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Pesticides and Chronic Diseases
Published in William J. Rea, Kalpana D. Patel, Reversibility of Chronic Disease and Hypersensitivity, Volume 4, 2017
William J. Rea, Kalpana D. Patel
The following common commercial pesticide products are listed approximately in order of decreasing toxicity: Highly toxic (acute oral LD50 in the rat <50 mg/kg): aldicarb (this carbamate is a systemic, for example, it is taken up by the plant and translocated into foliage and sometimes into the fruit) (Temik), oxamyl (Vydate), carbofuran (Furadan), methomyl (Lannate, Nudrin), formetanate HCI (Carzol, Dicazol), aminocarb (Matacil), dimetilan (Ship Fly Bands)Moderately toxic (acute oral LD50 in the rat above 50 mg/kg): promecarb (Carbamult), methiocarb (Mesurol, Draza), propoxur (Baygon), pirimicarb (Pirimor Aphox, Rapid), bufencarb (Bux), carbaryl (Sevin)
Animal Models for Percutaneous Absorption
Published in Rhoda G. M. Wang, James B. Knaak, Howard I. Maibach, Health Risk Assessment, 2017
Ronald C. Wester, Howard I. Maibach
Skin absorption in the rhesus monkey is considered to be relevant to that of humans. Table 11 shows the percutaneous absorption of testosterone,1,2 fenitrothion, aminocarb, and diethyltoulamide (DEET)25,26 in the rhesus monkey compared with the rat. Note that for the rhesus there is regional variation between forehead (scalp) and forearm. If one determines the ratio of forehead (scalp)/forearm for the rhesus and compares the results with humans, the similarities are the same (Table 12). Therefore, the rhesus monkey probably can be a relevant animal model for human regional variation.11
Differential interactions of carbamate pesticides with drug transporters
Published in Xenobiotica, 2020
Nelly Guéniche, Arnaud Bruyere, Mélanie Ringeval, Elodie Jouan, Antoine Huguet, Ludovic Le Hégarat, Olivier Fardel
If the concept that pesticides can interact with drug transporters is now well-established, as illustrated above, only a relatively small fraction of the total number of pesticides presently used in the world (more than 1000) has however been so far studied for potential interactions with drug transporters (Guéniche et al., 2020). Experimental data with respect to this topic remain thus limited. It is notably the case for carbamate pesticides, extensively used for agricultural and non-agricultural purposes, and presumed to exert various deleterious effects towards human health, including endocrine disruption and carcinogenicity (Dhouib et al., 2016; Miranda-Contreras et al., 2013; Patel & Sangeeta, 2019; Piel et al., 2019). Indeed, only few data have been reported with respect to putative interactions of carbamates with transporters; they demonstrated a lack of inhibitory effects of some carbamates towards activity of the human ABC efflux pump P-glycoprotein (P-gp/ABCB1) (Bain & LeBlanc, 1996) and an inhibition of the rabbit ABC transporter breast cancer resistance protein (BCRP/ABCG2) by propamocarb (Halwachs et al., 2016). The present study was therefore designed to get insights about putative alteration of transporter activities by carbamate pesticides, to which humans may be highly exposed (Bouvier et al., 2005, 2006; Mostafalou & Abdollahi, 2017). For this purpose, we have analysed the effects of four representative carbamates, i.e. the two N-methyl carbamates aminocarb and carbofuran, acting as insecticides through reversible inhibition of insect cholinesterase activity, the herbicide chlorpropham and the fungicide propamocarb, towards activities of main drug transporters implicated in pharmacokinetics. Such transporters were ABC pumps (P-gp, BCRP and multidrug-resistance associated proteins (MRPs/ABCCs)), SLC transporters of organic anions (organic anion transporting polypeptide (OATP) 1B1/SLCO1B1, OATP1B3/SLCO1B3, OATP2B1/SLCO2B1, organic anion transporter (OAT) 1/SLC22A6 and OAT3/SLC22A8) and SLC transporters of organic cations (organic cation transporter (OCT) 1/SLC22A1, OCT2/SLC22A2, multidrug and toxin extrusion protein (MATE) 1/SLC47A1 and MATE2-K/SLC47A2). The prototypical N-methylcarbamates aminocarb and carbofuran were found to not, or only poorly, inhibit drug transporters, whereas chlorpropham blocked OAT3 and BCRP activities. With respect to propamocarb, it inhibited activities of OCT1 and OCT2 and cis-stimulated that of MATE2-K, without being substrate for these transporters.