Transposable elements (TEs) comprise a group of repetitive sequences that bring positive, negative, as well as neutral effects to the host organism. Earlier considered as “junk DNA,” TEs are now well-accepted driving forces of evolution and critical regulators the of expression of genetic information. Their activity is regulated by epigenetic mechanisms, including methylation of DNA and histone modifications. The loss of epigenetic control over TEs, exhibited as loss of DNA methylation and decondensation of the chromatin structure, may result in TEs reactivation, initiation of their insertional mutagenesis (retrotransposition) and has been reported in numerous human diseases, including cancer. Accumulating evidence suggests that these alterations are not the simple consequences of the disease, but often may drive the pathogenesis, as they can be detected early during disease development. Knowledge derived from the in vitro, in vivo, and epidemiological studies, clearly demonstrates that exposure to ubiquitous environmental stressors, many of which are carcinogens or suspected carcinogens, are capable of causing alterations in methylation and expression of TEs and initiate retrotransposition events. Evidence summarized in this review suggests that TEs are the sensitive endpoints for detection of effects caused by such environmental stressors, as ionizing radiation (terrestrial, space, and UV-radiation), air pollution (including particulate matter [PM]-derived and gaseous), persistent organic pollutants, and metals. Furthermore, the significance of these effects is characterized by their early appearance, persistence and presence in both, target organs and peripheral blood. Altogether, these findings suggest that TEs may potentially be introduced into safety and risk assessment and serve as biomarkers of exposure to environmental stressors. Furthermore, TEs also show significant potential to become invaluable surrogate biomarkers in clinic and possible targets for therapeutic modalities for disease treatment and prevention.

The use of pen-based electronic questionnaires and conventional paper questionnaires was compared in a randomized crossover study. Forty-six patients, aged 17-81 years, suffering from gastro-intestinal disorders, initially filled in a paper quality of life questionnaire for familiarization purposes, then on two subsequent visits completed electronic and paper questionnaires in randomized order. At the last visit they completed a preference survey. The results showed a high degree of acceptability of the electronic questionnaire, with 57% of patient preferring electronic and 13% preferring paper, while the remaining 30% expressed no preference. Neither age, gender nor familiarity with technology showed any marked association with patients' preferences. All patients found both paper and electronic questionnaires easy to use. Data were more complete on the electronic questionnaire (100%) than on the paper (99.1%). Data handling procedures were greatly simplified. These results show that major benefits in completeness of data, speed of data flow, and data handling workload can be obtained from the use of pen-based electronic questionnaires.

This study was conducted to describe exposure prone behaviors of infants and toddlers in the farmworker community. Analysis of hand and mouth contact frequencies and durations aids understanding of how children interact with their environment and are exposed via contact with surfaces. All 23 participating children (8 female infants, 5 male infants, 5 female toddlers and 5 male toddlers) lived with at least one farmworker. Children were videotaped at home for 2–6 hours. Video footage was translated into micro- level activity time series (MLATS) for both hands and the mouth. MLATS were processed to calculate hourly duration in microenvironments, contact frequency, hourly contact duration and median contact duration. The median hourly duration spent indoors was 53 min/hr. The median hand-to-mouth frequency was 15.2 events/hr and the median object-to-mouth frequency was 27.2 events/hr. The hourly mouthing duration was 1.2 and 2.2 min/hr with the hands and objects respectively. The median mouthing duration with hands and objects was 2 seconds. The median contact frequency for both hands combined was 689.4 events/hr with an hourly contact duration of 100.5 min/hr and a median contact duration of 3 seconds. Infants had higher mouthing frequencies with non-dietary objects while toddlers had higher mouthing frequencies with objects associated with pica (i.e., paper). Boys had higher contact frequencies while girls had longer contact durations. These sub-group differences indicate factors such as age and gender should be accounted for when conducting exposure assessments. Contact frequencies in this study are higher than current U.S. EPA recommendations, questioning their protective value for infants and toddlers.

These MLATS are especially useful for describing intermittent dermal (i.e., second-by-second account of surfaces and objects contacted) and non-dietary ingestion (second-by-second account of objects or hands placed in the mouth) contact behavior. Second-by-second records of children contact behavior are amenable to quantitative and statistical analysis and allow for more accurate model estimates of human exposure and dose to environmental contaminants. Activity patterns data for modeling inhalation exposure (i.e., accounts of microenvironments visited) can also be extracted from the MLATS data. Since the pilot study, ERG has collected an immense MLATS data set for 92 children using more developed and refined videotaping and video-translation methodologies. This paper describes all aspects required for the collection of MLATS including: subject recruitment techniques, videotaping and video-translation processes, and potential data analysis. This paper also describes the quality assurance steps employed for these new MLATS projects, including: training, data management, and the application of interobserver and intraobserver agreement during video translation. The discussion of these issues and ERG's experiences in dealing with them can assist other groups in the conduct of research that employs these more quantitative techniques.

Microlevel activity time series (MLATS) data were gathered on hand contact activities of 38 children (1-6 years old) by videotaping in primarily outdoor residential environments. The videotape recordings were then translated into text files using a specialized software called VirtualTimingDevicet. Contact frequency (contacts/h), duration per contact (s/contact), and hourly contact duration (min/h) were summarized for outdoor hand contacts with 15 distinct object/surface categories

Background: Children must be recognized as a sensitive population based on having biological systems and organs in various stages of development. The processes of absorption, distribution, metabolism and elimination of environmental contaminants within a child’s body are considered less advanced than those of adults, making them more susceptible to disease outcomes following even small doses. Children’s unique activities of crawling and practicing increased hand-to-mouth ingestion also make them vulnerable to greater exposures by certain contaminants within specific environments. Approach: There is a need to review the field of children’s environmental exposures in order to understand trends and identify gaps in research, which may lead to better protection of this vulnerable and sensitive population. Therefore, explored here are previously published contemporary works in the broad area of children’s environmental exposures and potential impact on health from around the world. A discussion of children’s exposure to environmental contaminants is best organized under the last four steps of a risk assessment approach: hazard identification, dose-response assessment, exposure assessment (including children’s activity patterns) and risk characterization. We first consider the many exposure hazards that exist in the indoor and outdoor environments, and emerging contaminants of concern that may help guide the risk assessment process in identifying focus areas for children. A section on special diseases of concern is also included. Conclusions: The field of children’s exposures to environmental contaminants is broad. Although there are some well-studied areas offering much insight into children exposures, research is still needed to further our understanding of exposures to newer compounds, growing disease trends and the role of gene-environment interactions that modify adverse health outcomes. It is clear that behaviors of adults and children play a role in reducing or increasing a child’s exposure, where strategies to better communicate and implement risk modifying behaviors are needed, and can be more effective than implementing   changes in the physical environment.

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The Child-Specific Aggregate Cumulative Human Exposure and Dose (CACHED) framework integrates micro-level activity time series with mechanistic exposure equations, environmental concentration distributions, and physiologically-based pharmacokinetic components to estimate exposure for multiple routes and chemicals. CACHED was utilized to quantify cumulative and aggregate exposure and dose estimates for a population of young farmworker children and to evaluate the model for chlorpyrifos and diazinon. Micro-activities of farmworker children collected concurrently with residential measurements of pesticides were used in the CACHED framework to simulate 115,000 exposure scenarios and quantify cumulative and aggregate exposure and dose estimates. Modeled metabolite urine concentrations were not statistically different than concentrations measured in the urine of children, indicating that CACHED can provide realistic biomarker estimates. Analysis of the relative contribution of exposure route and pesticide indicates that in general, chlorpyrifos non-dietary ingestion exposure accounts for the largest dose, confirming the importance of the micro-activity approach. The risk metrics computed from the 115,000 simulations, indicate that greater than 95% of these scenarios might pose a risk to children’s health from aggregate chlorpyrifos exposure. The variability observed in the route and pesticide contributions to urine biomarker levels demonstrate the importance of accounting for aggregate and cumulative exposure in establishing pesticide residue tolerances in food.