LC-MS/MS determination of pesticide residues in fruits and vegetables

The aim of the research is to evaluate pesticide residue contamination of fresh and frozen fruits and vegetables, agricultural raw material, purchased from Polish farmers for production of frozen fruits and vegetables, and the estimation of the multiresidue method effectiveness expressed as the proportion of pesticides detected in food samples to the total number of pesticides analyzed by multiresidue methods. A total of 144 samples (of black currants, red currants, raspberries, cherries, strawberries, blackberries, cauliflowers and broccoli) were analyzed using LC-MS/MS method for the determination of 60 pesticides. QuEChERS extraction, matrix-matched calibration and dynamic multiple reaction monitoring method were used. Residues of 15 compounds, mainly fungicides and insecticides, were detected in 46 samples. The percentage of samples with residues above the maximum residue levels (MRL) was 15%, whereas samples with residues below MRL were 17%. A total of 13 samples contained more than one pesticide residue. Pesticide residues were detected most often in samples of black currants (50%), broccoli (36.4%), raspberries (29%) and red currants (21.8%). The most frequently detected pesticides were carbendazim and acetamiprid. The proportion of pesticides detected during our study to the total number of analyzed pesticides amounted to 25%. It was compared to literature findings. For three fourth of multiresidue methods, the proportion was below 50% for methods developed for the analysis of less than 100 pesticides, and below 30% for methods developed for the analysis of more than 100 pesticides. It appears that a lot of efforts and means is lost on pesticides never or rarely detected in examined samples. The workload and cost effectiveness of the development and application of multiresidue methods along with the range of pesticides covered by the method should be carefully and thoroughly considered anytime when a new method or workflow is developed. Including non-targeted screenings in pesticide residue control seems to be an alternative worth considering.     

Obsolete pesticides and application of colonizing plant species for remediation of contaminated soil in Kazakhstan

In Kazakhstan, there is a problem of finding ways to clean local sites contaminated with pesticides. In particular, such sites are the deserted and destroyed storehouses where these pesticides were stored; existing storehouses do not fulfill sanitary standards. Phytoremediation is one potential method for reducing risk from these pesticides. Genetic heterogeneity of populations of wild and weedy species growing on pesticide-contaminated soil provides a source of plant species tolerant to these conditions. These plant species may be useful for phytoremediation applications. In 2008–2009 and 2011, we surveyed substances stored in 80 former pesticide storehouses in Kazakhstan (Almaty oblast) to demonstrate an inventory process needed to understand the obsolete pesticide problem throughout the country, and observed a total of 354.7 t of obsolete pesticides. At the sites, we have found organochlorine pesticides residues in soil including metabolites of dichlorodiphenyltrichloroethane and isomers of hexachlorocyclohexane. Twenty-four of the storehouse sites showed pesticides concentrations in soil higher than maximum allowable concentration which is equal to 100 μg kg^?1 in Kazakhstan. Seventeen pesticide-tolerant wild plant species were selected from colonizing plants that grew into/near the former storehouse’s pesticides. The results have shown that colonizing plant annual and biannual species growing on soils polluted by pesticides possess ability to accumulate organochlorine pesticide residues and reduce pesticide concentrations in soil. Organochlorine pesticides taken up by the plants are distributed unevenly in different plant tissues. The main organ of organochlorine pesticide accumulation is the root system. The accumulation rate of organochlorine pesticides was found to be a specific characteristic of plant species and dependent on the degree of soil contamination. This information can be used for technology development of phytoremediation of pesticide-contaminated soils.     

Pesticides in urban multiunit dwellings: hazard identification using classification and regression tree (CART) analysis

Many units in public housing or other low-income urban dwellings may have elevated pesticide residues, given recurring infestation, but it would be logistically and economically infeasible to sample a large number of units to identify highly exposed households to design interventions. Within this study, our aim was to devise a low-cost approach to identify homes in public housing with high levels of pesticide residues, using information that would allow the housing authority and residents to determine optimal strategies to reduce household exposures. As part of the Healthy Public Housing Initiative, we collected environmental samples from 42 public housing apartments in Boston, MA, in 2002 and 2003 and gathered housing characteristics; for example, household demographics and self-reported pesticide use information, considering information available with and without a home visit. Focusing on five organophosphate and pyrethroid pesticides, we used classification and regression tree analysis (CART) to disaggregate the pesticide concentration data into homogenous subsamples according to housing characteristics, which allowed us to identify households and associated networks impacted by the mismanagement of pesticides. The CART analysis demonstrated reasonable sensitivity and specificity given more extensive household information but generally poor performance using only information available without a home visit. Apartments with high concentrations of cyfluthrin, a pyrethroid of interest given that it is a restricted use pesticide, were more likely to be associated with Hispanic residents who resided in their current apartment for more than 5 yr, consistent with documented pesticide usage patterns. We conclude that using CART as an exploratory technique to better understand the home characteristics associated with elevated pesticide levels may be a viable approach for risk management in large multiunit housing developments.     

Simultaneous determination of organochlorine and pyrethriod pesticide residues in the Chinese patent medicines by gas chromatography-tandem mass spectrometry

A simple, sensitive, reliable method was developed for the simultaneous determination of organochlorine and pyrethriod pesticide residues in Chinese patent medicines Six ingredient rehmannia pills and Xiaoyao pills. These pesticides were extracted by ethyl acetate. The extraction time and volume of ethyl acetate were optimized. Cleanup of extracts was performed with dispersive-solid phase extraction using graphitized carbon black as the sorbent. The determination of pesticides in the final extracts was carried out by gas chromatography–tandem mass spectrometry in multiple reaction monitoring mode (GC-MS/MS, MRM). The linearity of the calibration curves is good in matrix-matched standard and yields the coefficients of determination (R²) ≥0.99 for all of the target analytes. Under optimized conditions, the average recoveries (five replicates) for most pesticides range from 75.5% to 114.6%, and RSDs are less than 10.0%. The LODs of 18 pesticides in Six ingredient rehmannia pill and Xiaoyao pills are in the range of 0.01–8.82 μg kg^?1. The developed method meets the requirements of pesticide residue analysis and could be effectively used for routine analysis of the organochlorine and pyrethriod pesticide residues in Six ingredient rehmannia pills and Xiaoyao pills.     

The status of pesticide pollution in surface waters (rivers and lakes) of Greece. Part I. Review on occurrence and levels

This review evaluates and summarizes the results of long-term research projects, monitoring programs and published papers concerning the pollution of surface waters (rivers and lakes) of Greece by pesticides. Pesticide classes mostly detected involve herbicides used extensively in corn, cotton and rice production, organophosphorus insecticides as well as the banned organochlorines insecticides due to their persistence in the aquatic environment. The compounds most frequently detected were atrazine, simazine, alachlor, metolachlor and trifluralin of the herbicides, diazinon, parathion methyl of the insecticides and lindane, endosulfan and aldrin of the organochlorine pesticides. Rivers were found to be more polluted than lakes. The detected concentrations of most pesticides follow a seasonal variation, with maximum values occurring during the late spring and summer period followed by a decrease during winter. Nationwide, in many cases the reported concentrations ranged in low ppb levels. However, elevated concentrations were recorded in areas of high pesticide use and intense agricultural practices. Generally, similar trends and levels of pesticides were found in Greek rivers compared to pesticide contamination in other European rivers. Monitoring of the Greek water resources for pesticide residues must continue, especially in agricultural regions, because the nationwide patterns of pesticide use are constantly changing. Moreover, emphasis should be placed on degradation products not sufficiently studied so far.     

Pesticide residues in Portuguese strawberries grown in 2009–2010 using integrated pest management and organic farming

Pesticides are among the most widely used chemicals in the world. Because of the widespread use of agricultural chemicals in food production, people are exposed to low levels of pesticide residues through their diets. Scientists do not yet have a total understanding of the health effects of these pesticide residues. This work aims to determine differences in terms of pesticide residue content in Portuguese strawberries grown using different agriculture practices. The Quick, Easy, Cheap, Effective, Rugged, and Safe sample preparation method was conducted and shown to have good performance for multiclass pesticides extraction in strawberries. The screening of 25 pesticides residue was performed by gas chromatography?Ctandem mass spectrometry. In quantitative validation, acceptable performances were achieved with recoveries of 70?C120 and <12?% residual standard deviation for 25 pesticides. Good linearity was obtained for all the target compounds, with highly satisfactory repeatability. The limits of detection were in the range of 0.1?C28???g/kg. The method was applied to analyze strawberry samples from organic and integrated pest management (IPM) practices harvested in 2009?C2010. The results showed the presence of fludioxonil, bifenthrin, mepanipyrim, tolylfluanid, cyprodinil, tetraconazole, and malathion when using IPM below the maximum residue levels.     

Pesticide residues in products of plant origin in the European Union

The results of a co-ordinated monitoring programme for pesticide residues in the European Union and Norway carried out in 1996 and 1997 are presented. The aim of this programme is to work towards a system, which makes it possible to estimate actual dietary pesticide intake for the population of the European Union. Based on a statistically dérived sampling plan and within the limited number of pesticides/commodities analysed, the most critical pesticides (benomyl group and dithiocarbamates) and commodities (mandarine and lettuce) were identified. In case of detected non-compliances, repeated sampling and, if necessary, enforcement actions are to be taken by national authorities. The programme will be continued in the next years.     

Detection limits can influence the interpretation of pesticide monitoring data in Canadian surface waters

Water quality monitoring programs rely on residue data that are frequently left censored, due to some observations occurring below the Method Detection Limit (MDL). Our objective was to determine the influence the MDL has on the interpretation of pesticide residues in surface waters. Water samples from tributaries in southern and central Ontario were collected by Environment Canada from 2003 to 2008 and were analyzed for 27 pesticides, with MDLs that averaged 7.02 ng⁻¹ L (range 0.39-25.1 ng⁻¹ L). We then simulated MDLs ranging from 25 to 1700 ng⁻¹ L, to determine the impact this would have on the reporting of pesticide concentrations and detections. The mean number of pesticides detected simultaneously declined with increasing, i.e. less sensitive MDLs, from 5.02 pesticides (native MDL) to 0.08 pesticides detected (MDL < 1700 ng⁻¹ L). We compared the proportion of sites where pesticides were detected in surface waters under five MDL scenarios for 13 selected pesticides. The proportions decreased sharply with increasing MDLs. We calculated detection probabilities in an effort to compensate for higher MDLs using maximum likelihood; while adjusting for detection probabilities generally improved estimates of the presence of pesticides, as the MDLs increased the ability to compensate for detection probabilities deteriorated and became unviable at high MDLs. Depending on the method of substitution for observations below MDL (replacement with ½ × or 0 × MDL), the mean and median pesticide residues became increasingly over- and underestimated, respectively, at higher MDLs. Although monitoring programs that are focused on exceedences of water quality guidelines may not require low MDLs, the achievable goals of monitoring programs oriented towards other ecological and toxicological objectives may be limited by higher MDLs.     

Influence of humic substances on the photolysis of aqueous pesticide residues

The present work investigated the direct and indirect photolysis of pesticide residues (atrazine, imazaquin, iprodione), in aqueous solutions and under UV-visible radiation (280-480nm). Different kinds of humic substances (HS) were added to samples in order to evaluate their behaviour as possible photocatalysts and their effect on the photolysis of pesticides. The fulvic acids were purchased from the International Humic Substances Society, and they were added to samples in concentrations ranging from 1 to 150 mgl(-1). Titanium dioxide was used as the photocatalyst, in concentration ranging from 10 to 150 mgl(-1). Pesticides photolysis were measured by UV-visible absorption spectroscopy and differential pulse polarography with all used pesticides, reaching total degradation after 2h of irradiation, thus indicating a fast direct photolysis. Photocatalysis by TiO(2) could increase the pesticides photolysis rate up to 40%. This effect, however, was not observed for imazaquin photolysis. Again, except for imazaquin, HS presence showed a positive effect in increasing pesticide degradation, but only within specific concentration ranges (below 10mg l(-1) for iprodione and about 30mgl(-1) for atrazine). Above these ranges HS induce a decrease in the pesticides photolysis rate. Spin-trapping measurements by electronic paramagnetic resonance spectroscopy, using the spin-trap DMPO, showed that HS are able to photogenerate hydroxyl radicals, increasing the pesticides molecule degradation. However, the HS also react with the photogenerated hydroxyl radical, influencing the pesticide photolysis, leading to a decrease in the photolysis rate and causing it to be strongly dependent on the nature and concentration of residues in the water to be treated.     

A preliminary assessment of consumer's exposure to pesticide residues in fisheries products

The fisheries products in this study comprise fish, bivalve, crustacean and cephalopod collected from different types of markets in Taiwan between the years 2001 and 2003. A total of 91 pesticide residues belonging to four major pesticide groups were tested and analyzed. The test results show that 65.40% of fish, 93.55% of shellfish, 84.92% of crustacean and 98.33% of cephalopod samples contain no detectable residues. There are only two kinds (organochlorine and organophosphate) of totally six pesticides (DDTs, dieldrin, chlorpyrifos, fenitrotion, fenthion and prothion) that have been detected from the fisheries products in this study. For there were pesticides present in the fish products, consumption of fisheries product there was no zero risk. But the exposure of consumer did not exceed the acceptable daily intakes (ADI). For male, there was the highest risk in exposure to dieldrin, which the percentage of ADI was 93.56%. This study also suggests that a yearly monitoring program for organophosphate pesticide residues in fish is necessity.     

A field study to compare performance of stainless steel research monitoring wells with existing on-farm drinking water wells in measuring pesticide and nitrate concentrations

Existing drinking water wells are widely used for the collection of ground water samples to evaluate chemical contamination. A well comparison study was conducted to compare pesticide and nitrate-N data from specially designed stainless steel research monitoring wells with data from nearby existing on-farm drinking water wells. Results could help to determine whether adequate information concerning ground water contamination can be obtained from existing drinking water wells for use in making pollutant control decisions. The study was conducted during 1993-1994 in the Little Coharie Watershed, a 158 square mile area located in the coastal plain of eastern North Carolina. Statistical analysis indicated that research monitoring wells provided a greater probability of detecting pesticides in ground water than existing on-farm wells. Atrazine was the most frequently detected pesticide found in all wells, followed in order by fluometuron, carbofuran, metolachlor, alachlor, carbaryl, butylate, chlorothalonil, linuron and simazine. Ninety-seven percent of all wells had observed concentrations of nitrate-N, ranging from 0.1 to 30.1 mg/L. There was not a significant difference between research wells and existing wells for monitoring nitrate-N. Based on results of this study, existing drinking water wells can be used for monitoring nitrate; however, specialized stainless steel monitoring wells should be used for monitoring pesticides in ground water.     

Solid-phase extraction for multi-residue analysis of pesticides in honey

A fast and simple multi-residue method for the analysis of 15 organophosphorus (OP), 17 organochlorine (OC), 8 pyrethroids (PYR), 12 N-methyl-carbamate (NMC) pesticide residues and bromopropylate in honey is presented. Ready-to-use EXtrelutNT 20 column, eluted with dichloromethane, was used to extract the pesticide residues from the aqueous-acetone honey sample, obtaining a clean extract directly analyzable. Determination was carried out by gas chromatography (GC) coupled with flame photometric detector (FPD) for OP compounds and by GC coupled with mass spectrometry detector (MSD) for OC and PYR pesticides and bromopropylate. The NMC pesticides were analysed by liquid chromatography-double derivatization coupled with spectrofluorimetric detector (LC/DD/Fl). This method allows the determination of the 53 pesticide residues at low concentrations (0.0005-0.074 mg/kg) and can be used to assess the compliance with the Maximum Residues Levels (MRLs) set by the European Union. The performance of the method was evaluated and specificity, linearity, recovery, repeatability, reproducibility, limit of quantification (LOQ) and limit of detection (LOD) were determined. A good linearity (r(2)≥ 0.99) was found in the range 0.0005-0.074 mg/kg for the majority of the compounds studied. Most of the pesticides had recoveries in the range 70-103 % and values of relative standard deviation (RSD) < 20 for repeatability and reproducibility, showing good accuracy and precision of the method. Aldicarb partially degraded in aldicarb sulphoxide during the analytical procedure, giving anomalous values. The LOQ for all pesticides investigated was from 0.0005 to 0.025 mg/kg while the LOD ranged from 0.0002 to 0.008 mg/kg.     

Solid-phase extraction for multi-residue analysis of pesticides in honey

A fast and simple multi-residue method for the analysis of 15 organophosphorus (OP), 17 organochlorine (OC), 8 pyrethroids (PYR), 12 N-methyl-carbamate (NMC) pesticide residues and bromopropylate in honey is presented. Ready–to–use EXtrelut®NT 20 column, eluted with dichloromethane, was used to extract the pesticide residues from the aqueous-acetone honey sample, obtaining a clean extract directly analyzable. Determination was carried out by gas chromatography (GC) coupled with flame photometric detector (FPD) for OP compounds and by GC coupled with mass spectrometry detector (MSD) for OC and PYR pesticides and bromopropylate. The NMC pesticides were analysed by liquid chromatography-double derivatization coupled with spectrofluorimetric detector (LC/DD/Fl). This method allows the determination of the 53 pesticide residues at low concentrations (0.0005–0.074 mg/kg) and can be used to assess the compliance with the Maximum Residues Levels (MRLs) set by the European Union. The performance of the method was evaluated and specificity, linearity, recovery, repeatability, reproducibility, limit of quantification (LOQ) and limit of detection (LOD) were determined. A good linearity (r²? 0.99) was found in the range 0.0005–0.074 mg/kg for the majority of the compounds studied. Most of the pesticides had recoveries in the range 70–103 % and values of relative standard deviation (RSD) < 20 for repeatability and reproducibility, showing good accuracy and precision of the method. Aldicarb partially degraded in aldicarb sulphoxide during the analytical procedure, giving anomalous values. The LOQ for all pesticides investigated was from 0.0005 to 0.025 mg/kg while the LOD ranged from 0.0002 to 0.008 mg/kg.     

Pesticide distribution in an agricultural environment in Argentina

An assessment of the off-site migration of pesticides from agricultural activity into the environment in the Neuquen River Valley was performed. The aim of this study was to evaluate the distribution of pesticides in several compartments of a small agricultural sub-catchment. Soil, surface water, shallow groundwater and drift deposition were analyzed for pesticide residues. Results showed the presence of some pesticide residues in soil, surface water and shallow groundwater compartments. The highest detection frequencies in water (surface and subsurface) were found for azinphos-methyl and chlorpyrifos (>70%). In terms of concentration, the highest levels were observed in shallow groundwater for azinphos methyl (22.5 μg/L) and carbaryl (45.7 μg/L). In the soil, even before the application period had started, accumulation of residues was present. These residues increased during the period studied. Spray drift during pesticide application was found to be a significant pathway for the migration of pesticide residues in surface water, while leaching and preferential flows were the main transport routes contributing to subsurface contamination.     

Pesticide distribution in an agricultural environment in Argentina

An assessment of the off-site migration of pesticides from agricultural activity into the environment in the Neuquen River Valley was performed. The aim of this study was to evaluate the distribution of pesticides in several compartments of a small agricultural sub-catchment. Soil, surface water, shallow groundwater and drift deposition were analyzed for pesticide residues. Results showed the presence of some pesticide residues in soil, surface water and shallow groundwater compartments. The highest detection frequencies in water (surface and subsurface) were found for azinphos-methyl and chlorpyrifos (>70%). In terms of concentration, the highest levels were observed in shallow groundwater for azinphos methyl (22.5 μg/L) and carbaryl (45.7 μg/L). In the soil, even before the application period had started, accumulation of residues was present. These residues increased during the period studied. Spray drift during pesticide application was found to be a significant pathway for the migration of pesticide residues in surface water, while leaching and preferential flows were the main transport routes contributing to subsurface contamination.     

A list of fish species that are potentially exposed to pesticides in edge-of-field water bodies in the European Union—a first step towards identifying vulnerable representatives for risk assessment

Surrogate species are used in standard toxicity tests for the environmental risk assessment of chemicals. Test results are then extrapolated to the situation in the field, which is often associated with a large degree of uncertainty. Since a vulnerable species in the field is not only characterised by its intrinsic sensitivity to a stressor but also by its potential for exposure and its population resilience, the identification of focal species based on these three components of vulnerability is needed for a more ecologically relevant risk assessment. This study listed European fish species that are susceptible to pesticide exposure in the field and thus achieved the first step towards identifying focal species for the risk assessment of pesticides for fish in Europe. A step-wise filtering approach was applied to list freshwater fish species that are native to Europe and widespread in the European Union, which inhabit streams, ditches or ponds in agricultural landscapes and therefore, are at an elevated risk of being exposed to pesticides. Out of the 579 fish species occurring in European freshwater, 27 species met the filtering criteria. The resulting list was verified based on monitoring studies that were conducted in agricultural landscapes over the past 20 years. Focal fish species that can be used for a more ecologically relevant environmental risk assessment of pesticides in Europe can be identified from the produced list of species by further assessing their ecological (life history and dispersal characteristics) and intrinsic sensitivities.     

Contamination levels of selected organochlorine and organophosphate pesticides in the Selangor River, Malaysia between 2002 and 2003

In Malaysia, rivers are the main source of public water supplies. This study was conducted from 2002 to 2003 to determine the levels of selected organochlorine and organophosphate pesticides in the Selangor River in Malaysia. Surface water samples have been collected seasonally from nine sites along the river. A liquid-liquid extraction followed by gas chromatography-mass spectrometry technique was used to determine the trace levels of these pesticide residues. The organochlorine pesticides detected were lindane, heptachlor, endosulfan, dieldrin, endosulfan sulfate, o,p'-DDT, p,p'-DDT, o,p'-DDE and p,p'-DDE whereas for organophosphate pesticides, they were chlorpyrifos and diazinon. At the river upstream where a dam is located for public water supply, incidents of pesticide levels exceeding the European Economic Community Directive of water quality standards have occurred. Furthermore, the wetland ecosystems located at the downstream of the river which houses the fireflies community is being threatened by occasional pesticide levels above EPA limits for freshwater aquatic organisms. The occurrence of these residual pesticides in the Selangor River can be attributed to the intense agriculture and urban activity.     

Molecularly imprinted polymers for the detection of benomyl residues in water and soil samples

Benomyl is a benzimidazol fungicide used against various crop pathogens. Although banned in many countries, it is still widely used worldwide and is listed in different monitoring programs among the substances to be monitored to assess human exposure to pesticide residues. The assessment of benomyl is mainly based on the analysis of the residues of its most important metabolite, carbendazim. Existing methods often lack of selectivity and display a limited performance because of the presence of co-extracted compounds. Molecularly imprinted polymers (MIPs) offer an alternative methodology, adsorbing preferentially those target molecules for which the polymers are specifically prepared. In this study, we optimized the synthesis of a polymer imprinted with benomyl. Tests of specificity recognition showed a good performance for carbendazim compared with other similar pesticides. The mean recovery of benomyl (measured as carbendazim) from water samples was estimated to be 90% for MIPs while with real soil samples collected in Morocco the recovery efficiency was 62%. Preliminary tests also suggest that this MIP can implement traditional SPE techniques for assessing benomyl residual concentrations in environmental samples.     

Sensitized photodecomposition of high disperse pesticide chemicals exposed to sunlight and irradiation from halogen or mercury lamp

The kinetics of sensitized photolysis for four pesticides, deltamethrin (Decis), acrinathrin (Rufast), s-fenvalerate (Sumialpha), and propiconazol (Tilt) in thin films and aerosol particles was investigated under sunlight or the irradiation from halogen or mercury lamp. The peculiarities of principle of the photochemistry of pesticides in high disperse substance state were discussed. The quantum yields of sensitized and direct photolysis were measured, and the phenomenological kinetic mechanism of photolysis was proposed and examined. Four relations between six rate constants of reaction steps of the kinetic mechanism were determined. The use of sensitizers to accelerate the decomposition rates of pesticide pollutants under sunlight could minimize the contamination of agricultural commodities and the adjacent environment. The Shirvanol 2 sensitizer (a by-product of the full treatment of Caspian oils) can regulate decomposition of many pesticides in a wide range of photolysis rates, so that practically any desired lifetime could be really available for either pesticide residues on plant foliage or pesticide aerosol particles in the air.     

Effect of pesticide residues on health and different enzyme levels in the blood of farm workers from Gadap (rural area) Karachi-Pakistan

Persons from 14 different fruit and vegetable farm stations from Gadap (rural area), Karachi-Pakistan were examined for the presence of pesticide (cypermethrin, deltamethrin, polytrin-C, diazinon, monocrotophos, DDT and DDE) residues in their blood samples. The present study is concerned with effects of residue on the enzyme levels (GPT, GOT and ALP) as well as the health hazards of pesticide exposed persons. There is a significant increased in the enzyme levels at different stations. Exposed persons complained about liver and kidney dysfunctions and RTI. It may be concluded that exposure of multiple pesticides for prolonged period has affected the normal functioning of different organ systems and possibly produced characteristics clinical effects such as hepatitis, dyspnea and burning sensation in urine.