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 104°C (cis-)
112°C (trans-)
108°C (cis-/trans- mix)
Freezing point: -85°C (cis-)
Flash point 28.5°C (cis-)
28°C (trans-)
25°C (cis-/trans- mix)
Explosive limits: 4.3% to 10.3% (cis-/trans- mix)
Self-ignition: 555°C (cis-)
534°C (trans-)
Vapour pressure: (25°C)4850 Pa at 25°C (cis-)
3560 Pa at 25°C (trans-)
3700 Pa (cis-/trans- mix at 20°C)
Relative density: (20°C)
1.217 g/mL (cis-)
1.224 g/mL (trans-)
1.218-1.224 g/mL (cis-/trans- mix)
Solubility:
Water: (20°C, in g/L)
2.45 (cis-)
2.49 (trans-)
2.0 (cis-/trans- mix)
Partition coefficients:
Log octanol/water
1.82 (cis- at 20°C)
2.22 (trans- at 25°C)
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 (20°C)
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-92œ 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