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Carcinogenicity of Agricultural Pesticides in Adults and Children
Published in Ana Maria Osorio, Lynn R. Goldman, Proceedings from the Medical Workshop on Pesticide-Related Illnesses from the International Conference on Pesticide Exposure and Health, 2017
Michael C. R. Alavanja, Mary H. Ward, Peggy Reynolds
Prostate cancer is the most common malignancy among men in the United States and in most Western countries.59 Age, family history of prostate cancer, African-American ethnicity, hormonal factors, and possibly a high consumption of animal fat and red meat are the most consistent risk factors reported.60 The literature suggests that prostate cancer may also be elevated among farmers.61'62 Potential risk factors for prostate cancer found on the farm include insecticides, fertilizers, herbicides, and other chemicals.63-68 Consistent with those reports a large prospective study of pesticide applicators which included farmers and commercial applicators and the spouse of farmer applicators in the U.S.69 showed an overall small but significant excess-risk of prostate cancer in the cohort, which was also demonstrated in both Iowa and North Carolina and both among farmers and commercial applicators. Age and family history of prostate cancer were the only two significant demographic risk factors for prostate cancer within the cohort as a whole. When these factors were controlled, use of chlorinated pesticides among applicators over 50 years of age and methyl bromide use were significantly associated with prostate cancer risk. Among those with a family history of prostate cancer several pesticides including butylate, a widely used herbicide and four commonly used organothiophosphate insecticides including coumaphos, fonofos, chlorpyrifos and phorate and a pyrethriod, permethrin all showed significant interactions odds ratios. These associations suggest, but do not prove, that a family history of prostate cancer may increase the susceptibility to the carcinogenic effects of these insecticides. Additional studies confirming these associations are need, along with molecular epidemiological studies to establish biological plausibility and to suggest a mode(s) of action.
Interactions of organophosphorus pesticides with solute carrier (SLC) drug transporters
Published in Xenobiotica, 2019
Lisa Chedik, Arnaud Bruyere, Olivier Fardel
OPs, rhodamine 123, verapamil, probenecid, amitriptyline, fluorescein, 4′,6′-diamidino-2-phenylindole (DAPI), and tetra-ethylammonium bromide (TEA) were provided by Sigma-Aldrich (Saint-Quentin Fallavier, France). [1-14 C]-TEA (sp. act. 3.5 mCi/mmol), [6,7-3 H(N)]-estrone-3-sulfate (E3S) (sp. act. 51.8 Ci/mmol) and 3,4-[Ring-2,5,6-3 H]-dihydroxyphenylethylamine (dopamine) (sp. act. 46 Ci/mmol) were purchased from Perkin-Elmer (Boston, MA). Stocked solutions of chemicals were commonly prepared in dimethyl sulfoxide (DMSO); final concentrations of solvent in transport assay medium did not exceed 0.2% (vol/vol). The chemical structures of the 13 OPs analyzed in the study are shown in Supplementary Figure S1. Six of these OPs, i.e. dichlorvos, fenamiphos, metasystox, methamidophos, monocrotophos, and profenofos, were organophosphate pesticides, with a central phosphorus atom with double-bonded oxygen (P = O). The remaining OPs (n = 7), i.e. fenitrothion, malathion, methyl parathion, parathion, phosmet, propetamphos and temephos, were organothiophosphates compounds, with a central phosphorus atom with double-bonded sulfur atom (P = S). These thion OPs have to be metabolized in oxon metabolites by cytochrome P-450 enzymes, for inhibiting acetylcholinesterase (Elersek & Filipic, 2011). According to the PubChem database (U.S. National Library of Medicine, Bethesda, MA), all OPs tested in the study were predicted to be water-soluble at 100 µM, which was the OP concentration retained for initially screening their potential inhibitory effects towards SLC transporter activities.
Validation and kinetic of enzymatic method for the detection of organophosphate insecticides based on cholinesterase inhibition
Published in Toxicology Mechanisms and Methods, 2020
Fenitrothion is an organothiophosphate cholinesterase inhibitor in which the serine hydroxyl moiety in the enzyme active site is phosphorylated via a chemical reaction. It is effective against chewing, penetrating and sucking insect pests, and as a vector control agent for malaria (Worthing 1987; Thomson 1989; Holmes and Boag 1990).