Toxicology letters
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Organophosphate insecticides are the most commonly used pesticides in the world. In this study, quantitative structure-toxicity relationship (QSTR) models were derived for estimating the acute oral toxicity of organophosphate insecticides to male rats. The 20 chemicals of the training set and the seven compounds of the external testing set were described by means of using descriptors. ⋯ The model was validated internally and externally. In the present study, QSTR model was used for the first time to understand the inherent relationships between the organophosphate insecticide molecules and their toxicity behavior. Such studies provide mechanistic insight about structure-toxicity relationship and help in the design of less toxic insecticides.
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Agricultural and residential use of organophosphate (OP) pesticides has increased in recent decades after banning some persistent pesticides. Although there is evidence of the effects of OPs on neurodevelopment and behaviour in adults, limited information is available about their effects in children, who might be more vulnerable to neurotoxic compounds. This paper was aimed at analysing the scientific evidence published to date on potential neurodevelopmental and behavioural effects of prenatal and postnatal exposure to OPs. ⋯ A large variability in epidemiological designs and methodologies used for assessing exposure and outcome was observed across the different studies, which made comparisons difficult. Prenatal and to a lesser extent postnatal exposure to OPs may contribute to neurodevelopmental and behavioural deficits in preschool and school children. Standardised methodologies are needed to allow results to be better compared and to perform a quantitative meta-analysis before drawing any final conclusions.
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Concerns over effects of halogenated persistent environmental contaminants on the developing brain have been expressed for many years, and human biomonitoring has confirmed that low-level, prenatal and/or postnatal exposure of children to these chemicals is ubiquitous. Over the last decade there have been increasing reports in the epidemiological literature of the potential association of exposure to polybromo diphenylethers (PBDEs) and perfluorinated chemicals (PFCs) with neurodevelopmental and/or neurobehavioural effects in infants and children, such as adverse birth outcomes, cognitive deficits, developmental delay and attention deficit hyperactivity disorders (ADHD). However, direct evidence from epidemiology studies has been limited and contradictory. ⋯ Frequently observed shortcomings were the lack of consideration of confounding factors; uncertainties regarding exposure characterization; inadequate sample size; the lack of a clear dose-response; and the representativeness/generalizability of the results. Collectively, the epidemiological evidence does currently not support a strong causal association between PBDEs and PFCs and adverse neurodevelopmental and neurobehavioural outcomes in infants and children. However, despite their limitations, the studies raise questions that require further investigation through hypothesis-driven studies using more harmonized study designs and methodologies, more detailed exposure assessments and repeated testing with larger study populations.
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The birth of the twenty first century has provoked a substantial rise in the use of designer drugs, such as synthetic cathinones, because of a decrease in the availability and purity of other drugs of abuse. The khat plant or Catha edulis, contains cathinone, the parent compound. Synthetic cathinones are sold under the name "bath salts" as a ploy to circumvent legislation from banning their use. ⋯ Comparable mechanisms of action, between the synthetic cathinones and amphetamine, cocaine, and MDMA are attributed to the similarities in their chemical structures. Synthetic cathinone's potent stimulatory effects, coupled with their high abuse potential, and propensity for addiction demands additional pharmacological and toxicological evaluations for these existing and new designer drugs of abuse. If these drugs are designed carefully, they might also have a significant therapeutic value.
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Various therapeutic regimes have been proposed with limited success for treatment of phosgene-induced acute lung injury (P-ALI). Corticoids were shown to be efficacious against chlorine-induced lung injury but there is still controversy whether this applies also to P-ALI. This study investigates whether different regimen of curatively administered budesonide (BUD, 10 mg/kg bw, i.p. bid; 100 mg/m(3)×30 min, nose-only inhalation), mometasone (MOM, 3 mg/kg bw, i.p. bid) and dexamethasone (DEX, 10, 30 mg/kg bw, i.p. bid), show efficacy to alleviate P-ALI. ⋯ Collectively, protocols shown to be efficacious for chlorine (Chen et al., 2013) were ineffective and even increased adversity in the P-ALI model. This outcome warrants further study to seek for early biomarkers suitable to differentiate chlorine- and phosgene-induced acute lung injury at yet asymptomatic stage. The patterns of eNO and eCO2 observed following exposure to chlorine and phosgene may be suitable to guide the specialized clinical interventions required for each type of ALI.