1093 Metolachlor Widely used selective herbicides worldwide in corn, soybean and other crop cultures. Elevated concentrations of these herbicides and their degradation products have been detected in surface and groundwater. (A252) Metolachlor is an organic compound that is widely used as a herbicide. It is a derivative of aniline and is a member of the chloroacetanilide herbicides. It is highly effective toward grasses but its application is also controversial (L913). 51218-45-2 4169 C15H22ClNO2 283.133910 Off-white to colorless liquid (L913). -62.1°C 100°C at 0.001 mmHg 0.53 mg/mL at 20°C [WAUCHOPE,RD et al. (1992)] Inhalation (L914) ; oral (L914) ; dermal (L914) ; eye contact (L914). Metolachlor acts by inhibition of elongases and of the geranylgeranyl pyrophosphate (GGPP) cyclases, which are part of the gibberellin pathway. It also binds to nAChRs in nervous systems and causes endocrine disruption in humans by binding to and inhibiting the estrogen receptor. (T10, L913, A590) Metolachlor is metabolized via dechlorination, o-methylation, N-dealkylation and side-chain oxidation. Glutathione transferases mediathe the conjugation of metolachlor with with glutathione. Urinary metabolites included 2-ethyl-6-methylhydroxyacetanilide and N-(2-ethyl-6-methyl- phenyl)-N-(hydroxyacetyl)-DL-alanine). Fecal metabolites included 2-chloro-N-(2-ethyl-6-methylphenyl)-N-(2-hydroxy-l-methylethyl) and N-(2-ethyl-6-methylphenyl)-N-(hydroxyacetyl)-DL-alamine). Metolachlor is also excreted in urine. (A571, A270) LD50: 1200-2780 mg/kg (Oral, Oral) (L914) LD50: > 2000 mg/kg (Dermal, Rat) (L914) LC50: > 4.3 mg/L/4hr (L914) No indication of carcinogenicity to humans (not listed by IARC). Metolachlor is used for grass and broadleaf weed control in corn, soybean, peanuts, sorghum, and cotton. It is also used in combination with other herbicides. It been detected in ground and surface waters and concentrations ranging from 0.08 to 4.5 parts per billion (ppb) throughout the U.S. Evidence of the bioaccumulation of metolachlor in edible species of fish as well as its adverse effect on the growth and development raise concerns on its effects on human health. (L913). Health effects of metolachlor include CNS depression, dizziness, dyspnea, liver damage, nephritis, cardiovascular failure, and adverse reproductive effects. (A571) Signs of human intoxication from metolachlor and/or its formulations (presumably following acute deliberate or accidental exposures) include abdominal cramps, anemia, ataxia, dark urine, methemoglobinemia, cyanosis, hypothermia, collapse, convulsions, diarrhea, GI irritation, jaundice, weakness, nausea, shock, sweating, vomiting, skin irritation, dermatitis, sensitization dermatitis, eye and mucous membrane irritation, and corneal opacity. (A571) Consider gastric lavage, as well was dilution with milk or water after ingestion. Administer charcoal as a slurry following ingestion; however, activated charcoal should not be given to patients ingesting strong acidic or basic caustic chemicals. In case of 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 inhaled beta2 agonist and oral or parenteral corticosteroids. Irrigate exposed eyes with copious amounts of room temperature water for at least 15 minutes. Following dermal exposure, remove contaminated clothing and wash exposed area thoroughly with soap and water. Treat dermal irritation or burns with standard topical therapy. Patients developing dermal hypersensitivity reactions may require treatment with systemic or topical corticosteroids or antihistamines. Administer symptomatic treatment as necessary. (T36) 2009-06-18T21:54:33Z 2014-12-24T20:23:07Z Glutathione transferases mediathe the conjugation of metolachlor with with glutathione (A270). C10953 C051786 Metolachlor 6485 true Glutathione S-transferase P (P09211) Glutathione S-transferase Mu 1 (P09488) Glutathione S-transferase A1 (P08263) Glutathione S-transferase theta-2 (P30712) Glutathione S-transferase Mu 4 (Q03013) Glutathione S-transferase theta-1 (P30711) Glutathione S-transferase A4 (O15217) Glutathione S-transferase A2 (P09210) Glutathione S-transferase A3 (Q16772) Glutathione S-transferase Mu 3 (P21266) Glutathione S-transferase omega-1 (P78417) Glutathione S-transferase kappa 1 (Q9Y2Q3) Glutathione S-transferase Mu 2 (P28161) Glutathione S-transferase omega-2 (Q9H4Y5) Glutathione S-transferase A5 (Q7RTV2) Glutathione S-transferase Mu 5 (P46439) Glutathione S-transferase theta-4 (A8MPT4) Maleylacetoacetate isomerase (O43708) Microsomal glutathione S-transferase 1 (P10620) Microsomal glutathione S-transferase 2 (Q99735) Microsomal glutathione S-transferase 3 (O14880) Cytochrome P450 2B6 (P20813) Cytochrome P450 3A4 (P08684) (A269, A270) CCC1=CC=CC(C)=C1N(C(C)COC)C(=O)CCl C15H22ClNO2 InChI=1S/C15H22ClNO2/c1-5-13-8-6-7-11(2)15(13)17(14(18)9-16)12(3)10-19-4/h6-8,12H,5,9-10H2,1-4H3 InChIKey=WVQBLGZPHOPPFO-UHFFFAOYSA-N 283.794 283.13390666 Exogenous Liquid CHEMBL1884974 4025