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METOLACHLOR

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Classification   |    Detailed evidence-based information

Substances Included Synonyms

Therapeutic Toxic Class

    A) Metolachlor is a selective pre-emergence acetamide herbicide (Thomson, 1981-82).

Specific Substances

    1) 2-chloro-N-(2-ethyl-6-methylphenyl)-N-(2-methoxy-1
    2) -methylethyl) acetamide
    3) 2-chloro-6'-ethyl-N-(2-methoxy-1-methylethyl)
    4) acet-o-toluidide
    5) Metelilachlor
    6) CGA 24705
    7) Dual
    8) Bicep
    9) Acetamide,2-chlor-6'-ethyl-n-(1-methoxy-1
    10) -methylaethyl)-acet-o-toluidin
    11) Codal
    12) Cotoran Multi
    13) Metachlore
    14) Milocep
    15) Ontrack 8E
    16) Primagram
    17) Primextra
    18) 2-ethyl-6-methyl-1-N-(2-Methoxy-1-methylethyl)
    19) chloroacetanilide
    20) NIOSH/RTECS AN 3430000
    21) CAS 51218-45-2
    22) COTORAN METACHLORE
    23) METELILACHOR

Available Forms Sources

    A) FORMS
    1) Trade names include Dual, Humextra, Pennant, GCA 24705, Bicep, Codal, Cotoran Multi, Primagram, Primextra, Milocep, Ontrack 8E (Sine, 1987)
    B) USES
    1) Metolachlor is a selective, pre-emergence acetamide herbicide developed in 1974 by the Ciba-Geigy Chemical Company. It is used primarily on corn, peanuts, sorghum, and soybeans to kill various grasses, pigweed, purslane, chickweed, and other weeds (Thomson, 1981-82; (Chesters et al, 1989).

Overview

Life Support

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

Clinical Effects

    0.2.1) SUMMARY OF EXPOSURE
    A) There are very little data available on the toxicity of metolachlor to humans. Animal models have shown mild to moderate irritancy of skin. Burns have not been noticed. There may be a problem with persons who have G-6-PD deficiency, but this is only proposed, based on an animal model. Until more is known, the following basic measures apply.
    B) Exposed individuals should have a careful, thorough medical history and physical examination performed, looking for any abnormalities. Exposure to chemicals with a strong odor often results in such nonspecific symptoms as headache, dizziness, weakness, and nausea.
    C) Many chemicals cause irritation of the eyes, skin, and respiratory tract. In severe cases respiratory tract irritation can progress to ARDS/acute lung injury, which may be delayed in onset for up to 24 to 72 hours in some cases.
    D) Irritation or burns of the esophagus or gastrointestinal tract are also possible if caustic or irritant chemicals are ingested.
    0.2.14) DERMATOLOGIC
    A) Metolachlor may cause mild dermal irritation.
    0.2.19) IMMUNOLOGIC
    A) A number of chemical agents produce an allergic hypersensitivity dermatitis or asthma with bronchospasm and wheezing with chronic exposure.
    0.2.20) REPRODUCTIVE
    A) Metolachlor was not teratogenic in rabbit or rat models.
    B) At the time of this review, no data were available to assess the potential effects of exposure to this agent during pregnancy or lactation.
    0.2.21) CARCINOGENICITY
    A) Metolachlor has shown some evidence of exposure response for lung cancer in pesticide applicators .

Laboratory Monitoring

    A) No specific laboratory work is necessary unless otherwise clinically indicated.
    B) Monitor ABGs, chest x-ray, and pulmonary function test in patients with respiratory symptoms.

Treatment Overview

    0.4.2) ORAL/PARENTERAL EXPOSURE
    A) Care is symptomatic and supportive.
    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) ACTIVATED CHARCOAL: Administer charcoal as a slurry (240 mL water/30 g charcoal). Usual dose: 25 to 100 g in adults/adolescents, 25 to 50 g in children (1 to 12 years), and 1 g/kg in infants less than 1 year old.
    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.
    B) Inhaled sympathomimetic agents may be of value.
    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).

Range Of Toxicity

    A) Minimum lethal human exposure is unknown.
    B) The LD50 in animals is around 2780 mg/kg orally and over 3.7 g/kg dermally.

Clinical Effects

Summary Of Exposure

    A) There are very little data available on the toxicity of metolachlor to humans. Animal models have shown mild to moderate irritancy of skin. Burns have not been noticed. There may be a problem with persons who have G-6-PD deficiency, but this is only proposed, based on an animal model. Until more is known, the following basic measures apply.
    B) Exposed individuals should have a careful, thorough medical history and physical examination performed, looking for any abnormalities. Exposure to chemicals with a strong odor often results in such nonspecific symptoms as headache, dizziness, weakness, and nausea.
    C) Many chemicals cause irritation of the eyes, skin, and respiratory tract. In severe cases respiratory tract irritation can progress to ARDS/acute lung injury, which may be delayed in onset for up to 24 to 72 hours in some cases.
    D) Irritation or burns of the esophagus or gastrointestinal tract are also possible if caustic or irritant chemicals are ingested.

Neurologic

    3.7.3) ANIMAL EFFECTS
    A) ANIMAL STUDIES
    1) CNS EFFECTS
    a) Oral administration in rats caused hypoactivity, muscle weakness, tremors and seizures (HSDB , 2001).

Gastrointestinal

    3.8.3) ANIMAL EFFECTS
    A) ANIMAL STUDIES
    1) DIARRHEA
    a) Oral administration to rats and dogs caused diarrhea (HSDB , 2001).

Hematologic

    3.13.3) ANIMAL EFFECTS
    A) ANIMAL STUDIES
    1) ANEMIA HEMOLYTIC G6PD
    a) G6PD DEFICIENCY - Metolachlor has been tested in sheep that have blood similar to that of G6PD deficient individuals. The study concluded that metolachlor in concentrations of 100 ppm may produce an oxidative stress in blood for individuals with this deficiency (Geiger & Calabrese, 1985).

Dermatologic

    3.14.1) SUMMARY
    A) Metolachlor may cause mild dermal irritation.
    3.14.3) ANIMAL EFFECTS
    A) ANIMAL STUDIES
    1) RASH
    a) IRRITANCY - When 334 mg of metolachlor was placed on the skin of rabbits, it produced mild irritancy (RTECS , 2001).

Immunologic

    3.19.1) SUMMARY
    A) A number of chemical agents produce an allergic hypersensitivity dermatitis or asthma with bronchospasm and wheezing with chronic exposure.
    3.19.2) CLINICAL EFFECTS
    A) ACUTE ALLERGIC REACTION
    1) A number of chemical agents produce an allergic hypersensitivity dermatitis or asthma with bronchospasm and wheezing with chronic exposure.

Reproductive

    3.20.1) SUMMARY
    A) Metolachlor was not teratogenic in rabbit or rat models.
    B) At the time of this review, no data were available to assess the potential effects of exposure to this agent during pregnancy or lactation.
    3.20.2) TERATOGENICITY
    A) CONGENITAL ANOMALY
    1) Metolachlor was not teratogenic in rabbit or rat models (HSDB , 2001).
    3.20.3) EFFECTS IN PREGNANCY
    A) LACK OF INFORMATION
    1) At the time of this review, no data were available to assess the potential effects of exposure to this agent during pregnancy or lactation.

Carcinogenicity

    3.21.1) IARC CATEGORY
    A) IARC Carcinogenicity Ratings for CAS51218-45-2 (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) Not Listed
    3.21.2) SUMMARY/HUMAN
    A) Metolachlor has shown some evidence of exposure response for lung cancer in pesticide applicators .
    3.21.3) HUMAN STUDIES
    A) LUNG CANCER
    1) Metolachlor has shown some evidence of exposure response for lung cancer in pesticide applicators (Alavanja et al, 2004).
    3.21.4) ANIMAL STUDIES
    A) LACK OF EFFECT
    1) Metolachlor was not carcinogenic in a murine model (HSDB , 2001).

Genotoxicity

    A) Metolachlor has been evaluated in some bacterial models and has tested positive in some of these tests (Plewa et al, 1984).

Laboratory Monitoring

Monitoring Parameters Levels

    4.1.1) SUMMARY
    A) No specific laboratory work is necessary unless otherwise clinically indicated.
    B) Monitor ABGs, chest x-ray, and pulmonary function test in patients with respiratory symptoms.

Methods

    A) CHROMATOGRAPHY
    1) Can be analyzed by gas liquid chromatography with nitrogen-specific Coulson thermal-conductivity detection (Hartley & Kidd, 1987; Gale & Hofberg, 1985).
    2) Relatively low parts per billion (ppb) concentrations of this herbicide can be detected in water and soil samples by isotope dilution gas chromatography/mass spectrometry. The limit of detection was found to be 0.5 ppb in soil and 0.05 ppb in water, with an accuracy greater than 80% (Huang, 1989).
    B) OTHER
    1) Separation of alachlor, atrazine, and metolachlor from groundwater can be achieved rapidly and efficiently (average recoveries greater than 90%) by the use of solid-phase extraction (Brooks et al, 1989).

Treatment

Life Support

    A) Support respiratory and cardiovascular function.

Monitoring

    A) No specific laboratory work is necessary unless otherwise clinically indicated.
    B) Monitor ABGs, chest x-ray, and pulmonary function test in patients with respiratory symptoms.

Oral Exposure

    6.5.1) PREVENTION OF ABSORPTION/PREHOSPITAL
    A) 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).
    B) ACTIVATED CHARCOAL
    1) PREHOSPITAL ACTIVATED CHARCOAL ADMINISTRATION
    a) Consider prehospital administration of activated charcoal as an aqueous slurry in patients with a potentially toxic ingestion who are awake and able to protect their airway. Activated charcoal is most effective when administered within one hour of ingestion. Administration in the prehospital setting has the potential to significantly decrease the time from toxin ingestion to activated charcoal administration, although it has not been shown to affect outcome (Alaspaa et al, 2005; Thakore & Murphy, 2002; Spiller & Rogers, 2002).
    1) In patients who are at risk for the abrupt onset of seizures or mental status depression, activated charcoal should not be administered in the prehospital setting, due to the risk of aspiration in the event of spontaneous emesis.
    2) The addition of flavoring agents (cola drinks, chocolate milk, cherry syrup) to activated charcoal improves the palatability for children and may facilitate successful administration (Guenther Skokan et al, 2001; Dagnone et al, 2002).
    2) 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).
    6.5.2) PREVENTION OF ABSORPTION
    A) 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).
    B) ACTIVATED CHARCOAL
    1) 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.
    2) 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) SUPPORT
    1) There is no specific treatment and no specific antidote.

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) OBSERVATION REGIMES
    1) Carefully observe patients with inhalation exposure for the development of any systemic signs or symptoms and administer symptomatic treatment as necessary.
    B) 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).

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) SKIN ABSORPTION
    1) Some chemicals can produce systemic poisoning by absorption through intact skin. Carefully observe patients with dermal exposure for the development of any systemic signs or symptoms and administer symptomatic treatment as necessary.
    B) Treatment should include recommendations listed in the ORAL EXPOSURE section when appropriate.

Enhanced Elimination

    A) SUMMARY
    1) No studies have addressed the utilization of extracorporeal elimination techniques in poisoning with this agent.

Range Of Toxicity

Summary

    A) Minimum lethal human exposure is unknown.
    B) The LD50 in animals is around 2780 mg/kg orally and over 3.7 g/kg dermally.

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.

Workplace Standards

    A) ACGIH TLV Values for CAS51218-45-2 (American Conference of Governmental Industrial Hygienists, 2010):
    1) Not Listed

    B) NIOSH REL and IDLH Values for CAS51218-45-2 (National Institute for Occupational Safety and Health, 2007):
    1) Not Listed

    C) Carcinogenicity Ratings for CAS51218-45-2 :
    1) ACGIH (American Conference of Governmental Industrial Hygienists, 2010): Not Listed
    2) EPA (U.S. Environmental Protection Agency, 2011): C ; Listed as: Metolachlor
    a) C : Possible human carcinogen.
    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): Not Listed
    4) NIOSH (National Institute for Occupational Safety and Health, 2007): Not Listed
    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 CAS51218-45-2 (U.S. Occupational Safety, and Health Administration (OSHA), 2010):
    1) Not Listed

Toxicity Information

    7.7.1) TOXICITY VALUES
    A) ANIMAL DATA
    1) LD50- (ORAL)RAT:
    a) 2,200 mg/kg (RTECS, 2001)
    2) LD50- (SKIN)RAT:
    a) 3,170 mg/kg (RTECS, 2001)

Pharmacology Toxicology

Toxicologic Mechanism

    A) Some initial work in rats would seem to indicate that much of the toxic effects seen with the chloroacetanilide herbicides like metolachlor are due to their nitroso and aniline metabolites (Kimmel et al, 1986).

Physicochemical

Physical Characteristics

    A) A clear, white or tan, odorless liquid (Budavari, 1996).

Molecular Weight

    A) 283.81 (Budavari, 1996)

Other

    A) ODOR THRESHOLD
    1) Currently not available (CHRIS , 2002).

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.
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    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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