Assessment of environmental exposures from agricultural pesticides in childhood leukaemia studies: challenges and opportunities

Pesticides are ubiquitous in environments of many rural communities due to drift from agricultural applications and home/garden use. Studies of childhood leukaemia predominantly relied on retrospective pesticide exposure assessment and parental recall of use or proximity to fields or pesticide applications. Sample size requirements mostly preclude the collection of individual-level exposure information, biomarkers or environmental measurements of pesticides prospectively in cohorts. Yet such measures can be used in nested case-control approaches or for validating exposure models that can be applied to large populations. Recently developed models incorporate geographic information system technology and environmental databases of pesticide and/or crop data to assess exposure. Models developed in California to estimate residential exposures are presented by linking addresses to agricultural pesticide application data and land-use maps. Results from exposure validation and simulation studies and exposure measurement error issues are discussed.     

Exposure to infections through day-care attendance and risk of childhood leukaemia

There is growing evidence supporting a role for infections in the aetiology of childhood leukaemia. Hypotheses proposed by both Greaves and Kinlen describe childhood leukaemia to be a rare response to one or more common infections acquired through personal contacts. Previous epidemiological studies have used day-care attendance as an indicator of the increased likelihood of early and frequent exposure to infections. It is well-documented that in developed countries, exposures to common infections occur more frequently in this type of setting. Within the Northern California Childhood Leukaemia Study, the role of social contact has been assessed and a unique 'child-hours' summary measure incorporating information on the number of months attending a day-care, mean hours per week at this day-care and the number of children in the day-care setting was constructed. In this review, the previously reported day-care results have been described, showing that in non-Hispanic White children, children in the highest category of total child-hours of exposure had a reduced risk of acute lymphoblastic leukaemia (ALL), particularly common B-cell precursor ALL (c-ALL), compared with children without such exposures, with evidence of a dose-response effect. In addition, a literature review of relevant studies has been conducted, examining the relationship between day-care attendance and risk of childhood ALL. Overall, the 14 studies identified provided consistent support for this hypothesis, with the majority of studies reporting some evidence of a reduced risk. A meta-analysis is currently underway, which will provide a quantitative evaluation of the overall consistency and strength of the association between day-care attendance or social contact and risk of childhood ALL.     

Childhood leukaemia following medical diagnostic exposure to ionizing radiation in utero or after birth

A statistical association between childhood leukaemia and an abdominal X-ray examination of the pregnant mother was first reported in 1956 from a case-control study of childhood cancer mortality conducted in Great Britain. This study, later called the Oxford Survey of Childhood Cancers (OSCC), was continued and eventually showed a highly statistically significant approximately 50% proportional increase in the risk of childhood leukaemia associated with antenatal diagnostic radiography. The association has been confirmed by many case-control studies carried out around the world, the appropriately combined results of which show a highly statistically significant increase in risk that is compatible with the OSCC finding. There is no doubt about the reality of the statistical association, but a causal interpretation has been questioned. On balance, however, the evidence points to low-level irradiation of the fetus increasing the risk of leukaemia in childhood, with an excess relative risk coefficient of around 50 Gy(-1) (equivalent to an excess absolute risk coefficient of about 3% Gy(-1)), although the uncertainty associated with these coefficients is considerable and they are likely to be overestimates. In contrast to exposure in utero, the evidence from case-control studies for an association between childhood leukaemia and postnatal exposure to medical diagnostic irradiation is equivocal and sometimes conflicting. Since standard radiation risk models predict that low-level exposure in the early years of life should produce an increased risk of childhood leukaemia that is roughly similar to that arising from fetal exposure, this absence of persuasive evidence is likely to be due to various problems with the studies. This is unfortunate given the rise in relatively high dose diagnostic procedures (e.g. paediatric CT scans) that would be predicted to materially increase the relative risk of childhood leukaemia.     

Exposure to electromagnetic fields and the risk of childhood leukaemia: a review

Extremely low-frequency magnetic fields have been classified as possibly carcinogenic to humans, mainly based on epidemiological studies consistently showing an association between long-term average exposures to magnetic fields above 0.3/0.4 microT and the risk of childhood leukaemia. No mechanism to explain this finding has been established and no support for a causal link emerged from experimental studies. Chance or bias cannot be ruled out with reasonable confidence as an explanation for the observed association. If the association is causal, it explains only a small fraction of childhood leukaemia cases. There were some reports of childhood leukaemia clusters in the vicinity of high-power radio and television broadcast transmitters in studies in Australia and Italy. However, recent large-scale systematic studies in Korea and Germany show no association between exposure to radio frequency electromagnetic fields emitted from broadcast towers and childhood leukaemia risk. Studies on mobile phone use and leukaemia risk in adolescents and young adults may be indicated.     

Aetiology of childhood acute leukaemias: current status of knowledge

Acute leukaemia is a consequence of malignant transformation of a haematopoetic progenitor cell. Molecular studies have revealed a prenatal origin of many childhood leukaemias. According to current models, a preleukaemic stem cell clone is generated by a first mutation in utero which, in a minority of children, progresses to leukaemia after receiving further postnatal genetic hits. The nature of pre- and postnatal events involved in leukaemogenesis in children is not well understood. Although genetic predisposition and specific environmental exposures may account for individual cases, the bulk of childhood leukaemia cannot be explained by any of these factors. The higher incidence of the most common leukaemia subtype in affluent societies, as well as the age peak between 2-5 y, suggest a contributory role of socioeconomic factors. An abnormal immune response during delayed exposure to common infections provides a plausible mechanism for malignant progression of preleukaemic clones in a subgroup of children. As highlighted in this review, a common cause for all types and subtypes of childhood leukaemia is highly unlikely. Deeper insights into the pathogenesis of childhood leukaemia will rely on large-scale and combined epidemiological and biomolecular studies.     

Alginate and lignin-based formulations to control pesticides leaching in a calcareous soil

Important risk of groundwater pollution has been observed as a result of rapid leaching of highly soluble pesticides when used in agronomic practices as conventional formulations. This risk can be minimized through the application of the pesticide at a set rate using controlled release formulations (CRFs). In this research, CRFs of isoproturon, imidacloprid and cyromazine have been evaluated in a calcareous soil. The effects of two natural polymers (alginate and lignin) and two modifying sorbents (bentonite and activated carbon) on pesticide release kinetics from CRFs have been investigated, as well as mobility of pesticides using soil columns. The rate of pesticide release in soil from CRFs diminished in all cases in relation to technical products. From the analysis of the time taken for 50% of the active ingredient to be released into soil (T(50 soil)), it can be deduced that the release rate of pesticides can be controlled by using activated carbon in the alginate-based CRFs and mixing the pesticide with kraft lignin. Mobility experiments showed that the use of CRFs clearly reduces the presence of isoproturon and imidacloprid in the leachate compared to technical products, and to a lesser extent for cyromacine due to its high water solubility.     

Exposure assessment and other challenges in non-ionizing radiation studies of childhood leukaemia

Studies of electromagnetic fields (EMF) and the development of childhood leukaemia face unique difficulties. EMF are imperceptible, ubiquitous, have multiple sources, and can vary greatly over time and distances. Childhood leukaemia and high average exposures to magnetic fields are both quite rare. Thus, a major challenge in EMF epidemiology is the small number of highly exposed cases and the necessity for retrospective assessment of exposure. Only studies designed to minimize bias while maximizing our ability to detect an association, should one exist, would have a potential to contribute to our understanding. New approaches are needed; the most promising in the extremely low-frequency range involves a study of a highly exposed cohort of children who have lived in apartments next to built-in transformers or electrical equipment rooms. Another promising avenue is an investigation of possible joint effects of environmental exposures and genetic co-factors. An exposure assessment methodology for residential radiofrequency fields is still in its infancy. Rapid changes in technology and exponential increases in its use make exposure assessment more difficult and urgent.     

Childhood leukaemia and socioeconomic status: what is the evidence?

The objectives of this systematic review are to summarise the current literature on socioeconomic status (SES) and the risk of childhood leukaemia, to highlight methodological problems and formulate recommendations for future research. Starting from the systematic review of Poole et al. (Socioeconomic status and childhood leukaemia: a review. Int. J. Epidemiol. 2006;35(2):370-384.), an electronic literature search was performed covering August 2002-April 2008. It showed that (1) the results are heterogeneous, with no clear evidence to support a relation between SES and childhood leukaemia; (2) a number of factors, most importantly selection bias, might explain inconsistencies between studies; (3) there is some support for an association between SES at birth (rather than later in childhood) and childhood leukaemia and (4) if there are any associations, these are weak, limited to the most extreme SES groups (the 10-20% most or least deprived). This makes it unlikely that they would act as strong confounders in research addressing associations between other exposures and childhood leukaemia. Future research should minimise case and control selection bias, distinguish between different SES measures and leukaemia subtypes and consider timing of exposures and cancer outcomes.     

Exposure assessment: implications for epidemiological studies of ionizing radiation

Quantitative estimates of ionizing radiation exposure are often available for use in epidemiological studies. However, depending on the context, the quality of the exposure estimates can vary. For example, the estimates may be specific to individuals in the study or generic values averaged over populations; unavailable for some of the potential study subjects or vary in their form between individuals; based on contemporary measurements or assessed retrospectively; based on measurements alone, on surrogate measures of exposure, or on an exposure assessment model; or, as is often the case, cover one source of radiation exposure rather than all of them. Various ways in which ionizing radiation exposures have been assessed are illustrated through reference to some studies of childhood leukaemia, concerning environmental, medical, natural and parental occupational exposures. Based on this, implications for the interpretation of radiation epidemiological studies are discussed.     

The UK Childhood Cancer Study: maternal occupational exposures and childhood leukaemia and lymphoma

Risks of childhood leukaemia and lymphoma were investigated for specific work-related exposures of mothers in the UK Childhood Cancer Study. Interviews with parents of 1881 leukaemia and lymphoma cases (0-14 years) and 3742 controls collected job histories recording exposure to eight specific agents. Exposure was (1) self-reported and (2) reviewed, based mainly on exposure probability and exposure level. Completeness, consistency and sufficiency evaluated data quality. Of all job exposures which were self-reported as exposed, 33% cases and 34% controls remained classified as exposed after review, with the remainder designated as partially exposed or unexposed. No review of underreporting of exposure was made. Data quality was 'good' for 26% of cases and 24% of controls. For self-reported exposure, significant risks of acute lymphoblastic leukaemia (ALL) were observed for solvents and petrol in all time windows. For reviewed exposure, solvents remained significant for ALL during pregnancy and postnatally. Restricting analyses to good-quality information removed all significant results. Refinement of exposure assessment revealed misclassification of self-reported exposures and data quality influenced risk assessment. Maternal exposure to solvents should further be investigated. These findings must invoke caution in the interpretation of risks reliant on self-reported occupational data.     

Emerging role of graphene oxide as sorbent for pesticides adsorption:Experimental observations analyzed by molecular modeling

The accumulation of pesticide residues in the environment due to their persistence and stability is causing increasing health concern.Indeed,researchers have rekindled their interest in eliminating pesticides from the environment by a range of biological and chemical approaches.In particular,graphene oxide(GO)has drawn great attention because it impressively enhances adsorption of pesticides in aqueous solutions,which provides promising environmental applications on water purification to remove pesticide residuals.However,although multiple studies have highlighted the adsorption of environmental contaminants by GO,the underlining molecular mechanisms remain limited.Consequently,we further delved into the knowledge regarding their adsorption molecular mechanism that is of both practical and theoretical importance.It was revealed that theπ-πstacking and van der Waals interactions accounted for the major adsorption interactions between GO and its removing pesticides through integrating both density functional theory(DFT)calculation,fully atomistic molecular dynamics(MD)simulation,and binding free energy calculation.These findings not only bridged the theoretical gap of the adsorption mechanisms of GO,but also provided a venue for visualizing the adsorption process,which were essential for guiding its future adsorption applications.     

Construction and evaluation of a humic acid column: implication for pesticide risk assessment

In this paper, humic acid (HA), known to play a large role in the binding and transport of pesticides in soil, was immobilized on a chromatographic support. Then, the association of some herbicides and rodenticides with the main soil component HA was examined using this novel chromatographic column. It appeared that HA has a lower affinity for neutral than for charged pesticides. Moreover, the influence of various parameters was investigated on the pesticide retention in order to providevaluable information about both the binding mechanism and the utilization conditions of the HA column. For all the pesticides studied, a change was clearly vizualized in the HA-pesticide association mechanism at a critical value of the Na+ concentration in the bulk solvent, x(c), equal to 0.6 M. Around this value, the HA structure balanced between a flexible linear conformation for x < x(c) and a random coil form for x > x(c). This work confirmed the conformation change on HA immobilized on silica. As well, only for the charged pesticides, it was clearly pointed out that below a Na+ concentration equal to 0.3 M, the pesticide binding to HA decreased when the salt concentration was enhanced due to an ion pair formation and a competition effect between the sodium cation and pesticide to bind to the HA molecule. Furthermore, it was established that the HA column was stable during an extended period of time, indicating that the HA column could soon become very attractive to determine the risk assessment of pesticides.     

Epidemiological studies of leukaemia in children and young adults around nuclear facilities: a critical review

The existence of an increased risk of childhood leukaemia near nuclear installations is a recurrent issue. A review of the related epidemiological literature is presented here. Results for 198 nuclear sites throughout 10 countries were included in the review. In addition to local studies, 25 multi-site studies have been published for eight countries. A large variability was noticed in the quality of the data as well as in the definition of the study population and in the methods of analysis. Many studies present important limits that make the results difficult to interpret. The review confirms that some clusters of childhood leukaemia cases exist locally. However, results based on multi-site studies around nuclear installations do not indicate an increased risk globally. Many studies were launched to investigate possible origins of the observed clusters around specific sites, but up to now, none of the proposed hypotheses have explained them.     

Leukaemia following childhood radiation exposure in the Japanese atomic bomb survivors and in medically exposed groups

Incidence and mortality risks of radiation-associated leukaemia are surveyed in the Japanese atomic bomb (A-bomb) survivors exposed in early childhood and in utero. Leukaemia incidence and mortality risks are also surveyed in 16 other studies of persons who received appreciable doses of ionizing radiation in the course of treatment in childhood and for whom there is adequate dosimetry and cancer incidence or mortality follow-up. Relative risks tend to be lower in the medical series than in the Japanese A-bomb survivors. The relative risks in the medical studies tend to diminish with increasing average therapy dose. After taking account of cell sterilisation and dose fractionation, the apparent differences between the relative risks for leukaemia in the Japanese A-bomb survivors and in the medical series largely disappear. This suggests that cell sterilisation largely accounts for the discrepancy between the relative risks in the Japanese data and the medical studies. Excess absolute risk has also been assessed in four studies, and there is found to be more variability in this measure than in excess relative risk. In particular, there is a substantial difference between the absolute risk in the Japanese atomic bomb survivor data and those in three other (European) populations. In summary, the relative risks of leukaemia in studies of persons exposed to appreciable doses of ionizing radiation in the course of treatment for a variety of malignant and non-malignant conditions in childhood are generally less than those in the Japanese A-bomb survivor data. The effects of cell sterilisation can largely explain the discrepancy between the Japanese and the medical series.     

Evaluation of toxicity of the pesticides, chlorpyrifos and arsenic, in the presence of compost humic substances in aqueous systems

An improved understanding of pesticide toxicity in natural systems can have important consequences for pesticide management and remediation strategies for contaminated areas. The interaction between humic substances extracted from compost natural organic matter and both organic and inorganic pesticides was evaluated for its effect on the toxicity of pesticides in the aqueous phase. The toxicity of contaminants was measured using the Microtox toxicological bioassay. Solutions containing concentrations ranging from 2 to 42 mg C/l of humic substance extracted from a South Texas compost were added to concentrations of the organic pesticide, chlorpyrifos, and toxicity reduction ranging from 50 to 100% was demonstrated. Different concentrations of arsenic ranging from 0.5 to 5 mg/l were also associated with three different concentrations of humic substances and the arsenic toxicity was consistently reduced by a factor of 100%. These results demonstrate a significant relationship between humic substance interactions with organic and inorganic pesticides, and pesticide toxicity in natural systems, and may also suggest a mechanism for pesticide toxicity reduction in natural waters through compost humic addition for contaminated groundwaters and surface waters.     

基于高光谱技术的花椰菜农药残留检测

目的 为了快速、无损地检测花椰菜上的农药残留,采用高光谱成像技术分别对花椰菜上是否含有苏云金杆菌、高效氯氰菊酯和虫螨茚虫威等3种农药进行无损检测研究,并且跟踪研究检测效果最好的农药安全间隔期。方法 对含有农药和不含农药的花椰菜样本进行高光谱成像处理,提取感兴趣区域的光谱数据。剔除前后20个波段的原始光谱数据,以降低噪声的影响,针对剩余216个波段(950~1 666 nm)的数据分别采用卷积平滑(S–G)、多元散射校正(MSC)和变量标准化(SNV)等3种算法对光谱数据进行优化。为了提高判别运行速率,采用竞争性自适应重加权算法(CARS)提取3种农药光谱数据的特征波长,并建立偏最小二乘法(PLS)判别模型。结果 基于SNV优化后的PLS模型对花椰菜上3种农药的识别准确率相对最高,其中虫螨茚虫威农药样本的测试效果相对最好,识别率为100%,随后对该农药进行了连续7 d的检测,其结果符合农药的消散规律。结论 将高光谱图像技术应用于花椰菜的农药残留检测具有很好的应用前景。     

Extraction of chlorpyrifos and malathion from water by metal nanoparticles

The nanoparticles of gold and silver in solution state and supported over activated alumina are effective systems for the quantitative removal of chlorpyrifos and malathion, two common pesticides found in surface waters of developing nations, from water. In the solution phase, these pesticides adsorb onto the nanoparticles' surfaces and upon interaction for a long time, the nanoparticles with adsorbed pesticides precipitate. In contrast, complete removal of these pesticides occurs when contaminated water is passed over nanoparticles supported on alumina. A prototype of an on-line filter was made using a column of activated alumina powder loaded with silver nanoparticles and the device was used for pesticide removal for extended periods. We believe that the method has great technological potential in drinking water purification, especially using silver nanoparticles.     

Transmission lines, EMF and population mixing

Draper et al. found that the incidence of childhood leukaemia was slightly elevated for children living at distances of 200-600 m from high-voltage transmission lines. This elevation cannot be explained by EMF exposure and it is suggested that it may be due to population mixing in housing developments which followed the construction of the lines.     

A highly sensitive, dual-readout assay based on gold nanoparticles for organophosphorus and carbamate pesticides

This report presents a highly sensitive, rhodamine B-covered gold nanoparticle (RB-AuNP) -based assay with dual readouts (colorimetric and fluorometric) for detecting organophosphorus and carbamate pesticides in complex solutions. The detection mechanism is based on the fact that these pesticides can inhibit the activity of acetylcholinesterase (AChE), thus preventing the generation of thiocholine (which turns the RB-AuNP solutions blue and unquenches the fluorescence of RB simultaneously). The color of the RB-AuNP solution remains red and the fluorescence of RB remains quenched. By use of this dual-readout assay, the lowest detectable concentrations for several kinds of pesticides including carbaryl, diazinon, malathion, and phorate were measured to be 0.1, 0.1, 0.3, and 1 μg/L, respectively, all of which are much lower than the maximum residue limits (MRL) as reported in the European Union pesticides database as well as those from the U.S. Department Agriculture (USDA). This assay allows detection of pesticides in real samples such as agricultural products and river water. The results in detecting pesticide residues collected from food samples via this method agree well with those from high-performance liquid chromatography (HPLC). This simple assay is therefore suitable for sensing pesticides in complex samples, especially in combination with other portable platforms.     

The "genetics" of driving behavior: parents' driving style predicts their children's driving style

It can be hypothesized that children inherit their parents' driving habits both through genetic disposition and model learning. A few studies have shown indeed that parents' and their children's traffic convictions and accidents correlate which, however, may be due to life style and other exposure factors. This study aimed at investigating the relationships between parents' and their children's self-reported driving behavior. The subjects were 174 parent-child pairs who independently completed a questionnaire. Driving behavior-driving style-was evaluated by means of Manchester driver behavior questionnaire (DBQ), while data about driving exposure, life style, accidents, and traffic tickets were also collected. A series of regression models indicated that parents' self-reported driving behavior explains their children's respective self-reported behavior, even when exposure and demographic and life-style factors are controlled.