IPCS INCHEM HomePropanil
PROPANIL
International Programme on Chemical Safety
Poisons Information Monograph 440
Chemical
1. NAME
1.1 Substance
Propanil
1.2 Group
Acetanilide
1.3 Synonyms
3,3,4-Dichloropropionanilide;
1.4 Identification numbers
1.4.1 CAS number
4709-98-8
1.4.2 Other numbers
1.5 Main brand names, main trade names
Chem Rice; DPA; Rogue; Stam F 34; Stam M-4; Surcopur;
3,4-DCPA; FW-734; 3,4-D(1,2,3,4,5,6); Synpran; DCPA.
To be completed by the centre.
1.6 Main manufacturers, main importers
To be completed by the centre.
2. SUMMARY
2.1 Main risks and target organs
Methaemoglobinaemia is the main risk.
There is no evidence of a specific effect of propanil on a
target organ.
2.2 Summary of clinical effects
Principal effects are gastrointestinal irritation,
cyanosis, stupor and respiratory depression.
2.3 Diagnosis
The diagnosis is made from the history of exposure and
the presence of features of gastrointestinal irritation and
the effects of methaemoglobinaemia such as cyanosis,
respiratory depression, stupor and convulsions.
Measuring the methaemoglobin concentration in blood is
useful.
Measurement of blood concentrations of propanil is not
clinically useful other than to confirm exposure.
Collect vomitus or gastric contents and the container along
with the remaining herbicide for further
identification.
2.4 First-aid measures and management principles
Decontamination followed by supportive care, and
management of respiratory distress and decreased level of
consciousness if they occur. Admit to hospital. The
pesticide container should accompany the patient to
hospital.
Ingestion: Monitor respiration carefully and ensure adequate
airway. Use a cuffed endotracheal tube if respiration is
impaired. Carry out appropriate decontamination of the
gastrointestinal tract immediately.
Skin contact: Remove contaminated clothing and wash the
contaminated areas with soap and water.
Eye contact: Wash the eyes with at least 2 litres of saline
or clean water for 10 to 15 min.
3. PHYSICO-CHEMICAL PROPERTIES
3.1 Origin of the substance
Propanil is a synthetic chemical for herbicidal use. It
can be obtained by any of the methods used for the synthesis
of anilides of carboxylic acids.
3.2 Chemical structure
Chemical name: N-(3,4-dichlorophenyl) propionamide
Molecular weight: 218.09
Structural formula: C9H9Cl2NO (Hayes, 1982).
3.3 Physical properties
3.3.1 Colour
3.3.2 State/Form
3.3.3 Description
Appearance: White crystalline solid
(formulated preparations are usually liquids)
Melting point: 91 to 93ーC
Vapour pressure: 9 ラ 10-5 mm Hg at 60ーC
Solubility: water 0.02 g/100 ml ethanol 0.02 g/100ml
(25ーC)
Readily soluble in alcohol and chlorobenzene (Ismerov,
1984).
Relative molecular mass: 218.09
Stability: Stable in emulsion concentrates but is
hydrolysed in acid and alkaline media to
3,4-dichloroaniline and propionic acid (Hayes and
Laws, 1991).
3.4 Hazardous characteristics
Propanil is usually formulated with flammable solvents.
Environmental risks: Secondary uptake may follow its
evaporation from the soil surface. Once it is in soil the
chemical is quickly degraded.
4. USES
4.1 Uses
4.1.1 Uses
4.1.2 Description
Propanil is a highly effective herbicide with a
selective mode of action. It is used to control
numerous monocotyledonous (narrow leaf) and
dicotyledonous (broad leaf) weeds that occur in rice
fields and potato fields.
It is manufactured as a 30% emulsifiable concentrate
and a 50% solution for ultra low volume spraying. The
solvents used are generally highly inflammable liquids
such as cyclohexanone, petroleum solvent and OP-7
(Izmerov, 1984).
4.2 High risk circumstance of poisoning
Occupational exposure to the herbicide or ingestion of
the herbicide either intentionally or accidentally can cause
poisoning.
4.3 Occupationally exposed populations
Agricultural workers (especially those working with rice
and potato crops) as well as workers who are involved in
manufacturing, formulating and packaging the herbicide mixers
and applicators, are at risk.
5. ROUTES OF ENTRY
5.1 Oral
Intentional ingestion in suicide attempts or accidental
ingestion.
5.2 Inhalation
Occupational exposure to the propanil spray mist, or
vapours from treated soils for several hours after
application.
5.3 Dermal
Accidental or occupational exposure to propanil can occur.
5.4 Eye
Occupational exposure to propanil spray can occur.
5.5 Parenteral
No data available.
5.6 Other
No data available.
6. KINETICS
6.1 Absorption by route of exposure
No human data available.
In the rat, peak blood levels occurred after 1 h in an acute
feeding study. Human data not available.
Single dermal application in rats produces no effects at a
dose of 2000 mg/kg. Applications of 100 to 500 mg/kg for 14
doses produces mild effects. In the rat, the acute exposure
threshold by inhalation is 15 mg/kg.
6.2 Distribution by route of exposure
No human data available.
Five minutes after oral administration of single doses (1000
mg/kg, 650 mg/kg) to rats, propanil is detectable in blood
and all tissues. Maximum accumulation in lungs, liver,
kidneys, spleen, adrenals and heart occurs within 1 to 6
hours of administration.
Repeated inhalation (rat): after exposure to concentrations
of 5.6 to 0.2 mg/m3, propanil occurs in the blood, heart and
spleen (Izmerov, 1984).
6.3 Biological half-life by route of exposure
No human data available.
In rats given up to 1000 mg/kg orally, blood concentrations
are maintained for 24 h but undetectable after 48 to 72
h.
6.4 Metabolism
No human data available.
The main metabolite of propanil is the oxyderivative, 3,4
dichloroanilide of lactic or succinic acids.
This metabolite is formed shortly after administration and is
detectable for up to 48 h. Aniline derivatives are also
formed due to disruption of the CO-NH bond of propanil.
M-chloroaniline and aniline are subsequently formed,
consistent with the peak blood methaemoglobin level occurring
within 1 to 3 days of exposure (Izmerov, 1984).
6.5 Elimination and excretion
No human data available.
Irrespective of its route of entry the elimination of
propanil from the body after single dose exposure takes place
within 48 to 72 h (Izmerov, 1984).
In the cow, 1.4% of the total dose was recovered in the
faeces after administration for 4 days but no unchanged
propanil was detected in the urine or milk (Hayes, 1982).
Following repeated dosing in the rat, the parent compound and
its two metabolites are found in the urine.
7. TOXICOLOGY
7.1 Mode of Action
Acutely, propanil induces methaemoglobinaemia which
results in tissue hypoxia. Haemolytic anaemia has been
reported in some studies.
Propanil induces monoxygenase enzymes (Izmerov, 1984).
7.2 Toxicity
7.2.1 Human data
7.2.1.1 Adults
No data available.
7.2.1.2 Children
No data available.
7.2.2 Relevant animal data
Propanil has low toxicity in mammals.
Acute oral LD50 values for propanil in rats and dogs
are 1384 and 1271 mg/kg, respectively (Hayes, 1982).
In both species, death occurred over a 3 day period
and were characterized by central nervous system
depression.
7.2.3 Relevant in vitro data
No data available
7.2.4 Workplace standards
No data available
7.2.5 Acceptable daily intake (ADI)
No data available
7.3 Carcinogenicity
No data available
7.4 Teratogenicity
Propanil is not reported to have embryotoxic and
gonadotoxic activity. No evidence of propanil embryotoxicity
or teratogenicity has been reported in the albino rat
(Izmerov, 1984).
7.5 Mutagenicity
No human data available.
In the mouse, oral propanil 100 mg/kg increased the frequency
of chromosomal aberrations in bone marrow cells. There was no
effect at 100 mg/kg (Izmerov, 1984). At 10 mg/kg, no effect
was seen.
7.6 Interactions
No human 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
Sample collection
Obtain blood and urine samples for biomedical analysis.
Analysis of blood for methaemoglobin must be done within 1 h
or the assay may be inaccurate.
Biomedical analysis
Urine analysis may show methaemoglobinuria, but this is not
sensitive.
Measure methaemoglobin concentration in blood.
Arterial blood gases and full blood count should be performed
if cyanosis is present.
Toxicological analysis
Plasma and urine levels of propanil are not useful
clinically.
Other investigations
No data available.
8.6 References
9. CLINICAL EFFECTS
9.1 Acute poisoning
9.1.1 Ingestion
The gastrointestinal effects of propanil are
unknown. However, the formulated product is likely to
contain hydrocarbon solvents for field application.
Cyanosis due to methaemoglobinaemia (which occurs at
about 30% methaemoglobin) is a common feature.
When the blood concentration of methaemoglobin reaches
60%, stupor and respiratory depression may
occur.
9.1.2 Inhalation
No human data available.
Methaemoglobinaemia has been reported in the rat
(Izmerov, 1984).
9.1.3 Skin exposure
Irritation of skin may occur.
Repeated application has caused methaemoglobinaemia in
the rat (Izmerov, 1984).
9.1.4 Eye contact
Irritation of the mucosa of eyes (Izmerov, 1984).
9.1.5 Parenteral exposure
No data available.
9.1.6 Other
No data available.
9.2 Chronic poisoning
9.2.1 Ingestion
There have been no adverse findings in urinary
and liver function tests, although a reduction in body
weight has been noted in the dog (Ambrose et al,
1972).
9.2.2 Inhalation
No human data available.
Methaemoglobinaemia has been reported the rat
(Izmerov, 1984).
9.2.3 Skin exposure
Chloracne has been reported among workers in a
production facility. This was probably due to
contaminants in raw materials because chloracne has
not been reported in other settings.
9.2.4 Eye contact
No data available.
9.2.5 Parenteral exposure
No data available.
9.2.6 Other
No data available.
9.3 Course, prognosis, cause of death
No information available on the clinical course of
poisoning. Death can occur from respiratory paralysis.
9.4 Systematic description of clinical effects
9.4.1 Cardiovascular
Tachyvardia due to methaemoglobinaemia occurs
initially; when levels rise over 50% bradycardia may
occur.
9.4.2 Respiratory
Cyanosis is observed due to
methaemoglobinaemia. There may be tachypnoea,
dyspnoea and respiratory depression at methaemoglobin
levels greater than 30%.
9.4.3 Neurological
9.4.3.1 Central Nervous System (CNS)
Dizziness may occur.
When the blood concentration of
methaemoglobin reaches about 30%, general
symptoms such as fatigue, light-headedness
and headache occur in healthy people. At
concentrations of 50% to 70%, stupor,
respiratory depression and convulsions may
occur (Ellenhorn & Barceloux, 1988).
Impaired coordination of movements, urinary
incontinence and slight tremor have been
reported in the rat, mouse and cat (Izmerov,
1984).
9.4.3.2 Peripheral nervous system
No data available.
9.4.3.3 Autonomic nervous system
No data available.
9.4.3.4 Skeletal and smooth muscle
No data available.
9.4.4 Gastrointestinal
Propanil products may cause gastrointestinal
irritation, due to solvents in the
formulation.
9.4.5 Hepatic
Mild liver changes and biliary nephrosis have
been found in the rat (Gosselin et al. 1984).
9.4.6 Urinary
9.4.6.1 Renal
No data available.
9.4.6.2 Others
No data available.
9.4.7 Endocrine and reproductive systems
No human data available.
No effects on fertility, gestation, viability or
lactation have been found in the rat (Izmerov,
1984).
9.4.8 Dermatological
Propanil may irritate the skin, causing rashes
(Izmerov, 1984; Morse & Baker, 1979).
3,4,3,,4-tetrachloroazobenzene, a contaminant in
propanil, was believed to be the cause of chloracne in
exposed production workers (Morse & Baker,
1979).
9.4.9 Eye, ears, nose, throat: local effects
Irritation of the mucosa of the eyes may occur
(Izmerov, 1984).
An unpleasant sensation in the throat occurs after
prolonged exposure (Izmerov, 1984).
9.4.10 Haematological
Methaemoglobinaemia is the most important
feature of propanil poisoning.
Clinical features are related to the level of
methaemoglobinaemia:
15 to 20% clinical cyanosis but patient usually
asymptomatic
20 to 45% headache, lethargy, dizziness, syncope,
dyspnoea
45 to 55% increasing CNS depression
55 to 70% coma, convulsions, shock
> 70% high mortality
In the rat, administration of propanil 330 ppm in the
diet for 13 weeks, marked polychromatophilia indicated
haemolytic anaemia (Ambrose et al. 1972).
9.4.11 Immunological
No data available.
9.4.12 Metabolic
9.4.12.1 Acid-base disturbances
Characteristic changes of hypoxia may occur.
9.4.12.2 Fluid and electrolyte disturbances
9.4.12.3 Others
9.4.13 Allergic reactions
Propanil does not cause allergic reactions
(Izmerov, 1984).
9.4.14 Other clinical effects
No data available.
9.4.15 Special risks
Pregnancy: no data available.
Breast feeding: in the cow, propanil is excreted in
milk (Hayes, 1982).
Enzyme deficiencies: no data available.
9.5 Others
No data available.
9.6 Summary
10. MANAGEMENT
10.1 General principles
The minimum dose of propanil required to cause
methaemoglobinaemia in man is unknown. Methaemoglobinaemia
occurs after the metabolism of propanil; it may therefore be
delayed by the need for uptake and subsequent metabolism of
propanil. Therefore, exposed patients should be treated
symptomatically with close observation for
methaemoglobinaemia for 24 to 48 h in a hospital with
facilities for cardiac monitoring.
10.2 Life supportive procedures and symptomatic treatment
Methaemoglobinaemia:
Refer to the Treatment Guide for the management of
methaemoglobinaemia.
10.3 Decontamination
Skin contact: wash the contaminated skin with soap and
water.
Eye contact: flush the eyes with at least 2 litres of saline
or water for 15 min.
Ingestion of propanil in solvent vehicle: gastric aspiration
or lavage may be considered following ingestion of a
concentrated solution of propanil. A cuffed endotracheal tube
is essential to prevent aspiration of the solvent into the
lungs. Administer activated charcoal as a slurry in 0.9%
saline, and an appropriate cathartic.
10.4 Enhanced elimination
No data available.
10.5 Antidote treatment
10.5.1 Adults
No specific antidote is available.
Methaemoglobinaemia should be treated with methylene
blue. Refer to the treatment protocol.
10.5.2 Children
No specific antidote is available.
Methaemoglobinaemia should be treated with methylene
blue. Refer to the treatment protocol.
10.6 Management discussion
No data available.
11. ILLUSTRATIVE CASES
11.1 Case reports from literature
No information available.
12. ADDITIONAL INFORMATION
12.1 Specific preventive measures
Carefully study and strictly observe the directions for
safe use of the herbicide.
The following preventive measures should be observed in
general. Keep the herbicide out of the reach of children and
away from food and feed stuffs. Persons handling propanil at
work must be provided with adequate equipment to minimize
exposure and personal protection equipment as needed.
Use appropriate respiratory equipment consistent with the
exposure level to protect the respiratory tract.
Take appropriate measures to minimize skin contact.
To protect eyes use goggles.
To protect hands use gloves.
12.2 Other
No data available.
13. REFERENCES
Ambrose AM, Larson PS, Borzellica JF, Hennigar GR (1972).
Toxicology and Applied Pharmacology, 23: 650-659.
Ellenhorn MJ, Barceloux DS (1988) Eds. Medical Toxicology, New
York, Elsevier Science Publishing Company, Inc., pp. 844.
Gosselin RE, Smith RP, Hodge HC (1984) Eds. Clinical Toxicology
of Commercial Products, Baltimore, Williams & Wilkins.
Hayes WJ (1982) Ed. Pesticide Studies in Man, Baltimore, Williams
& Wilkins, pp. 538.
Hayes WJ, Laws ER (1991) Handbook of pesticide toxicology.
California, Academic Press Inc. 1345-1346.
Izmerov NF (1984) Ed. Propanide - Scientific Reviews of Soviet
literature on Toxicity and Hazards of Chemicals, Moscow, Centre of
International Projects.
Morse DL, Baker EL, Kimbrough RD, Wisseman CL (1979).
Propanil-Chloracne and Methomyl Toxicity in Workers of a Pesticide
Manufacturing Plant. Clinical Toxicology 15(1): 13-21.
Nishiuchi Y, Hashimoto Y (1967). Toxicity of pesticide
ingredients to some water organisms. Botyu-Kagaku, 32: 5-11.
Pesticides - A safety guide (1982). London, Shell Repographic,
pp. 85.
14. AUTHOR(S), REVIEWER(S), DATE(S) (INCLUDING UPDATES), COMPLETE
ADDRESS(ES)
Authors: Dr Ravindra Fernando and Miss Deepthi Widyaratna
National Poisons Information Centre
General Hospital
Colombo
Sri Lanka
Date: March 1990.
Peer Review: Strasbourg, France,
Date: April 1990