RESUMEN
Chlorpyrifos (CPF) is one of the most commonly used organophosphate pesticides. Because CPF was described as a toxic compound without safe levels of exposure for children, certain countries in Latin America and the European Union have banned or restricted its use; however, in Mexico it is used very frequently. The aim of this study was to describe the current situation of CPF in Mexico, as well as its use, commercialization, and presence in soil, water, and aquatic organisms in an agricultural region of Mexico. Structured questionnaires were applied to pesticide retailers to determine the sales pattern of CPF (ethyl and methyl); in addition, monthly censuses were conducted with empty pesticide containers to assess the CPF pattern of use. Furthermore, samples of soil (48 samples), water (51 samples), and fish (31 samples) were collected, which were analyzed chromatographically. Descriptive statistics were performed. The results indicate that CPF was one of the most sold (3.82%) and employed OP (14.74%) during 2021. Only one soil sample was found above the CPF limit of quantification (LOQ); in contrast, all water samples had CPF levels above the LOQ (xÌ = 4614.2 ng/L of CPF). In the case of fish samples, 6.45% demonstrated the presence of methyl-CPF. In conclusion, the information obtained in this study indicates the need for constant monitoring in the area, since the presence of CPF in soil, water, and fish constitutes a threat to the health of wildlife and humans. Therefore, CPF should be banned in Mexico to avoid a serious neurocognitive health problem.
Asunto(s)
Cloropirifos , Insecticidas , Plaguicidas , Animales , Niño , Humanos , Organismos Acuáticos , México , Insecticidas/toxicidad , Suelo , Peces , AguaRESUMEN
Temephos (O,O,O',O'-tetramethyl O,O'-thiodi-p-phenylene bis(phosphorothioate)) is a larvicide belonging to the family of organophosphate pesticides used for the control of different vectors of diseases, such as dengue, Zika, chikungunya, and dracunculiasis. The aim of this review was to discuss the available published information about temephos toxicokinetics and toxicity in mammals. Temephos is quickly absorbed in the gastrointestinal tract, distributed to all organs, and then it accumulates mainly in adipose tissue. It is metabolized by S-oxidation, oxidative desulfuration, and hydrolysis reactions, with the possible participation of cytochrome P450 (CYP). Temephos is mainly eliminated by feces, whereas some of its metabolites are eliminated by urine. The World Health Organization classifies it as class III: slightly dangerous with a NOAEL (no-observed adverse effect level) of 2.3 mg/kg/day for up to 90 days in rats, based on brain acetylcholinesterase (AChE) inhibition. A LOAEL (lowest observable adverse effect level) of 100 mg/kg/day for up to 44 days in rats was proposed based on cholinergic symptoms. However, some studies have shown that temephos causes toxic effects in mammals. The inhibition of the enzyme acetylcholinesterase (AChE) is one of its main demonstrated effects; however, this larvicide has also shown genotoxic effects and some adverse effects on male reproduction and fertility, as well as liver damage, even at low doses. We performed an extensive review through several databases of the literature about temephos toxicokinetics, and we recommend to revisit current assessment of temephos with the new available data.
Asunto(s)
Insecticidas , Temefós , Infección por el Virus Zika , Virus Zika , Acetilcolinesterasa/metabolismo , Animales , Masculino , Mamíferos/metabolismo , Ratas , Virus Zika/metabolismoRESUMEN
The organophosphate (OP) pesticides are neurotoxic compounds widely used around the world. Evaluation of OP exposure in human studies is important for enabling adequate data analyses and drawing accurate conclusions. The aim of this study was to analyze OP exposure biomarkers and their relationships in a Mexican population with different exposure levels. Dialkylphosphates (DAP) were determined through gas chromatography-mass spectrometry (GC-MSD); acetylcholinesterase (AChE), butyrylcholinesterase (BuChE), arylesterase (AREase), basal paraoxonase 1 (PONase), and ß-glucuronidase activities were detected using spectrophotometric methods. The albumin content was determined in a certified clinical laboratory. The DMTP metabolite was found in the highest concentration, and a negative and significant correlation between DAP and cholinesterase activity was observed. Our results suggested that BuChE is a considerably more sensitive biomarker than AChE. In addition, ß-glucuronidase was positively correlated with albumin, BuChE, and PONase. In conclusion, our data strongly support the use of two or more biomarkers of exposure in human monitoring and the application of a strong and validated questionnaire.
Asunto(s)
Exposición Profesional , Plaguicidas , Acetilcolinesterasa , Biomarcadores , Butirilcolinesterasa , Humanos , México , Compuestos OrganofosforadosRESUMEN
Temephos (Tem) is the larvicide of choice to control mosquito transmission of dengue, Zika, and chikungunya. The toxicokinetic and toxicological information of temephos is very limited. The aim of this work was to determine the toxicokinetics and dosimetry of temephos and its metabolites. Male Wistar rats were orally administered temephos (300 mg/kg) emulsified with saline solution and sacrificed over time after dosing. Temephos and its metabolites were analyzed in blood and tissues by high performance liquid chromatography-diode array detector. At least eleven metabolites were detected, including temephos-sulfoxide (Tem-SO), temephos-oxon (Tem-oxon), temephos-oxon-sulfoxide (Tem-oxon-SO), temephos-oxon-SO-monohydrolyzed (Tem-oxon-SO-OH), 4,4´-thiodiphenol, 4,4´-sulfinyldiphenol, and 4,4´-sulfonyldiphenol or bisphenol S (BPS). The mean blood concentrations of temephos were fitted to a one-compartment model for kinetic analysis. At 2 h, the peak was reached (t1/2 abs = 0.38 h), and only trace levels were detected at 36 h (t1/2 elim = 8.6 h). Temephos was detected in all tissues and preferentially accumulated in fat. Temephos-sulfone-monohydrolyzed (Tem-SO2-OH) blood levels remained constant until 36 h and gradually accumulated in the kidney. Tem-oxon was detected in the brain, liver, kidney, and fat. Clearance from the liver and kidney were 7.59 and 5.52 ml/min, respectively. These results indicate that temephos is well absorbed, extensively metabolized, widely distributed and preferentially stored in adipose tissue. It is biotransformed into reactive metabolites such as Tem-oxons, Tem-dioxons, and BPS. Tem-SO2-OH, the most abundant metabolite of temephos, could be used as an exposure biomarker for toxicokinetic modeling. These results could provide critical insight into the dosimetry and toxicity of temephos and its metabolites.
Asunto(s)
Biomarcadores/metabolismo , Insecticidas/administración & dosificación , Modelos Biológicos , Temefós/administración & dosificación , Administración Oral , Animales , Cromatografía Líquida de Alta Presión , Insecticidas/farmacocinética , Insecticidas/toxicidad , Masculino , Ratas , Ratas Wistar , Temefós/farmacocinética , Temefós/toxicidad , Factores de Tiempo , Análisis de Matrices Tisulares , ToxicocinéticaRESUMEN
Temephos is an organophosphorothioate (OPT) larvicide used for controlling vectors of diseases such as dengue, chikungunya, and Zika. OPTs require a metabolic activation mediated by cytochrome P540 (CYP) to cause toxic effects, such as acetylcholinesterase (AChE) activity inhibition. There is no information about temephos biotransformation in humans, and it is considered to have low toxicity in mammals. Recent studies have reported that temephos-oxidized derivatives cause AChE inhibition. The aim of this study was to propose the human biotransformation pathway of temephos using in silico tools. The metabolic pathway was proposed using the MetaUltra program of MultiCase software as well as the Way2Drug and Xenosite web servers. The results show the following three essential reactions of phase I metabolism: (1) S-oxidation, (2) oxidative desulfurization, and (3) dephosphorylation, as well as the formation of 19 possible intermediary metabolites. Temephos dephosphorylation is the most likely reaction, and it enables phase II metabolism for glucuronidation to be excreted. However, the CYP-dependent metabolism showed that temephos oxon can be formed, which could lead to toxic effects in mammals. CYP2B6, 2C9, and 2C19 are the main isoforms involved in temephos metabolism, and CYP3A4 and 2D6 have minor contributions. According to computational predictions, the highest probability of temephos metabolism is dephosphorylation and phase II reactions that do not produce cholinergic toxic effects; nonetheless, the participation of CYPs is highly possible if the primary reaction is depleted.
Asunto(s)
Inhibidores de la Colinesterasa/metabolismo , Temefós/metabolismo , Acetilcolinesterasa/metabolismo , Biotransformación , Inhibidores de la Colinesterasa/química , Sistema Enzimático del Citocromo P-450/metabolismo , Humanos , Estructura Molecular , Programas Informáticos , Temefós/químicaRESUMEN
Temephos (Tem) is an organophosphorus pesticide widely used to kill and prevent the growth of the main vectors for the transmission of dengue, zika, and chikungunya viruses. In chlorinated water, Tem is oxidized to its dioxon-sulfoxide (Tem-dox-SO), dioxon-sulfone (Tem-dox-SO2), and sulfoxide (Tem-SO) derivatives; however, these compounds are not commercially available to be used as standards and in toxicological studies. In the present study, we synthesized and characterized the Tem-oxidation products and the compound 4,4'-sulfinyldiphenol. These compounds were obtained by a simple reaction between Tem or 4,4'-thiodiphenol with sodium hypochlorite or potassium periodate, and were characterized by IR, NMR, and UPLC-HRESIMS. The in vitro evaluation of inhibitory potency of Tem-oxidized products on human red blood cell acetylcholinesterase (RBC AChE) showed that Tem-dox-SO2 was the most potent inhibitor of human RBC AChE, and its effect was more pronounced than that observed for ethyl-paraoxon, a potent typical inhibitor of AChE. An HPLC-DAD method for the analysis of metabolic products of Tem was developed, which may be useful for monitoring in biological and environmental samples. The ability of Tem-oxidized metabolites to inhibit human RBC AChE suggests that the addition of Tem to chlorinated drinking water could result in an increase in the risk of RBC AChE inhibition after exposure.