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Dichloropropene, 1,3-

1. NAME
   1.1 Substance
   1.2 Group
   1.3 Synonyms
   1.4 Identification numbers
      1.4.1 CAS number
      1.4.2 Other numbers
   1.5 Main brand names, main trade names
   1.6 Manufacturers, Importers
2. SUMMARY
   2.1 Main risks and target organs
   2.2 Summary of clinical effects
   2.3 Diagnosis
   2.4 First aid measures and management principles
3. PHYSICO-CHEMICAL PROPERTIES
   3.1 Origin of the substance
   3.2 Chemical structure
   3.3 Physical properties
      3.3.1 Colour
      3.3.2 State/Form
      3.3.3 Description
   3.4 Hazardous characteristics
4. USES
   4.1 Uses
      4.1.1 Uses
      4.1.2 Description
   4.2 High risk circumstance of poisoning
   4.3 Occupationally exposed populations
5. ROUTES OF EXPOSURE
   5.1 Oral
   5.2 Inhalation
   5.3 Dermal
   5.4 Eye
   5.5 Parenteral
   5.6 Other
6. KINETICS
   6.1 Absorption by route of exposure
   6.2 Distribution by route of exposure
   6.3 Biological half-life by route of exposure
   6.4 Metabolism
   6.5 Elimination and excretion
7. TOXICOLOGY
   7.1 Mode of action
   7.2 Toxicity
      7.2.1 Human data
         7.2.1.1 Adults
         7.2.1.2 Children
      7.2.2 Relevant animal data
      7.2.3 Relevant in vitro data
      7.2.4 Workplace standards
      7.2.5 Acceptable daily intake (ADI)
   7.3 Carcinogenicity
   7.4 Teratogenicity
   7.5 Mutagenicity
   7.6 Interactions
8. TOXICOLOGICAL ANALYSES AND BIOMEDICAL INVESTIGATIONS
   8.1 Material sampling plan
      8.1.1 Sampling and specimen collection
         8.1.1.1 Toxicological analyses
         8.1.1.2 Biomedical analyses
         8.1.1.3 Arterial blood gas analysis
         8.1.1.4 Haematological analyses
         8.1.1.5 Other (unspecified) analyses
      8.1.2 Storage of laboratory samples and specimens
         8.1.2.1 Toxicological analyses
         8.1.2.2 Biomedical analyses
         8.1.2.3 Arterial blood gas analysis
         8.1.2.4 Haematological analyses
         8.1.2.5 Other (unspecified) analyses
      8.1.3 Transport of laboratory samples and specimens
         8.1.3.1 Toxicological analyses
         8.1.3.2 Biomedical analyses
         8.1.3.3 Arterial blood gas analysis
         8.1.3.4 Haematological analyses
         8.1.3.5 Other (unspecified) analyses
   8.2 Toxicological Analyses and Their Interpretation
      8.2.1 Tests on toxic ingredient(s) of material
         8.2.1.1 Simple Qualitative Test(s)
         8.2.1.2 Advanced Qualitative Confirmation Test(s)
         8.2.1.3 Simple Quantitative Method(s)
         8.2.1.4 Advanced Quantitative Method(s)
      8.2.2 Tests for biological specimens
         8.2.2.1 Simple Qualitative Test(s)
         8.2.2.2 Advanced Qualitative Confirmation Test(s)
         8.2.2.3 Simple Quantitative Method(s)
         8.2.2.4 Advanced Quantitative Method(s)
         8.2.2.5 Other Dedicated Method(s)
      8.2.3 Interpretation of toxicological analyses
   8.3 Biomedical investigations and their interpretation
      8.3.1 Biochemical analysis
         8.3.1.1 Blood, plasma or serum
         8.3.1.2 Urine
         8.3.1.3 Other fluids
      8.3.2 Arterial blood gas analyses
      8.3.3 Haematological analyses
      8.3.4 Interpretation of biomedical investigations
   8.4 Other biomedical (diagnostic) investigations and their interpretation
   8.5 Overall interpretation of all toxicological analyses and toxicological investigations.
   8.6 References
9. CLINICAL EFFECTS
   9.1 Acute poisoning
      9.1.1 Ingestion
      9.1.2 Inhalation
      9.1.3 Skin exposure
      9.1.4 Eye contact
      9.1.5 Parenteral exposure
      9.1.6 Other
   9.2 Chronic poisoning
      9.2.1 Ingestion
      9.2.2 Inhalation
      9.2.3 Skin exposure
      9.2.4 Eye contact
      9.2.5 Parenteral exposure
      9.2.6 Other
   9.3 Course, prognosis, cause of death
   9.4 Systematic description of clinical effects
      9.4.1 Cardiovascular
      9.4.2 Respiratory
      9.4.3 Neurological
         9.4.3.1 Central nervous system (CNS)
         9.4.3.2 Peripheral nervous system
         9.4.3.3 Autonomic nervous system
         9.4.3.4 Skeletal and smooth muscle
      9.4.4 Gastrointestinal
      9.4.5 Hepatic
      9.4.6 Urinary
         9.4.6.1 Renal
         9.4.6.2 Other
      9.4.7 Endocrine and reproductive systems
      9.4.8 Dermatological
      9.4.9 Eye, ear, nose, throat: local effects
      9.4.10 Haematological
      9.4.11 Immunological
      9.4.12 Metabolic
         9.4.12.1 Acid-base disturbances
         9.4.12.2 Fluid and electrolyte disturbances
         9.4.12.3 Others
      9.4.13 Allergic reactions
      9.4.14 Other clinical effects
      9.4.15 Special risks
   9.5 Other
   9.6 Summary
10. MANAGEMENT
   10.1 General principles
   10.2 Life supportive procedures and symptomatic/specific treatment
   10.3 Decontamination
   10.4 Enhanced elimination
   10.5 Antidote treatment
      10.5.1 Adults
      10.5.2 Children
   10.6 Management discussion
11. ILLUSTRATIVE CASES
   11.1 Case reports from literature
12. Additional information
   12.1 Specific preventive measures
   12.2 Other
13. REFERENCES
14. AUTHOR(S), REVIEWER(S), DATE(S) (INCLUDING UPDATES), COMPLETE ADDRESS(ES)
    1,3-DICHLOROPROPENE

    International Programme on Chemical Safety
    Poisons Information Monograph 025
    Chemical

    1.  NAME

        1.1  Substance

             1,3-dichloropropene

        1.2  Group

             Halogenated aliphatic hydrocarbon

        1.3  Synonyms

             dichloro-1,3-propene;
             1,3-dichloro-1-propene;
             1,3-dichloro-2-propene;
             alpha-chloroallylchloride;
             gamma-chloroallylchloride;
             alpha,gamma-chloroallylchloride;
             3-chloroallyl chloride;
             3-chloroorpropenyl chloride;
             1,3-dichloropropylene;
             1,3-D;
             DCP

        1.4  Identification numbers

             1.4.1  CAS number

                    542-75-6

             1.4.2  Other numbers

                    EINECS number: 208-826-5
                    RTECS registry number: UC8310000
                    DOT number: UN2047
                    RCRA waste number: U084

        1.5  Main brand names, main trade names

             Telone(R)Dowfume N;
             Telone C-17(R)Vidden D;
             Telone II(R)Terr-O-Cide 15-D;
             Telone II(R) bTerr-O-Cide 30-D;
             DD(R)Terr-O-Gas 57/43T;

             DD-92(R)Vorlex;
             M-3993 D-D 95;
             Dedisol C Nematox II;
             Telone 2000

        1.6  Manufacturers, Importers

             DowElanco
             Division of Dow Chemical, USA
             2020 Dow Center
             Midland, MI 48674

    2.  SUMMARY

        2.1  Main risks and target organs

             1,3-dichloropropene is a volatile halogenated
             hydrocarbon; the most significant exposures occur via the
             pulmonary route due to application techniques and to its
             physico-chemical properties, however, oral and dermal
             exposures present the same effects. The target organs and
             main health effects resulting from exposure include,
             irritation of the skin and mucous membranes, coughing and
             respiratory distress, gastrointestinal distress, acute liver
             and kidney failure, headache, fatigue, and depression of the
             central nervous system (CNS).
    
             1,3-dichloropropene is a probable human carcinogen.
             1,3-dichloropropene has not been demonstrated as a
             reproductive toxin or teratogen.

        2.2  Summary of clinical effects

             Acute (ingestion):
             Acute exposure to 1,3-dichloropropene can cause irritation of
             mucous membranes, nausea, vomiting, headache, CNS depression
             and, multiorgan system failure including severe coagulopathy,
             hyperglycemia, acute renal and hepatic failure, and adult
             respiratory distress syndrome.
    
             Chronic:
             Chronic exposure to 1,3-dichloropropene can cause skin
             sensitization, fatigue, excessive sweating, weight loss,
             irritability, ulceration of mucous membranes, sexual
             impotence, subclinical hepatic enzyme enzyme induction, and
             breathing difficulty.
             The most significant chronic exposures occur via
             inhalation.

        2.3  Diagnosis

             The diagnosis is based on a history of ingestion,
             inhalation, or dermal exposure to 1,3-dichloropropene.
             Symptomatic patients with a history of exposure may present
             with signs and symptoms of irritation of mucous membranes,
             chest discomfort, headache, nausea, vomiting, and
             dizziness.
    
             Blood and urine analyses are limited in value when attempting
             to diagnosis chronic exposure to 1,3-dichloropropene.

        2.4  First aid measures and management principles

             Simple first aid measures for acute exposure:
             Induce vomiting for recent substantial ingestions.
             Irrigate of exposed eyes and skin with copious amounts of
             water.
             Provide oxygen to patients exposed to 1,3-dichloropropene via
             inhalation and evaluate for respiratory distress.
             Management principles for acute exposure:
             Make an assessment of airway, breathing, circulation and
             neurological status.
             Support respiratory and cardiovascular function.

    3.  PHYSICO-CHEMICAL PROPERTIES

        3.1  Origin of the substance

             1,3-dichloropropene was introduced as a synthetic soil
             fumigant in 1945. 1,3-dichloropropene is a halogenated,
             aliphatic hydrocarbon formed by the high-temperature
             chlorination of propylene, or from 1,3-dichloro-propanol by
             dehydration with POCl3 or with P2O5 in benzene.
             Commercial formulation of 1,3-dichloropropene is a mixture of
             cis- and trans- isomers, often containing 1,2-dichloropropane
             and 2,3-dichloropropene (Krijgsheld & Van der Gen,
             1986).

        3.2  Chemical structure

             Structural name: 1,3-dichloropropene (IUPAC)
             Molecular formula: C3H4Cl2
             Relative molecular mass: 110.98

        3.3  Physical properties

             3.3.1  Colour

                    Colourless to amber.

             3.3.2  State/Form

                    Liquid

             3.3.3  Description

                    Liquid at standard temperature and pressure.
    
                    Odour: chloroform-like, sweet, sharp
    
                    Odour threshold (in air):1 ppm
                    4.54 mg/m3
    
                    Boiling point     104C (cis-)
                                      112C (trans-)
                                      108C (cis-/trans- mix)
    
                    Freezing point:   -85C (cis-)
    
                    Flash point       28.5C (cis-)
                                      28C (trans-)
                                      25C (cis-/trans- mix)
    
                    Explosive limits: 4.3% to 10.3% (cis-/trans- mix)
    
                    Self-ignition:    555C (cis-)
                                      534C (trans-)
    
                    Vapour pressure:  (25C)4850 Pa at 25C (cis-)
                                      3560 Pa at 25C (trans-)
                                      3700 Pa (cis-/trans- mix at 20C)
    
                    Relative density: (20C)
                                      1.217 g/mL (cis-)
                                      1.224 g/mL (trans-)
                                      1.218-1.224 g/mL (cis-/trans- mix)
    
                    Solubility:
                             Water:   (20C, in g/L)
                                      2.45 (cis-)
                                      2.49 (trans-)
                                      2.0 (cis-/trans- mix)
    
                    Partition coefficients:
    
                             Log octanol/water 
                             1.82 (cis- at 20C)
                             2.22 (trans- at 25C)
                             1.4 to 2.0 (cis-/trans- mix)
    

                    Soil adsorption Kd: 0.23 to 1.09
    
                    Soil adsorption Koc: 20 to 42
    
                    Bioconcentration factor
                    Log BCF0.86
                    (From water solubility)
    
                    Henry's law constant (20C)
                    1.2 x 10-3 atm-m3/mol(cis-)
                    8.0 x 10-4 atm-m3/mol(trans-)
    
                    Environmental half-life
    
                    Soil: 133 to 271 hours
                    Air: 4.66 to 80.3 hours
                    Surface water: 133-271 hours
                    Ground water: 133-271 hours
    
                    Diffusivity in water 9.28 x 10-6 cm2/second
    
                    Diffusivity in air 4.86 x 10-3 cm2/second
    
                    From: Leistra, 1970; Hayuk & Laudie, 1974; Torkelson &
                    Owen, 1977;  Lyman et al., 1982; US EPA, 1981, 1992;
                    Verscheran, 1983; Krijgsheld & van der Gen, 1986;
                    Weast et al., 1988; Bennett & Ridge, 1989; Schuurman,
                    1989; Van Hooidonk, 1989; WHO, 1993.

        3.4  Hazardous characteristics

             1,3-dichloropropene is the primary component of numerous
             formulations used as a nematicide.  The current formulations
             contain approximately 92% by volume of cis- and trans-1,3-
             dichloropropene and epoxidized soybean oil. Previous
             formulations of 1,3-dichloropropene used in agriculture also
             contained 1,2-dichloropropane, epichlorohydrin, chloropicrin,
             2,2-dichloropropene, 3,3-dichloropropene,
             methylisothiocyanate, and other related chlorinated
             hydrocarbons and hexenes (US EPA, 1992).
    
             Primary degradation of 1,3-dichloropropene in ambient air
             occurs as a result of reactions with hydroxyl radicals (US
             EPA, 1992). Formyl chloride, chloroacetaldehyde, chloroacetic
             acid, formic acid, hydrogen chloride, carbon dioxide, and
             carbon monoxide have all been identified as products of
             reactions of 1,3-dichloropropene with hydroxyl radicals and
             ozone (Tuazon et al., 1984).
    
             The soil has the highest mass distribution of all
             compartments for 1,3-dichloropropene in agricultural use.
             However, bioaccumulation is not predicted.
    

             Approximately 5 to 75% of 1,3-dichloropropene will volatilize
             within 36 hours after soil injection (CSWRCB, 1983). The
             hydrolysis half-life has been reported between 4.6 to 13.5
             days, and field dissipation half-life at approximately 1 to 7
             days. In vitro half-lives of less than 5 hours in water have
             been reported. (US EPA, 1992).

    4.  USES

        4.1  Uses

             4.1.1  Uses

                    Pesticide

             4.1.2  Description

                    1,3-dichloropropene has been used extensively
                    as a pre-plant soil fumigant since 1956, with a recent
                    increase in use due to the restriction of ethylene
                    dibromide, dibromochloropropene, and methyl
                    bromide.
    
                    1,3-dichloropropene is used to kill nematodes,
                    insects, and weeds on potatoes, tomatoes, tobacco,
                    pineapples, flower bulbs, and other vegetable and
                    orchard crops in the United States, Europe, Japan, the
                    Philippines, and Africa (Cox, 1992).
    
                    1,3-dichloropropene is applied at rates of 45 to 120
                    litres per acre, injected 20 to 40 cm below the soil
                    surface (Albrecht, 1987; Braun and Supkoff,
                    1994).

        4.2  High risk circumstance of poisoning

             The highest levels of exposure to 1,3-dichloropropene
             occur in occupational settings where formulations are
             manufactured or applied.  Accidental releases during
             transport have also resulted in several poisoning cases
             (Markowitz and Crosby, 1984; Sterrett et al., 1986).

        4.3  Occupationally exposed populations

             Agricultural workers represent the majority of
             occupationally exposed workers.  The high risk activities
             during fumigation with 1,3-dichloropropene include the
             following (Albrecht, 1987):
    

             Filling operations
             Mixing operations
             Field applications 
             Irrigation workers
             Supply truck drivers
             Maintenance personnel
             Planters
             Mulch coverers

    5.  ROUTES OF EXPOSURE

        5.1  Oral

             Not typically reported in humans. Oral exposure is
             theoretically possible through contaminated ground water (US
             EPA, 1992).
             Well absorbed in rats (Climie et al., 1979).

        5.2  Inhalation

             The primary route of human exposure; rapidly absorbed
             from the lungs (Brouwer, 1991).

        5.3  Dermal

             Rapidly absorbed. Important route of occupational
             exposure (Mizell et al., 1988a, 1988b; US EPA, 1992).

        5.4  Eye

             No data available.

        5.5  Parenteral

             No data available.

        5.6  Other

             Not reported in humans.

    6.  KINETICS

        6.1  Absorption by route of exposure

             1,3-dichloropropene is rapidly absorbed by the oral,
             inhalational, and dermal routes.
    
             Oral
             In Fischer 344 rats and B6C3F1 mice, the extent of absorption
             of 1,3-dichloropropene via oral route was reported as high as
             90% and 79% respectively (Hudson et al., 1971; Dietz et al.,

             1984a). Blood levels of the glutathione conjugate reached
             steady state within 15 minutes, indicating rapid absorption
             (Fisher and Kilgore, 1989; US EPA, 1991).
    
             Inhalation
             Van Welie et al. (1991) reported a 58.5% mean recovery of
             N-acetyl-cysteine conjugates of 1,3-dichloropropene in urine
             from agricultural workers exposed to concentrations of
             technical grade 1,3-dichloropropene between 1.8-18.9 mg/m3
             via inhalation. The presence of N-acetyl-cysteine conjugates
             of 1,3-dichloropropene in the recovered urine of field
             applicators suggests that 1,3-dichloropropene is readily
             absorbed via inhalation in humans (Osterloh et al., 1989; Van
             Welie et al., 1991).

        6.2  Distribution by route of exposure

             Oral
             No oral human data is available.
             Following absorption in Fischer 344 rats, 1,3-dichloropropene
             is rapidly distributed in the blood and readily perfuses into
             tissues. Steady state blood levels of the glutathione-
             conjugate of 1,3-dichloropropene were reached within 15
             minutes after exposure (Fisher & Kilgore, 1989). Tissue
             concentrations of 1,3-dichloropropene were highest in the
             stomach, followed by the blood, bone, brain, heart, kidneys,
             liver, bladder, skin, skeletal muscle, spleen, ovaries,
             testes, and fat (Dietz et al., 1984a,b; Waechter and Kastl,
             1988).
    
             Inhalation
             No human data details the extent of 1,3-dichloropropene
             distribution in the body. Biological monitoring studies have
             reported the presence of mercapturic acid metabolites of
             1,3-dichloropropene in urine (Osterloh et al., 1989; Brouwer
             et al., 1991; Van Welie et al., 1991).

        6.3  Biological half-life by route of exposure

             Oral
             No human data is available.
    
             Inhalation
             The mean half-life of technical grade 1,3-dichloropropene in
             humans was 8 hours calculated from thioether excretion rates,
             and 9.5 hours based on urinary excretion (Van Welie et al.,
             1991).

        6.4  Metabolism

             The metabolism of 1,3-dichloropropene in humans has been
             suggested to proceed initially via oxidation in a phase I
             biotransformation (Stott & Kastl, 1986; Miyaoka et al., 1990;
             Martelli et al., 1993). The microsomal oxidation of
             1,3-dichloropropene may be catalyzed by the cytochrome P450
             mono-oxygenase system (Van Sittert et al., 1989). This may
             not be the only metabolic pathway. Typically, phase I
             reactions serve to modify a foreign compound enabling
             conjugation in a phase II reaction. However, epoxide
             intermediates produced in a phase I reaction may be involved
             in the mutagenic potential of 1,3-dichloropropene observed in
             Salmonella assays (Hutson, 1984).
    
             The metabolism of structurally similar aliphatic compounds,
             e.g. vinyl chloride, suggest that toxicity resulting from
             metabolism via an electrophilic epoxide intermediate is
             possible. The chemically reactive intermediate resulting from
             a phase I biotransformation reaction may directly bind with
             DNA, causing increased DNA fragmentation and lesions (Ghia et
             al., 1993; Martelli et al., 1993). This result may produce
             genotoxic effects. Protein binding and DNA adduct research is
             currently an active area (Stott & Kastl, 1986; Stott et al.,
             1988; Lomax et al., 1989). Specific toxicologic,
             carcinogenic, and mutagenic effects are discussed further in
             Sections 7.1, 7.3, and 7.5, respectively.
    
             With regards to conjugation of 1,3-dichloropropropene,
             urinary elimination has been suggested to proceed via a
             glutathione-dependent biotransformation (Osterloh et al.,
             1989; Van Welie et al., 1991, 1992; Brouwer et al., 1991).
             Enzyme-catalysed glutathione biotransformations have been
             identified, however, appreciable levels of non-enzymatic
             conjugation of 1,3-dichloropropene with glutathione have also
             been observed (Vos et al., 1991). The non-enzymatic
             conjugation potential of 1,3-dichloropropene provides
             supportive evidence for the direct acting mutagenic potential
             observed in Ames tests. Unfortunately the products of phase
             II biotransformations in humans have not been completely
             identified and the exact mechanistic pathway has not been
             directly observed. However, 58.5% of a glutathione conjugate
             of 1,3-dichloropropene does follow the classical mercapturic
             acid pathway in humans (Climie et al., 1979; Van Welie et
             al., 1991). The presence of 2 mercapturic acid metabolites,
             N-acetyl-S-(Z & E-chloropropenyl-2)-L-cysteine, in the urine
             of agricultural workers offers this supportive evidence
             (Osterloh et al., 1989; Brouwer et al., 1991; Van Welie et
             al., 1991, 1992). Mecapturic acid is excreted as a result of
             catabolism of the glutathione conjugates by -glutamyl-
             transpeptidase, cysteinylglycinase, and N-acetyltransferases
             (Brouwer, 1991). Although this pathway is suggested as the

             major detoxification pathway, mean recovery of the 2
             mercapturic acids was 58.5% (Van Welie et al., 1991),
             suggesting that additional as yet unidentified metabolic
             pathways may exist.
    
             Additionally, cysteine conjugates from structurally similar
             compounds have shown increased nephrotoxicity due to -lyase
             activity in the kidney (Dekant et al., 1989). In this
             process, the glutathione conjugate of 1,3-dichloropropene may
             undergo further catabolism to give additional reactive
             thiols.  However, metabolism and increased toxicity through
             this pathway remains speculative with regards to
             1,3-dichloropropene.
    
             Climie et al. (1979) reported that cis-1,3-dichloropropene is
             metabolized 5 times faster than the trans isomer in a rat
             model.

        6.5  Elimination and excretion

             Van Welie et al. (1991) reported a mean recovery of
             58.5% for N-acetyl-cysteine conjugates of cis-1,3-
             dichloropropene in the urine of agricultural field
             applicators.
    
             The metabolic elimination of 1,3-dichloropropene from the
             blood in rats primarily occurs via enzymatic conjugation of
             1,3-dichloropropene with GSH (Stott & Kastl, 1986). Recovery
             of the mercapturic acid conjugate of cis- and trans- isomers
             of 1,3-dichloropropene in a 24-hour urine sample has been
             reported between 82-84% and 55-60%, respectively (Hutson et
             al., 1971; Climie et al., 1979). Smaller amounts of each
             isomer were recovered in the faeces: 2-3% of the cis- and 2%
             of the trans- isomer (Hudson et al., 1971; US EPA,
             1992).

    7.  TOXICOLOGY

        7.1  Mode of action

             Human and animal health effects may include damage to
             the liver, kidney, lung, CNS, myocardium, GI tract, skin, and
             mucous membranes.
    
             Although substantial health effects have been documented as a
             result of 1,3-dichloropropene exposure, no data concerning
             exact mechanisms of toxicity exist. Current research has
             focused on biological monitoring, and utilisation of blood
             and renal function parameters as biomarkers of exposure.
    

             The major detoxification pathway for possible chemically
             reactive intermediates produced in phase I biotransformations
             in humans is suggested to occur via glutathione conjugation
             (Brouwer et al., 1991; Van Welie et al., 1991).
    
             Chemically reactive intermediates produced by a P450 mono-
             oxygenase-mediated metabolism may be implicated in the
             genotoxic effects observed in mutagenicity and
             carcinogenicity studies. In vitro research demonstrated that
             cytochrome P450 metabolically activates 1,3-dichloropropene,
             producing metabolites which increase the toxicity (Ghia et
             al., 1993; Martelli et al., 1993). These studies reported
             increased DNA fragmentation in liver, gastric mucosa, and
             kidney cells of rats. In addition, 1,3-dichloropropene was
             demonstrated to directly bind with DNA (Ghia et al., 1993;
             Martelli et al., 1993). Furthermore, the same studies
             reported the capability of 1,3-dichloropropene containing
             compounds to induce DNA damage in cells lacking enzymatic
             systems which catalyse phase II biotransformations (Ghia et
             al., 1993; Martelli et al., 1993). The formation of DNA
             adducts may predictably result in the increased incidence of
             fragmentation and abnormal DNA replication. The combined
             evidence suggests that 1,3-dichloropropene may possess
             significant genotoxic effects. Unfortunately, it has not been
             demonstrated if the increased toxicity of 1,3-dichloropropene
             occurs spontaneously, via oxidation, or after conjugation.
             Genotoxic effects may result in increased mutagenicity and
             carcinogenicity in organs such as the liver, kidney, spleen,
             gastrointestinal tract, and lungs (Van Welie et al., 1992).
             Specific mutagenic and carcinogenic properties are discussed
             further in subsequent sections. 
    
             The kidney is the major organ involved in metabolism of
             glutathione conjugates, usually resulting in mercapturic acid
             formation. Recent studies with other cysteine conjugates of
             structurally similar compounds have shown increased
             nephrotoxicity due to  -lyase activity in the kidney (Dekant
             et al., 1989; Van Welie et al., 1992). The action of  -lyase
             bioactivation on glutathione conjugates resulted in the
             production of reactive thiols which then formed covalent
             adducts with rat kidney mitochondrial phospholipids,
             eventually leading to cell death. The hypothesised site of S-
             cysteine conjugate toxicity is the proximal tubular
             epithelium (Dekant et al., 1989).
    
             This data suggests that there may be more than one
             mechanistic pathway which could lead to the formation of
             toxic metabolites in humans. Further research is required to
             determine the mechanism and extent of toxicity.

        7.2  Toxicity

             7.2.1  Human data

                    7.2.1.1  Adults

                             Limited  human data is available.
                             The early effects of subchronic exposure to
                             1,3-dichloropropene were studied
                             prospectively in 14 commercial agricultural
                             applicators to assess possible damage to
                             liver and kidney function (Brouwer et al.,
                             1991; Van Welie et al., 1991). The parameters
                             measured in the study included 6 different
                             hepatic enzymes, 6 different proteins
                             associated with renal function, glutathione
                             and glutathione-S-transferase. The results
                             revealed subclinical changes in total
                             bilirubin, creatinine, albumin, glutathione
                             and glutathione-S-transferase. The reduction
                             of glutathione and glutathione-S-transferase
                             could not be correlated to toxicity, however,
                             exposure to 1,3-dichloropropene was shown to
                             affect glutathione conjugating capacity
                             (Brouwer et al., 1991). Regarding liver
                             function, the researchers concluded the
                             reduction in total bilirubin coupled with a
                             moderate increase in serum  -
                             glutamyltranspeptidase was an indirect
                             indicator of moderate enzyme induction as
                             result of exposure to 1,3-dichloropropene.

                    7.2.1.2  Children

                             No data available.

             7.2.2  Relevant animal data

                    LD50 (Oral) Rat: 470 mg/kg (RTECS, 1990)
                    LD50 (Oral) Mouse: 640 mg/kg (RTECS, 1990)
                    LD50 (Dermal) Rabbit: 504 mg/kg (RTECS, 1990)
                    LC50 (Inhalation) Mouse: 4650 mg/m3/2 hours (RTECS,
                    1990)
    
                    LC50 levels for animals after inhalational exposure
                    vary from 253 ppm for Telone C-17 to 904 ppm for
                    Telone IIa (Cracknell et al., 1987; Streeter et al.,
                    1987; Streeter & Lomax, 1988; US EPA, 1992). The
                    significant differences reported in LD50 and LC50
                    levels are due in part to variations in formulations
                    of 1,3-dichloropropene-containing products.
    

                    The NOAEL and LOAEL for nasal epithelium in rats was
                    10 ppm and 30 ppm, respectively (Coate, 1979a; Lomax
                    et al., 1989). Nasal lesions occurred in rats at
                    exposures > 90 ppm (Breslin et al., 1989).
    
                    Rats exposed to 1,3-dichloropropene via inhalation
                    exhibited lung congestion, tracheal congestion, fluid
                    in the pleural cavity, atelectasis, emphysema, and/or
                    pulmonary edema, and lung hemorrhaging (Cracknell et
                    al., 1987; Streeter et al., 1987; Streeter & Lomax,
                    1988; US EPA, 1992).
    
                    Hyperplasia and hyperkeratosis of the forestomach and
                    urinary bladder hyperplasia were observed in mice
                    exposed to 60 ppm of Telone IIb in a 2-year inhalation
                    study (Lomax et al., 1989; US EPA, 1992). Neoplastic
                    and preneoplastic lesions of the stomach were found in
                    rats chronically exposed to 1,3-dichloropropene via
                    the oral route (NTP, 1985).
    
                    Stomach hemorrhage, and intestinal congestion and
                    hemorrhage were observed in rats dermally exposed to
                    1,3-dichloropropene (Jones & Collier, 1986b; Jones,
                    1988b; US EPA, 1992).
    
                    Mizell et al. (1988) reported skeletal muscle
                    hemorrhaging after dermal exposure to large amounts of
                    1,3-dichloropropene in rabbits.
    
                    Conjunctival irritation, corneal irritation, corneal
                    opacity, and erythema, edema, necrosis and
                    subcutaneous or skeletal muscle hemorrhage have all
                    been reported in rats, rabbits, and guinea pigs
                    exposed to 1,3-dichloropropene via ocular and dermal
                    routes, respectively (Lichy & Olson, 1975; Carreon &
                    Wall, 1983; Jones & Collier, 1986b; Jeffrey, 1987c;
                    Mizell, 1988a; US EPA, 1992).

             7.2.3  Relevant in vitro data

                    Suzuki et al. (1994) conducted research
                    concerning the mechanisms of hepatotoxicity caused by
                    1,3-dichloropropene, the compound shown to possess the
                    highest peroxidative effect of 11 hydrocarbons
                    previously studied. Lipid peroxidation is initiated by
                    the attack of free radicals on lipids, resulting in a
                    chain reaction of membrane degradation leading to cell
                    death. Phospholipid hydroperoxides and lactate
                    dehydrogenase (LDH) were directly measured as a
                    function of incubation time. Isolated rat hepatocytes
                    exposed to 1,3-dichloropropene exhibited increased
                    cytotoxicity, measured by LDH release, after increases
                    in phospholipid hydroperoxides were detected in vitro.

                    Researchers concluded that peroxidative membrane
                    degradation not only preceded cytotoxicity, but also
                    was one of the main causes of cytotoxicity resulting
                    from exposure to 1,3-dichloropropene (Suzuki et al.,
                    1994).

             7.2.4  Workplace standards

                    International Agency for Research on Cancer
                    (IARC, 1987):
                    Group 2B carcinogen
    
                    Occupational Safety and Health Administration,
                    permissible exposure limit (PEL) (OSHA, 1989):
                    1 ppm (skin)
    
                    American Conference of Governmental Industrial Hygienists,
                    threshold limit value (TLV) (ACGIH, 1989):
                    1 ppm 
    
                    Environmental Protection Agency, Reference
                    concentration (RfC), (IRIS, 1991):
                    0.02 mg/m3 (inhalation)

             7.2.5  Acceptable daily intake (ADI)

                    Environmental Protection Agency, Reference dose
                    (RfD), (IRIS, 1991):
                    0.0003 mg/kg/day (oral)
    
                    Environmental Protection Agency, Ambient water quality
                    criteria for protection of human health (US EPA,
                    1980):
                    87 ng/L

        7.3  Carcinogenicity

             Human data is limited. Two reported cases of non-Hodgkin
             lymphoma and one case of acute myelomonocytic leukemia were
             reported after accidental exposure by unknown routes to
             technical grade 1,3-dichloropropene (Markovitz & Crosby,
             1984).
    
             Exposure to oral technical grade 1,3-dichloropropene has
             shown increased incidence of dose-dependent benign and
             malignant tumours in both rats and mice (IARC, 1986). 
             Increased incidence of forestomach squamous cell papillomas
             and carcinomas, liver neoplastic nodules, thyroid adenomas
             and carcinomas, and adrenal gland pheochromocytomas were
             observed in both rats and mice (NTP, 1985).
    

             Urinary bladder transitional cell carcinomas, lung adenomas,
             carcinomas, and dose-related increases in bronchioalveolar
             adenomas were observed in mice (NTP, 1985,1989; Lomax et al.,
             1989).
    
             The strongest evidence for 1,3-dichloropropene related
             carcinogenic activity in mice and rats has been shown via
             oral routes of exposure (NTP, 1985). Unfortunately several
             problems were identified in the NTP (1985) data audit
             summary. The problems included the low survival of control
             male mice and the ineffective randomization of animals and
             body weight. Additional problems and discrepancies were
             noted, however, the NTP (1985) data audit summary concluded
             that there was clear evidence of carcinogenicity.
    
             Limited data is available to properly determine the
             carcinogenic potential of 1,3-dichloropropene via inhalation
             exposure.  Lomax et al. (1989) reported inconclusive results
             in rats and mice exposed via inhalation. However, in this study
             exposure to 1,3-dichloropropene did not exceed 60 ppm.
    
             The lack of human data, the lack of extensive and conclusive
             animal studies, the capability of 1,3-dichloropropene to
             cause DNA fragmentation and lesions, the structural
             similarity to known carcinogens, and mutagenic potential
             imply that further research is necessary with regards to
             1,3-dichloropropene containing compounds.
    
             IARC (1987) classifies 1,3-dichloropropene as a B2, or
             probable human carcinogen.

        7.4  Teratogenicity

             No human data is available.  1,3-dichloropropene is not
             fetotoxic or teratogenic in rats or rabbits (Hanley et al.,
             1987; Breslin et al., 1989; US EPA, 1992).

        7.5  Mutagenicity

             1,3-dichloropropene is structurally indicative of a DNA
             reactive compound, although no human data is available.
    
             Mutagenicity studies with 1,3-dichloropropene are positive in
             Salmonella assays with and without activation, positive in
             mouse lymphoma assays without activation, positive in sister
             chromatid exchange assay in V79 cells with and without
             activation, and 1,3-dichloropropene induced sex-linked
             recessive lethal mutation in Drosophila (IARC, 1986; US EPA,
             1992; Cal/EPA, 1994c).
    

             1,3-dichloropropene exposure indicated a dose and time
             dependent increase of DNA fragmentation and a reduction in
             the viability in V79 cells, rat hepatocytes, and human
             hepatocytes with the corresponding increases in
             1,3-dichloropropene concentration and duration of exposure
             (Martelli et al., 1993). Ames tests suggest that
             1,3-dichloropropene has mutagenic potential with and without
             activation. It has been demonstrated that 1,3-dichloropropene
             will directly bind with DNA. The formation of the chemically
             reactive intermediates which may bind with DNA may be
             facilitated by phase I P450 mono-oxygenated enzymes in
             conjunction with decreased glutathione levels which result
             from exposure to 1,3-dichloropropene containing compounds
             (Ghia et al., 1993; Martelli et al., 1993). DNA fragmentation
             in V79 cells is consistent with the direct acting mechanisms
             studied in Ames tests. Finally, researchers concluded that
             the epoxidation of the C=C double bond is involved due to the
             correlation between the inhibition of the cytochrome P450
             pathway and reduction in DNA fragmentation (Martelli et al.,
             1993).  The results of this research showed only slight
             interspecies variability.

        7.6  Interactions

             No data available.

    8.  TOXICOLOGICAL ANALYSES AND BIOMEDICAL INVESTIGATIONS

        8.1  Material sampling plan

             8.1.1  Sampling and specimen collection

                    8.1.1.1  Toxicological analyses

                    8.1.1.2  Biomedical analyses

                    8.1.1.3  Arterial blood gas analysis

                    8.1.1.4  Haematological analyses

                    8.1.1.5  Other (unspecified) analyses

             8.1.2  Storage of laboratory samples and specimens

                    8.1.2.1  Toxicological analyses

                    8.1.2.2  Biomedical analyses

                    8.1.2.3  Arterial blood gas analysis

                    8.1.2.4  Haematological analyses

                    8.1.2.5  Other (unspecified) analyses

             8.1.3  Transport of laboratory samples and specimens

                    8.1.3.1  Toxicological analyses

                    8.1.3.2  Biomedical analyses

                    8.1.3.3  Arterial blood gas analysis

                    8.1.3.4  Haematological analyses

                    8.1.3.5  Other (unspecified) analyses

        8.2  Toxicological Analyses and Their Interpretation

             8.2.1  Tests on toxic ingredient(s) of material

                    8.2.1.1  Simple Qualitative Test(s)

                    8.2.1.2  Advanced Qualitative Confirmation Test(s)

                    8.2.1.3  Simple Quantitative Method(s)

                    8.2.1.4  Advanced Quantitative Method(s)

             8.2.2  Tests for biological specimens

                    8.2.2.1  Simple Qualitative Test(s)

                    8.2.2.2  Advanced Qualitative Confirmation Test(s)

                    8.2.2.3  Simple Quantitative Method(s)

                    8.2.2.4  Advanced Quantitative Method(s)

                    8.2.2.5  Other Dedicated Method(s)

             8.2.3  Interpretation of toxicological analyses

        8.3  Biomedical investigations and their interpretation

             8.3.1  Biochemical analysis

                    8.3.1.1  Blood, plasma or serum

                    8.3.1.2  Urine

                    8.3.1.3  Other fluids

             8.3.2  Arterial blood gas analyses

             8.3.3  Haematological analyses

             8.3.4  Interpretation of biomedical investigations

        8.4  Other biomedical (diagnostic) investigations and their
             interpretation

        8.5  Overall interpretation of all toxicological analyses and
             toxicological investigations.

             No standard toxic blood or serum parameters have been
             established, however, N-acetylcysteine metabolites
             (mercapturic acids) are biomarkers which can be measured in
             urine following acute or chronic exposure to
             1,3-dichloropropene (Osterloh et al., 1989; Van Welie et al.,
             1991).
    
             Measurement of protein and DNA adducts has been proposed as a
             method for the assessment of internal and effective doses of
             1,3-dichloropropene (Van Welie et al., 1992; Skipper et al.,
             1994).

        8.6  References

    9.  CLINICAL EFFECTS

        9.1  Acute poisoning

             9.1.1  Ingestion

                    There is one reported case of acute
                    1,3-dichloropropene poisoning through ingestion
                    (Hernandez et al., 1994). Two hours after accidentally
                    ingesting a mouthful of 1,3-dichloropropene the
                    patient presented with acute gastrointestinal
                    distress, sweating, tachypnoea, tachycardia,
                    hypovolaemia and lividity on both legs. Adult
                    respiratory distress syndrome (ARDS) was reported
                    during the course of treatment. Multiorgan failure and
                    death occurred approximately 38 hours after ingestion
                    (Hernandez et al., 1994).

             9.1.2  Inhalation

                    Humans exposed to 1,3-dichloropropene in a
                    truck spill complained of mucous membrane irritation,
                    chest pain, cough and breathing difficulties
                    (Markovitz & Crosby, 1984; US EPA, 1992).

             9.1.3  Skin exposure

                    No human data available.  Necrosis and edema
                    were reported after acute exposure to 1,3-
                    dichloropropene in rabbits, rats, and guinea pigs
                    (Jones & Collier, 1986b; Jeffery, 1987a,b,c; Mizell,
                    1988a,b).

             9.1.4  Eye contact

                    Severe eye irritation was caused in animals
                    exposed to 1,3-dichloropropene (US EPA, 1992).
                    Concentration of 1000 ppm caused lacrimation in humans
                    (ACGIH, 1989).

             9.1.5  Parenteral exposure

                    No data available.

             9.1.6  Other

                    No data available.


        9.2  Chronic poisoning

             9.2.1  Ingestion

                    No human data available.

             9.2.2  Inhalation

                    Chronic exposure (1 to 150 ppm for 4 weeks to 2
                    years) to Telone IIa(R) and Telone IIb(R) in mice,
                    rats, guinea pigs, rabbits, and dogs did not effect
                    survival rates (Lomax et al., 1989).
                    In humans, chronic inhalation during agricultural
                    application has been reported to cause hepatic enzyme
                    induction and subclinical abnormalities of renal
                    enzymes, creatinine and albumin excretion (Brouwer et
                    al., 1991).

             9.2.3  Skin exposure

                    Contact hypersensitivity after repeated
                    cutaneous exposure has been reported (Hayes & Laws,
                    1991). Exposure to 1,3-dichloropropene during
                    manufacture of DD-92(R) resulted in skin sensitization
                    in a 26-year-old male (Van Joost & de Jong, 1988; US
                    EPA, 1992).

             9.2.4  Eye contact

                    No human data available.

             9.2.5  Parenteral exposure

                    No human data available.

             9.2.6  Other

                    No data available.

        9.3  Course, prognosis, cause of death

             Acute
             Following acute ingestion, vomiting may occur. Initial signs
             of severe toxicity include pulmonary edema and cardiovascular
             collapse. Acute respiratory distress syndrome (ARDS),
             tachycardia, hypotension, gastrointestinal hemorrhaging,
             acute liver and kidney failure, hyperglycemia, haemolytic
             anaemia and disseminated intravascular coagulation may
             develop leading to death (Hernandez et al., 1994).
             Markovitz & Crosby (1984) suggested a causal relationship
             between 3 people accidentally exposed to 1,3-dichloropropene
             and death due haematological malignancies. Initial symptoms
             at the time of exposure included headache, neck pain, nausea,
             and breathing difficulty.
    
             Toxicity to 1,3-dichloropropene is dose and time dependent in
             animals. Animals exposed to 2700 ppm suffered severe lung
             injury, liver and kidney damage.

        9.4  Systematic description of clinical effects

             9.4.1  Cardiovascular

                    Acute
                    Tachycardia and hypotension developed after acute
                    ingestion of 1,3-dichloropropene in a 27-year-old male
                    (Hernandez et al., 1994).

             9.4.2  Respiratory

                    Acute
                    Exposure via inhalation may result in dyspnea (IARC,
                    1986). Acute respiratory distress syndrome (ARDS)
                    developed after acute ingestion of 1,3-dichloropropene
                    in a 27-year-old male (Hernandez et al., 1994).
                    Chest X-ray abnormalities typically lag behind
                    clinical signs; it may require up to 6 or 8 hours
                    before findings are demonstrated even in symptomatic
                    patients (Hernandez et al., 1994).
    

                    Chronic
                    No human data

             9.4.3  Neurological

                    9.4.3.1  Central nervous system (CNS)

                             Depression of the central nervous
                             system was reported after inhalation exposure
                             from an accidental release of 1,3-
                             dichloropropene.  Fatigue has been reported
                             (Markovitz & Crosby, 1984).

                    9.4.3.2  Peripheral nervous system

                             No data available.

                    9.4.3.3  Autonomic nervous system

                             Profuse sweating was reported in a
                             27-year-old male following acute ingestion of
                             1,3-dichloropropene (Hernandez et al.,
                             1994).

                    9.4.3.4  Skeletal and smooth muscle

                             Muscle pain and weakness were
                             symptoms reported after inhalation exposure
                             from an accidental release of 1,3-
                             dichloropropene (Markovitz & Crosby,
                             1984).

             9.4.4  Gastrointestinal

                    Acute
                    Nausea, vomiting, bloody diarrhea, and acute
                    pancreatitis occurred in a 27-year-old male following
                    acute ingestion. According to the authors it is not
                    sure whether pancreatic damage resulted from a direct
                    toxic effect or was a consequence of multisystem
                    involvement and disseminated intravascular coagulation
                    (Hernandez et al., 1994).
    
                    Chronic
                    Weight loss was reported in a 52-year-old man
                    chronically exposed to 1,3-dichloropropene (Markovitz
                    & Crosby, 1984).

             9.4.5  Hepatic

                    Acute
                    Severe hepatoxicity was reported in a 27-year-old male
                    following ingestion of 1,3-dichloropropene. Sinusoidal
                    congestion and small biliary thrombi were found at
                    autopsy (Hernandez et al., 1994).
    
                    Chronic
                    Moderate hepatic enzyme induction was suggested by
                    Brouwer et al. (1991) in field applicators following
                    inhalation exposure to 1,3-dichloropropene over the
                    course of 4 months of application.

             9.4.6  Urinary

                    9.4.6.1  Renal

                             Acute
                             Renal failure was reported in a 27-year-old
                             male following ingestion; acute tubular
                             necrosis was found at autopsy (Hernandez et
                             al., 1994).
    
                             Chronic
                             Subclinical nephrotoxicity was suggested by
                             Brouwer et al. (1991) in field applicators
                             following inhalation exposure to
                             1,3-dichloropropene over the course of 4
                             months of application.

                    9.4.6.2  Other

                             No human data available.

             9.4.7  Endocrine and reproductive systems

                    Acute
                    Hyperglycemia was reported in a 27-year-old male
                    following ingestion (Hernandez et al., 1994).
                    Impotence has been reported (Markovitz & Crosby,
                    1984).
    
                    Chronic
                    Male fertility was not affected by exposure to a
                    mixture of 1,3-dichloropropene, epichlorohydrin, and
                    allyl chloride in a manufacturing environment (Venable
                    et al., 1980). Reproductive effects were not observed
                    in animals exposed to 1,3-dichloropropene via oral or
                    inhalation routes (Hanley et al.,
                    1987; Breslin et al., 1989; Lomax et al.,
                    1989).

             9.4.8  Dermatological

                    Acute
                    No human data available.
    
                    Chronic
                    Skin sensitization was reported in a 26-year-old male
                    exposed to DD-92(R) during manufacturing of the
                    product (van Joost & de Jong, 1988). 
    
                    Erythema was reported in a 52-year-old male
                    chronically exposed to 1,3-dichloropropene during the
                    course of soil injection (Markovitz & Crosby,
                    1984).

             9.4.9  Eye, ear, nose, throat: local effects

                    Acute
                    Mucousal membrane irritation was reported in IARC
                    (1986). Redness, swelling, and irritation of the eyes,
                    ears, nose, and throat are typical symptoms associated
                    with acute exposures to 1,3-dichloropropene (Markovitz
                    & Crosby, 1984; US EPA, 1992).
    
                    Chronic
                    Hyperemia and superficial ulcerations of the nasal
                    mucosa,  inflammation of the pharynx, and bleeding
                    from swollen gums was reported in a 52-year-old male
                    chronically exposed to 1,3-dichloropropene during the
                    course of soil injection (Markovitz & Crosby,
                    1984).

             9.4.10 Haematological

                    Acute
                    Severe coagulopathy and thrombocytopenia were reported
                    in a 27-year-old male following ingestion of
                    1,3-dichloropropene (Hernandez et al., 1994).
                    Markovitz & Crosby (1984) suggested a causal
                    relationship between 1,3-dichloropropene exposure and
                    haematologic malignancy.

             9.4.11 Immunological

                    No human data.

             9.4.12 Metabolic

                    9.4.12.1 Acid-base disturbances

                             Severe metabolic acidosis was
                             reported in a 27-year-old male following
                             ingestion of 1,3-dichloropropene (Hernandez
                             et al., 1994).

                    9.4.12.2 Fluid and electrolyte disturbances

                             Intravascular fluid depletion
                             secondary to haemorrhage.

                    9.4.12.3 Others

                             No data available.

             9.4.13 Allergic reactions

                    Skin sensitization was reported in a 26-year-
                    old male exposed to DD-92 during manufacturing of the
                    product (van Joost & de Jong, 1988).

             9.4.14 Other clinical effects

                    No data available.

             9.4.15 Special risks

                    No human data available.

        9.5  Other

             No data available.

        9.6  Summary

    10. MANAGEMENT

        10.1 General principles

             Acute
             Patients with a history of acute ingestion of
             1,3-dichloropropene should be monitored up to 24 to 72 hours
             after exposure. No specific antidote exists. Management of
             toxicity is supportive for respiratory, cardiovascular,
             pulmonary, hepatic and renal function. Activated charcoal
             administration should be considered. Induction of emesis
             should be carefully considered. Gastric decontamination may
             be appropriate following early presentation after
             ingestion.
    

             Chronic
             No specific therapy for chronic 1,3-dichloropropene poisoning
             exists. Prevention of initial and further exposure in an
             occupational setting by the enforcement of safety standards
             and worker education is the most effective management
             principle.

        10.2 Life supportive procedures and symptomatic/specific
             treatment

             Make a proper assessment of the airway, breathing,
             circulation and neurological status of the patient. Monitor
             blood pressure, ECG, fluid and electrolyte balance. Emergency
             life supportive measures may include endotracheal intubation,
             oxygen administration, support ventilation, and cardio-
             respiratory resuscitation. Correct hypotension as
             required.
             If pulmonary edema is apparent, place the patient in a
             sitting position with backrest. Monitor arterial pO2 while
             using intermittent or continuous positive pressure oxygen.
             Care should be taken to avoid exaggerating lung injury by
             limiting oxygen treatment. Morphine is contraindicated. If a
             secondary infection develops, administer antibiotics.
             Corticosteriod treatment is often recommended, however, the
             effectiveness of this treatment is unproven.

        10.3 Decontamination

             Skin & eyes
             1,3-dichloropropene is used as a fumigant and is well
             absorbed by dermal and ocular routes.  Exposed eyes should be
             irrigated with copious amounts of water or saline for at
             least 15 minutes.  Exposed skin should be washed with a
             copious amount of soap and water for at least 15 minutes. 
             Exposed clothing should be removed immediately and washed
             separately.
    
             Ingestion
             Emesis may be indicated for recent exposures. Emesis is
             contraindicated when CNS depression is evident or if oral,
             pharyngeal, or esophageal irritation is apparent.
             Gastric intubation, aspiration, and lavage is indicated. If
             the patient is obtunded, convulsing or comatose, insert an
             oro- or a naso-gastric tube and lavage after endotracheal
             intubation. Administer activated charcoal: 1 to 2 grams of
             charcoal per kilogram of body weight (FDA, 1985). Administer
             a saline cathartic or sorbitol unless already given with
             activated charcoal.

        10.4 Enhanced elimination

             No effective methods which enhance elimination of
             absorbed 1,3-dichloropropene are currently available.

        10.5 Antidote treatment

             10.5.1 Adults

                    No antidote exists.

             10.5.2 Children

                    No antidote exists.

        10.6 Management discussion

             Not relevant.

    11. ILLUSTRATIVE CASES

        11.1 Case reports from literature

             Markovitz & Crosby (1984) reported 3 cases suggesting a
             causal relationship between 1,3-dichloropropene exposure and
             haematologic malignancy. In 1973, an accidental spill of
             1,3-dichloropropene during transport resulted in inhalation
             exposure in nine fireman who experienced headache, neck pain,
             nausea, and breathing difficulty during clean-up. Two firemen
             developed diffuse histiocytic lymphoma 6 years after the
             exposure to 1,3-dichloropropene. Both firemen died in 1980. 
             The third case reported was a 52-yr-old male treated for
             external ear redness, hyperemia and superficial ulcerations
             of the nasal mucosa, and pharyngeal inflammation resulting
             from exposure during soil injection.  During four months of
             inhalation exposure, fatigue, irritability and weight loss
             developed. The patient returned approximately one year later
             with severe fatigue and bleeding gums and was hospitalized
             with acute myelomonocytic leukemia and died with pneumonia 5
             weeks after hospital admission.
    
             Hernandez et al. (1994) reported a 27-yr-old male admitted to
             the hospital after accidental ingestion of
             1,3-dichloropropene. He developed of gastrointestinal
             distress, sweating, tachypnoea, tachycardia, hypovolaemic
             shock and lividity on both legs. The patient progressed to
             respiratory arrest, hypotension, metabolic acidosis,
             elevation of serum peritoneal fluid amylase, liver failure,
             kidney failure, and pancreatic dysfunction. Treatment was
             supportive for multisystem involvement, however, the patient
             died 38 hours after hospital admission.

             Van Joost & de Jong (1988) reported a case of dermatitis in a
             26-yr-old male exposed to 1,3-dichloropropene during
             manufacture.  Although the patient wore protective equipment,
             after 4 weeks of exposure the patient developed an itchy rash
             on his hands and feet. The patient was treated with topical
             corticosteriods and completely recovered.

    12. Additional information

        12.1 Specific preventive measures

             Research conducted in Europe in the 1990's has reported
             exposures ranging from 1.9 mg/m3 to 18.9 mg/m3 (Van Welie et
             al., 1991). Although limited environmental monitoring has
             been conducted to date, the recent exposure  monitoring
             measurements in the Nederlands exceeds the threshold limit
             value on 30% of the observed working days for agricultural
             applicators (Van Welie et al., 1991).
    
             Management of 1,3-dichloropropene poisoning begins with
             prevention of exposure through engineering controls, worker
             education, and personal protective equipment. Occupationally
             exposed population should be aware of the rapid and easy
             absorption, volatility, and toxicity of 1,3-dichloropropene.
             The initial clinical effects associated with exposure to
             1,3-dichloropropene should be explained thoroughly. Initial
             signs and symptoms include headaches, nausea, dizziness,
             fatigue, nasopharyngeal irritation, chest discomfort, and
             breathing difficulty.
    
             Engineering controls may include closed-loop injection
             systems, enclosed cabs on agricultural equipment, and
             installing flow monitoring equipment on nematicide injection
             lines. Proper respirators and protective clothing should be
             worn at all times during manufacture and handling of
             1,3-dichloropropene.
    
             Obvious gaps in environmental health and toxicity data need
             to be addressed. Mechanisms of toxicity, establishment of
             true dose-response relationships, and complete
             multicompartmental environmental risk assessments are only a
             few areas of future health research. Furthermore, groundwater
             contamination still remains a concern with
             1,3-dichloropropene use. With a recent increased focus on
             ecotoxicity of pesticides, research which studies the effects
             of 1,3-dichloropropene in aquatic environments could
             elucidate tremendous information.
    

             Little or no data exists regarding chronic, neurologic,
             carcinogenic, developmental, reproductive, or genotoxic
             health effects in humans after exposure to
             1,3-dichloropropene by any route. Little or no data exists
             concerning death in humans after inhalation or dermal
             exposure. Structurally similar compounds, i.e. vinyl
             chloride, are known carcinogens, however, the carcinogencity
             of 1,3-dichloropropene still remains a matter of debate. This
             warrants serious concern given existing inconclusive animal
             studies conducted by the NTP and Lomax et al. (1989). An area
             of current and active research involves the use of DNA
             adducts as biomarkers of exposure. This research may advance
             medical surveillance in the future and promote early
             detection and treatment (US EPA, 1992).
    
             1,3-dichloropropene will be re-registered by the EPA for
             agricultural use in the United States in 1997. The EPA
             10-year special review of 1,3-dichloropropene should be
             released in 1997. This report will contain a current review
             of environmental health effects associated with
             1,3-dichloropropene use and recommendations for handling and
             use. In addition, with the phase out of the fumigant methyl
             bromide, production and use is predicted to increase in the
             future (Braun & Supkoff, 1994).

        12.2 Other

             Not relevant.

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    14. AUTHOR(S), REVIEWER(S), DATE(S) (INCLUDING UPDATES), COMPLETE
        ADDRESS(ES)

        Author: Matthew Kowalczyk
        University of California, Los Angeles
        School of Public Health
        Environmental Health Sciences
        56-070 Center for Health Science 
        Los Angeles, CA. 90095-1772
        June 9, 1997
    
        Reviewer: MO Rambourg Schepens
        Centre Anti-Poisons de Champagne Ardenne
        Centre Hospitalier Universitaire
        F-51092 Reims Cedex France
        August 1997
    
        Peer review: INTOX-10 Meeting, Rio, Brazil September 2, 1997
        (M Kowalczyk, L Lubomirov, R McKeown, J Szajewski, W  Watson)
    
        Finalization: MO Rambourg Schepens, M Ruse
        October 1997
    



    See Also:
       Toxicological Abbreviations
       Dichloropropene, 1,3- (IARC Summary & Evaluation, Volume 71, 1999)