Recurrent tonic-clonic seizures and coma due to ingestion of Type I pyrethroids in a 19-month-old patient.

CONTEXT: Pyrethroids are synthetic pyrethrin analogues that induce sodium-channel depolarization and hyperexcitation. Severe pyrethroid poisoning is manifested by a "Tremor Syndrome" (Type I cyano-agents) or a "Choreoathetosis/Salivation Syndrome" (Type II non cyano-agents). Very few reports of neurotoxic effects caused by Type I pyrethroids ingestion are available, and no human data concerning Type I pyrethroid blood levels in pediatric poisoning are reported in the medical literature. CASE DETAILS: A 19-month-old female patient presented with irritability and inconsolable crying that rapidly worsened to tonic-clonic seizures and coma (GCS 6). On admission vital signs including BP 110/70 mmHg, HR 110 beats/min, and SpO2 98% on room air were normal. Orotracheal intubation, oxygen administration, and midazolam infusion (4 µg/kg/min) were performed. Intravenous thiopental sodium, up to 18 mg/kg/hour, was administered to control convulsions. An inquiry revealed that 9 h before presentation the patient had ingested an unknown amount of an insecticide containing 7% piperonyl-butoxide and a mixture of the Type I pyrethroids bifenthrin (5%) and esbiothrin (3%). Consequently, gastric lavage was performed, followed by administration of activated charcoal and cathartics. On the subsequent 48 h, the patient returned progressively alert; she was extubated on day 4 and discharged asymptomatically 12 days after hospitalization. After 9, 48, and 72 h of ingestion, the plasma levels were 500, 95, and 40 ng/mL for bifenthrin and 1,640, 640, and 165 ng/mL for piperonyl-butoxide respectively. DISCUSSION: This pediatric case showed severe pyrethroid neurotoxicity associated with measurable plasma levels of bifenthrin and piperonyl-butoxide. In pediatric pyrethroid poisoning, coma and seizures may represent the main life-threatening features. First-aid therapy including airway maintenance and control of muscle fasciculation and seizures is of major importance. Benzodiazepines and high-dose thiopental sodium were effective treatments for convulsion.

Sublethal toxicity of esbiothrin relationship with total antioxidant status and in vivo genotoxicity assessment in fish (Cyprinus carpio L., 1758) using the micronucleus test and comet assay.

Esbiothrin, synthetic pyrethroid with quick activity against insects, is widely used against household pests and in public health. Despite widespread use, data on ecotoxicity and genotoxic effects are extremely scarce. The aim of the present study is to evaluate the genotoxic potential of esbiothrin on a model fish species Cyprinus carpio L., 1758 (Pisces: Cyprinidae, koi) using the micronucleus test and comet assay in peripheral blood erythrocytes. Effects of two sublethal exposure concentrations on plasma total antioxidant status (TAS mmol/L), and Hct values were examined. On the basis of the 96 h LC50 data from U.S. EPA ecotox database (32 µg/L) two sublethal exposure concentrations (5 and 10 µg/L) were used together with ethyl methanesulfonate (EMS) (5 mg/L) as positive control. Five fish were used for each dose/duration group (24, 48, and 72 h) under controlled laboratory conditions. The fish showed behavioral changes at the higher dose. Plasma TAS (mmol/L) levels decreased in 24 h; an increase was observed slightly for 48 and obviously for 72 h in both exposure doses. Similarly, hematocrit (Hct) values differed between exposure duration but no significant differences in mean values were found between groups of the same exposure time. The general trend was a rise after 48 h, which decreased afterwards. Our results revealed significant increases in the frequencies of micronuclei and levels of DNA strand breaks and thus demonstrated the genotoxic potential of this pesticide on fish, a nontarget organism of the aquatic ecosystem. To our knowledge this is the first study to report observable genotoxic effects of esbiothrin on fish.

Enantioseparation of esbiothrin by cyclodextrin-modified microemulsion and micellar electrokinetic chromatography.

A comparison between chiral cyclodextrin-modified microemulsion electrokinetic chromatography (CD-MEEKC) and cyclodextrin-modified micellar electrokinetic chromatography (CD-MEKC) for the enantiomeric separation of esbiothrin was carried out. For both methods, the separation conditions were optimized by varying CD types and concentration, running buffer pH and compositions, organic modifiers, and temperature. The optimal CD-MEEKC conditions were 0.8% n-heptane, 2.3% SDS, 6.6% n-butanol, 90.3% 10 mM sodium tetraborate containing 3% (w/v, the ratio of CD mass to microemulsion volume) methyl-beta-cyclodextrin, pH 10, 25 degrees C. The optimized CD-MEKC conditions were 3.3% SDS, 96.7% 10 mM sodium tetraborate containing 5% (w/v) beta-CD, pH 10, 25 degrees C. The difference in physicochemical properties of the buffer and CDs resulted in different optimal CD type. The competitive distribution between the microemulsion (or micelle) and chiral CD contributed to the chiral separation. Both methods provided excellent separation (R(s) approximately 3) with similar migration time (ca. 15 min). CD-MEEKC provided higher separation efficiencies (>300000) than CD-MEKC (>200000). The LODs for CD-MEEKC and CD-MEKC were 4.7 microg/mL and 3.2 microg/mL, respectively. The RSDs of migration time and peak area for CD-MEEKC were slightly higher than for CD-MEKC. Both the demonstrated CD-MEEKC and CD-MEKC methods provided high efficiencies, low LODs, and reproducible enantioseparations of esbiothrin.

Lack of insecticidal effect of mosquito coils containing either metofluthrin or esbiothrin on Anopheles gambiae sensu lato mosquitoes.

Use of mosquito coils for personal protection against malaria and mosquito nuisance is advocated under mosquito and malaria control programmes. We performed field studies of mosquito coils containing either metofluthrin or esbiothrin in experimental huts situated in Kamhororo village, Gokwe district, Zimbabwe. All tests were performed on 3-5 day old reared female Anopheles gambiae sensu lato mosquitoes. The burning times were 9hr 20min for mosquito coils containing metofluthrin and 8 hr for those containing esbiothrin and the results were significantly different (p = <0.001). The mean knock down rate for mosquito coils containing metofluthrin was 90% and that for esbiothrin was 73.3% and the results were significantly different (p = 0.00). Mosquito coils containing metofluthrin had a mean repellence of 92.7% as compared to 85.4% for esbiothrin and the results were not significantly different (p=0.27). The protection time as required by EPA (1999) was 6 hr for mosquito coils containing metofluthrin and 5 hr for those containing esbiothrin. The mean insecticidal effect of mosquito coils containing metofluthrin was 84% as compared to 83% for those containing esbiothrin and the results were not significantly different (p = 0.56). Both mosquito formulations could not be classified as having insecticidal effect since none of them met the 95% mortality rate criteria.

Liquid chromatography-tandem mass spectrometry for the identification of impurities in d-allethrin samples.

A previous GC/MS study highlighting the impurity profile of the synthetic pesticide d-allethrin is extended here to validate and confirm the impurities identity through the development of soft ionisation HPLC-MS methods. To accomplish this, we developed a reverse phase LC-MS analysis in gradient elution with two distinct soft ionisation techniques, the atmospheric pressure ionisation with electrospray source (API-ESI) and the chemical ionisation (APCI). A single quadrupole and an ion trap, which allowed the simultaneous determination of the molecular masses and structural information of the impurities by acquisition of collisionally induced (CID) product ions spectrum and in-source fragmentation, were employed as analysers. Single quadrupole and ion trap analysers resulted perfectly matching in the d-allethrin impurity fragmentation patterns. All the main impurities over 0.1% identified by GC/MS were confirmed. Results indicate that the proposed HPLC/MS method was found appropriate to confirm the presence of impurities such as chrysolactone, chloro allethrin derivatives, allethrolone and chrysanthemic acid, excluding their formation under GC/MS strong ionisation condition.

Field trial of esbiothrin-impregnated rope in Ramgarh village, Dadri PHC, District Ghaziabad (U.P.).

A village-scale field trial was carried out to assess the operational feasibility and efficacy of smouldering 250 ppm esbiothrin-impregnated rope in repelling mosquitoes and its impact on transmission of malaria. Entomological monitoring revealed that smoke from smouldering rope resulted in 67.2-97.9% reduction of An. culicifacies densities in human and mixed dwellings. The reduction was obviously due to diversion of An. culicifacies population to cattlesheds where ropes were not burnt. The impact was more pronounced when indoor mosquito landing rate on human bait was compared with that of experimental and control areas. This was also reflected in reduced anthropophilic index and curtailment of malaria transmission in experimental area.

Use of kerosene lamp containing synthetic pyrethroids to repel mosquitoes.

An indigenous and appropriate method of personal protection was developed and tested in rural areas. It consists of an ordinary kerosene lamp made of tin with a regulator to adjust the wick. Different concentrations of esbiothrin, a synthetic pyrethroid, were mixed in kerosene and allowed to burn in living rooms and cattlesheds from dusk to dawn to observe hourly entry of mosquitoes. The tin lamp (100 ml capacity) without chimney provided the most efficient protection from mosquito bites. The protection varied from 84.2 +/- 8.2 to 97.8 +/- 2.8. Maximum protection was observed against An. culicifacies. Esbiothrin kerosene lamp (0.01%) lighted in living room provided 99.7% protection to exposed human baits seated at a distance of 1 m from the lamp. The technique is simple, cost-effective and does not require electricity and can be used both for illumination and repelling mosquitoes in remote and inaccesible areas.

Esbiothrin-impregnated ropes as mosquito repellent.

Esbiothrin [(+/-)-3-allyl-2-methyl-4-oxocylopent-2-enyl-(+)-trans- chrysanthemate] is an improved isomeric composition of allethrin series and consists essentially of esters of chrysanthemic acid and allethrolone. Jute rope was impregnated with esbiothrin and the smoke from smouldering ropes was evaluated as mosquito repellent in human dwellings and cattlesheds with open doors and windows at different dosages. Esbiothrin-impregranted (500 ppm) ropes prevented the entry of more than 95% An. culicifacles and other anophelines, 90.9-88.8% Culex quinquefasciatus and 96-95.1% total mosquitoes in open rooms of houses and cattlesheds respectively. The impact of ropes was more pronounced on the biting rate of mosquitoes. Indoors and outdoors human baits seated at a distance of about 3 m from smouldering esbiothrin ropes experienced no bite at all from An. culicifacies. An iron mesh around the rope prevents fire hazards.

Comparison of the synthetic pyrethroids Esbiothrin and Bioresmethrin with Scourge and Cythion against adult mosquitoes in a laboratory wind tunnel.

Both candidate adulticides, Esbiothrin and Bioresmethrin, exhibited quick knockdown 1-h posttreatment. Esbiothrin elicited the fastest knockdown, but Bioresmethrin was more effective at both 1- and 24-h posttreatment than either Esbiothrin or Scourge against both Aedes taeniorhynchus and Culex quinquefasciatus. Mosquitoes treated with Scourge required more time and a higher dosage to respond in a physiological manner similar to those treated with either of the candidate adulticides. More than twice the dosage rate of Cythion was required than either candidate adulticide to cause a similar physiological response in treated mosquitoes.

Efficacy of Esbiothrin mosquito coils at community level in northern Tanzania.

Field trials with mosquito coils containing 0.15% Esbiothrin at Usa River settlement, northern Tanzania, during 1986 achieved a 52% reduction in biting rates of Anopheles arabiensis Patton and a 73% reduction of Culex quinquefasciatus Say mosquitoes. No mosquito biting activity occurred during the coil burning period which started at 20.00 hours daily and lasted for an average of 8.6 h. A sociological survey indicated that the coils were favourably accepted and produced no serious side-effects.

The effectiveness of mosquito coils containing esbiothrin under laboratory and field conditions.

Tests were made to correlate the chemical content of mosquito coils with the knockdown and bite-inhibitory action of the smoke in the laboratory and with the protective effect in field use. Smoke from a blank coil, containing no pyrethroid, gave no knockdown, 10% inhibition of biting in the laboratory using Aedes aegypti, and 39% protection in field tests in village huts on the Kenyan coast with a mixed population of mosquitoes including 71% Anopheles gambiae. Coils containing low experimental contents of 0.044% and 0.099% Esbiothrin, an isomer blend rich in the D-allethrolone ester of D-trans-chrysanthemic acid, gave rapid knockdown in both small chamber and 25 m3 room tests, and 71% and 94% inhibition of biting respectively in the laboratory. In the field they gave 74% and 84% protection from mosquitoes alighting. Chemical content was therefore a good guide to knockdown and bite inhibition in the laboratory and also to the considerable protection found in the field.