Fenitrothion [BSA]

Background: An insecticide susceptibility study was carried out on Anopheles gambiae sensu lato vectors in 11 districts in Ghana between October 2012 and January 2013. Methods: An. gambiae s.l. larvae were collected, bred under standard conditions, and 3-5 d postemerged females were used for bioassay. Between 22 and 25 female An. gambiae s.l. fed only 10% sugar were used for testing. Exposure was for 1 h (2 h for fenitrothion). An. gambiae that were knocked down were recorded every 10 min and mortalities recorded 24 h posttest. Eleven insecticides from four chemical classes were used: organochlorines, organophosphates, carbamates, and pyrethroids. Subsamples of An. gambiae were analyzed by polymerase chain reaction for species and knockdown resistance (kdr) allele determination. Results: Malathion was effective in killing An. gambiae in seven districts, fenitrothion in three districts, and propoxur in one district. The organophosphate and carbamate insecticides were effective in killing An. gambiae compared to pyrethroids and organochlorines. Of the limited samples analyzed, An. gambiae sensu stricto (39/110), An. coluzzii (66/110), and An. arabiensis (5/110) were identified. Few kdr (11/110) susceptible mosquitoes were detected. Homozygous kdr(RR) (65/110) and heterozygous kdr(RS) (8/110) genotypes were identified. Conclusions: An organophosphate insecticide is considered appropriate for indoor residual spraying (IRS) in the 11 districts earmarked for the IRS program in Ghana.

Acute exposure to environmental factors strongly affects the metabolic activity of cytochrome P450 (P450). As a consequence, the risk of interaction could be increased, modifying the clinical outcomes of a medication. Because toxic agents cannot be administered to humans for ethical reasons, in vitro approaches are therefore essential to evaluate their impact on P450 activities. In this work, an extensive cocktail mixture was developed and validated for in vitro P450 inhibition studies using human liver microsomes (HLM). The cocktail comprised eleven P450-specific probe substrates to simultaneously assess the activities of the following isoforms: 1A2, 2A6, 2B6, 2C8, 2C9, 2C19, 2D6, 2E1, 2J2 and subfamily 3A. The high selectivity and sensitivity of the developed UHPLC-MS/MS method were critical for the success of this methodology, whose main advantages are: (i) the use of eleven probe substrates with minimized interactions, (ii) a low HLM concentration, (iii) fast incubation (5 min) and (iv) the use of metabolic ratios as microsomal P450 activities markers. This cocktail approach was successfully validated by comparing the obtained IC50 values for model inhibitors with those generated with the conventional single probe methods. Accordingly, reliable inhibition values could be generated 10-fold faster using a 10-fold smaller amount of HLM compared to individual assays. This approach was applied to assess the P450 inhibition potential of widespread insecticides, namely, chlorpyrifos, fenitrothion, methylparathion and profenofos. In all cases, P450 2B6 was the most affected with IC50 values in the nanomolar range. For the first time, mixtures of these four insecticides incubated at low concentrations showed a cumulative inhibitory in vitro effect on P450 2B6. (C) 2016 Elsevier Inc. All rights reserved.