Pyrethroid insecticides: poisoning syndromes, synergies, and therapy.
ABSTRACT BACKGROUND: Pyrethroid insecticides are widely used, but there have been relatively few reports of systemic poisoning. These reports have, however, shown that pharmacotherapy is difficult and that the duration of poisoning can be unexpectedly long. Pyrethroids are ion channel toxins prolonging neuronal excitation, but are not directly cytotoxic. Two basic poisoning syndromes are seen. Type I pyrethroids produce reflex hyperexcitability and fine tremor. Type II pyrethroids produce salivation, hyperexcitability, choreoathetosis, and seizures. Both produce potent sympathetic activation. Local effects are also seen: skin contamination producing paresthesia and ingestion producing gastrointestinal irritation. The slow absorption of pyrethroids across the skin usually prevents systemic poisoning, although a significant reservoir of pyrethroid may remain bound to the epidermis. Carboxyesterase inhibitors can enhance pyrethroid toxicity in high-dose experimental studies. Hence, the unauthorized pyrethroid/organophosphate mixtures marketed in some developing countries may precipitate human poisoning. Pyrethroid paresthesia can be treated by decontamination of the skin, but systemic poisoning is difficult to control with anticonvulsants. Pentobarbitone, however, is surprisingly effective as therapy against systemic type II pyrethroid poisoning in rats, probably due to its dual action as a chloride channel agonist and a membrane stabilizer.
SourceAvailable from: Lesliam Quirós-Alcalá[Show abstract] [Hide abstract]
ABSTRACT: Background: Use of pyrethroid insecticides has increased dramatically over the past decade; however, data on their potential health effects, particularly on children, are limited. Objective: We examined the cross-sectional association between postnatal pyrethroid exposure and parental report of learning disability (LD) and attention deficit/hyperactivity disorder (ADHD) in children 6–15 years of age. Methods: Using logistic regression, we estimated associations of urinary metabolites of pyrethroid insecticides with parent-reported LD, ADHD, and both LD and ADHD in 1,659–1,680 children participating in the National Health and Nutrition Examination Survey (1999–2002). Results: The prevalence rates of parent-reported LD, ADHD, and both LD and ADHD were 12.7%, 10.0%, and 5.4%, respectively. Metabolite detection frequencies for 3-PBA [3-phenoxybenzoic acid], cis-DCCA [cis-(2,2-dichlorovinyl)-2,2-dimethylcyclopropane-1-carboxylic acid], and trans-DCCA [trans-(2,2-dichlorovinyl)-2,2-dimethylcyclopropane-1-carboxylic acid] were 77.1%, 35.6%, and 33.9%, respectively. The geometric mean 3-PBA concentration was 0.32 μg/L (median = 0.31 μg/L; interquartile rage = 0.10–0.89 μg/L). cis- and trans-DCCA 75th-percentile concentrations were 0.21 μg/L and 0.68 μg/L, respectively. Log10-transformed 3-PBA concentrations were associated with adjusted odds ratios (ORs) of 1.18 (95% CI: 0.92, 1.51) for parent-reported LD, 1.16 (95% CI: 0.85, 1.58) for ADHD, and 1.45 (95% CI: 0.92, 2.27) for both LD and ADHD. Adjusted ORs remained nonsignificant and decreased after controlling for creatinine and other environmental chemicals previously linked to altered neurodevelopment. Similarly, no significant associations were observed for cis- and trans-DCCA. Conclusions: Postnatal pyrethroid exposure was not associated with parental report of LD and/or ADHD. Given the widespread and increasing use of pyrethroids, future research should evaluate exposures at current levels, particularly during critical windows of brain development. Citation: Quirós-Alcalá L, Mehta S, Eskenazi B. 2014. Pyrethroid pesticide exposure and parental report of learning disability and attention deficit/hyperactivity disorder in U.S. Children: NHANES 1999–2002. Environ Health Perspect 122:1336–1342; http://dx.doi.org/10.1289/ehp.1308031Environmental Health Perspectives 09/2014; 122(12). DOI:10.1289/ehp.1308031 · 7.03 Impact Factor
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ABSTRACT: The farnesoid X receptor (FXR) regulates the homeostasis of bile acids, lipids, and glucose. Because endogenous chemicals bind and activate FXR, it is important to examine which xenobiotic compounds would disrupt normal receptor function. We used a cell-based human FXR β-lactamase (Bla) reporter gene assay to profile the Tox21 10K compound collection of environmental chemicals and drugs. Structure-activity relationships of FXR-active compounds revealed by this screening were then compared against the androgen receptor, estrogen receptor α, peroxisome proliferator-activated receptors δ and γ, and the vitamin D receptor. We identified several FXR-active structural classes including anthracyclines, benzimidazoles, dihydropyridines, pyrethroids, retinoic acids, and vinca alkaloids. Microtubule inhibitors potently decreased FXR reporter gene activity. Pyrethroids specifically antagonized FXR transactivation. Anthracyclines affected reporter activity in all tested assays, suggesting non-specific activity. These results provide important information to prioritize chemicals for further investigation, and suggest possible modes of action of compounds in FXR signaling.Scientific Reports 09/2014; 4:6437. DOI:10.1038/srep06437 · 5.08 Impact Factor
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ABSTRACT: The Pakistanian Acorus calamus (Fam.: Araceae) is locally found (Nasir, 1978) in Chitral, Peshawar, Jhelum valley, Thalawan valley, Mandi and Kashmir. The common name of A. calamus is sweet flag. It is found in marshy places and along the river banks from 600-2000m. The root-stock (modified stem) commonly called as rhizome, is medicinal and yields an essential oil used in the manufacture of soap, cosmetics and in the liquor industry. It is also used as medicine for stomach complaints, snake bite, as an insect repellent and for remittent fevers. The essential oil of A. calamus is volatile (Aromatic) and contains acorenone, β-gyrjunene, Isoshyobunine, β-asarone, Calamendiol, α-selinene, α-calacorene, Calamusenone, Camphene and Shyobunone as main active ingredients. In the present paper the essential oil of A. calamus was tested against dengue fever virus vector mosquito Ae. aegypti larvae (late 3 rd instar) The LC 50 was found to be 1250ppm by WHO-method, (Anon., 1970). The IGR effects were observed on lower i.e. 150, 300, 450, 600 and 750ppm dose. The abnormalities were increased with the increase of dose. Phytotoxicity on cotton crop was recorded @ 1.5 litre/acre, whereas no phytotoxicity was recorded on mango tree and coconut plants upto the dose of 2 litres/acre. While 70-90% control of mango hoppers on mango trees in Mirpurkhas Sindh and rhinoceros beetles on coconut plants in Hub, Balochistan was recorded. Anti-fungal activity was recorded on cuts and wounds on sheep in Hub, Balochistan. The acorus oil prevents the cuts and wounds from fungal growth and the cuts & wounds heal up rapidly as compared to control. Systematic control of root knot nematode was also recorded in cotton and brinjal plants by using 0.25% solution of calamus oil, given to the infected plants. The scale insects were also controlled by the same systematic method by using 0.5% dilution to the infected cotton plants. The control of mealy bugs on cotton, brinjal and Abutilon indicum was achieved by spray method using 0.5% solution, repeated weekly for one month in Sindh and Balochistan. Beside this the different aspects of acorus oil activity and suggestions for implementation as biopesticide in agriculture and health sector with special reference to Pakistan have been discussed in detail.