Do environmental and occupational exposure to pyrethroids and organophosphates affect human semen parameters? Results of a systematic review and meta-analysis

Our purpose was to review and analyse the impact of pyrethroids and organophosphates exposure on human semen parameters. A comprehensive literature search was performed through MEDLINE via PubMed, Scopus and Webscience. Only cohort studies examining semen parameters in workers or general populations exposed to pyrethroids or organophosphates were included. Ejaculate volume, sperm count, concentration, motility, viability, normal morphology and seminal pH alterations were pooled using the Cochran–Mantel–Haenszel Method with the random effect model and expressed as weighted mean difference, risk ratios, 95% confidence intervals and p-values. Seven cross-sectional studies regarding pyrethroids were included. Four of them were eligible for meta-analysis. The only parameter affected by pyrethroid exposure was normal sperm morphology (WMD-7,61%, 95%CI –11,92 to −3,30;p = 0,0,005). Nine studies were selected to evaluate the impact of organophosphates on semen parameters with six of them eligible for meta-analysis. A significant reduction was detected for the following: ejaculate volume (WMD −0,47ml, 95%CI −0,69 to −0,25; p < 0,0001), sperm count (WMD-40,03, 95%CI −66,81 to −13,25;p = 0,003), concentration (WMD-13,69 x10⁶/mL, 95%CI −23, 27 to-4,12;p = 0,005) and motility (WMD −5,70%, 95%CI −12,89 to 1,50;p = 0,12). Despite the increase in sperm abnormality, it has been shown that pyrethroids are unrelated to reduced sperm quality. However, the negative association of organophosphates with spermatogenesis is noteworthy.     

Insecticide resistance in head lice: clinical,parasitological and genetic aspects

Insecticide treatment resistance is considered to be a major factor in the increasing number of infestations by head lice. The large insecticide selection pressure induced by conventional topical pediculicides has led to the emergence and spread of resistance in many parts of the world. Possible mechanisms of resistance include accelerated detoxification of insecticides by enzyme-mediated reduction, esterification, oxidation that may be overcome by synergistic agents such as piperonyl butoxide, alteration of the binding site, e.g. altered acetylcholinesterase or altered nerve voltage-gated sodium channel, and knockdown resistance (kdr). Clinical, parasitological and molecular data on resistance to conventional topical pediculicides show that treatments with neurotoxic insecticides have suffered considerable loss of activity worldwide. In particular, resistance to synthetic pyrethroids has become prominent, probably because of their extensive use. As other treatment options, including non-insecticidal pediculicides such as dimeticone, are now available, the use of older insecticides, such as lindane and carbaryl, should be minimized, owing to their loss of efficacy and safety concerns. The organophosphorus insecticide malathion remains effective, except in the UK, mostly in formulations that include terpineol.     

The spread of the Leu-Phe kdr mutation through Anopheles gambiae complex in Burkina Faso: genetic introgression and de novo phenomena

During extensive sampling in Burkina Faso and other African countries, the Leu-Phe mutation producing the kdr pyrethroid resistance phenotype was reported in both Anopheles gambiae ss and A. arabiensis. This mutation was widely distributed at high frequency in the molecular S form of A. gambiae while it has been observed at a very low frequency in both the molecular M form and A. arabiensis in Burkina Faso. While the mutation in the M form is inherited through an introgression from the S form, its occurrence is a new and independent mutation event in A. arabiensis. Three nucleotides in the upstream intron of the kdr mutation differentiated A. arabiensis from A. gambiae ss and these specific nucleotides were associated with kdr mutation in A. arabiensis. Ecological divergences which facilitated the spread of the kdr mutation within the complex of A. gambiae ss in West Africa, are discussed.     

Development of a physiologically based pharmacokinetic model for deltamethrin in the adult male Sprague-Dawley rat.

Deltamethrin (DLT) is a type II pyrethroid insecticide widely used in agriculture and public health. DLT is a potent neurotoxin that is primarily cleared from the body by metabolism. To better understand the dosimetry of DLT in the central nervous system, a physiologically based pharmacokinetic (PBPK) model for DLT was constructed for the adult, male Sprague-Dawley rat that employed both flow-limited (brain, gastrointestinal [GI] tract, liver, and rapidly perfused tissues) and diffusion-limited (fat, blood/plasma, and slowly perfused tissues) rate equations. The blood was divided into plasma and erythrocytes. Cytochrome P450-mediated metabolism was accounted for in the liver and carboxylesterase (CaE)-mediated metabolism in plasma and liver. Serial blood, brain, and fat samples were taken for DLT analysis for up to 48 h after adult rats received 2 or 10 mg DLT/kg po. Hepatic biotransformation accounted for approximately 78% of these administered doses. Plasma CaEs accounted for biotransformation of approximately 8% of each dosage. Refined PBPK model forecasts compared favorably to the 2- and 10-mg/kg po blood, plasma, brain, and fat DLT profiles, as well as profiles subsequently obtained from adult rats given 1 mg/kg iv. DLT kinetic profiles extracted from published reports of oral and iv experiments were also used for verification of the model's simulations. There was generally good agreement in most instances between predicted and the limited amount of empirical data. It became clear from our modeling efforts that there is considerably more to be learned about processes that govern GI absorption and exsorption, transport, binding, brain uptake and egress, fat deposition, and systemic elimination of DLT and other pyrethroids. The current model can serve as a foundation for construction of models for other pyrethroids and can be improved as more definitive information on DLT kinetic processes becomes available.     

Differential effects of pyrethroids on volume-sensitive anion and organic osmolyte pathways

1. There are no effective ways of screening for potential modulators of volume-regulated anion channels in their native cell type. Generally, cell lines are used for this purpose. Using HeLa and C6 glioma cells, we identified the pyrethroids as a novel class of compounds that inhibit taurine efflux through volume-regulated anion transport pathways in these cells. Subsequently, we examined their effects on volume-regulated anion channels in guinea-pig ventricular myocytes to determine whether results obtained using cell lines could be extrapolated to other tissues. 2. Tetramethrin inhibited taurine efflux in both HeLa and C6 glioma cells with Ki values of approximately 26 and 16 micro mol/L, respectively. Bioallethrin and fenpropathrin inhibited volume-sensitive taurine efflux from C6 glioma cells, but not from HeLa cells. The Ki values for bioallethrin and fenpropathrin were 70 and 59 micro mol/L, respectively. 3. Volume-sensitive I- efflux was observed in HeLa cells but not in C6 glioma cells, suggesting that the taurine efflux pathway in C6 glioma cells may be different to that of the I- efflux pathway. Cyfluthrin, tetramethrin, fenpropathrin, tefluthrin and bioallethrin all significantly inhibited volume-sensitive I- efflux from HeLa cells at 100 micro mol/L. 4. Patch-clamp experiments have shown inhibition of ICl,vol in guinea-pig ventricular myocytes by fenpropathrin, but not tetramethrin or cypermethrin, at 100 micro mol/L. This revealed that further differences exist between ICl,vol in guinea-pig ventricular myocytes and the anion transport pathways in C6 glioma and HeLa cells. 5. In conclusion, we have shown that pyrethroids differentially inhibit volume-regulated anion and taurine efflux in a number of cell types. Because these compounds have different effects in different cells, it is likely that: (i) more than one pathway is involved in the volume-sensitive transport of anions and organic osmolytes; and (ii) the molecular identities of the channels underlying anion transport are different. Finally, for the reasons given above, care should be taken when extrapolating data from one cell type to another. However, in the absence of an existing high-throughput screen, taurine efflux still represents a viable route for the identification of potential modulators of volume-regulated ion channels.     

急性拟除虫菊酯中毒的临床表现及诊断

国外迄今尚未见有急性拟除虫菊酯中毒的临床报告。国内医学文献自1982年至1988年则已报道急性拟除虫菊酯中毒共573例,其中生产性中毒229例,意外性中毒344例。以急性溴氰菊酯中毒最为多见(325例),其次为戊氰菊酯(196例)及氯氰菊酯(45例)等急性中毒。本文对573例急性拟除虫菊酯中毒的临床表现进行综述与分析,并探讨其诊断分级与鉴别诊断,为制定职业性急性拟除虫菊酯中毒诊断标准提供参考。     

Molecular determinants on the insect sodium channel for the specific action of type II pyrethroid insecticides

Pyrethroid insecticides are classified as type I or type II based on their distinct symptomology and effects on sodium channel gating. Structurally, type II pyrethroids possess an α-cyano group at the phenylbenzyl alcohol position, which is lacking in type I pyrethroids. Both type I and type II pyrethroids inhibit deactivation consequently prolonging the opening of sodium channels. However, type II pyrethroids inhibit the deactivation of sodium channels to a greater extent than type I pyrethroids inducing much slower decaying of tail currents upon repolarization. The molecular basis of a type II-specific action, however, is not known. Here we report the identification of a residue G¹¹¹¹ and two positively charged lysines immediately downstream of G¹¹¹¹ in the intracellular linker connecting domains II and III of the cockroach sodium channel that are specifically involved in the action of type II pyrethroids, but not in the action of type I pyrethroids. Deletion of G¹¹¹¹, a consequence of alternative splicing, reduced the sodium channel sensitivity to type II pyrethroids, but had no effect on channel sensitivity to type I pyrethroids. Interestingly, charge neutralization or charge reversal of two positively charged lysines (Ks) downstream of G¹¹¹¹ had a similar effect. These results provide the molecular insight into the type II-specific interaction of pyrethroids with the sodium channel at the molecular level.     

Enantiomer-specific,bifenthrin-induced apoptosis mediated by MAPK signalling pathway in Hep G2 Cells

Enantioselectivity in toxicology, and health risk of chiral xenobiotics have become important topics at the forefront of chemistry and toxicology research. Our previous results showed that cis-bifenthrin (cis-BF) induced cytotoxicity and genotoxicity in human amnion epithelial (FL) cells, in an enantioselective manner. However, the exact molecular mechanisms of synthetic pyrethroid-induced, enantioselective apoptosis and cytotoxicity remain unclear. In this study, enantiomers of the synthetic pyrethroid-based insecticide, cis-BF, were separated on selected chiral columns by HPLC. Enantioselectivity in cytotoxicity and apoptosis, mediated by the mitogen-activated protein kinase (MAPK) signalling pathway, were evaluated in the human hepatocellular liver carcinoma (Hep G2) cell line. Exposure to 1S-cis-BF resulted in increased levels of phosphorylated JNK (Jun-N-terminal Kinases)/MAPKs, while exposure to 1R-cis-BF did not affect phosphorylated JNK levels. Pre-treatment with the JNK inhibitor SP600125, blocked 1S-cis-BF-induced cytotoxicity and apoptosis. In addition, 1S-cis-BF enhanced the production of ROS, while pre-treatment with the antioxidant agent MnTBAP resulted in decreased phosphorylation of JNK. To the best of our knowledge, this is the first report demonstrating that cis-BF-induced apoptosis might occur, at least in part, through the enantioselective activation of JNK/MAPK signalling pathway in Hep G2 cells. The results suggest that enantioselectivity should be considered when evaluating eco-toxicological effects and health risks of chiral contaminants, and could also improve the understanding of molecular mechanisms responsible for chiral chemical-induced cytotoxicity and apoptosis.     

Malaria control by residual insecticide spraying in Chingola and Chililabombwe,Copperbelt Province,Zambia

Malaria is endemic in the whole of Zambia and is the leading cause of morbidity and mortality. Prior to 1980, effective malaria control was achieved in the northern mining towns of Chingola and Chililabombwe by means of annual residual spraying programmes. In the 1970s, incidence rates were as low as 20/1000 p.a., but by 2000 had increased to 68/1000 p.a. in Chingola and to 158/1000 p.a.in Chililabombwe. Konkola Copper Mines (KCM) initiated a malaria control programme in which all dwellings in the two towns and within a 10-km radius were sprayed with either dichlorodiphenyltrichloroethane or a synthetic pyrethroid (Icon by ZENECA or Deltamethrin by Aventis). Houses were sprayed in November and December 2000, at the start of the peak transmission period. There was a statistically significant reduction in malaria incidence recorded at KCM health facilities in the two towns, representing a protective incidence rate ratio of 0.65 (95% CI 0.44, 0.97) when comparing the post-spraying period with the corresponding period of the previous 2 years. This reduction followed a single round of house spraying during a year with higher rainfall than the preceding two and in an area where chloroquine was first-line treatment. This house-spraying programme is an example of private/public sector collaboration in malaria control.