Cis-/trans-1,3-dichloropropene: inhalation pharmacokinetics and metabolism in human volunteers. Toxicologist 13:A1090.Google Scholar
  80. Watson WP, Brooks TM, Huckle KR, Hutson DH, Land KL, Smith RJ, Wright AS (1987) Microbial mutagenicity studies with (Z)-1,3-dichloropropene. Chem-Biol Interact 61:17–30.PubMedCrossRefGoogle Scholar
  81. WHO (World Health Organization) (1993) International Programme on Chemical Safety, 1,3-Dichloropropene, 1,2-Dichloropropane and Mixtures. Environmental Health Criteria No. 146. World Health Organization, Geneva.Google Scholar
  82. Yang RSH, Huff JE, Boorman GA, Haseman JK, Kornreich M, Stookey JL (1986) Chronic toxicology and carcinogenesis studies of TELONE II by gavage in Fischer 344 rats and B6C3F1 mice. J Toxicol Environ Health 18:377–392.PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2001

Authors and Affiliations

  • William T. Stott
    • 1
  • B. Bhaskar Gollapudi
    • 1
  • K. S. Rao
    • 2
  1. 1.Toxicology & Environmental Research and ConsultingThe Dow Chemical CompanyMidlandUSA
  2. 2.Dow AgroSciences, LLCIndianapolisUSA

Personalised recommendations