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CARBAMATE HERBICIDES AND FUNGICIDES

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Classification   |    Detailed evidence-based information

Substances Included Synonyms

Therapeutic Toxic Class

    A) This is a group of broad-spectrum herbicides and fungicides used as dusts, sprays, or solutions for both agricultural and home use.

Specific Substances

    A) ASULAM
    1) Methyl sulfanilylcarbamate
    2) Methyl [(4-aminophenyl)sulfonyl]carbamate
    3) CAS 3337-71-1 (asulam)
    4) CAS 2302-17-2 (asulam sodium)
    BUTYLATE
    1) S-ethyl-di-isobutylthiocarbamte
    2) CAS 2008-41-5
    CARBENDAZIM
    1) 2-Benzimidazolecarbamic acid, methyl ester
    2) Benzimidazole-2-carbamic acid, methyl ester
    3) Carbendazole
    4) Carbendazym
    5) FB642
    6) Methyl-2-benzimidazolecarbamate
    7) CAS 10605-21-7
    8) CAS 63090-40-4
    9) CAS 63278-70-6
    10) CAS 105268-95-9
    CARBETAMIDE
    1) CAS 16118-49-3
    CHLORPROPHAM
    1) Isopropyl 3-chlorocarbanilate
    2) 1-methylethyl (3-chlorophenyl)carbamate
    3) CAS 101-21-3
    CYCLOATE
    1) Heylthiocarbam
    2) S-ethyl N-cyclohexyl(N-ethyl)thiocarbamate
    3) CAS 1134-23-2
    ETHYLENETHIOUREA
    1) ETU
    FERBAM
    1) Iron tris(dimethyldithiocarbamate)
    2) Ferric dimethyldithiocarbamate
    3) CAS 14484-64-1
    MANCOZEB
    1) Manganese ethylenebis (dithiocarbamate) (polymeric) complex with zinc salt
    2) CAS 8018-01-7
    MANEB
    1) Manganese ethylenebis (dithiocarbamate) polymeric
    2) [1,2-ethanediylbis[carbamodithioato](2)]manganese
    3) CAS 12427-38-2
    MOLINATE
    1) S-ethyl azepane-1-carbothioate
    2) CAS 2212-67-1
    NABAM
    1) Disodium ethylenebis(dithiocarbamate)
    2) CAS 142-59-6
    PEBULATE
    1) S-propyl butyl(ethyl)thiocarbamate
    2) CAS 1114-71-2
    PHENMEDIPHAM
    1) Methyl 3-(3-methylcarbaniloyloxy)carbanilate
    2) CAS 13684-63-4
    PROPAMOCARB
    1) Propyl 3-(dimethylamino)propylcarbamate
    2) Propamocarb hydrochloride
    3) CAS 2506-41-1 (propamocarb hydrochloride)
    PROPHAM
    1) Isoproyl phenylcarbamate
    2) 1-methylethyl phenylcarbamate
    3) CAS 122-42-9
    THIRAM
    1) Bis(dimethylcarbamoyl) disulfide
    2) Bis(dimethylthiocarbamoyl) disulfide
    3) Tetramethylthioperoxydicarbonic diamide
    4) Tetramethyl thiuram disulfide
    5) Thirame
    6) TMTD
    7) TTD
    8) TMTDS
    9) CAS 137-26-8
    ZINEB
    1) Zebenide
    2) Zinc, (ethylenebis(dithiocarbamato))-
    3) Zinosan
    4) Molecular Formula: C4-H6-N2-S4.Zn
    5) CAS 142-14-3
    6) CAS 12122-67-7
    7) CAS 14039-25-9
    ZIRAM
    1) Bis(dimethyldithiocarbamato)zinc
    2) Carbazinc
    3) Dimethyldithiocarbamate zinc salt
    4) Methyl Ziram
    5) Zinc, bis(dimethyldithiocarbamato)-
    6) Ziradin
    7) Ziride
    8) Molecular Formula: C6-H12-N2-S4.Zn
    9) CAS 137-30-4
    10) CAS 8059-74-3
    11) CAS 8070-07-3
    GENERAL TERMS
    1) FUNGICIDES, CARBAMATE
    2) CARBAMATE HERBICIDES/ FUNGICIDES
    3) CARBAMATE FUNGICIDES AND HERBICIDES
    4) BIS(DIMETHYLTHIO CARBAMOYL)DISULPHIDE
    5) HERBICIDES, CARBAMATE

Available Forms Sources

    A) FORMS
    1) TABLE OF CARBAMATE COMPOUNDS BY CHEMICAL CLASS:
    CHEMICAL CLASSABBREVIATIONCOMPOUNDS
    CarbamatesCARBasulam, propamocarb prophamchloropropham phenmedipham
    Monothio-carbamatedT-CARBcycloate, butylate,molinatepebulate
    Bisdithio-carbamatedBDT-CARB, Thiuramsthiram, methiram
    DimethyldithiocarbamatesMBDT-CARB, DMDCziram,ferbam
    Ethylene bis- dithiocarbamatesEBDT-CARB EBDCmancozeb, maneb, metiram, nabam, zineb

    B) SOURCES
    1) Some are found in suntan and antiseptic sprays, and some medicated cleansing agents. Some are also used in the plastic industry as an antioxidant, and as a rubber accelerator (Dalvi, 1988).
    C) USES
    1) These chemicals are applied as dusts, sprays of solutions, and wettable powder suspensions and emulsions, depending on the chemical and physical properties of the various agents. Formulations are widely used for pest control in home gardens and in commercial agriculture.
    2) CARBENDAZIM: Used as a systemic broad-spectrum fungicide for prevention and control of plant diseases on a variety of crops (e.g., vegetables, fruits, nuts, cereals, cotton, ornamentals, mushrooms). It is a major metabolite of benomyl. The fungicidal property is due to binding of carbendazim to tubulins, thus disrupting microtubule formation and mitosis. Carbendazim is also used as a preservative in the paint, textile, papermaking and leather industries (Selmanoglu et al, 2001). Carbendazim is also currently undergoing clinical trials in adult patients with advanced malignancies (i.e., breast cancer, melanoma, colon cancer) (Hao et al, 2002).
    3) ETU (Ethylenethiourea): Used as an accelerator in rubber vulcanization, in dyes, synthetic resins, electroplating baths, and pharmaceuticals (Kurttio & Savolainen, 1990).
    4) THIRAM: Used for foliage and seed treatment, as a disinfectant for nuts, fruits, and mushrooms, and as a rodent and large animal repellent.

Overview

Life Support

    A) This overview assumes that basic life support measures have been instituted.

Clinical Effects

    0.2.1) SUMMARY OF EXPOSURE
    A) USES: These products are used to control noxious plants and fungi in home gardens and agriculture. Common examples are thiram, carbendazim, maneb, ethylene thiourea, zineb, and ziram.
    B) TOXICOLOGY: Some of these agents may inhibit aldehyde dehydrogenase and cause disulfiram-like reactions. Carbamate herbicides and fungicides do not inhibit the cholinesterase enzyme; therefore exposure to these agents will NOT result in cholinergic findings.
    C) EPIDEMIOLOGY: Exposure to these products is very rare, and there are only a few cases of serious toxicity reported in the literature.
    D) WITH POISONING/EXPOSURE
    1) MILD TO MODERATE POISONING: The main effects are dermal, respiratory, and gastrointestinal irritation. Dermal exposure to some of these agents may cause a disulfiram-like reaction.
    2) SEVERE POISONING: Seizures, altered mental status, and coma have been rarely reported. Renal failure has been suggested, but the reports are of questionable quality.
    0.2.3) VITAL SIGNS
    A) WITH POISONING/EXPOSURE
    1) Hypothermia has been reported in a child following exposure to maneb.
    0.2.7) NEUROLOGIC
    A) WITH POISONING/EXPOSURE
    1) Based on animal studies, exposure to thiram or dimethyldithiocarbamate (MBDT-CARB) fungicides may cause weakness, ataxia, ascending paralysis and hypothermia.
    2) Status epilepticus and coma were reported in a child following exposure to maneb.
    0.2.8) GASTROINTESTINAL
    A) WITH POISONING/EXPOSURE
    1) Nausea, vomiting, abdominal pain, and diarrhea may occur.
    0.2.10) GENITOURINARY
    A) WITH POISONING/EXPOSURE
    1) Two cases of renal failure following maneb exposure have been reported in Japan.
    0.2.14) DERMATOLOGIC
    A) WITH POISONING/EXPOSURE
    1) Exposure to dusts, sprays, solutions, wettable powder suspensions or emulsions of these agents may lead to skin and mucous membrane irritation.
    0.2.20) REPRODUCTIVE
    A) No adverse reproductive effects (testicular parameters) in male mice were observed following methyl thiophanate doses up to 1000 mg/kg orally for 5 consecutive days (Traina et al, 1998). Maternal toxicity was evident in female rats.

Laboratory Monitoring

    A) Monitor vital signs and mental status.
    B) No specific lab work is needed in most patients.

Treatment Overview

    0.4.2) ORAL/PARENTERAL EXPOSURE
    A) MANAGEMENT OF MILD TO MODERATE TOXICITY
    1) Rinse any dermal exposures with water. Administer IV fluids for hypotension and antihistamines for flushing from a disulfiram-like reaction.
    B) MANAGEMENT OF SEVERE TOXICITY
    1) Massive ingestion may lead to altered mental status, seizures, and acidosis. Intubate patients with significant altered mental status or airway injury. Treat acidosis with adequate ventilation and hydration. If the patient has severe acidosis, consider sodium bicarbonate. Treat seizures with benzodiazepines.
    C) DECONTAMINATION
    1) PREHOSPITAL: Wash exposed skin with soap and water. Remove contaminated clothing. Irrigate exposed eyes with water. Prehospital gastrointestinal decontamination is not recommended.
    2) HOSPITAL: These chemicals are likely bound by activated charcoal. Patients who present after large ingestions should be treated with activated charcoal if they are able to drink the charcoal or if they are intubated.
    D) AIRWAY MANAGEMENT
    1) Indicated for airway injury or altered mental status.
    E) ANTIDOTE
    1) None
    F) ENHANCED ELIMINATION
    1) There are no data evaluating repeat-dose activated charcoal or hemodialysis.
    G) PATIENT DISPOSITION
    1) HOME CRITERIA: Asymptomatic patients with inadvertent exposures can be managed at home.
    2) OBSERVATION CRITERIA: Patients with symptoms more than mild irritation and those with deliberate ingestions should be referred to a healthcare facility for evaluation.
    3) ADMISSION CRITERIA: Patients with seizures or altered mental status should be admitted to an intensive care unit.
    4) CONSULT CRITERIA: Consult a poison center or medical toxicologist for assistance in decision making regarding whether or not admission is advisable, managing patients with severe toxicity, or in whom the diagnosis is not clear.
    H) PITFALLS
    1) The ingestion of carbamate herbicides and fungicides must be differentiated from carbamate insecticides, which can cause more significant toxicity. Patients should be instructed to avoid the use of ethanol for 7 days after exposure.
    I) PHARMACOKINETICS
    1) These chemicals are moderately well-absorbed after oral ingestion and can be absorbed through the skin. The half-lives vary from hours to days depending on the chemical.
    J) DIFFERENTIAL DIAGNOSIS
    1) Other chemicals causing mild irritation.
    0.4.3) INHALATION EXPOSURE
    A) Treatment of toxicity following inhalation exposure should include recommendations listed in the ORAL EXPOSURE section when appropriate.
    0.4.4) EYE EXPOSURE
    A) Irrigate exposed eyes with water. Treatment of toxicity following ocular exposure should include recommendations listed in the ORAL EXPOSURE section when appropriate.
    0.4.5) DERMAL EXPOSURE
    A) OVERVIEW
    1) Wash exposed skin with soap and water. Remove contaminated clothing. Treatment of toxicity following dermal exposure should include recommendations listed in the ORAL EXPOSURE section when appropriate.

Range Of Toxicity

    A) TOXICITY: Severe toxicity appears to be very rare; inadvertent exposure rarely causes significant toxicity.

Clinical Effects

Summary Of Exposure

    A) USES: These products are used to control noxious plants and fungi in home gardens and agriculture. Common examples are thiram, carbendazim, maneb, ethylene thiourea, zineb, and ziram.
    B) TOXICOLOGY: Some of these agents may inhibit aldehyde dehydrogenase and cause disulfiram-like reactions. Carbamate herbicides and fungicides do not inhibit the cholinesterase enzyme; therefore exposure to these agents will NOT result in cholinergic findings.
    C) EPIDEMIOLOGY: Exposure to these products is very rare, and there are only a few cases of serious toxicity reported in the literature.
    D) WITH POISONING/EXPOSURE
    1) MILD TO MODERATE POISONING: The main effects are dermal, respiratory, and gastrointestinal irritation. Dermal exposure to some of these agents may cause a disulfiram-like reaction.
    2) SEVERE POISONING: Seizures, altered mental status, and coma have been rarely reported. Renal failure has been suggested, but the reports are of questionable quality.

Vital Signs

    3.3.1) SUMMARY
    A) WITH POISONING/EXPOSURE
    1) Hypothermia has been reported in a child following exposure to maneb.
    3.3.3) TEMPERATURE
    A) WITH POISONING/EXPOSURE
    1) HYPOTHERMIA: A 7-year-old child developed status epilepticus, coma and hypothermia (a rectal temperature of 32.5 degrees C) following suspected ingestion of maneb (deTollenaer et al, 2006).

Heent

    3.4.3) EYES
    A) WITH POISONING/EXPOSURE
    1) CONJUNCTIVITIS may be a symptom following thiram exposure (Dalvi, 1988).
    3.4.5) NOSE
    A) WITH POISONING/EXPOSURE
    1) SNEEZING may be seen after exposure to thiram (Dalvi, 1988).
    2) RHINITIS may also be seen following exposure to thiram dust (Dalvi, 1988).

Cardiovascular

    3.5.2) CLINICAL EFFECTS
    A) HEART FAILURE
    1) WITH POISONING/EXPOSURE
    a) Transient cardiac failure has been reported after Ethylene bisdithiocarbamate (EBDC) exposure (Koizumi et al, 1979).

Respiratory

    3.6.2) CLINICAL EFFECTS
    A) COUGH
    1) WITH POISONING/EXPOSURE
    a) Some workers experience upper respiratory congestion, hoarseness, and cough if they breathe sprays or dusts containing these compounds (Dalvi, 1988).

Neurologic

    3.7.1) SUMMARY
    A) WITH POISONING/EXPOSURE
    1) Based on animal studies, exposure to thiram or dimethyldithiocarbamate (MBDT-CARB) fungicides may cause weakness, ataxia, ascending paralysis and hypothermia.
    2) Status epilepticus and coma were reported in a child following exposure to maneb.
    3.7.2) CLINICAL EFFECTS
    A) NEUROLOGICAL FINDING
    1) WITH POISONING/EXPOSURE
    a) Headache, confusion, and fatigue may occur following ingestion of carbamate fungicides (Liesivuori & Savolainen, 1994).
    B) ATAXIA
    1) WITH POISONING/EXPOSURE
    a) Extraordinary dosage of thiram or dimethyldithiocarbamate (MBDT-CARB) compounds may be expected to cause weakness, ataxia, and dizziness (Liesivuori & Savolainen, 1994; Dalvi, 1988).
    C) SEIZURE
    1) WITH POISONING/EXPOSURE
    a) Coma, seizures, and right hemiparesis were reported after 2 spraying exposures to maneb and zineb (Liesivuori & Savolainen, 1994)(Israel et al, 1983).
    b) CASE REPORT: A 7-year-old girl, who had a 3-day history of abdominal pain, nausea, vomiting, hypothermia (35 degrees C measured by her mother), and headache, presented to the ED with status epilepticus. On physical examination, the patient was unresponsive to pain with a Glasgow Coma Scale (GCS) score of 3, and her head and eyes were fixed to the right. A repeat temperature reading, taken rectally, showed a body temperature of 32.5 degrees C. The status epilepticus resolved following administration of benzodiazepines, and her GCS and temperature normalized with supportive care. She was discharged without sequelae 72 hours post-admission. Liquid chromatography-mass spectrometry found maneb in blood samples of the patient. Due to the gastrointestinal effects present, it is suspected that the child may have ingested the fungicide (deTollenaer et al, 2006).
    D) EXTRAPYRAMIDAL DISEASE
    1) WITH POISONING/EXPOSURE
    a) CASE REPORT: Occupational exposure to maneb-containing fungicides was associated with development of a parkinsonian syndrome in 2 agricultural workers.
    1) Bradykinesia, cogwheel rigidity, resting tremor, and emotional instability were present (Ferraz et al, 1988). No manganese levels were measured. Association was drawn from history of exposure.
    b) CASE REPORT: Chronic exposure to maneb was associated with permanent parkinsonism 2 years after exposure had ceased in a 37-year-old man. Mild tremor associated with paresthesias were reported at initial presentation. Symptoms progressed to generalized bradykinesia, rigidity, postural tremor and abnormal gait.
    1) Association was drawn from history of exposure (about 45 kg of fungicide) (approximately 5 g maneb per sack of fungicide} in a closed environment, with no personal protection, over a 2 year period) (Meco et al, 1994).
    E) CLOUDED CONSCIOUSNESS
    1) WITH POISONING/EXPOSURE
    a) Confusion may occur after poisoning with thiram (Dalvi, 1988).
    F) DROWSY
    1) WITH POISONING/EXPOSURE
    a) Drowsiness may occur with thiram (Dalvi, 1988).
    b) Lethargy has been reported with human thiram poisoning (Dalvi, 1988).
    G) PARALYSIS
    1) WITH POISONING/EXPOSURE
    a) Flaccid paralysis has been seen with human thiram poisoning (Dalvi, 1988).
    H) COMA
    1) WITH POISONING/EXPOSURE
    a) CASE REPORT: A 7-year-old girl presented to the ED with status epilepticus, unresponsive to pain with a Glasgow Coma Scale (GCS) score of 3, and her head and eyes fixed to the right. A temperature reading, taken rectally, showed a body temperature of 32.5 degrees C. The status epilepticus resolved following administration of benzodiazepines, and her GCS and temperature normalized with supportive care. She was discharged without sequelae 72 hours post-admission. Liquid chromatography-mass spectrometry found maneb in blood samples of the patient. It is suspected that the child may have ingested the fungicide (deTollenaer et al, 2006).
    3.7.3) ANIMAL EFFECTS
    A) ANIMAL STUDIES
    1) CEREBROVASCULAR DISORDER
    a) RATS: Brain lesions have been seen in rats fed diets of ferbam. Other rats exhibited neurologic signs of hind leg stiffness (Hodge et al, 1956). Mice given IV injections of benzazoles exhibited semi-flaccid paralysis that began in the hindlimbs (Domino et al, 1952).

Gastrointestinal

    3.8.1) SUMMARY
    A) WITH POISONING/EXPOSURE
    1) Nausea, vomiting, abdominal pain, and diarrhea may occur.
    3.8.2) CLINICAL EFFECTS
    A) GASTROENTERITIS
    1) WITH POISONING/EXPOSURE
    a) If swallowed, carbamate fungicides are likely to cause nausea, vomiting, abdominal pain, and diarrhea (deTollenaer et al, 2006; Liesivuori & Savolainen, 1994; Dalvi, 1988).
    b) Diarrhea has been reported after thiram ingestion (Dalvi, 1988).

Hepatic

    3.9.3) ANIMAL EFFECTS
    A) ANIMAL STUDIES
    1) HEPATIC NECROSIS
    a) Focal necrosis was noted in animals fatally poisoned with thiram (Dalvi, 1988).
    b) RATS: In a 15 week oral dosing study, rats were given up to 600 mg/kg/day of carbendazim. At the end of the study, dose-dependent congestion in portal veins, sinusoid enlargement, increased numbers of Kupffer cells and mononuclear cell infiltration of the liver, and hydropic liver degeneration was observed (Selmanoglu et al, 2001).

Genitourinary

    3.10.1) SUMMARY
    A) WITH POISONING/EXPOSURE
    1) Two cases of renal failure following maneb exposure have been reported in Japan.
    3.10.2) CLINICAL EFFECTS
    A) RENAL FAILURE SYNDROME
    1) WITH POISONING/EXPOSURE
    a) Two cases of renal failure following maneb exposure have been reported from Japan (Koizumi et al, 1979).
    3.10.3) ANIMAL EFFECTS
    A) ANIMAL STUDIES
    1) RENAL TUBULAR DISORDER
    a) Renal tubule damage was reported in animals acutely poisoned with thiram (Dalvi, 1988).
    2) RENAL FIBROSIS
    a) In a 15 week oral dosing study, rats were given up to 600 mg/kg/day of carbendazim. At the end of the study, a dose-dependent tubular degeneration and kidney fibrosis was observed (Selmanoglu et al, 2001).

Acid-Base

    3.11.2) CLINICAL EFFECTS
    A) ACIDOSIS
    1) WITH POISONING/EXPOSURE
    a) CASE REPORT: A combined respiratory and metabolic acidosis was reported in a 7-year-old child who developed status epilepticus following suspected ingestion of maneb. Arterial blood gas analysis revealed a pH of 7.04, pCO2 of 14.5 kPa, pO2 of 41.8 kPa, and a base excess (BE) of -7 mmol/L. Liquid chromatography-mass spectrometry of the patient's blood samples confirmed the presence of maneb. Following supportive care, the patient's acidosis resolved within a few hours post-admission (deTollenaer et al, 2006).

Hematologic

    3.13.3) ANIMAL EFFECTS
    A) ANIMAL STUDIES
    1) LEUKOPENIA
    a) RATS: In a 15 week oral dosing study, rats were given up to 600 mg/kg/day of carbendazim. At the end of the study, hematological studies showed dose-dependent, significant decreases in white blood cell and lymphocyte counts. On the other hand, mean cell hemoglobin and mean cell hemoglobin concentrations were increased, but were not dose-dependent effects (Selmanoglu et al, 2001).

Dermatologic

    3.14.1) SUMMARY
    A) WITH POISONING/EXPOSURE
    1) Exposure to dusts, sprays, solutions, wettable powder suspensions or emulsions of these agents may lead to skin and mucous membrane irritation.
    3.14.2) CLINICAL EFFECTS
    A) SKIN IRRITATION
    1) WITH POISONING/EXPOSURE
    a) To some degree, all of these chemicals, the sulfur-containing in particular, are irritating to the skin and mucous membranes.
    b) MITC: Dermatitis was seen in workers cleaning a river after a spill of the soil fumigant metam sodium. The major component, methyldithiocarbamate (MTIC), breaks down to the skin irritant methylisothiocyanate (MMWR, 1991).
    B) CONTACT DERMATITIS
    1) WITH POISONING/EXPOSURE
    a) THIRAM: Dermatitis has been noted with thiram, as have urticaria and erythema (Dalvi, 1988; Brusilovskiy & Fiallkovskiy, 1973; Shelley, 1964). Not all studies have shown thiram to cause dermatitis.
    1) Repeated application of thiram to rabbit skin at doses of 50 mg/kg did not produce dermal irritation (Matthiaschk, 1973).
    b) MANEB-MANCOZEB: Contact dermatitis was reported in 2 patients to maneb, and in one patient to zineb, all after occupational exposures (Manuzzi et al, 1988).
    1) A 1% incidence of maneb sensitization was seen in agricultural workers (Lisi et al, 1986).
    2) Pellagroid dermatitis has been reportedly suspected following mancozeb exposure (Lisi & Caraffini, 1985).
    3) Contact allergy to zineb and mancozeb was reported in an apple orchard horticulturist who sprayed a mixture of pesticides the day before (Oakley, 1988).
    4) Allergic contact dermatitis of the face and arms was seen in a 53-year-old agricultural worker exposed to maneb. Diagnosis was confirmed by patch testing (Piraccini et al, 1991).
    c) ZIRAM: Patients allergic to ziram should not wear rubber gloves, since cross-sensitization may occur to the rubber accelerator zinc diethyldithiocarbamate (Manuzzi et al, 1988).
    d) Ethylene bisidithiocarbamates (EBDCs) and ethylenethiourea (ETU) are thought to be sensitizers of skin (Burry, 1976; Nater et al, 1979) Kleibl & Rac'kova, 1980; (Adams & Manchester, 1982; Bruze & Fregert, 1983), although some controversy still exists (van Ketel & van den Berg, 1984; Rudzki et al, 1976). The EBDC fungicides appear to have greater sensitizing properties than the thiuram or dimethyldithiocarbamate (DMDC) fungicides (Liesivuori & Savolainen, 1994).
    C) FLUSHING
    1) WITH POISONING/EXPOSURE
    a) DISULFIRAM-LIKE REACTION: Dermal exposure to thiram in conjunction with ethanol ingestion may result in a disulfiram-like reaction, characterized by erythema, edema, and burning of the face and neck (Shelley, 1964).

Endocrine

    3.16.2) CLINICAL EFFECTS
    A) FINDING OF THYROID FUNCTION
    1) WITH POISONING/EXPOSURE
    a) Ethylenethiourea (ETU) causes thyroid hyperplasia and significant changes in the level of thyroid hormones in rats and humans (Kurttio et al, 1986; Szepvolgyi et al, 1989; Smith, 1984).
    3.16.3) ANIMAL EFFECTS
    A) ANIMAL STUDIES
    1) THYROID DISORDER
    a) In a 15 week oral dosing study, rats were given up to 600 mg/kg/day of carbendazim. At the end of the study, a dose-related incidence of observed lesions in the thyroid, parathyroid and adrenal glands was reported. In the parathyroid gland, minimal congestion, cellular degeneration and amyloid lesions were observed. A significant elevation of triiodothyronine (T3) concentrations was noted in the 300 mg/kg/day dose level (Barlas et al, 2002).
    2) ADRENAL INSUFFICIENCY
    a) In a 15 week oral dosing study, rats were given up to 600 mg/kg/day of carbendazim. At the end of the study, cellular degeneration and many lipid droplets were noted in adrenal tissue, particularly in the zone fasciculata layer of the cortex. No histopathological changes were found in pituitary glands (Barlas et al, 2002).

Reproductive

    3.20.1) SUMMARY
    A) No adverse reproductive effects (testicular parameters) in male mice were observed following methyl thiophanate doses up to 1000 mg/kg orally for 5 consecutive days (Traina et al, 1998). Maternal toxicity was evident in female rats.
    3.20.2) TERATOGENICITY
    A) CONGENITAL ANOMALY
    1) THIRAM - Teratogenic in mice (Matthiaschk, 1973) and in hamsters (Robens, 1969).
    2) MANCOZEB - INHALATION - Doses nontoxic to pregnant rats are not teratogenic. Embryotoxicity may occur at doses toxic to the dam, at concentrations of 55 mg/m(3) or above (Lu & Kennedy, 1986).
    3) ETU - Single intragastric doses to rats and hamsters produce an incidence of teratogenicity ranging from 16% to 100% (Frakes, 1988). Teratogenicity has also been reported in mice (Khera, 1984).
    4) CARBENDAZIM - In female rats exposed to doses 35 to 160 mg/kg/day on days 6-15 of gestation, significant maternal toxicity, embryonal lethality, teratogenic effects, and retarded fetal development were reported. Malformations reported included encephalocele, umbilical hernia, missing or shorter tail, and internal malformations of brain, kidneys, and skeletal malformations of ribs, arch, and vertebrae. A NOEL of 8 mg/kg/day was reported for the dam and fetus (Sitarek, 2001).
    B) LACK OF EFFECT
    1) No adverse effects on the early embryo were observed when rat dams were given oral methyl thiophanate 650 mg/kg/day during pre-implantation (gestational day or GD 2-5) or peri-implantation (GD 6-9) phases (Traina et al, 1998).
    3.20.5) FERTILITY
    A) OVULATION FAILURE
    1) RAT STUDIES - A single IP injection of sodium N-methyldithiocarbamate resulted in blockade of ovulation in the female rat via a probable effect on the hypothalamic mechanisms regulating LH secretion. Suppression of the LH surge occurred (Goldman et al, 1994).

Carcinogenicity

    3.21.1) IARC CATEGORY
    A) IARC Carcinogenicity Ratings for CAS137-26-8 (International Agency for Research on Cancer (IARC), 2016; International Agency for Research on Cancer, 2015; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010a; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2008; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2007; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2006; IARC, 2004):
    1) IARC Classification
    a) Listed as: Thiram
    b) Carcinogen Rating: 3
    1) The agent (mixture or exposure circumstance) is not classifiable as to its carcinogenicity to humans. This category is used most commonly for agents, mixtures and exposure circumstances for which the evidence of carcinogenicity is inadequate in humans and inadequate or limited in experimental animals. Exceptionally, agents (mixtures) for which the evidence of carcinogenicity is inadequate in humans but sufficient in experimental animals may be placed in this category when there is strong evidence that the mechanism of carcinogenicity in experimental animals does not operate in humans. Agents, mixtures and exposure circumstances that do not fall into any other group are also placed in this category.
    3.21.3) HUMAN STUDIES
    A) CARCINOMA
    1) Ethylene thiourea (ETU): A contaminant and breakdown product of ethylene bisdithiocarbamate fungicides (maneb, nabam, zineb) is a recognized carcinogen in animals.
    a) Hepatomas, lymphomas, and thyroid carcinomas have been described. ETU is classified as a probable human carcinogen by the EPA (Frakes, 1988).

Genotoxicity

    A) Mancozeb was not clastogenic in mice (Vasudev & Krishnamurthy, 1994).
    B) Ethylenethiourea (ETU) is not believed to be genotoxic to mammals (Elia et al, 1995).

Laboratory Monitoring

Monitoring Parameters Levels

    4.1.1) SUMMARY
    A) Monitor vital signs and mental status.
    B) No specific lab work is needed in most patients.

Methods

    A) CHROMATOGRAPHY
    1) A high performance liquid chromatography (HPLC), with UV detection, method was described for the measurement of carbendazim in plasma. The lower limit of quantitation was reported as 0.10 mcg/mL (Hao et al, 2002).
    2) HPLC has also been used to measure ethylenethiourea (ETU), the main metabolite of ethylene bisdithiocarbamates, in urine, as well as thiram, the metabolite of ferbam and ziram fungicides (Liesivuori & Savolainen, 1994).
    B) OTHER
    1) As a metabolite of dithiocarbamate fungicides, measurement of urinary carbon disulfide (CS2) has been suggested as a way to assess toxic exposure (Liesivuori & Savolainen, 1994), but it is unlikely that this would be useful in management of exposure to these chemicals.

Treatment

Life Support

    A) Support respiratory and cardiovascular function.

Patient Disposition

    6.3.1) DISPOSITION/ORAL EXPOSURE
    6.3.1.1) ADMISSION CRITERIA/ORAL
    A) Patients with seizures or altered mental status should be admitted to an intensive care unit.
    6.3.1.2) HOME CRITERIA/ORAL
    A) Asymptomatic patients with inadvertent exposures can be managed at home.
    6.3.1.3) CONSULT CRITERIA/ORAL
    A) Consult a poison center or medical toxicologist for assistance in decision making regarding whether or not admission is advisable, managing patients with severe toxicity, or in whom the diagnosis is not clear.
    6.3.1.5) OBSERVATION CRITERIA/ORAL
    A) Patients with symptoms more than mild irritation and those with deliberate ingestions should be referred to a healthcare facility for evaluation.

Monitoring

    A) Monitor vital signs and mental status.
    B) No specific lab work is needed in most patients.

Oral Exposure

    6.5.1) PREVENTION OF ABSORPTION/PREHOSPITAL
    A) Wash exposed skin with soap and water. Remove contaminated clothing. Irrigate exposed eyes with water. Prehospital gastrointestinal decontamination is not recommended.
    6.5.2) PREVENTION OF ABSORPTION
    A) ACTIVATED CHARCOAL
    1) These chemicals are likely bound by activated charcoal. Patients who present after large ingestions should be treated with activated charcoal if they are able to drink the charcoal or if they are intubated.
    2) CHARCOAL ADMINISTRATION
    a) Consider administration of activated charcoal after a potentially toxic ingestion (Chyka et al, 2005). Administer charcoal as an aqueous slurry; most effective when administered within one hour of ingestion.
    3) CHARCOAL DOSE
    a) Use a minimum of 240 milliliters of water per 30 grams charcoal (FDA, 1985). Optimum dose not established; usual dose is 25 to 100 grams in adults and adolescents; 25 to 50 grams in children aged 1 to 12 years (or 0.5 to 1 gram/kilogram body weight) ; and 0.5 to 1 gram/kilogram in infants up to 1 year old (Chyka et al, 2005).
    1) Routine use of a cathartic with activated charcoal is NOT recommended as there is no evidence that cathartics reduce drug absorption and cathartics are known to cause adverse effects such as nausea, vomiting, abdominal cramps, electrolyte imbalances and occasionally hypotension (None Listed, 2004).
    b) ADVERSE EFFECTS/CONTRAINDICATIONS
    1) Complications: emesis, aspiration (Chyka et al, 2005). Aspiration may be complicated by acute respiratory failure, ARDS, bronchiolitis obliterans or chronic lung disease (Golej et al, 2001; Graff et al, 2002; Pollack et al, 1981; Harris & Filandrinos, 1993; Elliot et al, 1989; Rau et al, 1988; Golej et al, 2001; Graff et al, 2002). Refer to the ACTIVATED CHARCOAL/TREATMENT management for further information.
    2) Contraindications: unprotected airway (increases risk/severity of aspiration) , nonfunctioning gastrointestinal tract, uncontrolled vomiting, and ingestion of most hydrocarbons (Chyka et al, 2005).
    6.5.3) TREATMENT
    A) MONITORING OF PATIENT
    1) Monitor vital signs and mental status.
    2) No specific lab work is needed in most patients.
    B) SUPPORT
    1) There are no specific antidotes for poisoning by these chemicals. Care is symptomatic and supportive.
    C) FLUID/ELECTROLYTE BALANCE REGULATION
    1) Intravenous fluids may be useful in restoring extracellular fluid volume if this has been depleted by vomiting and diarrhea.
    D) OXYGEN
    1) Oxygen inhalation is effective in relieving the distress of disulfiram-like reactions rarely associated with exposure to thiram and possibly the MBDT-CARB compounds if alcohol has been consumed. Ventilatory support may be necessary in cases of respiratory insufficiency (possibly induced by hydrocarbon based solvent).
    E) SEIZURE
    1) SUMMARY
    a) Attempt initial control with a benzodiazepine (eg, diazepam, lorazepam). If seizures persist or recur, administer phenobarbital or propofol.
    b) Monitor for respiratory depression, hypotension, and dysrhythmias. Endotracheal intubation should be performed in patients with persistent seizures.
    c) Evaluate for hypoxia, electrolyte disturbances, and hypoglycemia (or, if immediate bedside glucose testing is not available, treat with intravenous dextrose).
    2) DIAZEPAM
    a) ADULT DOSE: Initially 5 to 10 mg IV, OR 0.15 mg/kg IV up to 10 mg per dose up to a rate of 5 mg/minute; may be repeated every 5 to 20 minutes as needed (Brophy et al, 2012; Prod Info diazepam IM, IV injection, 2008; Manno, 2003).
    b) PEDIATRIC DOSE: 0.1 to 0.5 mg/kg IV over 2 to 5 minutes; up to a maximum of 10 mg/dose. May repeat dose every 5 to 10 minutes as needed (Loddenkemper & Goodkin, 2011; Hegenbarth & American Academy of Pediatrics Committee on Drugs, 2008).
    c) Monitor for hypotension, respiratory depression, and the need for endotracheal intubation. Consider a second agent if seizures persist or recur after repeated doses of diazepam .
    3) NO INTRAVENOUS ACCESS
    a) DIAZEPAM may be given rectally or intramuscularly (Manno, 2003). RECTAL DOSE: CHILD: Greater than 12 years: 0.2 mg/kg; 6 to 11 years: 0.3 mg/kg; 2 to 5 years: 0.5 mg/kg (Brophy et al, 2012).
    b) MIDAZOLAM has been used intramuscularly and intranasally, particularly in children when intravenous access has not been established. ADULT DOSE: 0.2 mg/kg IM, up to a maximum dose of 10 mg (Brophy et al, 2012). PEDIATRIC DOSE: INTRAMUSCULAR: 0.2 mg/kg IM, up to a maximum dose of 7 mg (Chamberlain et al, 1997) OR 10 mg IM (weight greater than 40 kg); 5 mg IM (weight 13 to 40 kg); INTRANASAL: 0.2 to 0.5 mg/kg up to a maximum of 10 mg/dose (Loddenkemper & Goodkin, 2011; Brophy et al, 2012). BUCCAL midazolam, 10 mg, has been used in adolescents and older children (5-years-old or more) to control seizures when intravenous access was not established (Scott et al, 1999).
    4) LORAZEPAM
    a) MAXIMUM RATE: The rate of intravenous administration of lorazepam should not exceed 2 mg/min (Brophy et al, 2012; Prod Info lorazepam IM, IV injection, 2008).
    b) ADULT DOSE: 2 to 4 mg IV initially; repeat every 5 to 10 minutes as needed, if seizures persist (Manno, 2003; Brophy et al, 2012).
    c) PEDIATRIC DOSE: 0.05 to 0.1 mg/kg IV over 2 to 5 minutes, up to a maximum of 4 mg/dose; may repeat in 5 to 15 minutes as needed, if seizures continue (Brophy et al, 2012; Loddenkemper & Goodkin, 2011; Hegenbarth & American Academy of Pediatrics Committee on Drugs, 2008; Sreenath et al, 2010; Chin et al, 2008).
    5) PHENOBARBITAL
    a) ADULT LOADING DOSE: 20 mg/kg IV at an infusion rate of 50 to 100 mg/minute IV. An additional 5 to 10 mg/kg dose may be given 10 minutes after loading infusion if seizures persist or recur (Brophy et al, 2012).
    b) Patients receiving high doses will require endotracheal intubation and may require vasopressor support (Brophy et al, 2012).
    c) PEDIATRIC LOADING DOSE: 20 mg/kg may be given as single or divided application (2 mg/kg/minute in children weighing less than 40 kg up to 100 mg/min in children weighing greater than 40 kg). A plasma concentration of about 20 mg/L will be achieved by this dose (Loddenkemper & Goodkin, 2011).
    d) REPEAT PEDIATRIC DOSE: Repeat doses of 5 to 20 mg/kg may be given every 15 to 20 minutes if seizures persist, with cardiorespiratory monitoring (Loddenkemper & Goodkin, 2011).
    e) MONITOR: For hypotension, respiratory depression, and the need for endotracheal intubation (Loddenkemper & Goodkin, 2011; Manno, 2003).
    f) SERUM CONCENTRATION MONITORING: Monitor serum concentrations over the next 12 to 24 hours. Therapeutic serum concentrations of phenobarbital range from 10 to 40 mcg/mL, although the optimal plasma concentration for some individuals may vary outside this range (Hvidberg & Dam, 1976; Choonara & Rane, 1990; AMA Department of Drugs, 1992).
    6) OTHER AGENTS
    a) If seizures persist after phenobarbital, propofol or pentobarbital infusion, or neuromuscular paralysis with general anesthesia (isoflurane) and continuous EEG monitoring should be considered (Manno, 2003). Other anticonvulsants can be considered (eg, valproate sodium, levetiracetam, lacosamide, topiramate) if seizures persist or recur; however, there is very little data regarding their use in toxin induced seizures, controlled trials are not available to define the optimal dosage ranges for these agents in status epilepticus (Brophy et al, 2012):
    1) VALPROATE SODIUM: ADULT DOSE: An initial dose of 20 to 40 mg/kg IV, at a rate of 3 to 6 mg/kg/minute; may give an additional dose of 20 mg/kg 10 minutes after loading infusion. PEDIATRIC DOSE: 1.5 to 3 mg/kg/minute (Brophy et al, 2012).
    2) LEVETIRACETAM: ADULT DOSE: 1000 to 3000 mg IV, at a rate of 2 to 5 mg/kg/min IV. PEDIATRIC DOSE: 20 to 60 mg/kg IV (Brophy et al, 2012; Loddenkemper & Goodkin, 2011).
    3) LACOSAMIDE: ADULT DOSE: 200 to 400 mg IV; 200 mg IV over 15 minutes (Brophy et al, 2012). PEDIATRIC DOSE: In one study, median starting doses of 1.3 mg/kg/day and maintenance doses of 4.7 mg/kg/day were used in children 8 years and older (Loddenkemper & Goodkin, 2011).
    4) TOPIRAMATE: ADULT DOSE: 200 to 400 mg nasogastric/orally OR 300 to 1600 mg/day orally divided in 2 to 4 times daily (Brophy et al, 2012).
    7) RECURRING SEIZURES
    a) If seizures are not controlled by the above measures, patients will require endotracheal intubation, mechanical ventilation, continuous EEG monitoring, a continuous infusion of an anticonvulsant, and may require neuromuscular paralysis and vasopressor support. Consider continuous infusions of the following agents:
    1) MIDAZOLAM: ADULT DOSE: An initial dose of 0.2 mg/kg slow bolus, at an infusion rate of 2 mg/minute; maintenance doses of 0.05 to 2 mg/kg/hour continuous infusion dosing, titrated to EEG (Brophy et al, 2012). PEDIATRIC DOSE: 0.1 to 0.3 mg/kg followed by a continuous infusion starting at 1 mcg/kg/minute, titrated upwards every 5 minutes as needed (Loddenkemper & Goodkin, 2011).
    2) PROPOFOL: ADULT DOSE: Start at 20 mcg/kg/min with 1 to 2 mg/kg loading dose; maintenance doses of 30 to 200 mcg/kg/minute continuous infusion dosing, titrated to EEG; caution with high doses greater than 80 mcg/kg/minute in adults for extended periods of time (ie, longer than 48 hours) (Brophy et al, 2012); PEDIATRIC DOSE: IV loading dose of up to 2 mg/kg; maintenance doses of 2 to 5 mg/kg/hour may be used in older adolescents; avoid doses of 5 mg/kg/hour over prolonged periods because of propofol infusion syndrome (Loddenkemper & Goodkin, 2011); caution with high doses greater than 65 mcg/kg/min in children for extended periods of time; contraindicated in small children (Brophy et al, 2012).
    3) PENTOBARBITAL: ADULT DOSE: A loading dose of 5 to 15 mg/kg at an infusion rate of 50 mg/minute or lower; may administer additional 5 to 10 mg/kg. Maintenance dose of 0.5 to 5 mg/kg/hour continuous infusion dosing, titrated to EEG (Brophy et al, 2012). PEDIATRIC DOSE: A loading dose of 3 to 15 mg/kg followed by a maintenance dose of 1 to 5 mg/kg/hour (Loddenkemper & Goodkin, 2011).
    4) THIOPENTAL: ADULT DOSE: 2 to 7 mg/kg, at an infusion rate of 50 mg/minute or lower. Maintenance dose of 0.5 to 5 mg/kg/hour continuous infusing dosing, titrated to EEG (Brophy et al, 2012)
    b) Endotracheal intubation, mechanical ventilation, and vasopressors will be required (Brophy et al, 2012) and consultation with a neurologist is strongly advised.
    c) Neuromuscular paralysis (eg, rocuronium bromide, a short-acting nondepolarizing agent) may be required to avoid hyperthermia, severe acidosis, and rhabdomyolysis. If rhabdomyolysis is possible, avoid succinylcholine chloride, because of the risk of hyperkalemic-induced cardiac dysrhythmias. Continuous EEG monitoring is mandatory if neuromuscular paralysis is used (Manno, 2003).

Inhalation Exposure

    6.7.1) DECONTAMINATION
    A) Move patient from the toxic environment to fresh air. Monitor for respiratory distress. If cough or difficulty in breathing develops, evaluate for hypoxia, respiratory tract irritation, bronchitis, or pneumonitis.
    B) OBSERVATION: Carefully observe patients with inhalation exposure for the development of any systemic signs or symptoms and administer symptomatic treatment as necessary.
    C) INITIAL TREATMENT: Administer 100% humidified supplemental oxygen, perform endotracheal intubation and provide assisted ventilation as required. Administer inhaled beta-2 adrenergic agonists, if bronchospasm develops. Consider systemic corticosteroids in patients with significant bronchospasm (National Heart,Lung,and Blood Institute, 2007). Exposed skin and eyes should be flushed with copious amounts of water.

Eye Exposure

    6.8.1) DECONTAMINATION
    A) EYE IRRIGATION, ROUTINE: Remove contact lenses and irrigate exposed eyes with copious amounts of room temperature 0.9% saline or water for at least 15 minutes. If irritation, pain, swelling, lacrimation, or photophobia persist after 15 minutes of irrigation, an ophthalmologic examination should be performed (Peate, 2007; Naradzay & Barish, 2006).

Dermal Exposure

    6.9.1) DECONTAMINATION
    A) DERMAL DECONTAMINATION
    1) DECONTAMINATION: Remove contaminated clothing and jewelry and place them in plastic bags. Wash exposed areas with soap and water for 10 to 15 minutes with gentle sponging to avoid skin breakdown. Rescue personnel and bystanders should avoid direct contact with contaminated skin, clothing, or other objects (Burgess et al, 1999). Since contaminated leather items cannot be decontaminated, they should be discarded (Simpson & Schuman, 2002).

Enhanced Elimination

    A) ENHANCED ELIMINATION
    1) There are no data evaluating repeat-dose activated charcoal or hemodialysis.

Range Of Toxicity

Summary

    A) TOXICITY: Severe toxicity appears to be very rare; inadvertent exposure rarely causes significant toxicity.

Workplace Standards

    A) ACGIH TLV Values for CAS137-26-8 (American Conference of Governmental Industrial Hygienists, 2010):
    1) Editor's Note: The listed values are recommendations or guidelines developed by ACGIH(R) to assist in the control of health hazards. They should only be used, interpreted and applied by individuals trained in industrial hygiene. Before applying these values, it is imperative to read the introduction to each section in the current TLVs(R) and BEI(R) Book and become familiar with the constraints and limitations to their use. Always consult the Documentation of the TLVs(R) and BEIs(R) before applying these recommendations and guidelines.
    a) Adopted Value
    1) Thiram
    a) TLV:
    1) TLV-TWA: 0.05 mg/m(3)
    2) TLV-STEL:
    3) TLV-Ceiling:
    b) Notations and Endnotes:
    1) Carcinogenicity Category: A4
    2) Codes: IFV, SEN
    3) Definitions:
    a) A4: Not Classifiable as a Human Carcinogen: Agents which cause concern that they could be carcinogenic for humans but which cannot be assessed conclusively because of a lack of data. In vitro or animal studies do not provide indications of carcinogenicity which are sufficient to classify the agent into one of the other categories.
    b) IFV: Inhalable fraction and vapor.
    c) SEN: The designation SEN refers to the potential for an agent to produce sensitization, as confirmed by human or animal data. The notation does not imply that this is the critical effect or that this is the sole basis for the TLV. Although, for those TLVs that are based on sensitization, the TLV is meant to protect workers from induction of this effect, but cannot protect workers who have already become sensitized. The notation should be used to assist in identifying sensitization hazards and reducing respiratory, dermal, and conjunctival exposures to sensitizing agents in the workplace. Please see "Definitions and Notations" (in TLV booklet) for full definition.
    c) TLV Basis - Critical Effect(s): Body weight and hematologic eff
    d) Molecular Weight: 240.44
    1) For gases and vapors, to convert the TLV from ppm to mg/m(3):
    a) [(TLV in ppm)(gram molecular weight of substance)]/24.45
    2) For gases and vapors, to convert the TLV from mg/m(3) to ppm:
    a) [(TLV in mg/m(3))(24.45)]/gram molecular weight of substance
    e) Additional information:

    B) NIOSH REL and IDLH Values for CAS137-26-8 (National Institute for Occupational Safety and Health, 2007):
    1) Listed as: Thiram
    2) REL:
    a) TWA: 5 mg/m(3)
    b) STEL:
    c) Ceiling:
    d) Carcinogen Listing: (Not Listed) Not Listed
    e) Skin Designation: Not Listed
    f) Note(s):
    3) IDLH:
    a) IDLH: 100 mg/m3
    b) Note(s): Not Listed

    C) Carcinogenicity Ratings for CAS137-26-8 :
    1) ACGIH (American Conference of Governmental Industrial Hygienists, 2010): A4 ; Listed as: Thiram
    a) A4 :Not Classifiable as a Human Carcinogen: Agents which cause concern that they could be carcinogenic for humans but which cannot be assessed conclusively because of a lack of data. In vitro or animal studies do not provide indications of carcinogenicity which are sufficient to classify the agent into one of the other categories.
    2) EPA (U.S. Environmental Protection Agency, 2011): Not Assessed under the IRIS program. ; Listed as: Thiram
    3) IARC (International Agency for Research on Cancer (IARC), 2016; International Agency for Research on Cancer, 2015; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010a; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2008; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2007; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2006; IARC, 2004): 3 ; Listed as: Thiram
    a) 3 : The agent (mixture or exposure circumstance) is not classifiable as to its carcinogenicity to humans. This category is used most commonly for agents, mixtures and exposure circumstances for which the evidence of carcinogenicity is inadequate in humans and inadequate or limited in experimental animals. Exceptionally, agents (mixtures) for which the evidence of carcinogenicity is inadequate in humans but sufficient in experimental animals may be placed in this category when there is strong evidence that the mechanism of carcinogenicity in experimental animals does not operate in humans. Agents, mixtures and exposure circumstances that do not fall into any other group are also placed in this category.
    4) NIOSH (National Institute for Occupational Safety and Health, 2007): Not Listed ; Listed as: Thiram
    5) MAK (DFG, 2002): Not Listed
    6) NTP (U.S. Department of Health and Human Services, Public Health Service, National Toxicology Project ): Not Listed

    D) OSHA PEL Values for CAS137-26-8 (U.S. Occupational Safety, and Health Administration (OSHA), 2010):
    1) Listed as: Thiram
    2) Table Z-1 for Thiram:
    a) 8-hour TWA:
    1) ppm:
    a) Parts of vapor or gas per million parts of contaminated air by volume at 25 degrees C and 760 torr.
    2) mg/m3: 5
    a) Milligrams of substances per cubic meter of air. When entry is in this column only, the value is exact; when listed with a ppm entry, it is approximate.
    3) Ceiling Value:
    4) Skin Designation: No
    5) Notation(s): Not Listed

Toxicity Information

    7.7.1) TOXICITY VALUES
    A) CARBENDAZIM
    1) LD50- (ORAL)MOUSE:
    a) 7700 mg/kg (RTECS , 2002)
    2) LD50- (ORAL)RAT:
    a) 6400 mg/kg (RTECS , 2002)
    3) LD50- (SKIN)RAT:
    a) >2 g/kg (RTECS , 2002)
    B) THIRAM
    1) LD50- (ORAL)MOUSE:
    a) 1250 mg/kg (RTECS , 2002)
    b) 2050-2500 mg/kg (Dalvi, 1988)
    2) LD50- (ORAL)RAT:
    a) 560 mg/kg (RTECS , 2002)
    b) 620-640 mg/kg (Dalvi, 1988)
    C) VONDOZEB
    1) LD50- (ORAL)RAT:
    a) 5 g/kg (RTECS , 2002)
    2) LD50- (SKIN)RAT:
    a) >10 g/kg (RTECS , 2002)
    D) ZINEB
    1) LD50- (ORAL)MOUSE:
    a) 7600 mg/kg (RTECS , 2002)
    2) LD50- (ORAL)RAT:
    a) 1850 mg/kg (RTECS , 2002)
    3) LD50- (SKIN)RAT:
    a) >2500 mg/kg (RTECS , 2002)
    E) ZIRAM
    1) LD50- (ORAL)MOUSE:
    a) 480 mg/kg (RTECS , 2002)
    2) LD50- (ORAL)RAT:
    a) 267 mg/kg (RTECS , 2002)
    3) LD50- (SKIN)RAT:
    a) >6 g/kg (RTECS , 2002)

Pharmacology Toxicology

Toxicologic Mechanism

    A) Unlike the carbamate insecticides, carbamate herbicides and fungicides do not inhibit the cholinesterase enzyme (Machemer & Pickel, 1994).
    B) THIRAM
    1) Inhibits acetaldehyde oxidase. This action accounts for the Antabuse(R) reaction to imbibed alcohol following extraordinary absorption of thiram. The dimethyldithiocarbamate (MBDT-CARB) compounds have some potential for causing the same enzyme inhibition.
    2) Thiram and the MBDT-CARB compounds are metabolized, in part, to carbon disulfide. This may be one mechanism whereby these chemicals are neurotoxic at extraordinary dosage.
    3) Persons sensitive to rubber may, in fact, be sensitive to thiram, used as a curing agent. These individuals must avoid contact with thiram and probably the MBDT-CARB compounds as well.
    C) The ethylene bisdithiocarbamate (EBDT-CARB) compounds degrade in the environment and in mammalian tissues to ethylene thiourea (ETU). This substance is a goitrogen, mutagen, and carcinogen (Liesivuori & Savolainen, 1994).
    1) Special care is recommended in removing residues of EBDT-CARB compounds from agricultural produce and in protecting workers from these residues.
    D) CANCER: Animal experiments have demonstrated a potentiation of carcinogenesis when rats consuming disulfiram in the diet were exposed to ethylene dibromide. A similar potentiation may exist in the case of concurrent exposures to thiram and ethylene dibromide.
    E) MANGANESE TOXICITY: Maneb is an organic manganese compound. It has been suggested that CNS toxicity may be related to the manganese content (Ferraz et al, 1988).

Physicochemical

Physical Characteristics

    A) Is a white, crystalline solid.

Molecular Weight

    A) 240.44

Animal Toxicology

Clinical Effects

    11.1.1) AVIAN/BIRD
    A) Thiram contaminated feed given by Spanish chicken farmers caused soft egg shells, depressed growth and leg abnormalities (Guitart et al, 1996).
    11.1.2) BOVINE/CATTLE
    A) Zineb (an EBDC herbicide) is known to cause decreased fertility, decreased drug metabolism, and impaired thyroid fuction (Nebbia et al, 1991).
    1) The thyroid gland weight was increased, associated with epithelial vacuolization and foci of hyperplasia (Nebbia et al, 1991).
    2) The dose given was 200 mg of zineb per kilogram of body weight for 80 days.

References

General Bibliography

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    2) 40 CFR 372.65: Environmental Protection Agency - Toxic Chemical Release Reporting, Community Right-To-Know, Chemicals and Chemical Categories to which this part applies. National Archives and Records Association (NARA) and the Government Printing Office (GPO), Washington, DC. Final rules current as of Apr 3, 2006.
    3) 49 CFR 172.101 - App. B: Department of Transportation - Table of Hazardous Materials, Appendix B: List of Marine Pollutants. National Archives and Records Administration (NARA) and the Government Printing Office (GPO), Washington, DC. Final rules current as of Aug 29, 2005.
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    7) 65 FR 77866: Notice of the National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances - Proposed AEGL Values, Environmental Protection Agency, NAC/AEGL Committee. National Archives and Records Administration (NARA) and the Government Publishing Office (GPO), Washington, DC, 2000.
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    9) 67 FR 7164: Notice of the National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances - Proposed AEGL Values, Environmental Protection Agency, NAC/AEGL Committee. National Archives and Records Administration (NARA) and the Government Publishing Office (GPO), Washington, DC, 2002.
    10) 68 FR 42710: Notice of the National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances - Proposed AEGL Values, Environmental Protection Agency, NAC/AEGL Committee. National Archives and Records Administration (NARA) and the Government Publishing Office (GPO), Washington, DC, 2003.
    11) 69 FR 54144: Notice of the National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances - Proposed AEGL Values, Environmental Protection Agency, NAC/AEGL Committee. National Archives and Records Administration (NARA) and the Government Publishing Office (GPO), Washington, DC, 2004.
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