Quantification of Changes in Chemical Pesticide Human Health Risk Following the Introduction of Bt Cotton and Herbicide-tolerant Soybean: A Case Study

Human health risks associated with changes in synthetic chemical pesticide use following the introduction of genetically modified crops are quantified in this article. Bacillus thuringiensis ( Bt ) cotton and herbicide-tolerant (HT) soybean, two genetically modified crops, were chosen as the focus for this study based on their global popularity. An innovative multimedia total exposure model, CalTOX, was used to calculate the health risks for two target populations, before and after the introduction of Bt cotton and HT soybean. Major results include the quantification of incremental lifetime cancer risk based on a time-weighted average exposure, and the quantification of hazard ratios for non-cancer effects based on the maximum exposure rate value, both computed over the exposure duration. Results show that human health risks are not intuitively and necessarily reduced with the reduction of pesticide use. For example, more trifluralin was used after the introduction of HT soybeans in Iowa and Minnesota, leading to higher risks. Moreover, the general population may have larger exposures to pesticides when compared with the population living in areas where pesticides are actually applied. This may occur because exposure to pesticides is not only dependent on geographical distance from the contaminated area, but also strongly dependent on other factors, such as the characteristic travel distance and environmental persistence.     

Imprecise exposure assessment and the sample size requirements of case-control studies of residential magnetic field exposure and cancer in adults

A computer program simulating case-control studies is described. It is used to estimate the minimum sample size required and to assess how this is affected by imprecise exposure assessment. In particular, the consequences of neglecting measurements of nonresidential exposure in case-control studies of residentially exposed adults are investigated. According to this model, while the consequent loss of power is not as large as was predicted by algebraic methods, it would be unwise to neglect it when planning a study. © 1995 Wiley-Liss, Inc.     

The Role of Human Error Analysis in Occupational and Environmental Risk Assessment: A Serbian Experience

Human error analysis is certainly a challenge today for all involved in safety and environmental risk assessment. The risk assessment process should not ignore the role of humans in accidental events and the consequences that may derive from human error. This article presents a case study of the Success Likelihood Index Method (SLIM) applied to the Electric Power Company of Serbia (EPCS), with the aim to disclose the importance of human error analysis in risk assessment. A database on work-related injuries, accidents, and critical interventions that occurred over a 10-year period in the EPCS provided the basis for this study. The research comprised analysis of 1074 workplaces, with a total of 3997 employees. A detailed analysis identified 10 typical human errors, performance shaping factors (PSFs), and estimated human error probability (HEP). Based on the obtained research results one can conclude that PSF control remains crucial for human error reduction, and thus prevention of occupational injuries and fatalities (the number of injuries decreased from 58 in 2012 to 44 in 2013, no fatalities recorded). Furthermore, the case study performed at the EPCS confirmed that the SLIM is highly applicable for quantification of human errors, comprehensive, and easy to perform.     

Comparative Study between CalTOX and Soil Screening Levels Modeling Approaches

A comparison was made between two different approaches to environmental modeling and risk assessment, specifically the one-medium approach of the USEPA Soil Screening Levels (SSL) and the multimedia approach in the CalEPA (CalTOX). Eleven priority pollutants were selected to represent different classes of chemicals as per their toxicity, physical and chemical properties, and persistence in the environment. Benzene, dioxin, PCB, B(a)P, chlo-rdane, chloroform, and TCE represent carcinogens, while xylene, toluene, phenol, chlordane, pyrene, TCE, and chloroform represent noncarcinogens. The highly volatile contaminants, including benzene, chloroform, xylene, toluene, and TCE, were selected to compare the volatilization from soil and the significance of inhalation pathways of the two models. The contaminants with strong sorption to soil and dust particles (dioxin, B(a)P, PCB, and chlordane) exhibited a preferential soil ingestion pathway. In contrast with CalTOX, inhalation was not considered as the dominant pathway for all the volatile contaminants in SSL. Furthermore, the risk assessment component of CalTOX accounts for multiple pathways as a consequence of its multimedia representation. Because the two models were based on different approaches, it is expected that the results would be different. For example, the results of the SSL were more conservative compared with CalTOX for all 11 chemicals. This observation still holds when considering the total risk from CalTOX vs. the risk based on the dominant pathway in SSL. Finally, the cancer slope factors and references doses were not the same for all the chemicals used in this study and resulted in different risk estimates.     

What Can Be Done to Ensure the Usefulness of Epidemiologic Data for Risk Assessment Purposes?

Epidemiologic studies can play a central role in risk assessments. They are used in all risk assessment phases: hazard identification, dose-response, and exposure assessment. Epidemiologic studies have often been the first to show that a particular environmental exposure is a hazard to health. They have numerous advantages with respect to other sources of data which are used in risk assessments, the most important being that they do not require the assumption that they are generalizable to humans. For this reason, fewer and lower uncertainty factors may be appropriate in risk characterization based on epidemiologic studies. Unfortunately, epidemiologic studies have numerous problems, the most important being that the exposures are often not precisely measured. This article presents in detail the advantages of and problems with epidemiologic studies. It discusses two approaches to ensure their usefulness, biomarkers and an ordinance which requires baseline and subsequent surveillance of possible exposures and health effects from newly sited potentially polluting facilities. Biomarkers are biochemical measures of exposure, susceptibility factors, or preclinical pathological changes. Biomarkers are a way of dealing with the problems of poor measures, differential susceptibility and lack of early measures of disease occurrence that inherent in many environmental epidemiologic studies. The advantages of biomarkers is they can provide objective information on exposure days, months or even years later and evidence of pathology perhaps years earlier. The ordinance makes possible the use of a powerful epidemiologic study design, the prospective cohort study, where confounder(s) are best measured, and exposures, pathological changes, and health effects can be detected as soon as possible.     

Current problems of estimation of genetic risk of human exposure to radiation

The methodology of assessing the genetic risk of radiation exposure is based on the concept of "hitting the target" in development of which N.V. Timofeeff-Ressovsky has played and important role. To predict genetic risk posed by irradiation, the UN Scientific Committee on the Effects of Atomic Radiation (UNSCEAR) has worked out direct and indirect methods of assessment, extrapolational, integral and populational criteria of risk analysis that together permit calculating the risk from human exposure on the basis of data obtained for mice. Laboratory mice are the main objects in studying radiation mutagenesis due to the fact that the data on the frequency of radiation-induced human mutations are rather scarce. The method of doubling dose based on the determination of a dose doubling the level of natural mutational process in humans is the main one used to predict the genetic risk. The evolution of views about the genetics risk of human exposure to radiation for last 40 years is considered. Till 1972 the main model for assessing the genetic risk was the "human/mouse" model (the use of data on the spontaneous human variability and data on the frequency of induced mutations in mice). In the period form 1972 till 1994 the "mouse/mouse" model was intensively elaborated in many laboratories. This model was also used in this period by UNSCEAR experts to analyze the genetic risk from human irradiation. Recent achievements associated with the study of the molecular nature of many hereditary human diseases as well as the criticism of number fundamental principles of the "mouse/mouse" model for estimating the genetic risk on a new basis. The estimates of risk for the different classes of genetic diseases have been obtained using the doubling-dose method. The estimate of doubling dose used in the calculations is 1 Gy for low dose/chronic low-LET radiation conditions.     

Detection of risk of cancer to man.

Epidemiology can pick out large-scale determinants of human cancer, such as smoking. Also, epidemiology can pick out carcinogens such as asbestos to which groups of perhaps a few hundred or a few thousand workers have been heavily exposed for decades. However, if highly exposed groups cannot be studied then epidemiology cannot recognize carcinogens which, although perhaps widely distributed, produce only a small percentage increase in particular cancers. Almost all of the environmental pollutants that can affect human cancer incidence will do so only to a very minor extent, at the levels to which we are currently exposed. For this reason, and also because it is often difficult to define an exposed and an unexposed group which do not differ in other ways as well, it will almost always be impossible to do anything epidemiologically except to set a very crude upper limit on their likely hazards. The only way, therefore, to get any direct estimate of these hazards is by laboratory studies of the effects of high doses on various model systems. For this and for other reasons, it would be highly desirable to have good laboratory models for human carcinogenesis. The characteristics required of satisfactory laboratory systems are reviewed, and it is argued that systematic errors may arise unless one studies epithelial cells from large, long-lived species under conditions of chronic, low-dose exposure to noxious test agents in conjunction with standard chronic doses of agents which may be synergistic with the test agents. (Carcinogenic mutagens may be synergistic with carcinogenic non-mutagens.) For reasons of expense and speed, such studies must be done in vitro. If such in-vitro systems can be developed, either by using tissue explants or cell cultures, an important criterion which they will have to satisfy to be trusted will be that under chronic exposure the rate of transformation should be proportional to something like the fourth power of exposure duration. This paper chiefly reviews the reasons for choosing these specifications for a trustworthy in-vitro model for human carcinogenesis.     

Underestimation of Risk Due to Exposure Misclassification

Aim. Exposure misclassification constitutes a major obstacle when developing dose-response relationships for risk assessment. A non-differentional error results in underestimation of the risk. If the degree of misclassification is known, adjustment may be achieved by sensitivity analysis. The purpose of this study was to examine the full magnitude of measurement error in determining the prenatal exposure to methylmercury. Materials and methods. We used data from a prospective study of a Faroese birth cohort. Two biomarkers of methylmercury exposure were available, i.e., the mercury concentrations in cord blood and in maternal hair (sampled at the time of parturition). The laboratory imprecision on both chemical analyses was thought to be below 5% (coefficient of variation, CV). As a third exposure parameter, we used the dietary questionnaire response on frequency of whale meat dinners. Factor analysis and structural equation analysis were applied to assess the full extent of the imprecision. Results. The calculated total imprecision much exceeded the known laboratory variation: the CV was 28–30% for the cord-blood concentration and 52–55% for the maternal hair concentration. The dietary questionnaire response was even more imprecise. Conclusions. These findings illustrate that measurement error may be greatly underestimated if judged solely from reproducibility or laboratory quality data. Adjustment by sensitivity analysis is meaningful only if realistic measurement errors are applied. When exposure measurement errors are overlooked or underestimated, decisions based on the precautionary principle will not appropriately reflect the degree of precaution that was intended.     

Effects of exposure misclassification on regression analyses of epidemiologic follow-up study data

In epidemiologic studies, subjects are often misclassified as to their level of exposure. Ignoring this misclassification error in the analysis introduces bias in the estimates of certain parameters and invalidates many hypothesis tests. For situations in which there is misclassification of exposure in a follow-up study with categorical data, we have developed a model that permits consideration of any number of exposure categories and any number of multiple-category covariates. When used with logistic and Poisson regression procedures, this model helps assess the potential for bias when misclassification is ignored. When reliable ancillary information is available, the model can be used to correct for misclassification bias in the estimates produced by these regression procedures.     

Dosimetry of electromagnetic field exposure of an active armlet and its electromagnetic interference to the cardiac pacemakers using adult,child and infant models

ABSTRACT

Wearable devices have been popularly used with people from different age groups. As a consequence, the concerns of their electromagnetic field (EMF) exposure to the human body and their electromagnetic interference (EMI) to the implanted medical devices have attracted many studies. The aim of this study was to evaluate the human exposure to the EMF of an active radiofrequency identification (RFID) armlet as well as its EMI to the cardiac pacemaker (CP). Different human models from various age groups were applied to assess the result variability. The scalar potential finite element method was utilized in the simulation. Local EMF exposure and the exposure to the central nerve system tissues were evaluated using different metrics. EMI to the CP was assessed in terms of the conducted voltage to the CP. The results from all the models revealed that the studied RFID armlet would not produce the EMF exposure exceeding the safety limits. The calculated interference voltage was highly dependent on the distance between the RFID armlet and the CP (i.e. the physical dimension of the individual model). The results proposed to evaluate the appropriateness of the current EMI measurement protocol for this kind of devices used by the infants.     

Quantitative microbiological risk assessment: principles applied to determining the comparative risk of salmonellosis from chicken products

Since causal links have been established between food-borne illness and particular microorganisms, it has been possible to assess the public health risks of their presence in foods and propose measures to ensure the safety of customers. Effective control measures for food safety have been based on knowledge of the resistance of pathogenic microorganisms to the treatments used for preservation (e.g. acidification or reduced water activity) or decontamination (e.g. pasteurisation or sterilisation). Using this principle, food safety has been managed informally and successfully within the food industry for many years. Recently, formal risk assessment schemes, for example from Codex Alimentarius, have developed and placed the elements of decision-making on suitable control measures into a formal framework with clearly identifiable stages. The output of the four stages of a formal risk assessment (hazard identification, hazard characterisation, exposure assessment and risk characterisation) provides the basis for decisions on actions needed to control the identified hazard. There are many difficulties in ensuring that risk assessments are realistic and accessible to potential users, in many cases their value is limited by the data available. The study reported here on control of Salmonella in poultry products illustrates that it is possible to produce a comparative risk assessment based on published data. This study is not a full quantitative risk assessment, but provide useful pointers for a risk manager. Differences are discussed between the exposure assessment data needed to propose controls for infectious or toxigenic pathogens. For infectious pathogens, the presence of viable and infectious microorganisms is itself the hazard, but for toxigenic microorganisms, absence or destruction of viable cells at ingestion does not in itself ensure the absence of toxin. For toxin hazards, exposure assessment needs to consider previous conditions that may have led to toxin formation and persistence, rather than just the level of microbes at ingestion.     

Mercapturic acids as biomarkers of exposure to electrophilic chemicals:applications to environmental and industrial chemicals

The use of mercapturic acids (N-acetyl-L-cysteine S-conjugates, MAs) in the biological monitoring of human exposure to environmental and industrial chemicals is receiving more and more attention. Mercapturic acids (MAs) are formed from glutathione (GSH) S-conjugates via the MA-pathway. Although this pathway can lead to different end-products, the formation of MAs is the predominant route in most species, including man. Two GSH S-transferases (GSTs) show genetic polymorphisms in humans and this can have major consequences for individual susceptibility to toxic effects and for MA formation. In occupational toxicology, adducts to biomacromolecules are also used as biomarkers. DNA adducts are a measure for the effective dose, while protein adducts are related to the dose at critical site. Both type of adducts are normally determined in blood, while MAs are determined in urine. Most MAs are excreted with relatively short half-lifes, allowing a direct evaluation of the occupational circumstances. For many compounds similar (linear) dose-dependency was found for MA excretion, formation of macromolecular adducts, and for various biomarkers of toxic effects. These relations together with fact that MAs relate to the electrophilic character of compounds, allows for the conclusion that MAs are biomarkers of toxicologically relevant internal doses of chemicals or their metabolites. An overview will be given here of the use of MAs in the assessment of internal human exposure to electrophilic environmental and industrial chemicals. Additionally, the formation of GSH S-conjugates, their catabolism to MAs and several of the frequently used analytical approaches are discussed. When appropriate, the influence of genetic polymorphisms on formation of MAs and on susceptibility to toxicity will be discussed for different chemicals as well.     

Mercapturic acids as biomarkers of exposure to electrophilic chemicals:applications to environmental and industrial chemicals

The use of mercapturic acids (N-acetyl-L-cysteine S-conjugates, MAs) in the biological monitoring of human exposure to environmental and industrial chemicals is receiving more and more attention. Mercapturic acids (MAs) are formed from glutathione (GSH) S-conjugates via the MA-pathway. Although this pathway can lead to different end-products, the formation of MAs is the predominant route in most species, including man. Two GSH S-transferases (GSTs) show genetic polymorphisms in humans and this can have major consequences for individual susceptibility to toxic effects and for MA formation. In occupational toxicology, adducts to biomacromolecules are also used as biomarkers. DNA adducts are a measure for the effective dose, while protein adducts are related to the dose at critical site. Both type of adducts are normally determined in blood, while MAs are determined in urine. Most MAs are excreted with relatively short half-lifes, allowing a direct evaluation of the occupational circumstances. For many compounds similar (linear) dose-dependency was found for MA excretion, formation of macromolecular adducts, and for various biomarkers of toxic effects. These relations together with fact that MAs relate to the electrophilic character of compounds, allows for the conclusion that MAs are biomarkers of toxicologically relevant internal doses of chemicals or their metabolites. An overview will be given here of the use of MAs in the assessment of internal human exposure to electrophilic environmental and industrial chemicals. Additionally, the formation of GSH S-conjugates, their catabolism to MAs and several of the frequently used analytical approaches are discussed. When appropriate, the influence of genetic polymorphisms on formation of MAs and on susceptibility to toxicity will be discussed for different chemicals as well.     

Monogonont rotifers as model systems for the study of micro-evolutionary adaptation and its eco-evolutionary implications

A better understanding of the ability of organisms to adapt to local selection conditions is essential for a better insight in their ecological dynamics. The study of micro-evolutionary adaptation and its eco-evolutionary consequences is challenging for many reasons and the choice of a suitable model organism is particularly important. In this paper, we explain why monogonont rotifers, through their unique combination of traits, are ideal study organisms for this purpose. With a literature review, we demonstrate the capacity of monogonont populations to adapt to a variety of selection conditions (e.g., salinity, food shortage, elemental limitation, and disturbance regimes) within very short-time frames and highlight some potential eco-evolutionary implications. Although monogononts are increasingly used in eco-evolution-oriented studies, their potential is still underappreciated compared to other model organisms. No doubt the high prevalence of cryptic species complexes and the lack of genomic tools form important obstacles that may discourage researchers to work with this group. Here, we argue that none of these difficulties should prevent monogonont rotifers from becoming commonly used model organisms in micro-evolutionary studies and make suggestions for future research.     

Effects of exposure uncertainties in the TSCE model and application to the Colorado miners data

The simulations in this paper show that exposure measurement error affects the parameter estimates of the biologically motivated two-stage clonal expansion (TSCE) model. For both Berkson and classical error models, we show that likelihood-based techniques of correction work reliably. For classical errors, the distribution of true exposures needs to be known or estimated in addition to the distribution of recorded exposures conditional on true exposures. Usually the exposure uncertainty biases the model parameters toward the null and underestimates the precision. But when several parameters are allowed to be dependent on exposure, e.g. initiation and promotion, then their relative importance is also influenced, and more complicated effects of exposure uncertainty can occur. The application part of this paper shows for two different types of Berkson errors that a recent analysis of the data for the Colorado plateau miners with the TSCE model is not changed substantially when correcting for such errors. Specifically, the conjectured promoting action of radon remains as the dominant radiation effect for explaining these data. The estimated promoting action of radon increases by a factor of up to 1.2 for the largest assumed exposure uncertainties.     

Unmasking a killer: DNA O(6)-methylguanine and the cytotoxicity of methylating agents

Methylating agents are potent carcinogens that are mutagenic and cytotoxic towards bacteria and mammalian cells. Their effects can be ascribed to an ability to modify DNA covalently. Pioneering studies of the chemical reactivity of methylating agents towards DNA components and their effectiveness as animal carcinogens identified O(6)-methylguanine (O(6)meG) as a potentially important DNA lesion. Subsequent analysis of the effects of methylating carcinogens in bacteria and cultured mammalian cells - including the discovery of the inducible adaptive response to alkylating agents in Escherichia coli - have defined the contributions of O(6)meG and other methylated DNA bases to the biological effects of these chemicals. More recently, the role of O(6)meG in killing mammalian cells has been revealed by the lethal interaction between persistent DNA O(6)meG and the mismatch repair pathway. Here, we briefly review the results which led to the identification of the biological consequences of persistent DNA O(6)meG. We consider the possible consequences for a human cell of chronic exposure to low levels of a methylating agent. Such exposure may increase the probability that the cell's mismatch repair pathway becomes inactive. Loss of mismatch repair predisposes the cell to mutation induction, not only through uncorrected replication errors but also by methylating agents and other mutagens.     

Construction of Vapor Chambers Used to Expose Mice to Alcohol During the Equivalent of all Three Trimesters of Human Development

Exposure to alcohol during development can result in a constellation of morphological and behavioral abnormalities that are collectively known as Fetal Alcohol Spectrum Disorders (FASDs). At the most severe end of the spectrum is Fetal Alcohol Syndrome (FAS), characterized by growth retardation, craniofacial dysmorphology, and neurobehavioral deficits. Studies with animal models, including rodents, have elucidated many molecular and cellular mechanisms involved in the pathophysiology of FASDs. Ethanol administration to pregnant rodents has been used to model human exposure during the first and second trimesters of pregnancy. Third trimester ethanol consumption in humans has been modeled using neonatal rodents. However, few rodent studies have characterized the effect of ethanol exposure during the equivalent to all three trimesters of human pregnancy, a pattern of exposure that is common in pregnant women. Here, we show how to build vapor chambers from readily obtainable materials that can each accommodate up to six standard mouse cages. We describe a vapor chamber paradigm that can be used to model exposure to ethanol, with minimal handling, during all three trimesters. Our studies demonstrate that pregnant dams developed significant metabolic tolerance to ethanol. However, neonatal mice did not develop metabolic tolerance and the number of fetuses, fetus weight, placenta weight, number of pups/litter, number of dead pups/litter, and pup weight were not significantly affected by ethanol exposure. An important advantage of this paradigm is its applicability to studies with genetically-modified mice. Additionally, this paradigm minimizes handling of animals, a major confound in fetal alcohol research.     

A Probabilistic Human Health Risk Assessment for Environmental Exposure to Dibutylphthalate

In the European Union, Directive 92/32/EC and EC Council Regulation (EC) 793/93 require the risk assessment of industrial chemicals. In this framework, it is agreed to characterise the level of “risk” by means of the deterministic quotient of exposure and effects parameters. Decision makers require that the uncertainty in the risk assessment be accounted for as explicitly as possible. Therefore, this paper intends to show the advantages and possibilities of a probabilistic human health risk assessment of an industrial chemical, dibutylphthalate (DBP). The risk assessment is based on non-cancer endpoints assumed to have a threshold for toxicity. This example risk assessment shows that a probabilistic risk assessment in the EU framework covering both the exposure and the effects assessment is feasible with currently available techniques. It shows the possibility of comparing the various uncertainties involved in a typical risk assessment, including the uncertainty in the exposure estimate, the uncertainty in the effect parameter, and the uncertainty in assessment factors used in the extrapolation from experimental animals to sensitive human beings. The analysis done did not confirm the reasonable worst-case character of the deterministic EU-assessment of DBP. Sensitivity analysis revealed the extrapolation procedure in the human effects assessment to be the main source of uncertainty. Since the probabilistic approach allows determination of the range of possible outcomes and their likelihood, it better informs both risk assessors and risk managers.     

Potential Sequential Exposures to 2-Butoxyethanol After Use of a Hard-Surface Cleaner

Professional workers and consumers frequently use hard-surface cleaning products and these products may contain glycol ethers (GEs), such as 2-Butoxyethanol (2-BE). Governmental agencies have set exposure limits for some chemicals used in cleaning products and these exposure limits have been used as guides to protect human health. The study objectives were to determine realistic inhalation exposures for professional workers performing multiple, sequential cleaning tasks and compare the exposures to the acute reference exposure level (REL), which California established for 2-BE. The ConsExpo model was acceptable for evaluating exposure based on a comparison of its predictions to experimentally measured 2-BE vapor concentrations from hard-surface cleaning. The typical worker exposure was predicted for a cleaning scenario consisting of three bathrooms and three kitchens (or three bedrooms) in a 1-h period. This exposure scenario would not be expected to result in significant health consequences because the predicted exposure was much lower than the REL. The predicted chronic and aggregate exposures were also acceptable. This analysis identified two important variables that affect inhalation exposure: cleaners should be used with adequate ventilation and wet wiping towels should be properly disposed so that they are not a source of continuing exposure.     

Chemical Vapor Intrusion from Soil or Groundwater to Indoor Air: Significance of Unsaturated Zone Biodegradation of Aromatic Hydrocarbons

The soil vapor to indoor air exposure pathway is considered in a wide number of risk-based site management programs. In screening-level assessments of this exposure pathway, models are typically used to estimate the transport of vapors from either subsurface soils or groundwater to indoor air. Published studies indicate that the simple models used to evaluate this exposure pathway often over estimate the impact for aromatic hydrocarbons (e.g., benzene, toluene, ethylbenzene, and xy-lene or BTEX), while showing reasonable agreement for estimates of chlorinated hydrocarbon impacts (e.g., PCE, TCE, DCE). Aerobic biodegradation of the petroleum hydrocarbons is most often attributed as the source of this disparity in the model/ data comparisons. This paper looks at the significance of aerobic biodegradation of aromatic hydrocarbons as part of the assessment of chemical vapor intrusion from soil or groundwater to indoor air. A review of relevant literature summarizing the available field data as well as various modeling approaches that include biodegradation is presented. This is followed by a simple modeling analysis that demonstrates the potential importance of biodegradation in the assessment of the soil vapor to indoor air exposure pathway. The paper concludes with brief discussions of other model considerations that are often not included in simple models but may have a significant impact on the intrusion of vapors into indoor air.