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PubMed2006

In vitro screening of 200 pesticides for agonistic activity via mouse peroxisome proliferator-activated receptor (PPAR)alpha and PPARgamma and quantitative analysis of in vivo induction pathway.

Peroxisome proliferator-activated receptors (PPARs) are ligand-dependent transcription factors and key regulators of lipid metabolism and cell differentiation. However, there have been few studies reporting on a variety of environmental chemicals, which may interact with these receptors. In the present study, we characterized mouse PPARalpha and PPARgamma agonistic activities of 200 pesticides (29 organochlorines, 11 diphenyl ethers, 56 organophosphorus pesticides, 12 pyrethroids, 22 carbamates, 11 acid amides, 7 triazines, 8 ureas and 44 others) by in vitro reporter gene assays using CV-1 monkey kidney cells. Three of the 200 pesticides, diclofop-methyl, pyrethrins and imazalil, which have different chemical structures, showed PPARalpha-mediated transcriptional activities in a dose-dependent manner. On the other hand, none of the 200 pesticides showed PPARgamma agonistic activity at concentrations <or =10(-5) M. To investigate the in vivo effects of diclofop-methyl, pyrethrins and imazalil, we examined the gene expression of PPARalpha-inducible cytochrome P450 4As (CYP4As) in the liver of female mice intraperitoneally injected with these compounds (< or =300 mg/kg). RT-PCR revealed significantly high induction levels of CYP4A10 and CYP4A14 mRNAs in diclofop-methyl- and pyrethrins-treated mice, whereas imazalil induced almost no gene expressions of CYP4As. In particular, diclofop-methyl induced as high levels of CYP4A mRNAs as WY-14643, a potent PPARalpha agonist. Thus, most of the 200 pesticides tested do not activate PPARalpha or PPARgamma in in vitro assays, but only diclofop-methyl and pyrethrins induce PPARalpha agonistic activity in vivo as well as in vitro.

Animals↗
PubMed2006

Modulation of aromatase activity and mRNA by various selected pesticides in the human choriocarcinoma JEG-3 cell line.

Aromatase enzyme plays a central role in steroidogenesis by converting androgens to estrogens and has been proposed as an important molecular target for many environmental endocrine disrupters chemicals. In this study, we have screened 30 selected pesticides with known, unknown or supposed effects on aromatase activity, for their ability to modulate aromatase activity in the human choriocarcinoma JEG-3 cell line after both short (2 h) and long exposure (24 h). All pesticides were tested at concentrations up to 10 microM that did not cause cytotoxicity after 24h of exposure, as verified by the MTT viability assay. Four pesticides inhibited aromatase activity after 2 h of exposure: prochloraz (IC(50)<1 microM), fenbuconazole (IC(50)=1.1 microM), propiconazole (IC(50)=1.5 microM) and fenarimol (IC(50)=3.3 microM). Among them, prochloraz and fenbuconazole also exerted inhibitory effects after 24h. Toxaphen (10 microM) and heptachlor (10 microM) inhibited aromatase activity after 24h exposure only. Nine pesticides induced aromatase activity: aldrin, chlordane, cypermethrin, parathion-methyl, endosulfan, methoxychlor, oxadiazon, metolachlor and atrazine after 24 h of exposure, while tributyltin induced aromatase activity at 1 nM and 3 nM after both 2 h and 24 h of exposure, respectively. To further investigate the mechanisms of aromatase induction we measured CYP19 mRNA expression and showed that methoxychlor, aldrin, chlordane and tributyltin induced the transcription of the cyp19 gene. In addition, none of the aromatase inducers transactivated the retinoic acid receptor (RAR) in JEG-3 stably transfected with a RARE-luciferase plasmid while the RAR agonist TTNPB induced both aromatase and luciferase expression in these cells. Our results, which provide new data for fenbuconazole, as an inhibitor of human aromatase, and for eight pesticides as aromatase inducers, are discussed with regards to the regulation of aromatase expression in the JEG-3 cellular context.

Aromatase↗
PubMed2001

Data on application frequency of pesticide for risk assessment purposes.

In risk assessment, information from toxicity studies is combined with information on worker exposure. In general, agricultural practice implies long-term intermittent exposure to various pesticides. This issue can only be addressed when sufficient information exist, on exposure regimes. Patterns of application of pesticides and the use frequency of single pesticide products on a number of representative key crops from various agricultural sectors in the Netherlands were studied. The results show that there is an enormous variation in pesticide usage between and within sectors. On nearly all crops studied the number of applications with insecticides and fungicides was higher than the number of applications with herbicides. The average frequency of application of a the most used insecticide and fungicide products on the most intensively treated crops was between 10 and 20 times a year. But on most crops single pesticide products were used not more than seven times a year.

Agriculture↗
PubMed1998

Occupational exposure through spraying remedial pesticides.

A total of 20 surveys at 15 sites of remedial in-situ timber and masonry treatment took place in the latter half of 1996. Two of these surveys concerned wall washes (biocides), the remainder were non-agricultural pesticides. The purpose was to measure the surface deposition and inhalation exposure of the operatives to the pesticide spray fluids used. The diluted spray fluids were found to have significantly different concentrations from those intended by the sprayer. The pesticides were applied at pressures between 320 and 1050 kPa. Deposition rates for spray fluid on coveralls covered a wide range, with more than 30 fold difference between the median and the highest results (median 209 mg/minute; range 27.4 to 6550 mg/min). Contamination of coveralls occurred in all surveys, with the pesticide getting beneath the coveralls in 95% of surveys, with a median 5% contamination beneath the overall. The averaged and normalised deposition pattern was 75% legs, 11% arms, 12% torso and 2% head. Exposure of hands to pesticide (expressed as spray fluid) beneath protective gloves occurred in 89% of surveys (median 5.78 mg/minute; range 0.23 to 358 mg/min) and contamination of socks by spray fluid in 78% of surveys (median 2.08 mg/minute; range 0.12 to 260 mg/min). Exposure by inhalation to spray fluid was measurable in 72% of surveys (median 53.5 mg/m3 TWA; range 4.33 to 1320 mg/m3; 2 data excluded). Inhalation exposure and deposition on coveralls rose markedly at spray pressures above 700 kPa (100 psi).

Agricultural Workers' Diseases↗
PubMed2000

Simultaneous determination of acidic and non-acidic pesticides in natural waters by liquid chromatography-mass spectrometry.

There is increasing interest and demand for real multi-residue methods able to simultaneously determine pesticides with a broad spectrum of chemical characteristics in environmental and biological matrices. A method based on solid-phase extraction with a Carbograph 4 cartridge and liquid chromatography with electrospray mass spectrometry (LC-ES-MS) enabling simultaneous determination of non-acidic and acidic pesticides in real water samples is described. On repeatedly (n=5) extracting 4 l of drinking water (spike level 50 ng/l), 2 l of ground water (spike level 100 ng/l) and 1 l of river water (spike level 200 ng/l), recovery of 26 base/neutral pesticides and 13 acidic pesticides were equal to or better than 80%, except for carbendazim (67%), butocarboxim (73%), aldicarb (75%) and molinate (77%). Relative standard deviations ranged between 4 and 15%. Final extracts containing acidic and non-acidic pesticides were analyzed in a single chromatographic run while the ES-MS system was operated in both positive and negative ion modes. With the aim of finding the best operating conditions, in terms of sensitivity, the pH of the LC eluent was varied in the 2.9-8.4 range. Altogether, the best results were obtained by using an LC eluent containing 1 mmol/l formic acid. Over the entire pH range considered, well shaped peaks for both basic and acidic analytes were achieved by the use of a new generation LC column. By extracting selected ion current profiles from the total ion current mass chromatogram relative to analysis of 4 l of drinking water spiked with 50 ng/l of each of the 39 analytes, estimated limits of detection ranged between 0.05 and 1.5 ng/l, except for propyzamide (8 ng/l) and 2,4-DB (3 ng/l).

Acids↗
PubMed2000

Pesticide residue analysis in foodstuffs applying capillary gas chromatography with mass spectrometric detection. State-of-the-art use of modified DFG-multimethod S19 and automated data evaluation.

This paper focuses on recent developments in the author's laboratory and reports on the "ultimate" analysis scheme which has evolved over the last 20 years in our laboratory. This demonstrates the feasibility of screening analyses for pesticide residue identification, mainly by full scan GC-MS, down to the 0.01 ppm concentration level in plant foodstuffs. It is based on a miniaturized DFG S19 extraction applying acetone for extraction followed by liquid-liquid extraction with ethyl acetate-cyclohexane followed by gel permeation chromatography. The final chromatographic determination is carried out with a battery of three parallel operating gas chromatographic systems using effluent splitting to electron-capture and nitrogen-phosphorus detection, one with a SE-54 the other with a OV-17 capillary column and the third one with a SE-54 capillary column and mass selective detection for identification and quantitation. The method is established for monitoring more than 400 pesticides amenable to gas chromatography. These pesticide residues are identified in screening analyses by means of the dedicated mass spectral library PEST.L containing reference mass spectra and retention times of more than 400 active ingredients and also metabolites applying the macro program AuPest (Automated residue analysis on Pesticides) for automated evaluation which runs with Windows based HP ChemStation software. The two gas chromatographic systems with effluent splitting to electron-capture and nitrogen-phosphorus detection are used to check the results obtained with the automated GC-MS screening and also to detect those few pesticides which exhibit better response to electron-capture and nitrogen-phosphorus detection than to mass spectrometry in full scan.

Automation↗
PubMed1978

Separation of polychlorobiphenyls from chlorinated pesticides in sediment and oyster samples for analysis by gas chromatography.

Polychlorobiphenyls (PCBs) have been separated from DDT and its analogs and from the other common chlorinated pesticides by adsorption chromatography on columns of alumina and charcoal. Elution from alumina columns with increasing fractional amounts of hexane first isolates dieldrin and heptachlor epoxide from a mixture of chlorinated pesticides and PCBs. The remaining fraction, when added to a charcoal column, can be separated into two fractions, one containing the chlorinated pesticides, the other containing the PCBs, by eluting with acetone-diethyl ether (25:75) and benzene, respectively. The PCBs and the pesticides are then determined by gas chromatography on the separate column eluates without cross interference. The method is applicable to sample extracts prepared for gas chromatography. Recoveries of the PCBs (Aroclors) and the chlorinated pesticides are good and the method is applicable to sediment and marine biota samples.

Chromatography, Gas↗
PubMed2001

On the signal response of various pesticides in electrospray and atmospheric pressure chemical ionization depending on the flow-rate of eluent applied in liquid chromatography-tandem mass spectrometry.

The API-MS signal response of several pesticides (atrazine, simazine, isoproturon, diuron, chlorfenvinphos, chlorpyrifos, alachlor, trifluralin) depending on the flow-rate of eluent entering the MS interface was investigated. The investigations were based on API-MS-MS analyses of standard pesticide mixtures in the flow injection mode (FIA) at systematically varied eluent flow-rates using both an ESI interface (Turboionspray) and a heated nebulizer type APCI source. In the result, the individual compounds included in this study showed significant differences in their signal response behaviour depending on the flow-rate of eluent applied. The most hydrophobic compounds among the investigated pesticides (chlorpyrifos and trifluralin) showed drastic losses of sensitivity with increasing eluent flow-rate in both ESI and APCI, while more hydrophilic compounds like atrazine, simazine and isoproturon showed the expected signal response (concentration-sensitive in ESI, mass-flow-sensitive in APCI) at least within a certain range of flow-rates (200-600 microl/min in ESI, 200-2000 microl/min in APCI). These findings lead to the conclusion that application of a programmed HPLC eluent flow-rate may be advantageous to achieve maximum sensitivity of API-MS detection for all pesticides of interest. This is exemplified by the implementation of a flow gradient into an online SPE-HPLC-APCI-MS/MS method for improved analysis of pesticides in drinking water.

Atmospheric Pressure↗
PubMed1991

Evaluation of eluents in thermospray liquid chromatography-mass spectrometry for identification and determination of pesticides in environmental samples.

The influence of different eluents in positive and negative ion mode thermospray liquid chromatography-mass spectrometry was studied with several groups of pesticides, including carbamates, chlorotriazines, phenylureas, phenoxy acids and organophosphorus and quaternary ammonium compounds, and the corresponding degradation products. Using the positive ion mode in combination with reversed-phase eluents the base peaks generally corresponded either to [M + H]+ for the chlorotriazines and their hydroxy metabolites or to [M + NH4]+ for the carbamates, the phenylureas, the organophosphorus pesticides and their oxygen analogues. In the negative ion mode different processes such as (dissociative) electron-capture and anion attachment mechanisms occurred. Fragment ions such as [M - CONHCH3]- for the carbamates, [M - H]- for the chlorotriazines, phenylureas and chlorinated phenoxy acids and [M].-, [M - R]- (R being a methyl or ethyl group) for organophosphorus pesticides were usually formed. Depending on the eluent additive used (ammonium acetate, ammonium formate and/or chloroacetonitrile), three different adduct ions were formed: [M + CH3COO]-, [M + HCOO]- and [M + Cl]-. Normal-phase eluents with cyclohexane, n-hexane and/or dichloromethane provided more structural information and enhanced the response of several compounds. The positive ion mode was useful for the detection of chlorinated phenoxy acids and chlorophenols which could not be detected in the positive ion mode using reversed-phase systems. The base peaks generally corresponded to [M].+, [M + H]+ or [M - Cl]+. For the characterization of difenzoquat, a quaternary ammonium pesticide of which trace level analysis is troublesome, a post-column ion-pair extraction system was used. An aqueous mobile phase with a sulphonate-type counter ion was applied and an extraction solvent containing cyclohexane-dichloromethane-n-butanol (45:45:10) was used in thermospray liquid chromatography-mass spectrometry. Illustrative examples of the determination of residue levels of pesticides in soil matrices are shown.

Carbamates↗
PubMed2002

Application of gas chromatography-tandem mass spectrometry to the analysis of pesticides in fruits and vegetables.

A new analytical method was devised using gas chromatography with tandem mass spectrometry (GC-MS-MS) for the routine analysis of 31 multi-class pesticide residues and approximately 8000 fresh fruit and vegetable samples (green bean, cucumber, pepper, tomato, eggplant, watermelon, melon, and marrow). Extraction of the pesticides with dichloromethane was carried out. The optimal ionization mode, either electron impact or chemical ionization, was selected for each pesticide in the same run. Carbofrit was used in the liner and combined with the selectivity of the detector this avoided additional clean-up. Thus, not only was money and time saved, the uncertainty of the method was decreased in its application to routine analysis. The average recoveries in cucumber obtained for each pesticide ranged between 71 and 119% at two different fortification levels (n=10 each) that ranged between 7 and 300 ng g(-1) (depending on the pesticide). The relative standard deviation was lower than 19% for all compounds tested. The calculated limits of detection and quantification were typically <1 ng g(-1) which were much lower than the maximum residue levels established by European legislations.

Fruit↗
PubMed2002

Comparison of three different poly(dimethylsiloxane)-divinylbenzene fibres for the analysis of pesticide multiresidues in water samples: structure and efficiency.

Despite the continuing development of SPME (solid-phase microextraction) fibre coatings, their selection presents some difficulties for analysts in choosing the appropriate fibre for a certain application. There are two distinct types of SPME coatings available commercially. The most widely used are poly(dimethylsiloxane) (PDMS) and poly(acrylate) (PA). Supelco has developed new mixed phases consisting of porous polymer particles, either poly(divinylbenzene) (DVB) or Carboxen suspended in a matrix of PDMS or Carbowax for extracting analytes via adsorption. In addition to the nature of the extracting phase, the thickness of the polymeric film must be taken into account and, surprisingly, the construction of the fibres when apparently they bear the same coating, as it is the case of the three PDMS-DVB fibres available. Other fibre structure properties not well explored were identified and must be taken into consideration. To elucidate their extraction efficiency, three PDMS-DVB fibres, namely 60 microm for HPLC use, 65 microm for GC use and 65 microm StableFlex for GC use, were compared with regard to the extraction of 36 compounds included in four pesticide groups. The first was particularly suited for the extraction of organophosphorus pesticides and triazines whereas the StableFlex exhibited advantages in the analysis of organochlorine pesticides and pyrethroids. An explanation for the extraction differences is suggested based on the different structure of the fibres. Detection limits in the range of 1-10 ng/l for organochlorine pesticides, 1-30 ng/l for organophosphorus pesticides, 8-50 ng/l for triazines and 10-20 ng/l for pyrethroids were attained in a method using the 60 microm PDMS-DVB fibre. The fibre maintains its performance at well above 100 extractions with between-day precision below 10%.

Chromatography, Gas↗
PubMed2003

Automated hollow fiber-protected dynamic liquid-phase microextraction of pesticides for gas chromatography-mass spectrometric analysis.

Dynamic liquid-phase microextraction (LPME) controlled by a programmable syringe pump was evaluated for extracting pesticides in water prior to GC-MS analysis. A conventional microsyringe with a 1.3-cm length of hollow fiber attached to its needle was connected to a syringe pump to perform the extraction. The microsyringe was used as both the microextraction device as well as the sample introduction device for GC-MS analysis. The attached hollow fiber served as the "holder" and protector" of 3 microl of organic solvent. The solvent was repeatedly withdrawn into and discharged from the hollow fiber by the syringe pump. Pesticides were extracted from 4-ml water samples into the organic solvent impregnated in the hollow fiber. The effects of organic solvents, plunger movement pattern, agitation and extraction time were investigated. Good repeatabilities of extraction performance were obtained, with the RSD values ranging from 3.0% (alachlor) to 9.8% (4-chlorophenol) for the 14 pesticides; most RSD values were under 5.0%. The method provided a 490-fold preconcentration of the target pesticides. The limits of detection were in the range of 0.01-5.1 microg/l (S/N = 3) in the GC-MS selected ion monitoring mode. In addition, sample clean-up was achieved during LPME because of the selectivity of the hollow fiber, which prevented undesirable large molecules from being extracted. A slurry sample (mixture of 40 mg soil/ml of water) containing seven pesticides was extracted using this method which also gave good linearity and precision (most RSDs <7.0%, n = 3).

Gas Chromatography-Mass Spectrometry↗
PubMed2003

Screening and determination of pesticides in soil using continuous subcritical water extraction and gas chromatography-mass spectrometry.

In the present work the efficiency of water under subcritical conditions for the extraction of pesticides having a broad spectrum of polarities from soils was evaluated. The pesticides under study were carbofuran, hexachlorobenzene, dimethoate, simazine, atrazine, lindane, diazinon, methylparathion, alachlor, aldrin-R, metholachlor, chlorpyrifos, heptachlor epoxide, dieldrin, endrin, 4,4-DDT and metoxichlor. Optimization studies were carried out using a blank soil (Non-Polluted Soil 1, CLN-1, RTC) and a real soil which were previously spiked with the pesticide mixture and aged for 60 days. A laboratory-made aluminum oven with controlled temperature was used to carry out the leaching process with subcritical water, where it is placed a pre-heater and the extraction cell. The following variables were studied, keeping the pressure controlled about 1200 p.s.i.: the extraction temperature, the time of static and dynamic extraction and the flow-rate of water (1 p.s.i. = 6894.76 Pa). The extraction efficiency of the pesticides increases with the temperature trending to the quantitative extraction at temperatures near to 300 degrees C. After the extraction process, the analytes were transferred quantitatively to 5 ml dichloromethane, before the determination by GC-MS. The results indicate that under the optimized conditions mostly of the analytes are extracted quantitatively in 90 min with recoveries quite similar to those obtained by the standard Soxhlet extraction procedure. Alternatively, by using an extraction time of 25 min, the method can be used as screening for all the pesticides, with recoveries depending on their polarity.

Gas Chromatography-Mass Spectrometry↗
PubMed2003

Multi-residue screening of pesticides in vegetables, fruits and baby food by stir bar sorptive extraction-thermal desorption-capillary gas chromatography-mass spectrometry.

The performance of stir bar sorptive extraction (SBSE) for the enrichment of pesticides from vegetables, fruits and baby food samples is discussed. After extraction with methanol, an aliquot is diluted with water and SBSE is performed for 60 min. By applying a new thermal desorption unit (TDU), fully automated and unattended desorption of 98 stir bars is feasible, making SBSE very cost-effective. The presence of pesticide residues is elucidated with the retention time locked gas chromatography-mass spectroscopy method (RTL-capillary GC-MS). With SBSE-RTL-capillary GC-MS operated in the scan mode, more than 300 pesticides can be monitored in vegetables, fruits and baby food. The multi-residue method (MRM) described provides detectabilities from the mg/kg (ppm) to the sub-microg/kg (ppb) level, thereby complying with the maximum residue levels (MRLs) set by regulatory organizations for pesticides in different matrices. Several examples, i.e. pesticide residues in lettuce, pears, grapes and baby food, illustrate the potential of SBSB-RTL-capillary GC-MS.

Fruit↗
PubMed2003

Investigation of preconcentration strategies for the trace analysis of multi-residue pesticides in real samples by capillary electrophoresis.

In this work, on-line preconcentration strategies were investigated for the multi-residue analysis of pesticides in drinking water and vegetables using micellar electrokinetic chromatography. Among the on-line strategies, sweeping and stacking with reverse migration of micelles (SRMM), with and without the insertion of a plug of water before sample injection, were contrasted. A new version of SRMM was also introduced. The modification consisted of momentarily applying a positive voltage at the inlet vial right after sample has been injected, increasing the efficiency by which the analytes are captured. Nine pesticides from different classes, carbendazim (benzimidazole), simazine, atrazine, propazine and ametryn (triazine), diuron and linuron (urea), carbaryl and propoxur (carbamate), were baseline separated in less than 6 min with a electrolyte composed of 20 mmol l(-1) phosphate buffer at pH 2.5, containing 25 mmol l(-1) sodium dodecyl sulfate and 10% methanol. Limits of detection (LODs) in the order of 2-46 microg l(-1) for the pesticides under investigation were obtained solely using the on-line strategies. Enrichment factors of 3-18-fold were obtained. These factors were computed as the improvement of the concentration LODs with respect to the reference condition (injection of 10 s at 2.5 kPa pressure). The proposed methodologies were applied to the analysis of pesticides in complex matrices such as carrot extracts where the detection of 2.5 microg l(-1) was illustrated. By combining off-line solid-phase extraction and the proposed on-line strategies, the detection of pesticides in drinking water at the 0.1 microg l(-1) level was conceived.

Electrophoresis, Capillary↗
PubMed1997

Selective extraction of pyrethroid pesticide residues from milk by solid-matrix dispersion.

A rapid procedure has been developed that allows a single-step, selective extraction and clean-up of pyrethroid (PYR) pesticide residues from milk dispersed on solid-matrix diatomaceous material filled into disposable cartridges and eluted by means of light petroleum saturated with acetonitrile and ethanol. The extract was cleaned up by high-performance size-exclusion chromatography. Determinations were carried out by gas chromatography with electron-capture detection. Recovery experiments were carried out on homogenized commercial milk (3.6% fat content) that was spiked with solutions of 14 PYR pesticides, viz., tefluthrin, tetramethrin, cyphenothrin, cyfluthrin, flucythrinate, fluvalinate, deltamethrin, bioallethrin, fenpropathrin, lambda-cyhalothrin, permethrin, alpha-cypermethrin, esfenvalerate and tralomethrin, at levels ranging from 0.04 to 0.41 mg/kg for the different PYR pesticides. Average recoveries were in the range 60-119% for the different PYR pesticides, with relative standard deviations from ca. 2.5 to 14.4%. Coextracted fatty material amounted to an average of ca. 5 mg/ml of milk. The sole extraction step requires about 30 min. The main advantages of the procedure are that extraction of PYR pesticides (with a minimum carry over of fat) is performed in a single step, emulsions do not occur, several samples can be run in parallel by a single operator, reusable glassware is not needed and simple operations are required.

Animals↗
PubMed1997

Evaluation of a fibrous cellulose drying agent in supercritical fluid extraction and pressurized liquid extraction of diverse pesticides.

A fibrous cellulose powder (CF-1) was investigated as a drying agent for supercritical fluid extraction (SFE) and pressurized liquid extraction (PLE), also known as accelerated solvent extraction. Analysis of fifty-eight diverse pesticides was performed using gas chromatography-ion-trap mass spectrometric detection (GC-ITD). Extraction efficiencies were correlated versus pesticide polarity with samples of different water-CF-1 ratios. The effect of water was much more pronounced in SFE using CO2 than PLE using acetonitrile. Pesticide recoveries and limits of detection of fortified tomato samples mixed with CF-1 were determined. PLE gave recoveries > 80% for nearly all pesticides, and SFE gave similar recoveries except for the most polar and non-polar pesticides. SFE typically gave lower detection limits than PLE due to fewer matrix interferants.

Cellulose↗
PubMed2004

[Relationship between pesticide exposure and low-grade superficial bladder urothelial carcinoma].

BACKGROUND AND OBJECTIVE: Few studies have been published analyzing the association between pesticides use and the increased risk of developing urothelial cancer of the bladder (UCB). The aim of this work was to investigate, in a geographical area with a high prevalence of UCB (Axarquia, Malaga province, southern Spain) if a) subjects with occupational exposure to pesticides have greater risk of developing UCB and b) there are histopathological differences with regard to UCB in patients without any exposure. PATIENTS AND METHOD: Case control study. During two years (1994-1996) 96 cases of UCB were included. The histologic grade and the depth of the invasion as well as the associated inflammatory infiltrate were analyzed. A questionnaire was answered by the patients. RESULTS: 58.3% of the case group were working with or had history of exposure to pesticides, compared to 40.6% in the control group (OR = 2.04; 95% CI, 1.1-3.6). The risk increased with a greater time of exposure. In exposed subjects, low grade tumors (OR = 2.6; 95% CI, 1.3-5.2) as well as superficial tumors (OR = 2.3; 95% CI, 1.2-4.4) were more frequent. They were more frequently accompanied by a chronic inflammatory infiltrate (OR = 4.5; 95% CI, 1.8-11.1). CONCLUSIONS: The subjects with occupational exposure to pesticide have greater risk of developing UCB, which is directly proportional to the exposure time. In comparison with the population in the zone without exposure, patients who use pesticides present low grade UCB and less invasive tumors more frequently. These facts were not modified when they were adjusted for tobacco consumption. Exposed patients have UCB with chronic (moderate) inflammatory reaction more frequently than the tumors in non-exposed subjects.

Adult↗