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CHLOROTHALONIL

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Classification   |    Detailed evidence-based information

Substances Included Synonyms

Therapeutic Toxic Class

    A) Chlorothalonil is an industrial agricultural and horticultural fungicide, and may be used as a wood preservative in some countries. It is also used as a mildewicide in paints.

Specific Substances

    1) Chloroalonil
    2) Chlorthalonil (German)
    3) Tetrachloroisophthalonitrile
    4) m-TCPN
    5) m-tetrachlorophthalonitrile
    6) NCI-c 00102
    7) CAS 1897-45-6
    8) NOPCOCIDE N40D & N96
    1.2.1) MOLECULAR FORMULA
    1) C8-Cl4-N2

Available Forms Sources

    A) FORMS
    1) Chlorothalonil is a white crystalline, odorless solid (HSDB, 2003; Lewis, 1996).
    2) Chlorothalonil is available as a 75% wettable powder, 20% and 90% exothermic powder, and 500 g/liter flowable suspension concentrate (HSDB , 2002). The exothermic powder is heated to 600 to 800 degrees F, and vaporizes to form a gas which condenses on plant surfaces.
    3) CONTAMINANTS - Technical chlorothalonil is about 98% pure. Impurities that have been noted include (WHO, 1983):
    1) tetrachlorophthalonitrile <0.1%
    2) tetrachloroterephthalonitrile 0.5%
    3) pentachlorobenzonitrile 1.2%
    4) partially chlorinated dicyanobenzenes 0.4%
    5) unchlorinated dicyanobenzenes 0.3%
    B) USES
    1) Chlorothalonil is a chlorinated isophthalic acid derivative which is used as a fungicide. It also has bactericidal and nematocidal properties (Budavari, 2001). It is registered by the United States Environmental Protection Agency for use as a fungicide to control a wide variety of fungal diseases on fruits, vegetables, and peanuts. It is also used on lawns and turf, and as a paint and grout additive(HSDB, 2003; EPA, 1988).
    2) Used as a wood preservative in Europe, usually in less than 1% concentrations.

Overview

Life Support

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

Clinical Effects

    0.2.1) SUMMARY OF EXPOSURE
    A) WITH POISONING/EXPOSURE
    1) In customary use of this fungicide, it may be dissolved in an organic solvent prior to use. If a solvent mixture is ingested, the primary toxicological consideration should be given to the solvent, along with the strong irritant potential of chlorothalonil.
    2) Concentrations of 0.1% and greater in organic solvents are moderate dermal irritants in animals and would be expected to be irritant to eyes and gastrointestinal tract. Lawn applications are generally of aqueous solutions of 0.08% to 0.14% and are expected to produce mild dermatitis.
    3) Occupational asthma has been reported following inhalational exposure to chlorothalonil. Chlorothalonil concentrations of 0.01% were reported to cause an anaphylactoid reaction. Aspiration pneumonitis may occur due to the solvents in fungicide formulations.
    0.2.4) HEENT
    A) WITH POISONING/EXPOSURE
    1) Undiluted chlorothalonil is a strong skin irritant and produces irreversible corneal injury in animals.
    0.2.8) GASTROINTESTINAL
    A) WITH POISONING/EXPOSURE
    1) Spontaneous emesis may occur.
    0.2.14) DERMATOLOGIC
    A) WITH POISONING/EXPOSURE
    1) Irritant contact dermatitis can occur with exposure to concentrations of greater than 0.01% or 0.001% in acetone. Photosensitive and allergic reactions are also possible.
    2) Dermatitis may occur in the absence of direct skin contact, due to high volatility.
    0.2.19) IMMUNOLOGIC
    A) WITH POISONING/EXPOSURE
    1) Anaphylactic as well delayed hypersensitivity reactions may occur.
    0.2.20) REPRODUCTIVE
    A) Chlorothalonil has not been found to be teratogenic in animal studies.

Laboratory Monitoring

    A) No specific lab work (CBC, electrolytes, urinalysis) is needed unless otherwise clinically indicated.

Treatment Overview

    0.4.2) ORAL/PARENTERAL EXPOSURE
    A) Emesis is not indicated due to irritant properties and lack of systemic effects of dilute chlorothalonil. Risk of aspiration of the solvent vehicle also makes induced emesis potentially hazardous.
    B) DILUTION: If no respiratory compromise is present, administer milk or water as soon as possible after ingestion. Dilution may only be helpful if performed in the first seconds to minutes after ingestion. The ideal amount is unknown; no more than 8 ounces (240 mL) in adults and 4 ounces (120 mL) in children is recommended to minimize the risk of vomiting.
    C) Undiluted chlorothalonil is a strong irritant. However, corrosive effects have not been reported. Patients should be examined for signs of mucous membrane or tissue damage. Except under unusual circumstances, esophagoscopy, steroids, and antibiotics are not expected to be necessary.
    0.4.3) INHALATION EXPOSURE
    A) INHALATION: Move patient to fresh air. Monitor for respiratory distress. If cough or difficulty breathing develops, evaluate for respiratory tract irritation, bronchitis, or pneumonitis. Administer oxygen and assist ventilation as required. Treat bronchospasm with an inhaled beta2-adrenergic agonist. Consider systemic corticosteroids in patients with significant bronchospasm.
    0.4.4) EYE EXPOSURE
    A) DECONTAMINATION: 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, the patient should be seen in a healthcare facility.
    0.4.5) DERMAL EXPOSURE
    A) OVERVIEW
    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. A physician may need to examine the area if irritation or pain persists (Burgess et al, 1999).
    2) Delayed irritant dermatitis may occur 48 to 72 hours after cessation of exposure.
    3) Antihistamines or topical steroids may be useful in treating allergic contact dermatitis.

Range Of Toxicity

    A) Acute LD50 values in animals indicate minimal systemic toxicity from acute exposure. No human data are available.

Clinical Effects

Summary Of Exposure

    A) WITH POISONING/EXPOSURE
    1) In customary use of this fungicide, it may be dissolved in an organic solvent prior to use. If a solvent mixture is ingested, the primary toxicological consideration should be given to the solvent, along with the strong irritant potential of chlorothalonil.
    2) Concentrations of 0.1% and greater in organic solvents are moderate dermal irritants in animals and would be expected to be irritant to eyes and gastrointestinal tract. Lawn applications are generally of aqueous solutions of 0.08% to 0.14% and are expected to produce mild dermatitis.
    3) Occupational asthma has been reported following inhalational exposure to chlorothalonil. Chlorothalonil concentrations of 0.01% were reported to cause an anaphylactoid reaction. Aspiration pneumonitis may occur due to the solvents in fungicide formulations.

Heent

    3.4.1) SUMMARY
    A) WITH POISONING/EXPOSURE
    1) Undiluted chlorothalonil is a strong skin irritant and produces irreversible corneal injury in animals.
    3.4.3) EYES
    A) WITH POISONING/EXPOSURE
    1) Undiluted chlorothalonil is a strong irritant and produced irreversible corneal, iridal, and conjunctival effects in rabbits. Corneal opacities reversed within 2 weeks in monkeys (Technical Information, 1985; HSDB, 2003).

Respiratory

    3.6.2) CLINICAL EFFECTS
    A) PULMONARY ASPIRATION
    1) WITH POISONING/EXPOSURE
    a) Aspiration pneumonitis might develop after ingestion secondary to the organic solvent in which chlorothalonil is usually dissolved.
    B) OCCUPATIONAL ASTHMA
    1) WITH POISONING/EXPOSURE
    a) Occupational asthma was suggested in 2 workers exposed to powdered chlorothalonil and fluazinam in a fungicide formulation plant (Draper et al, 2003).
    3.6.3) ANIMAL EFFECTS
    A) ANIMAL STUDIES
    1) HYPERVENTILATION
    a) RATS: Tachypnea was noted in chronic studies on rats (Gosselin et al, 1984).

Neurologic

    3.7.3) ANIMAL EFFECTS
    A) ANIMAL STUDIES
    1) SOMNOLENCE
    a) Weakness and sedation preceded death in animals given acute toxic doses intraperitoneally (Spencer, 1973).
    2) ATAXIA
    a) RATS - Chronic oral administration to rats resulted in ataxia (Gosselin et al, 1984).

Gastrointestinal

    3.8.1) SUMMARY
    A) WITH POISONING/EXPOSURE
    1) Spontaneous emesis may occur.
    3.8.2) CLINICAL EFFECTS
    A) GASTROENTERITIS
    1) WITH POISONING/EXPOSURE
    a) Undiluted chlorothalonil is extremely irritating to skin and would be expected to produce gastrointestinal irritation if ingested. Spontaneous emesis was reported in animals (Gosselin et al, 1984).

Genitourinary

    3.10.3) ANIMAL EFFECTS
    A) ANIMAL STUDIES
    1) HEMATURIA
    a) RATS: Bright yellow urine and hematuria were noted in rats during chronic feeding studies (Gosselin et al, 1984).

Hematologic

    3.13.3) ANIMAL EFFECTS
    A) ANIMAL STUDIES
    1) EPISTAXIS
    a) RATS: Hematuria, vaginal bleeding, and epistaxis were seen in rats following chronic oral exposure (Gosselin et al, 1984).

Dermatologic

    3.14.1) SUMMARY
    A) WITH POISONING/EXPOSURE
    1) Irritant contact dermatitis can occur with exposure to concentrations of greater than 0.01% or 0.001% in acetone. Photosensitive and allergic reactions are also possible.
    2) Dermatitis may occur in the absence of direct skin contact, due to high volatility.
    3.14.2) CLINICAL EFFECTS
    A) CONTACT DERMATITIS
    1) WITH POISONING/EXPOSURE
    a) Chlorothalonil is a strong primary skin irritant and may also cause allergic contact dermatitis. Patch testing with concentrations greater than 0.01% may produce primary irritant reactions (Bach & Bang Pedersen, 1980).
    b) CASE SERIES: Facial erythema, periorbital erythema and edema, eczema, and pruritus were noted in 14 of 20 workers in a wooden-ware factory using a 0.5% wood preservative. Seven of the 14 demonstrated positive skin tests to chlorothalonil (Johnsson et al, 1983). Of 88 Japanese farmers patch tested, 10 to 28% were sensitive to chlorothalonil. Photosensitivity reactions were seen in some (Horiuchi & Ando, 1980).
    c) Exposure to chlorothalonil was possibly associated with erythema dyschromicum perstans-like dermatitis in 39 banana farm workers. Patch testing was positive to 0.001% chlorothalonil in acetone. Biopsies showed lichenoid tissue reaction compatible with chronic pigmented dermatitis (Penagos et al, 1996).
    d) Contact dermatitis was studied in 281 banana plantation workers exposed to pesticides, among them chlorothalonil. The most affected areas were the hands (82%), thorax and abdomen (9%), legs and feet (5%), and genitalia (4%). A positive pesticides patch test was observed in 27.8% of the exposed workers; 51.4% of them were positive to chlorothalonil (Penagos, 2002).
    B) SKIN IRRITATION
    1) WITH POISONING/EXPOSURE
    a) High concentrations produce delayed irritant reactions. In controls patch tested with 1%, irritancy increased in intensity after removal of the patch at 24 hours. Marginal irritation and faint redness were seen in 4 of 17 controls tested with 0.01% at 48 and 72 hours (Bruynzeel & van Ketel, 1986).
    C) DERMATITIS
    1) WITH POISONING/EXPOSURE
    a) FACIAL dermatitis has been reported in occupational exposures, and can occur in the absence of direct skin contact, presumably due to the high volatility of chlorothalonil (Liden, 1990).
    3.14.3) ANIMAL EFFECTS
    A) ANIMAL STUDIES
    1) IRRITATION
    a) In chronic dermal exposures in animals to chlorothalonil dissolved in acetone, the "no effect" level for irritation was 0.001%. The 0.01% concentration was a mild irritant and the 0.1% a moderate irritant (Flannigan et al, 1986).
    b) In a similar rabbit experiment, a 0.1% in saline or petrolatum was minimally irritating (Flannigan & Tucker, 1985).

Endocrine

    3.16.2) CLINICAL EFFECTS
    A) KETOSIS
    1) WITH POISONING/EXPOSURE
    a) CASE REPORT: A 56-year-old male farmer was admitted with severe dehydration, hypotension, vomiting, and general malaise. Laboratory analysis revealed elevated blood glucose (861 mg/dL; reference range 70 to 110 mg/dL), an HbA1c of 14.3% (reference range, 4% to 6%), acidosis (pH 7.05, HCO3 3.8 mEq/L), and severe ketonuria, consistent with a diagnosis of diabetic ketoacidosis. Approximately 2 months prior to presentation, the patient had been hired to clean a farm shed and various pesticides were used, including chlorothalonil; however, no protective equipment (eg, gloves, clothing, or respiratory devices) was used. Within 3 weeks, the patient had developed polyuria, polydipsia, and steady weight loss. Approximately 6 weeks later, malaise, progressive weakness, and abdominal pain had developed. After admission, the patient's serum chlorothalonil concentration was 160 ng/mL. Residues of other pesticides were undetectable. The patient recovered and achieved glycemic control (HbA1c 5.7%), 1 year later, following avoidance of exposure to pesticides and continued therapy with metformin (Fernandez-Garcia et al, 2014).

Immunologic

    3.19.1) SUMMARY
    A) WITH POISONING/EXPOSURE
    1) Anaphylactic as well delayed hypersensitivity reactions may occur.
    3.19.2) CLINICAL EFFECTS
    A) ANAPHYLACTOID REACTION
    1) WITH POISONING/EXPOSURE
    a) Anaphylaxis has been seen following inhalational contact with chlorothalonil as well as a delayed-type hypersensitivity.
    b) Within 15 to 30 minutes after inhalation exposure to chlorothalonil a patient experienced pruritus, severe facial edema as well as generalized edema, nasal congestion, chest tightness, laryngospasm, dysphagia, dyspnea, and wheezing (Dannaker et al, 1993). Skin patch testing of 0.01% chlorothalonil to the patient's intact forearm skin without occlusion resulted in an anaphylactoid reaction, including marked facial flushing, eyelid edema, dysphagia, and dyspnea.

Reproductive

    3.20.1) SUMMARY
    A) Chlorothalonil has not been found to be teratogenic in animal studies.
    3.20.2) TERATOGENICITY
    A) LACK OF EFFECT
    1) Chlorothalonil has not been found to be teratogenic in rats and rabbits (Technical Information, 1987).
    3.20.3) EFFECTS IN PREGNANCY
    A) ANIMAL STUDIES
    1) RATS: Oral administration of chlorothalonil to pregnant rats did not effect body weight gain of dams and offspring (de Castro et al, 2000).

Carcinogenicity

    3.21.1) IARC CATEGORY
    A) IARC Carcinogenicity Ratings for CAS1897-45-6 (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: Chlorothalonil
    b) Carcinogen Rating: 2B
    1) The agent (mixture) is possibly carcinogenic to humans. The exposure circumstance entails exposures that are possibly carcinogenic to humans. This category is used for agents, mixtures and exposure circumstances for which there is limited evidence of carcinogenicity in humans and less than sufficient evidence of carcinogenicity in experimental animals. It may also be used when there is inadequate evidence of carcinogenicity in humans but there is sufficient evidence of carcinogenicity in experimental animals. In some instances, an agent, mixture or exposure circumstance for which there is inadequate evidence of carcinogenicity in humans but limited evidence of carcinogenicity in experimental animals together with supporting evidence from other relevant data may be placed in this group.
    3.21.4) ANIMAL STUDIES
    A) Carcinoma
    1) Rats fed 20 g/kg in the diet developed a dose-related increased incidence of renal tubular adenomas and adenocarcinomas. A similar study in mice had negative results (WHO, 1983).
    2) Chronic dietary chlorothalonil treatment of rats and mice caused an increased incidence of papillomas and carcinomas of the forestomach squamous epithelium and adenomas. Carcinomas of the renal proximal tubule epithelium were induced in rats and male mice. These effects probably resulted from cytotoxicity followed by compensatory cell proliferation and hyperplasia, a threshold-based mechanism rather than genotoxicity. Exposure has to be intense and prolonged in order to be irreversible. Species difference may render these carcinogenic effects inappropriate for the evaluation of human cancer risk from chlorothalonil (Rakitsky et al, 2000; Wilkinson & Killeen, 1996).

Laboratory Monitoring

Monitoring Parameters Levels

    4.1.1) SUMMARY
    A) No specific lab work (CBC, electrolytes, urinalysis) is needed unless otherwise clinically indicated.

Methods

    A) CHROMATOGRAPHY
    1) Measurement of chlorothalonil in occupational exposures may be accomplished with normal phase HPLC with hexane-dioxane as the eluent and UV detection at either 254 or 325 nm. The limit of detection is approximately 0.5 mcg/liter. Cellulose filters may be used for collection of aerosol samples (Jongen et al, 1991).
    2) Gas chromatography with electron capture detection (ECD) and gas chromatography-mass spectrometric methods were developed for sampling and analyzing chlorothalonil in greenhouse air. The detection and quantitation limits, using the gas chromatographic with ECD method, were 1.9 and 6.2 ng/mL, respectively (Egea Gonzalez et al, 1997).

Treatment

Life Support

    A) Support respiratory and cardiovascular function.

Patient Disposition

    6.3.5) DISPOSITION/DERMAL EXPOSURE
    6.3.5.5) OBSERVATION CRITERIA/DERMAL
    A) DERMAL EXPOSURE - Delayed dermal irritant effects have been noted 48 to 72 hours after cessation of exposure. Patients should be followed up after decontamination for at least 48 hours and referred to a physician if signs of irritation develop.

Monitoring

    A) No specific lab work (CBC, electrolytes, urinalysis) is needed unless otherwise clinically indicated.

Oral Exposure

    6.5.1) PREVENTION OF ABSORPTION/PREHOSPITAL
    A) SUMMARY -
    1) Emesis and activated charcoal are not indicated due to the irritant properties and lack of systemic effects of chlorothalonil as well as risk of aspiration of the solvent vehicle.
    B) DILUTION -
    1) DILUTION: If no respiratory compromise is present, administer milk or water as soon as possible after ingestion. Dilution may only be helpful if performed in the first seconds to minutes after ingestion. The ideal amount is unknown; no more than 8 ounces (240 mL) in adults and 4 ounces (120 mL) in children is recommended to minimize the risk of vomiting (Caravati, 2004).
    6.5.2) PREVENTION OF ABSORPTION
    A) EMESIS
    1) Emesis is not indicated due to the irritant properties and lack of systemic effects of chlorothalonil.
    B) DILUTION
    1) DILUTION: If no respiratory compromise is present, administer milk or water as soon as possible after ingestion. Dilution may only be helpful if performed in the first seconds to minutes after ingestion. The ideal amount is unknown; no more than 8 ounces (240 mL) in adults and 4 ounces (120 mL) in children is recommended to minimize the risk of vomiting (Caravati, 2004).
    6.5.3) TREATMENT
    A) ORGANIC CHEMICAL SOLVENT
    1) If mixed with an organic solvent, toxicity from the solvent should be considered. Systemic effects are unlikely.
    B) IRRITATION SYMPTOM
    1) Undiluted chlorothalonil is a strong irritant. However, corrosive effects have not been reported. Patients should be examined for signs of mucous membrane or tissue damage.
    2) Except under unusual circumstances, esophagoscopy, steroids, and antibiotics are not expected to be necessary.

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.
    6.7.2) TREATMENT
    A) MONITORING OF PATIENT
    1) A chest x-ray may be needed following significant inhalation exposure. Some irritants produce delayed pulmonary edema.
    B) ACUTE LUNG INJURY
    1) ONSET: Onset of acute lung injury after toxic exposure may be delayed up to 24 to 72 hours after exposure in some cases.
    2) NON-PHARMACOLOGIC TREATMENT: The treatment of acute lung injury is primarily supportive (Cataletto, 2012). Maintain adequate ventilation and oxygenation with frequent monitoring of arterial blood gases and/or pulse oximetry. If a high FIO2 is required to maintain adequate oxygenation, mechanical ventilation and positive-end-expiratory pressure (PEEP) may be required; ventilation with small tidal volumes (6 mL/kg) is preferred if ARDS develops (Haas, 2011; Stolbach & Hoffman, 2011).
    a) To minimize barotrauma and other complications, use the lowest amount of PEEP possible while maintaining adequate oxygenation. Use of smaller tidal volumes (6 mL/kg) and lower plateau pressures (30 cm water or less) has been associated with decreased mortality and more rapid weaning from mechanical ventilation in patients with ARDS (Brower et al, 2000). More treatment information may be obtained from ARDS Clinical Network website, NIH NHLBI ARDS Clinical Network Mechanical Ventilation Protocol Summary, http://www.ardsnet.org/node/77791 (NHLBI ARDS Network, 2008)
    3) FLUIDS: Crystalloid solutions must be administered judiciously. Pulmonary artery monitoring may help. In general the pulmonary artery wedge pressure should be kept relatively low while still maintaining adequate cardiac output, blood pressure and urine output (Stolbach & Hoffman, 2011).
    4) ANTIBIOTICS: Indicated only when there is evidence of infection (Artigas et al, 1998).
    5) EXPERIMENTAL THERAPY: Partial liquid ventilation has shown promise in preliminary studies (Kollef & Schuster, 1995).
    6) CALFACTANT: In a multicenter, randomized, blinded trial, endotracheal instillation of 2 doses of 80 mL/m(2) calfactant (35 mg/mL of phospholipid suspension in saline) in infants, children, and adolescents with acute lung injury resulted in acute improvement in oxygenation and lower mortality; however, no significant decrease in the course of respiratory failure measured by duration of ventilator therapy, intensive care unit, or hospital stay was noted. Adverse effects (transient hypoxia and hypotension) were more frequent in calfactant patients, but these effects were mild and did not require withdrawal from the study (Wilson et al, 2005).
    7) However, in a multicenter, randomized, controlled, and masked trial, endotracheal instillation of up to 3 doses of calfactant (30 mg) in adults only with acute lung injury/ARDS due to direct lung injury was not associated with improved oxygenation and longer term benefits compared to the placebo group. It was also associated with significant increases in hypoxia and hypotension (Willson et al, 2015).
    C) Treatment should include recommendations listed in the ORAL EXPOSURE section when appropriate.

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).
    6.8.2) TREATMENT
    A) IRRITATION SYMPTOM
    1) If in a medical facility, sterile saline should be used to irrigate the eyes. A slit lamp examination should be considered following thorough irrigation.
    2) Administration of antibiotics, cycloplegic, mydriatic, or local anesthetic agents may be necessary in rare circumstances.
    B) Treatment should include recommendations listed in the ORAL EXPOSURE section when appropriate.

Dermal Exposure

    6.9.1) DECONTAMINATION
    A) DERMAL DECONTAMINATION
    1) DECONTAMINATION: Remove contaminated clothing and wash exposed area thoroughly with soap and water for 10 to 15 minutes. A physician may need to examine the area if irritation or pain persists (Burgess et al, 1999).
    6.9.2) TREATMENT
    A) DERMATITIS
    1) The skin reaction is said to resemble a mild sunburn of short duration if treated. If not treated, the skin should peel and heal in about 2 weeks (Technical Information, 1987).
    2) Allergic contact dermatitis may be treated with antihistamines, topical steroids, and/or systemic steroids (Technical Information, 1985).
    B) Treatment should include recommendations listed in the ORAL EXPOSURE section when appropriate.

Range Of Toxicity

Summary

    A) Acute LD50 values in animals indicate minimal systemic toxicity from acute exposure. No human data are available.

Minimum Lethal Exposure

    A) GENERAL/SUMMARY
    1) The minimum lethal human dose to this agent has not been delineated.

Maximum Tolerated Exposure

    A) GENERAL/SUMMARY
    1) The maximum tolerated human exposure to this agent has not been delineated.
    B) ANIMAL DATA
    1) In animls, using chronic dermal exposures to chlorothalonil dissolved in acetone, the "no effect" level for irritation was 0.001%. The 0.01% concentration was mildly irritating and 0.1% moderately irritating (Flannigan et al, 1986).
    2) In a similar rabbit experiment, 0.1% chlorothalonil in saline or petrolatum was minimally irritating (Flannigan & Tucker, 1985).

Workplace Standards

    A) ACGIH TLV Values for CAS1897-45-6 (American Conference of Governmental Industrial Hygienists, 2010):
    1) Not Listed

    B) NIOSH REL and IDLH Values for CAS1897-45-6 (National Institute for Occupational Safety and Health, 2007):
    1) Not Listed

    C) Carcinogenicity Ratings for CAS1897-45-6 :
    1) ACGIH (American Conference of Governmental Industrial Hygienists, 2010): Not Listed
    2) EPA (U.S. Environmental Protection Agency, 2011): Not Assessed under the IRIS program. ; Listed as: Chlorothalonil
    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): 2B ; Listed as: Chlorothalonil
    a) 2B : The agent (mixture) is possibly carcinogenic to humans. The exposure circumstance entails exposures that are possibly carcinogenic to humans. This category is used for agents, mixtures and exposure circumstances for which there is limited evidence of carcinogenicity in humans and less than sufficient evidence of carcinogenicity in experimental animals. It may also be used when there is inadequate evidence of carcinogenicity in humans but there is sufficient evidence of carcinogenicity in experimental animals. In some instances, an agent, mixture or exposure circumstance for which there is inadequate evidence of carcinogenicity in humans but limited evidence of carcinogenicity in experimental animals together with supporting evidence from other relevant data may be placed in this group.
    4) NIOSH (National Institute for Occupational Safety and Health, 2007): Not Listed
    5) MAK (DFG, 2002): Category 3B ; Listed as: Chlorothalonil
    a) Category 3B : Substances for which in vitro or animal studies have yielded evidence of carcinogenic effects that is not sufficient for classification of the substance in one of the other categories. Further studies are required before a final decision can be made. A MAK value can be established provided no genotoxic effects have been detected. (Footnote: In the past, when a substance was classified as Category 3 it was given a MAK value provided that it had no detectable genotoxic effects. When all such substances have been examined for whether or not they may be classified in Category 4, this sentence may be omitted.)
    6) NTP (U.S. Department of Health and Human Services, Public Health Service, National Toxicology Project ): Not Listed

    D) OSHA PEL Values for CAS1897-45-6 (U.S. Occupational Safety, and Health Administration (OSHA), 2010):
    1) Not Listed

Toxicity Information

    7.7.1) TOXICITY VALUES
    A) References: RTECS, 2002 Lewis, 1996
    1) LD50- (INTRAPERITONEAL)MOUSE:
    a) 2500 mcg/kg
    2) LD50- (ORAL)MOUSE:
    a) 3700 mg/kg
    b) 6 g/kg
    3) LD50- (ORAL)RAT:
    a) 10 g/kg
    4) LD50- (SKIN)RAT:
    a) >2500 mg/kg
    5) LD50- (SUBCUTANEOUS)RAT:
    a) >5 g/kg

Pharmacology Toxicology

Pharmacologic Mechanism

    A) Chlorothalonil acts as an alkylating agent and reacts with cellular sulfhydryl compounds (HSDB , 1990).

Physicochemical

Physical Characteristics

    A) Chlorothalonil is a white crystalline, odorless solid, soluble in organic solvents and practically insoluble in water (HSDB, 2003; S Budavari , 2001; Lewis, 1996).
    1) The technical product (approximately 98% pure) has a slightly pungent odor (HSDB , 2002).

Ph

    1) No information found at the time of this review.

Molecular Weight

    A) 265.89

References

General Bibliography

    1) 40 CFR 372.28: Environmental Protection Agency - Toxic Chemical Release Reporting, Community Right-To-Know, Lower thresholds for chemicals of special concern. National Archives and Records Administration (NARA) and the Government Printing Office (GPO). Washington, DC. Final rules current as of Apr 3, 2006.
    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.
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