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Captan

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 Main manufacturers, main 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/CIRCUMSTANCES OF POISONING
   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 Others
      9.4.7 Endocrine and reproductive systems
      9.4.8 Dermatological
      9.4.9 Eye, ears, 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 Others
   9.6 Summary
10. MANAGEMENT
   10.1 General principles
   10.2 Life supportive procedures and symptomatic 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 ADDRESSES
    CAPTAN

    International Programme on Chemical Safety
    Poisons Information Monograph 098
    Chemical

    1.  NAME

        1.1  Substance

             Captan

        1.2  Group

             Chloroalkyl thio fungicide

        1.3  Synonyms

             Captab (Republic of South Africa);
             Captane (France);
             N-((trichloromethyl(thio)-4-cyclohexene-1,2-dicarboximide;
             N-((trichloromethyl)thio)tetrahydrophthalimide;
             N-(trichloromethylmercapto)-delta4-tetrahydrophthalimide;
             N-(trichloromethylthio)cyclohex-4-ene-1,2-dicarboximide
             (IUPAC);
             N-trichloromethylmercapto-4-cyclohexene-1,2-dicarboximide;
             N-trichloromethylthio-cis-delta4-cyclohexene-
             1,2-dicarboximide;
             N-trichloromethylthiocyclohex-4-ene-1,2-dicarboximide;

        1.4  Identification numbers

             1.4.1  CAS number

                    133-06-2

             1.4.2  Other numbers

                    EC:     613-044-00-6
                    ICSC:   0120
                    RTECS:  GW5075000
                    SR:     406
                    UN:     2773

        1.5  Main brand names, main trade names

             Orthocide
             Orthocide 406
             Vancide 89
    
             A number of formulations are commercially available which
             include captan together with other pesticides.

        1.6  Main manufacturers, main importers

             To be completed by each centre.

    2.  SUMMARY

        2.1  Main risks and target organs

             The acute oral toxicity is low.  Other than dermatitis
             and conjunctivitis, no signs of toxicity directly due to
             captan have been reported.
    
             Studies in mice but not in rats have demonstrated a
             carcinogenic potential.

        2.2  Summary of clinical effects

             Captan has caused allergic dermatitis and eye irritation
             in man. No other serious adverse effects have been
             identified.  Evidence from animal experiments indicates that
             ingestion of large quantities may produce gastrointestinal
             effects such as vomiting and diarrhoea. Solvent vehicles and
             other components of the formulated pesticide may complicate
             the clinical picture and should be considered.

        2.3  Diagnosis

             It is based on history of exposure and occurrence of
             dermatitis and/or conjunctivitis.  Although a sensitive
             analytical assay is available for captan, its clinical value
             in the management of poisoning seems remote in view of its
             low toxicity.

        2.4  First-aid measures and management principles

             In the event of exposure to captan, contaminated
             clothing and (in case of eye contact) contact lenses should
             be removed to prevent further absorption. In the case of skin
             contact, the affected area should be washed carefully with
             soap and water. Wash eyes for 10-15 minutes with clean
             running water. First aid personnel should wear rubber or
             plastic gloves and avoid contamination.
    
             Ingestion of small amounts of captan does not constitute a
             significant risk, and may be managed by dilution with water.
             The management of large quantities of ingested captan should
             be primarily directed towards decontamination and supportive
             care, as there is no specific antidote. The use of Ipecac
             Syrup and activated charcoal are indicated in the event of
             ingestion.

    3.  PHYSICO-CHEMICAL PROPERTIES

        3.1  Origin of the substance

             Captan, a synthetic chloroalkyl thio fungicide, was
             introduced in 1949 by the Standard Oil Development Company,
             and later by the Chevron Chemical Company. World production
             in 1983 was estimated to be 13,000 tonnes.
    
             Captan is formed by reacting tetrahydrophthalimide
             (synthesized from maleic anhydride butadiene and ammonia)
             with perchloromethylmercaptan (Sittig, 1980).

        3.2  Chemical structure

             The empirical formula for captan is C9H8CI3NO2S with a
             molecular weight of 300.57.

        3.3  Physical properties

             3.3.1  Colour

                    White

             3.3.2  State/Form

                    Solid

             3.3.3  Description

                    Pure captan is an odourless, white crystalline
                    solid. The technical product is an amorphous powder
                    that is colourless to beige with a pungent odour.
    
                    Melting Point: 178C (pure compound) 158-170C
                    (technical grade, 90-95% pure)
                    Slowly decomposes
                    Vapour Pressure: < 0.133 mPa at 25C
    
                    Solubility at 25C  Practically insoluble in water
                    (3.3 mg/L)
                    Soluble in acetone (21 g/L)
                    Soluble in chloroform (70 g/L)
                    Soluble in cyclohexanone (23 g/L)
                    Soluble in isopropanol (1.7 g/L)
                    Soluble in xylene (20 g/L)

        3.4  Hazardous characteristics

             In the dry state, captan is stable at room temperature.
             However, in aqueous solution, it is hydrolysed at a rate that
             is dependent on the pH. In alkaline solution, the breakdown
             is rapid.
    

             Captan is not flammable but on heating may produce toxic
             fumes such as sulphur dioxide, hydrochloric acid, and
             phosgene. These may be harmful by inhalation and skin
             contact. Extinguish small fires with carbon dioxide, dry
             powder or alcohol-resistant foam. Water spray can be used for
             larger fires and for the cooling of unaffected stock, but
             avoid the accumulation of polluted run-off from the site.
             Fire fighters should wear full protective clothing including
             self-contained breathing apparatus.
    
             Although the pure substance is practically insoluble in
             water, the formulated product may pose an environmental risk
             if released into an aquatic environment. Captan is highly
             toxic to fish: a LC50 (96h) range of 0.03 - 0.07 mg/L has
             been reported for various species. Captan is moderately toxic
             to freshwater invertebrates, such as daphnia (48h LC50
             between 1 and 8 mg/L). Captan is not persistent, and its use
             is not considered to be a threat to terrestrial wildlife. It
             is not toxic to bees.
    
             The environmental impact of the pesticide is likely to be
             limited by its high rate of hydrolysis and the lack of any
             tendency to bioaccumulate. The half-life in lake water is 7h
             at 12C and 1 h at 23C. However, because of its demonstrated
             high toxicity, exposure of aquatic organisms to captan
             through drift and/or run-off is a cause for concern (WHO,
             1990).
    
             Alkaline treatment of captan leads to the formation of
             non-toxic degradation products and is considered to be an
             environmentally acceptable disposal method (Dillon, 1981).
             Small spillages and residues could be treated with alkali
             before burial in an approved landfill area. During
             neutralization, hydrogen sulphide may be formed if
             insufficient alkali is used. Personnel involved in captan
             disposal should be provided with protective equipment which
             should minimize skin, ocular and respiratory exposure.

    4.  USES/CIRCUMSTANCES OF POISONING

        4.1  Uses

             4.1.1  Uses

             4.1.2  Description

                    Captan is fungicide used to control diseases of
                    many fruit and ornamental and vegetable crops. It is
                    also used as a spray, root dip or seed treatment, to
                    protect young plants against rot and damping off
                    (Worthing, 1987).  Captan is also used as a fungicide
                    in wallpaper pastes and in hormone rooting
                    powders.

        4.2  High risk circumstance of poisoning

             Accidents among adult farm workers and secondary
             exposure of their children.
    
             Exposure of the general population may occur through the
             consumption of foodstuffs treated incorrectly with captan or
             harvested prematurely before residues have declined to
             acceptable levels or from contact with treated areas.
    
             Accidental ingestion of wallpaper pastes and hormone rooting
             powders by children.

        4.3  Occupationally exposed populations

             Factory workers involved in synthesizing captan. 
             Workers involved in formulating and dispensing pesticides. 
             Agricultural spray workers.  Crop harvesters during disease
             vector control periods.

    5.  ROUTES OF EXPOSURE

        5.1  Oral

             Although no literature accounts were available at the
             time of preparation of this monograph, the ingestion of
             captan either accidentally or intentionally is
             possible.

        5.2  Inhalation

             Inhalation of captan as spray mists or powders is
             possible, particularly in an occupational context. A TLV has
             been established by ACGIH (see Section 7.2.4).

        5.3  Dermal

             The extent of dermal absorption in humans is not known,
             however it is considered to be very limited (WHO,
             1990).

        5.4  Eye

             No data available.

        5.5  Parenteral

             No data available.

        5.6  Other

             No data available.

    6.  KINETICS

        6.1  Absorption by route of exposure

             Following oral administration of [35S]captan to rats at
             a dose of 143 or 390 mg/kg, at least 60% was excreted in the
             urine (Seidler et al, 1971).

        6.2  Distribution by route of exposure

             Both captan and its metabolites are rapidly eliminated
             (> 90% within 24h) (WHO, 1990).
    
             When captan tagged with 14C in the trichloromethyl group was
             administered to rats orally, activity was recovered as
             follows:
    
             51.8% urine
             22.8% expired air
             15.9% faeces
             0.6% tissues (De-Baun et al., 1974)

        6.3  Biological half-life by route of exposure

             No data available.

        6.4  Metabolism

             Urinary metabolites from the rats fed 14C-captan
             included thiozolidine-2-thione-4-carboxylic acid, a salt of
             dithiobis (methane sulphonic acid), and the disulphide
             monoxide derivative of dithiobis (methane sulphonic acid).
             The latter two derivatives were not detected in the urine of
             rats that received captan intra-peritoneally. This, and other
             evidence, indicates that degradation in the gastrointestinal
             tract plays a major role in the metabolism of captan (De-Baun
             et al 1974).
    
             A greater proportion of a high dose of captan reaches the
             small intestine of the mouse compared with the rat (WHO,
             1990).

        6.5  Elimination and excretion

             Following an oral dose of [35S]captan to rats at a rate
             of 143 or 390 mg/kg, at least 60% was excreted in the urine
             (Seidler et al, 1971). Within the first 24 hours, more than
             90% was excreted in the urine and faeces, and almost all the
             rest was excreted during the next two days. Only 0.01-0.05%
             of the radioactivity was deposited in the organs in the form
             of metabolites or of moieties incorporated into normal body
             constituents.
    
             After oral administration of 14C-captan to rats, 52% of the
             dose appeared in the urine; 23% in expired air; and 16% in
             the faeces (De-Baun et al, 1974).

    7.  TOXICOLOGY

        7.1  Mode of Action

             No data available.

        7.2  Toxicity

             7.2.1  Human data

                    7.2.1.1  Adults

                             The acute oral toxicity of captan
                             (technical grade) for humans is considered to
                             be low (WHO, 1990).

                    7.2.1.2  Children

                             No data available.

             7.2.2  Relevant animal data

                    Most investigators have found that captan has a
                    low oral toxicity in laboratory animals. LD50 (oral)
                    in the rat of 12,600 mg/kg and > 17,000 mg/kg have
                    been found.  The reported effect of very severe
                    protein deficiency increases the susceptibility of
                    rats far more to captan than to any other pesticide
                    investigated. The mechanism of this action is unknown
                    (Hayes & Laws, 1991).
    
                    In the most thorough study of repeated doses of captan
                    given by stomach tube to rats, the 100-day LD50 was
                    916 mg/kg/day (Hayes & Laws, 1991).
    
                    Mouse LD50 7000 mg/kg (oral)
                    Mouse LD50 462 mg/kg (ip)
                    Mouse LC50 5000 mg/m3/2h (inhalation)(RTECS, 1987)
    
                    Sheep and, to a lesser degree, cattle, are especially
                    susceptible to captan.  A single oral dose of 250
                    mg/kg may be fatal in sheep (Hayes and Laws,
                    1991).

             7.2.3  Relevant in vitro data

                    Captan, which is an alkylating agent, has
                    demonstrated genotoxic properties in in-vitro systems
                    (WHO, 1990).

             7.2.4  Workplace standards

                    The threshold limit value (TWA) recommended by
                    the US ACGIH for captan is 5 mg/m3 in the air (WHO,
                    1990).

             7.2.5  Acceptable daily intake (ADI)

                    The Joint FAO/WHO Meeting on Pesticide Residues
                    has established an ADI of 0 - 0.1 mg/kg bodyweight.
                    Using the same data base, the EEC calculated the same
                    ADI value at 0.013 mg/kg/day. On the basis of
                    reproduction studies, a reference dose of 0.013
                    mg/kg/day for non-neoplastic effects has been
                    established by the US Environmental Protection Agency
                    (WHO, 1990).

        7.3  Carcinogenicity

             Long-term administration of high dietary levels of
             captan to mice resulted in the induction of benign and
             malignant tumours of the small intestine. The situation
             regarding carcinogenicity in the rat is less clear: in one
             study, a slight increase in the incidence of kidney tumours
             was found.  However, the carcinogenic potential of captan in
             rodents relative to other experimental carcinogens is
             low.

        7.4  Teratogenicity

             The results of animal studies on the teratogenicity of
             captan are contradictory.  To date, there is no evidence of
             teratogenicity in mice or primates (see Section 9.4.15). In
             one experiment in hamsters, there was no teratogenic
             response; in another (the only difference in experimental
             regimen being the day of treatment), captan induced central
             nervous system and rib defects in 23% of foetuses. Similar
             results were observed in the rabbit: one experiment found no
             congenital abnormalities, while another with an identical
             regimen demonstrated limb and head defects and cleft palate
             with a frequency of nearly 50%.  In the dog, no defects were
             produced in one study, but tail, closure defects, and
             hydrocephalus were induced in another.
    
             It is difficult to assess the risk from this evidence and
             definitive experiments are required adequately to determine
             the full spectrum of developmental toxicity with this
             compound (Schardein, 1985).

        7.5  Mutagenicity

             Captan appears to be mutagenic in susceptible cell
             cultures, but expert opinion holds that it is not mutagenic
             in intact higher animals except perhaps at the doses
             encountered in suicide attempts (Hayes & Laws, 1991).
    
             Captan is an alkylating agent and is genotoxic in vitro but
             not in vivo.  Although captan may be able to induce genotoxic
             events in somatic cells, present evidence indicates that the
             potential for causing inheritable effects is extremely low
             (WHO, 1990).

        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

             Sample collection
    
             Not relevant.
    
             Biomedical analysis
    
             Not relevant.
    
             Toxicological analysis
    
             No specific laboratory tests are necessary unless clinically
             indicated. Although a sensitive assay is available for
             captan, its clinical value in the management of exposure
             seems limited in view of the low toxicity of captan.
    

             Other investigations
    
             No data available.

        8.6  References

    9.  CLINICAL EFFECTS

        9.1  Acute poisoning

             9.1.1  Ingestion

                    The acute oral toxicity of captan is low and
                    acute overdosage is not expected to result in severe
                    toxicity. Evidence from animal experiments using
                    structurally related compounds indicates that
                    gastrointestinal effects (vomiting and diarrhoea) may
                    occur (Hayes & Laws,1991)

             9.1.2  Inhalation

                    No data available.

             9.1.3  Skin exposure

                    Allergic dermatitis has been reported (Hayes
                    and Laws, 1991).

             9.1.4  Eye contact

                    Conjuctivitis has been reported (Hayes and
                    Laws, 1991)

             9.1.5  Parenteral exposure

                    The toxicity of captan in the mouse is greater
                    after peritoneal injection than after oral
                    administration. Toxicity may therefore be greater in
                    the unlikely event of intravenous
                    administration.

             9.1.6  Other

                    No data available.

        9.2  Chronic poisoning

             9.2.1  Ingestion

                    No human data are available.
    
                    In dogs fed captan 300 mg/kg/day for 48 weeks
                    following 18 weeks at lower doses, there was a slight
                    increase in liver and kidney weight (Hayes and Laws,
                    1991).
    
                    In a 100-day LD50 study in the rat, signs of toxicity
                    included weight loss, decreased food intake, increased
                    water intake, diarrhoea, hypothermia and prostration.
                    These were most marked during the first three weeks of
                    administration (Boyd and Carsky, 1971).
    
                    No data available in humans.

             9.2.2  Inhalation

                    No data available.

             9.2.3  Skin exposure

                    Allergic dermatitis has been reported (Hayes &
                    Laws, 1991).

             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 human fatalities have been reported. The toxicity is
             low.

        9.4  Systematic description of clinical effects

             9.4.1  Cardiovascular

                    No data available.

             9.4.2  Respiratory

                    No data available.

             9.4.3  Neurological

                    9.4.3.1  Central nervous system (CNS)

                             No data available.

                    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

                    The acute oral toxicity of captan is low and
                    acute overdosage is not expected to result in severe
                    toxicity. Evidence from animal experiments using
                    structurally related compounds indicates that
                    gastrointestinal effects (vomiting and diarrhoea) may
                    occur (Hayes & Laws,1991).

             9.4.5  Hepatic

                    Chronic feeding studies using high oral doses
                    of captan in dogs showed a slight increase in liver
                    weight (see section 9.2.1).

                    Animal studies showed that large doses of captan (1000
                    mg/kg/day for 7 days) induced alterations of serum
                    concentrations of liver enzymes (Hayes & Laws,
                    1991).

             9.4.6  Urinary

                    9.4.6.1  Renal

                             Chronic feeding studies using high
                             oral doses of captan in dogs showed a slight
                             increase in kidney weight (see section
                             9.2.1).

                    9.4.6.2  Others

                             No data available.

             9.4.7  Endocrine and reproductive systems

                    A study on pseudo-pregnant and pregnant rats
                    showed a reduction in uterine weight, particularly
                    affecting the endometrium, occurring in a
                    dose-dependent fashion up to 10,000 ppm (Hayes and
                    Laws, 1991).

             9.4.8  Dermatological

                    Allergic dermatitis has been reported in humans
                    (Hayes and Laws, 1991).
    
                    Sensitivity to captan was demonstrated among
                    volunteers following application to the skin of the
                    back (Jordan and King, 1977).

             9.4.9  Eye, ears, nose, throat: local effects

                    Conjunctivitis has been reported in humans
                    (WHO, 1990).

             9.4.10 Haematological

                    No data available.

             9.4.11 Immunological

                    Allergic dermatitis has been reported in
                    humans (Hayes and Laws, 1991).
    
                    Immunological function was not significantly altered
                    in weanling rats fed 2,000 mg/kgdid (Hayes and Laws,
                    1991).

             9.4.12 Metabolic

                    9.4.12.1 Acid-base disturbances

                             No data available.

                    9.4.12.2 Fluid and electrolyte disturbances

                             No data available.

                    9.4.12.3 Others

                             No data available.

             9.4.13 Allergic reactions

                    Allergic dermatitis has been reported in
                    humans (Hayes and Laws, 1991).

             9.4.14 Other clinical effects

                    No data available.

             9.4.15 Special risks

                    Captan was administered to pregnant rhesus
                    monkeys at dosages of 10, 25 and 75 mg/kg/day and to
                    stump-tailed macaques at dosages of 10 and 75
                    mg/kg/day during days 21-24 or 34 of gestation. The
                    highest dose was given from day 21 through 34.
                    Thalidomide at a dosage of 5 or 10 mg/kg/day was
                    administered as a positive control. Captan produced no
                    abortions, no anomalies in the young,and no injury for
                    the mothers. Typical deformities and numerous
                    abortions were produced by thalidomide in both kinds
                    of non-human primate (Vondruska et al, 1971) (see
                    section 7.4).

        9.5  Others

             No data available.

        9.6  Summary

    10. MANAGEMENT

        10.1 General principles

             Ingestions of small amounts of captan (less than 10
             mg/kg body weight) do not constitute a significant risk, and
             may be managed by dilution with water.
    
             The management of large quantities of ingested captan (more
             than 10 mg/kg bodyweight) should be primarily directed
             towards decontamination and supportive care, as there is no
             specific antidote. The use of Ipecac Syrup and activated
             charcoal are indicated in the event of ingestion.

        10.2 Life supportive procedures and symptomatic treatment

             Following large ingestions of captan, there are no
             specific procedures recommended other than the basic
             techniques for maintaining airways, breathing and
             circulation.

        10.3 Decontamination

             Wash contaminated skin with soap and water.
    
             Flush contaminated eyes (remove contact lenses if worn) with
             copious amounts of fresh water for 10 to 15 minutes.
    
             Ingestions of small amounts (less than 10 mg/kg bodyweight)
             occurring less than one hour before treatment are probably
             best managed by simple dilution with water.Ingestions of
             large amounts (more than 10 mg/kg bodyweight) occurring less
             than one hour before treatment, are probably best treated by:
             syrup of ipecac and activated charcoal.
    
             Ingestions occurring more than one hour before treatment are
             probably best treated only by: activated charcoal (30 to
             50 g)

        10.4 Enhanced Elimination

             No specific elimination procedures have been established.

        10.5 Antidote treatment

             10.5.1 Adults

                    There is no specific antidote for
                    captan.

             10.5.2 Children

                    There is no specific antidote for
                    captan.

        10.6 Management discussion

             There is an absence of clinical data on ingestion of
             captan in man; research into the allergic response mechanism
             and definitive experiments are required adequately to
             determine the full spectrum of foetal toxicity.

    11. ILLUSTRATIVE CASES

        11.1 Case reports from literature

             Case 1: adult male, occupational exposure.  Skin
             reaction.  A 73-year-old retired fruit grower exhibited
             persistent erythema, itching, and desquamation of the face
             and backs of hands.  The condition was exacerbated when he
             was close to spraying operations using captan.  Skin testing
             revealed reaction to captan (Dooms-Goossens et al, 1986).
    
             Case 2: adult male, occupational exposure. Skin reaction.  An
             18-year-old gardener was sufficiently sensitive to captan
             that he reacted to treated plants as well as to the
             formulation. Inhalation and skin test established that captan
             was the factor in the formulation to which the patient
             reacted.  Recovery was prompt after exposure was stopped
             (Hayes & Laws, 1991).

    12. ADDITIONAL INFORMATION

        12.1 Specific preventive measures

             It is essential that persons intending to use captan
             are provided with adequate health precautions and other
             safety instructions prior to usage. This information should
             be provided by the manufacturer in the form of either an
             information leaflet or on a labal attached to the captan
             container.
    
             Protective clothing is important. Captan may cause skin
             irritation and sensitization. The risk of this is greatest in
             hot weather when the user is sweating. Protective measures
             may include wearing a long-sleeved shirt, long trousers or
             overalls, and a hat. Respiratory protection should be
             considered. The label should give these details.
    
             Clothing worn during spraying should be washed daily after
             use. Contaminated clothing should be washed separately from
             the general wash to avoid cross-contamination. When working
             with liquids, there is often a danger of a splash in the
             eyes. Simple goggles or a face shield will protect against
             this. Eye protection is most important if wearing contact
             lenses: captan may seep behind the lenses and, in the time
             taken to remove them from the eyes prior to irrigation,
             serious damage can occur.
    
             Greater precautions are necessary when mixing the
             concentrated material than when spraying. Measurements should
             be accurate and spillages should be cleaned up promptly. Mix
             the chemical carefully using a stick or paddle. Minimise skin
             exposure by wearing gloves. If any concentrate is spilled on
             the skin, it should be washed off as soon as possible.

    
             The hazards of spraying increase dramatically on windy days
             as there is an increased risk of inhaling spray drift or
             contaminating the skin. Also, the risk of drift onto other
             properties or crops is increased.
    
             Always wash hands before eating, drinking or smoking. After
             spraying, shower and change clothing.
    
             Captan should be stored in a locked shed, safely out of reach
             of children and animals. Captan should also be kept away from
             work areas and separate from other stored materials such as
             animal foods. Always leave captan in its original containers,
             or if it must be transferred to another container ensure that
             this is one not normally used for food or drink. This
             container should be well-labelled and of a variety that is
             not likely to leak.
    
             Empty containers must be disposed of carefully, so as to
             ensure that rivers, streams, and other water sources are not
             polluted, and that unsuspecting people or animals are not
             exposed to residues or concentrate. Crushing or burning,
             followed by burial, is generally the best method. Workers
             involved in harvesting crops must adhere carefully to
             re-entry standards which have been set in order to prevent
             toxicity from captan.

        12.2 Other

             First-aid sheet:
    
                    Poisoning from captan may occur after it is absorbed
                    following:
    
             Ingestion
    
                    Contact with the skin
                    Contact with the eyes
                    Inhalation
    
             Signs and Symptoms
    
                    Ingestion may cause vomiting and diarrhoea.
                    Skin contact and inhalation may result in local
                    irritation and also sensitisation.
                    Eye contact may produce conjunctivitis.
    

             Decontamination
    
                    It is important that captan is removed as quickly as
                    possible. Contaminated clothing and contact lenses
                    should be removed. Avoid contact of captan with skin
                    and eyes; first aid personnel should wear rubber or
                    plastic gloves and avoid contamination.

             Treatment - General
    
                    Never give fluids or induce vomiting if the patients
                    is unconscious or fitting.
                    The patient must be watched constantly.
                    It is important to keep the airways open and to
                    prevent inhaling the vomit if nausea and vomiting is a
                    problem.
                    Give artificial respiration if the patient is not
                    breathing.
    
             Treatment - Ingestion
    
                    Give one to two cups of cold water.  Vomiting may be
                    induced if advised by medical personnel.  Obtain
                    medical attention.
    
             Treatment - Skin
    
                    Remove all contaminated clothing immediately.
                    Wash affected area carefully with soap and rinse with
                    copious amounts of water. Obtain medical
                    attention.
    
             Treatment - Eyes
    
                    Make sure any contact lenses are removed.
                    Flush with water for 10-15 minutes. Obtain medical
                    attention.
    
             Treatment - Inhalation
    
                    Remove the patient from the area of exposure.  Be
                    careful to avoid any contact with captan.  Protect
                    skin and eyes. Give oxygen if available. Obtain
                    medical attention.

    13. REFERENCES

        Boyd E and Carsky E (1971)  The 100-day LD50 Index of Captan.
        Acta Pharmacol. Toxicol. 29: 226-240.
    
        De-Baun JR, Miaullis JB, Knarr J., Mihailovski A and Menn JJ
        (1974)  The fate of
        N-trichloro14Cmethylthio-4-cyclohexane-1,2-dicarboximide (14C
        captan) in the rat.  Xenobiotica, 4: 101-110.
    
        Dillon AP, ed. (1981)  Pesticide disposal and detoxification. 
        Processes and techniques.  Noyes Data Corporation, New Jersey,
        USA, 588 pp.
    
        Dooms-Goossens AE, Debusschere KM, Gevers DM, Dupr_ KM, Degreef
        HJ, Loncke JP and Snauwaert JE (1986)  Contact dermatitis caused
        by airborne agents. J. Am. Acad. Dermatol., 15: 1-9.
    
        Hayes WJ Jr and Laus ER Jr (1991)  Pesticides studied in man. 
        Volume 3. Williams and Wilkinson, Baltimore, 1576 pp.
    
        Jordan WP and King SE (1977)  Delayed hypersensitivity in females. 
        The development of allergic contact dermatitis in females during
        the comparison of two predictive patch tests.
        Contact Dermatitis, 3: 19-26.

        RTECS (1987)  Registry of Toxic Effects of Chemical Substances,
        1985-1986 Edition.  US Department of Health and Human Services,
        Public Health Service, Centers for Disease Control, National
        Institute for Occupational Safety and Health, 5147 pp.
    
        Schardein JL, ed. (1985)  Chemically induced birth defects. 
        Marcel Dekker Incorporated, New York, USA, 879 pp.
    
        Seidler H, Haertig M, Schnaak W and Engst R (1971) Studies on the
        metabolism of some insecticides and fungicides in the rat. 3.
        Excretion, distribution and metabolism of 35S captan. Nahrung, 
        15: 177-185 (in German).
    
        Sittig M, ed. (1980)  Pesticide Manufacturing and Toxic Control
        Encyclopaedia. Noyes Data Corporation, Park Ridge, New Jersey,
        USA, 810 pp.
    
        Vondruska JF, Fancher OE and Calandra JC (1971) An investigation
        into the teratogenic potential of captan, folpet and Difolatan in
        non-human primates.  Toxicol. Appl. Pharmacol., 18: 619-624.
    
        WHO (1990) IPCS Health and Safety Guide No. 50. Captan Health and
        Safety Guide. World Health Organization, Geneva.
    
        Worthing CR, ed. (1987)  The Pesticide Manual. British Crop
        Protection Council, Worcestershire, 1077 pp.

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

    Authors:        Dr Wayne A. Temple
                    National Poisons and Hazardous Chemicals Information
                    Centre
    
                    Dr Nerida A. Smith
                    School of Pharmacy
                    University of Otago Medical School
                    P.O. Box 913
                    Dunedin
                    New Zealand
    
                    Tel:     64-3-4797244
                    Fax:     64-3-4770509
    
    Date:           29 October 1992
    
    Reviewer:       Ms J. Tempowski
                    London Poisons Unit
                    New Cross Hospital
                    Avonley Road
                    London SE14 5ER
                    United Kingdom
    
                    Tel:     44-71-9555095
                    Fax:     44-71-6392101
    
    Date:           February 1992
    
    Peer Review:    Newcastle-upon-Tyne, United Kingdom, February 1992
    
    Review:         IPCS, May 1994
    




    See Also:
       Toxicological Abbreviations
       Captan (HSG 50, 1990)
       Captan (ICSC)
       Captan (FAO/PL:1969/M/17/1)
       Captan (WHO Pesticide Residues Series 3)
       Captan (WHO Pesticide Residues Series 4)
       Captan (Pesticide residues in food: 1977 evaluations)
       Captan (Pesticide residues in food: 1978 evaluations)
       Captan (Pesticide residues in food: 1980 evaluations)
       Captan (Pesticide residues in food: 1982 evaluations)
       Captan (Pesticide residues in food: 1984 evaluations)
       Captan (Pesticide residues in food: 1984 evaluations)
       Captan (Pesticide residues in food: 1990 evaluations Toxicology)
       Captan (Pesticide residues in food: 1995 evaluations Part II Toxicological & Environmental)
       Captan (IARC Summary & Evaluation, Volume 30, 1983)