Chlorothalonil (Synonyms: 2,4,5,6-Tetrachloroisophthalonitrile)

Chlorothalonil is a broad-spectrum organochlorine fungicide that forms adducts with glutathione and cysteine residues on enzymes leading to GST depletion and enzyme deactivation, respectively.¹ In vitro, it inhibits the growth of C. albicans and C. orbiculare fungi, S. aureus and B. cereus Gram-positive bacteria, and E. coli and P. aeruginosa Gram-negative bacteria (MICs = 0.7, 5, 1.3, 0.7, 0.5, and 1.7 µg/ml, respectively).^2,3 In vivo, chlorothalonil (100 µg/ml) completely inhibits the growth of P. infestans, the tomato late blight pathogen, on tomato plants.⁴ It is toxic to aquatic organisms, including species of fish, crustaceans, molluscs, and algae with tenth percentile of toxicity values of 25.23, 40.59, 0.69, and 3.94 µg/L, respectively, as well as to other aquatic invertebrates.⁵ Chlorothalonil is carcinogenic in animal models and induces neoplasms in the forestomach and kidneys of rats when administered at a dose of 3.8 mg/kg per day, but it is not genotoxic.⁶ Formulations containing chlorothalonil have been used as fungicides in agriculture.

1.Tillman, R.W., Siegel, M.R., and Long, J.W.Mechanism of action and fate of the fungicide chlorothalonil (2,4,5,6-tetrachloroisophthalonitrile) in biological systems. I. Reactions with cells and subcellular components of Saccharomyces pastorianusPestic. Biochem. Physiol.3(2)160-167(1973) 2.Shi, L.-P., Jiang, K.-M., Jiang, J.-J., et al.Synthesis and antimicrobial activity of polyhalobenzonitrile quinazolin-4(3H)-one derivativesBioorg. Med. Chem. Lett.23(21)5958-5963(2013) 3.Lee, J.Y., Moon, S.S., and Hwang, B.K.Isolation and antifungal activity of kakuol, a propiophenone derivative from Asarum sieboldii rhizomePest. Manag. Sci.61(8)821-825(2005) 4.Lee, Y.M., Moon, J.S., Yun, B.-S., et al.Antifungal activity of CHE-23C, a dimeric sesquiterpene from Chloranthus henryiJ. Agric. Food. Chem.57(13)5750-5755(2009) 5.DeLorenzo, M.E., and Fulton, M.H.Comparative risk assessment of permethrin, chlorothalonil, and diuron to coastal aquatic speciesMar. Pollut. Bull.64(7)1291-1299(2012) 6.Wilkinson, C.F., and Killeen, J.C.A mechanistic interpretation of the oncogenicity of chlorothalonil in rodents and an assessment of human relevanceRegul. Toxicol. Pharmacol.24(1 Pt 1)69-84(1996)