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314 Abstracts / Toxicology L

ion procedure was in HR-P columns precondition with methanolnd water. The subsequent elution of diazinon was performed withmixture of hexane–ethyl acetate (1:1, v/v) prior to the deter-ination by GC–NPD and GC–MS/MS. Standards were prepared

piking blank juice samples to contract the observed matrix effect.ccuracy (<9/6%), precision (<7/1%), specificity (quantitative, noeaking interaction), sensitivity LOD(1) ng/ml and LOQ(5) ng/mlnd reproducibility (>95/4%) were acceptable. Detection limitas 1 ng/ml. Linear relation with good correlation coefficients

R2 > 0/99) was obtained. Mean recovery for diazinon was 95/4%ith relative standard deviation lower than 9% in the concentra-

ion range of 5–200 ng/ml. Mean and SD of diazinon in melons was07/64 ± 38/5 ng/kg. Diazinon was not detected in cucumber sam-les. It was later confirmed that diazinon was not used for the cropsf these cucumbers. GC–NPD and MS/MS was developed to deter-ine residue of diazinon in melons and cucumbers. The GC–MS/MS

nalytical method showed a high efficacy for determination ofiazinon residues in the fruits

oi:10.1016/j.toxlet.2010.03.991

308-007DT-derivatives pesticides could modulate GH-IGF axis inoungsters

. Zumbado 1, E.E. Álvarez-León 2, P. Lara 1, M.lmeida-González 1, O.P. Luzardo 1, G. Hernández-Rodríguez 1,.D. Boada 1

University of Las Palmas de Gran Canaria and Instituto Canario denvestigación del Cáncer, Spain, 2 Canary Health Service and Institutoanario de Investigación del Cáncer, Spain

nsulin-like growth factor 1 (IGF-I) and its binding proteins (mainly,GFBP-3) and DDT-derivative pesticides (DDTs) have been involvedn the pathogenesis of several malignancies, such as cancer, dia-etes and growth disorders. Recently, it has been suggested thatDTs may influence IGF levels in adults. Due to the fact that IGF-Ieak levels at puberty could determine IGF-I levels in adulthood,e developed a cross-sectional study to evaluate the potential rela-

ionship between the serum levels of DDTs and IGF-I in youngsters160 people between 6 and 19 years; 81 boys and 79 girls) fromrepresentative sample of the general population of the Canary

slands (Spain). Multivariate models (ANCOVA) tests were useddjusting for confounding variables (age, BMI, and IGFBP-3), andtratifying by gender. Our results showed that IGF-I serum lev-ls were significantly lower in pre-pubertal male children (6–15ears) who showed detectable levels of p,pı̌-DDE and p,pı̌-DDDhan in pre-pubertal male children who presented non-detectableevels of these DDTs (p = 0.023 and p = 0.049, respectively). Addi-ionally, in this multivariate model, a non-linear dose–responseurve was observed between Total DDT body burden (sum of thehree DDTs measured in serum: p,pı̌-DDT, p,pı̌-DDE, and p,pı̌-DDD)nd IGF-I in pre-pubertal male children (p = 0.043). These findingsgree with previous studies that related p,pı̌-DDE serum levels withecreased height and weight in children. Our results seem to indi-ate that DDTs could modulate the IGF-system in a way that isighly influenced by gender and age. Such circumstance implies

hat environmental contaminants could influence the long-termisk of several diseases related to GH-IGF axis (diabetes, cancer,llergies, growth disorders, etc.).

oi:10.1016/j.toxlet.2010.03.992

196S (2010) S37–S351

P308-008Progress of acetylcholinesterase reactivators againstorganophosphorus pesticides—Almost 60 years sincepralidoxime

K. Musilek 1, O. Holas 2, M. Pohanka 1, V. Opletalova 2, K. Kuca 1

1 University of Defence, Faculty of Military Health Sciences, CzechRepublic, 2 Charles University, Faculty of Pharmacy, Czech Republic

The OP pesticides are considered to be annually responsible for200,000 deaths [1]. The reactivators of acetylcholinesterase (AChE,EC 3.1.1.7) are very important components in the treatment ofintoxications caused by organophosphate inhibitors such as nerveagents and OP pesticides. OP inhibitors covalently bind to active siteof AChE and irreversibly inhibit its activity. The reactivator breaksthe inhibitor-AChE covalent bond and restores its activity. Unfortu-nately, there is no reactivator applicable for every type of inhibitor;it means that every structural change in the molecule of OP inhibitorneeds a specific structure of the reactivator.

The pralidoxime became a very first reactivator available forOP pesticide intoxications [2]. Though it is not significantly ben-eficial in the treatment of OP pesticide intoxication, it is still inuse worldwide. Since its introduction, over 300 oximes have beenproduced or tested against OP pesticide poisoning, and severalnovel compounds show very promising abilities as comparable (orhigher) to commercial AChE reactivators [3]. The overview of vari-ous approaches to OP pesticide treatment is going to be presented.

Reference

Eddleston, M., Buckley, N.A., Eyer, P., Dawson, A.H., 2008. Lancet 371, 597.Wilson, I.B., Ginsburg, S.A., 1955. Biochim. Biophys. Acta 18, 168.Musilek, K., Dolezal, M., Gunn-Moore, F., Kuca, K., Med. Res. Rev., doi:

10.1002/med.20192.

doi:10.1016/j.toxlet.2010.03.993

P308-009Neurotoxic effects of endosulfan administered throughoutpregnancy and lactation on striatal amino acid concentration

A. Caride, T. Cabaleiro, G. Bernardez, A. Lafuente

University of Vigo, Spain

Endosulfan is an organochlorine insecticide that constitutes a majorhealth concern because of their prolonged persistence in the envi-ronment and bioaccumulation through the food chain. Exposure tothis xenobiotic has been shown to induce neurotoxicity. It accu-mulates in fatty tissues, can cross the placenta and can be excretedthrough maternal milk, so evaluation of endosulfan effects inoffspring male rats after in utero and lactational exposure to endo-sulfan is of interest. For this purpose, dams were treated orally with0.61 mg or 6.12 mg endosulfan/kg/day from the gestation begin-ning until the weaning. At postnatal days (PND) 15, 30 and 60male offspring rats were sacrificed. In these animals we studiedthe variations of the amino acids aspartate, glutamate, glutamine,taurine and gamma amino butyric acid (GABA) concentration instriatum. In 15-day-old male offsprings, the highest administereddose decreased aspartate concentration, and both studied doses

decreased glutamate, glutamine, taurine and GABA content. Treat-ment with 6.12 mg of endosulfan/kg/day increased all amino acidsconcentration at PND 30, as well as excitatory amino acid (aspar-tate, glutamate and glutamine) contents at PND 60. These resultssuggest that endosulfan exposure during pregnancy and lactation