Biomonitoring of 2,4-dichlorophenoxyacetic acid (2,4-D) herbicide: A global view.

We conducted a literature review of urinary 2,4-D in populations not associated with a herbicide application. Of the 33 studies identified, the median/mean concentrations were similar for children, adults, and pregnant women regardless of geography. Individuals with highest concentrations may have had opportunities to directly contact 2,4-D outside of an application. Most studies were conducted in populations in North America and did not examine potential sources of 2,4-D, or what factors might influence higher or lower urinary 2,4-D concentrations. In the future, prioritizing the examination of 2,4-D biomonitoring in other regions and collecting information on sources and factors influencing exposures would better our understanding of 2,4-D exposures globally. In all the studies reviewed the concentrations of urinary 2,4-D observed were orders of magnitude below the US regulatory endpoints, suggesting that people are not being exposed to 2,4-D at levels high enough to result in adverse health effects.

Research on COVID-19 and air pollution: A path towards advancing exposure science.

The COVID-19 pandemic has resulted in an extraordinary incidence of morbidity and mortality, with almost 6 million deaths worldwide at the time of this writing (https://covid19.who.int/). There has been a pressing need for research that would shed light on factors - especially modifiable factors - that could reduce risks to human health. At least several hundred studies addressing the complex relationships among transmission of SARS-CoV-2, air pollution, and human health have been published. However, these investigations are limited by available and consistent data. The project goal was to seek input into opportunities to improve and fund exposure research on the confluence of air pollution and infectious agents such as SARS-CoV-2. Thirty-two scientists with expertise in exposure science, epidemiology, risk assessment, infectious diseases, and/or air pollution responded to the outreach for information. Most of the respondents expressed value in developing a set of common definitions regarding the extent and type of public health lockdown. Traffic and smoking ranked high as important sources of air pollution warranting source-specific research (in contrast with assessing overall ambient level exposures). Numerous important socioeconomic factors were also identified. Participants offered a wide array of inputs on what they considered to be essential studies to improve our understanding of exposures. These ranged from detailed mechanistic studies to improved air quality monitoring studies and prospective cohort studies. Overall, many respondents indicated that these issues require more research and better study design. As an exercise to solicit opinions, important concepts were brought forth that provide opportunities for scientific collaboration and for consideration for funding prioritization. Further conversations on these concepts are needed to advance our thinking on how to design research that moves us past the documented limitations in the current body of research and prepares us for the next pandemic.

Using the Matrix to bridge the epidemiology/risk assessment gap: a case study of 2,4-D.

BACKGROUND: The Matrix is designed to facilitate discussions between practitioners of risk assessment and epidemiology and, in so doing, to enhance the utility of epidemiology research for public health decision-making. The Matrix is comprised of nine fundamental "asks" of epidemiology studies, focusing on the types of information valuable to the risk assessment process. OBJECTIVE: A 2,4-dichlorophenoxyacetic acid (2,4-D) case study highlights the extent to which existing epidemiology literature includes information generally needed for risk assessments and proffers suggestions that would assist in bridging the epidemiology/risk assessment gap. METHODS: Thirty-one publications identified in the US Environmental Protection Agency 2,4-D epidemiology review were assessed. These studies focused on associations between 2,4-D exposure and non-Hodgkin lymphoma (NHL), respiratory effects, and birth outcomes. RESULTS: Many of the papers met one or more specific elements of the Matrix. However, from this case study, it is clear that some aspects of risk assessment, such as evaluating source-to-intake pathways, are generally not considered in epidemiology research. Others are incorporated, but infrequently (e.g. dose-response information, harmonization of exposure categories). We indicated where additional analyses or modifications to future study design could serve to improve the translation. DISCUSSION: Interaction with risk assessors during the study design phase and using the Matrix "asks" to guide the conversations could shape research and provide the basis for requests for funds to support these additional activities. The use of the Matrix as a foundation for communication and education across disciplines could produce more impactful and consequential epidemiology research for robust risk assessments and decision-making.

Does ozone inhalation cause adverse metabolic effects in humans? A systematic review.

We utilized a practical, transparent approach for systematically reviewing a chemical-specific evidence base. This approach was used for a case study of ozone inhalation exposure and adverse metabolic effects (overweight/obesity, Type 1 diabetes [T1D], Type 2 diabetes [T2D], and metabolic syndrome). We followed the basic principles of systematic review. Studies were defined as "Suitable" or "Supplemental." The evidence for Suitable studies was characterized as strong or weak. An overall causality judgment for each outcome was then determined as either causal, suggestive, insufficient, or not likely. Fifteen epidemiologic and 33 toxicologic studies were Suitable for evidence synthesis. The strength of the human evidence was weak for all outcomes. The toxicologic evidence was weak for all outcomes except two: body weight, and impaired glucose tolerance/homeostasis and fasting/baseline hyperglycemia. The combined epidemiologic and toxicologic evidence was categorized as weak for overweight/obesity, T1D, and metabolic syndrome,. The association between ozone exposure and T2D was determined to be insufficient or suggestive. The streamlined approach described in this paper is transparent and focuses on key elements. As systematic review guidelines are becoming increasingly complex, it is worth exploring the extent to which related health outcomes should be combined or kept distinct, and the merits of focusing on critical elements to select studies suitable for causal inference. We recommend that systematic review results be used to target discussions around specific research needs for advancing causal determinations.

Cancer and occupational exposure to pesticides: an umbrella review.

PURPOSE: The aim was to identify the scope of the epidemiology literature reviewed regarding the risk of cancer as related to occupational exposure to pesticides and to compare regulatory toxicity results where feasible. METHODS: Review studies of breast, lung, prostate, non-Hodgkin lymphoma, and colorectal cancer were identified from the published literature from 2010 to 2020 using a priori inclusion and exclusion criteria. Epidemiology observations were first assessed and then compared against carcinogenicity profiles derived from regulatory toxicology studies. RESULTS: Several active ingredients were associated with specific cancer but overall, there was neither strong nor consistent epidemiologic data supportive of a positive association between pesticide exposure in occupational settings and cancer. Authors noted common themes related to the heterogeneity of exposure, study design, control for confounders, and the challenge to collect these data reliably and validly with an adequate sample size. Toxicology studies in laboratory animals that assessed carcinogenic potential did not reveal cancer outcomes that were concordant with reported epidemiologic findings. CONCLUSIONS: Farming and pesticides represent diverse exposures that are difficult to quantify in epidemiologic studies. Going forward, investigators will need creative and novel approaches for exposure assessment. Integration of epidemiologic and toxicological studies with attention to biological plausibility, mode of toxicological action and relevance to humans will increase the ability to better assess associations between pesticides and cancer.

Pyrethroid epidemiology: a quality-based review.

Pyrethroids are commonly used around the home and in agricultural production to control insects. Human contact to one or more pyrethroid insecticides is likely. Numerous epidemiology studies have evaluated the association between health outcomes in humans and pyrethroid exposure. The purpose of this review was to identify and evaluate the quality of pyrethroid-related epidemiology studies that addressed chronic health effects, and compare findings with animal toxicology studies. We evaluated the quality of 61 studies published between 2000 and 2016 by using elements of outcome, exposure metric, exposure level, and study design. None of the 61 publications demonstrated strong quality for all elements. A few of the outcome measures were strong, particularly those relying upon medical diagnoses. Most of the pyrethroid epidemiology studies used a poor exposure metric, relying upon a single sample of pyrethroid urinary metabolites, which is subject to misclassification of past exposures. In addition, many studies were a cross-sectional design, preventing an evaluation of the temporality of the exposure-disease association. Furthermore, none of the effects observed in the epidemiological literature was concordant with toxicological effects noted in extensive testing of pyrethroids in animals. In order to provide more robust data on potential health outcomes from low dose exposure to pyrethroid insecticides, future epidemiological studies should fully characterize an adverse outcome, include exposure validation components, and quantify exposure over time.

Critical and systematic evaluation of data for estimating human exposures to 2,4-dichlorophenoxyacetic acid (2,4-D) - quality and generalizability.

The herbicide 2,4-dichlorophenoxyacetic acid (2,4-D) has been commercially available since the 1940's. Despite decades of data on 2,4-D in food, air, soil, and water, as well as in humans, the quality the quality of these data has not been comprehensively evaluated. Using selected elements of the Biomonitoring, Environmental Epidemiology, and Short-lived Chemicals (BEES-C) instrument (temporal variability, avoidance of sample contamination, analyte stability, and urinary methods of matrix adjustment), the quality of 156 publications of environmental- and biomonitoring-based 2,4-D data was examined. Few publications documented steps were taken to avoid sample contamination. Similarly, most studies did not demonstrate the stability of the analyte from sample collection to analysis. Less than half of the biomonitoring publications reported both creatinine-adjusted and unadjusted urine concentrations. The scope and detail of data needed to assess temporal variability and sources of 2,4-D varied widely across the reviewed studies. Exposures to short-lived chemicals such as 2,4-D are impacted by numerous and changing external factors including application practices and formulations. At a minimum, greater transparency in reporting of quality control measures is needed. Perhaps the greatest challenge for the exposure community is the ability to reach consensus on how to address problems specific to short-lived chemical exposures in observational epidemiology investigations. More extensive conversations are needed to advance our understanding of human exposures and enable interpretation of these data to catch up to analytical capabilities. The problems defined in this review remain exquisitely difficult to address for chemicals like 2,4-D, with short and variable environmental and physiological half-lives and with exposures impacted by numerous and changing external factors.

Derivation of human Biomonitoring Guidance Values for chlorpyrifos using a physiologically based pharmacokinetic and pharmacodynamic model of cholinesterase inhibition.

A number of biomonitoring surveys have been performed for chlorpyrifos (CPF) and its metabolite (3,5,6-trichloro-2-pyridinol, TCPy); however, there is no available guidance on how to interpret these data in a health risk assessment context. To address this gap, Biomonitoring Guidance Values (BGVs) are developed using a physiologically based pharmacokinetic and pharmacodynamic (PBPK/PD) model. The PBPK/PD model is used to predict the impact of age and human variability on the relationship between an early marker of cholinesterase (ChE) inhibition in the peripheral and central nervous systems [10% red blood cell (RBC) ChE inhibition] and levels of systemic biomarkers. Since the PBPK/PD model characterizes variation of sensitivity to CPF in humans, interspecies and intraspecies uncertainty factors are not needed. Derived BGVs represent the concentration of blood CPF and urinary TCPy associated with 95% of the population having less than or equal to 10% RBC ChE inhibition. Blood BGV values for CPF in adults and infants are 6100 ng/L and 4200 ng/L, respectively. Urinary TCPy BGVs for adults and infants are 2100 µg/L and 520 µg/L, respectively. The reported biomonitoring data are more than 150-fold lower than the BGVs suggesting that current US population exposures to CPF are well below levels associated with any adverse health effect.

Pesticide exposure and neurodevelopmental outcomes: review of the epidemiologic and animal studies.

Assessment of whether pesticide exposure is associated with neurodevelopmental outcomes in children can best be addressed with a systematic review of both the human and animal peer-reviewed literature. This review analyzed epidemiologic studies testing the hypothesis that exposure to pesticides during pregnancy and/or early childhood is associated with neurodevelopmental outcomes in children. Studies that directly queried pesticide exposure (e.g., via questionnaire or interview) or measured pesticide or metabolite levels in biological specimens from study participants (e.g., blood, urine, etc.) or their immediate environment (e.g., personal air monitoring, home dust samples, etc.) were eligible for inclusion. Consistency, strength of association, and dose response were key elements of the framework utilized for evaluating epidemiologic studies. As a whole, the epidemiologic studies did not strongly implicate any particular pesticide as being causally related to adverse neurodevelopmental outcomes in infants and children. A few associations were unique for a health outcome and specific pesticide, and alternative hypotheses could not be ruled out. Our survey of the in vivo peer-reviewed published mammalian literature focused on effects of the specific active ingredient of pesticides on functional neurodevelopmental endpoints (i.e., behavior, neuropharmacology and neuropathology). In most cases, effects were noted at dose levels within the same order of magnitude or higher compared to the point of departure used for chronic risk assessments in the United States. Thus, although the published animal studies may have characterized potential neurodevelopmental outcomes using endpoints not required by guideline studies, the effects were generally observed at or above effect levels measured in repeated-dose toxicology studies submitted to the U.S. Environmental Protection Agency (EPA). Suggestions for improved exposure assessment in epidemiology studies and more effective and tiered approaches in animal testing are discussed.

Literature landscape of neurodevelopment and pesticides: A scoping review of methodologies.

Pesticides are highly tested and regulated chemicals. There is currently great interest in the role that pesticides may play in childhood neurodevelopment. The objective was to identify and describe the body of evidence and to assess the ability to synthesize effect estimates. The epidemiologic literature from 2011 to 2022 was searched for publications on the association between pesticide exposure and neurodevelopment, behavior, and/or cognition in children. We identified 114 publications, representing 67 unique studies. While organochlorine and other insecticides were the most common classes of pesticides studied, up to 159 different metabolites or active ingredients were reported. Nine pesticides or their metabolites were reported in >10 publications. Similarly, multiple assessment methods were administered across studies to evaluate outcomes in neurodevelopment at ages which ranged from birth to 18 years of age. This scoping review reveals the heterogeneity among published studies with respect to exposures and health outcomes, in the methods used to assess and classify them, and in combinations of the two. This limits the adequacy of the evidence to evaluate specific risk estimates for a particular exposure-outcome pair. Intentional coordination among researchers to increase consistency in methodologies would facilitate the synthesis of results across studies. Research opportunities also exist to validate assumptions in exposure and outcome assessment which are implicit in many of the studies reviewed. In conclusion, there are many ongoing epidemiologic studies with a focus on pesticides and neurodevelopment. The variety of exposures, exposure assessment methods and tests for each outcome can be overwhelming. Interdisciplinary collaboration is recommended to harmonize data collection and to enable meaningful interpretation of the study results across populations.

Review of 2,4-dichlorophenoxyacetic acid (2,4-D) biomonitoring and epidemiology.

A qualitative review of the epidemiological literature on the herbicide 2,4-dichlorophenoxyacetic acid (2,4-D) and health after 2001 is presented. In order to compare the exposure of the general population, bystanders and occupational groups, their urinary levels were also reviewed. In the general population, 2,4-D exposure is at or near the level of detection (LOD). Among individuals with indirect exposure, i.e. bystanders, the urinary 2,4-D levels were also very low except in individuals with opportunity for direct contact with the herbicide. Occupational exposure, where exposure was highest, was positively correlated with behaviors related to the mixing, loading and applying process and use of personal protection. Information from biomonitoring studies increases our understanding of the validity of the exposure estimates used in epidemiology studies. The 2,4-D epidemiology literature after 2001 is broad and includes studies of cancer, reproductive toxicity, genotoxicity, and neurotoxicity. In general, a few publications have reported statistically significant associations. However, most lack precision and the results are not replicated in other independent studies. In the context of biomonitoring, the epidemiology data give no convincing or consistent evidence for any chronic adverse effect of 2,4-D in humans.

Elements to increase translation in pyrethroid epidemiology research: A review.

Pyrethroid insecticides have been the subject of numerous epidemiology studies in the past two decades. We examined the pyrethroids epidemiology literature published between 2016 and 2021. Our objective with this exercise was to inform interested readers regarding information on methodological elements that strengthen a study's use for translation (i.e., use in risk assessment) and to describe aspects of future research methods that could improve utility for decision-making. We focused on the following elements: (i) study design that provided evidence that pyrethroid exposure preceded the outcome, (ii) evidence that the method used for exposure characterization was reliable and sufficiently accurate for the intended purpose, and (iii) use of a robust approach for outcome ascertainment. For each of the 74 studies identified via the literature search, we categorized the methodological elements as Acceptable or Supplemental. A study with three Acceptable elements was considered Relevant for risk assessment purposes. Based on our evaluative approach, 18 (24%) of the 74 publications were considered to be Relevant. These publications were categorized as Acceptable for all three elements assessed: confirmed exposure (N = 24), confirmed outcome (N = 64), exposure preceded the outcome (N = 44). Three of these studies were birth cohorts. There were 15 Relevant publications of adults which included 10 Agricultural Health Study cohort publications of self-reported permethrin. Overall, the majority of the reviewed studies used methods that did not permit a determination that pyrethroid exposure preceded the outcome, and/or did not utilize robust methods for exposure assessment and outcome ascertainment. There is an opportunity for investigators and research sponsors to build on the studies reviewed here and to incorporate more translational approaches to studying exposure/outcome associations related to pesticides and other chemicals.

Experimental and theoretical comparison of the O K-edge nonresonant inelastic X-ray scattering and X-ray absorption spectra of NaReO4.

Accurate X-ray absorption spectra (XAS) of first row atoms, e.g., O, are notoriously difficult to obtain due to the extreme sensitivity of the measurement to surface contamination, self-absorption, and saturation affects. Herein, we describe a comprehensive approach for determining reliable O K-edge XAS data for ReO(4)(1-) and provide methodology for obtaining trustworthy and quantitative data on nonconducting molecular systems, even in the presence of surface contamination. This involves comparing spectra measured by nonresonant inelastic X-ray scattering (NRIXS), a bulk-sensitive technique that is not prone to X-ray self-absorption and provides exact peak intensities, with XAS spectra obtained by three different detection modes, namely total electron yield (TEY), fluorescence yield (FY), and scanning transmission X-ray microscopy (STXM). For ReO(4)(1-), TEY measurements were heavily influenced by surface contamination, while the FY and STXM data agree well with the bulk NRIXS analysis. These spectra all showed two intense pre-edge features indicative of the covalent interaction between the Re 5d and O 2p orbitals. Density functional theory calculations were used to assign these two peaks as O 1s excitations to the e and t(2) molecular orbitals that result from Re 5d and O 2p covalent mixing in T(d) symmetry. Electronic structure calculations were used to determine the amount of O 2p character (%) in these molecular orbitals. Time dependent-density functional theory (TD-DFT) was also used to calculate the energies and intensities of the pre-edge transitions. Overall, under these experimental conditions, this analysis suggests that NRIXS, STXM, and FY operate cooperatively, providing a sound basis for validation of bulk-like excitation spectra and, in combination with electronic structure calculations, suggest that NaReO(4) may serve as a well-defined O K-edge energy and intensity standard for future O K-edge XAS studies.

Translation of Exposure and Epidemiology for Risk Assessment: A Shifting Paradigm.

Risk assessment is a well-established process used for various types of public health decision-making, such as setting chemical site clean-up levels, developing limits on exposures to chemicals in soil, water, air and food, and determining occupational exposure limits[...].

Trends in covalency for d- and f-element metallocene dichlorides identified using chlorine K-edge X-ray absorption spectroscopy and time-dependent density functional theory.

We describe the use of Cl K-edge X-ray absorption spectroscopy (XAS) and both ground-state and time-dependent hybrid density functional theory (DFT) to probe the electronic structure and determine the degree of orbital mixing in M-Cl bonds for (C(5)Me(5))(2)MCl(2) (M = Ti, 1; Zr, 2; Hf, 3; Th, 4; U, 5), where we can directly compare a class of structurally similar compounds for d- and f-elements. Pre-edge features in the Cl K-edge XAS data for the group IV transition-metals 1-3 provide direct evidence of covalent M-Cl orbital mixing. The amount of Cl 3p character was experimentally determined to be 25%, 23%, and 22% per M-Cl bond for 1-3, respectively. For actinides, we find a pre-edge shoulder for 4 (Th) and distinct and weak pre-edge features for U, 5. The amount of Cl 3p character was determined to be 9% for 5, and we were unable to make an experimental determination for 4. Using hybrid DFT calculations with relativistic effective core potentials, the electronic structures of 1-5 were calculated and used as a guide to interpret the experimental Cl K-edge XAS data. For transition-metal compounds 1-3, the pre-edge features arise due to transitions from Cl 1s electrons into the 3d-, 4d-, and 5d-orbitals, with assignments provided in the text. For Th, 4, we find that 5f- and 6d-orbitals are nearly degenerate and give rise to a single pre-edge shoulder in the XAS. For U, 5, we find the 5f- and 6d-orbitals fall into two distinct energy groupings, and Cl K-edge XAS data are interpreted in terms of Cl 1s transitions into both 5f- and 6d-orbitals. Time-dependent DFT was used to calculate the energies and intensities of Cl 1s transitions into empty metal-based orbitals containing Cl 3p character and provide simulated Cl K-edge XAS spectra for 1-4. For 5, which has two unpaired 5f electrons, simulated spectra were obtained from transition dipole calculations using ground-state Kohn-Sham orbitals. To the best of our knowledge, this represents the first application of Cl K-edge XAS to actinide systems. Overall, this study allows trends in orbital mixing within a well-characterized structural motif to be identified and compared between transition-metals and actinide elements. These results show that the orbital mixing for the d-block compounds slightly decreases in covalency with increasing principal quantum number, in the order Ti > Zr approximately = Hf, and that uranium displays approximately half the covalent orbital mixing of transition elements.

Mortality in employees at a New Zealand agrochemical manufacturing site.

BACKGROUND: Previous studies at the Dow AgroSciences (Formerly Ivon Watkins-Dow) plant in New Plymouth, New Zealand, had raised concerns about the cancer risk in a subset of workers at the site with potential exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin. As the plant had been involved in the synthesis and formulation of a wide range of agrochemicals and their feedstocks, we examined the mortality risk for all workers at the site. AIMS: To quantify the mortality hazards arising from employment at the Dow AgroSciences agrochemical production site in New Plymouth, New Zealand. METHODS: Workers employed between 1 January 1969 and 1 October 2003 were followed up to the end of 2004. Standardized mortality ratios (SMRs) were calculated using national mortality rates by employment duration, sex, period of hire and latency. RESULTS: A total of 1754 employees were followed during the study period and 247 deaths were observed. The all causes and all cancers SMRs were 0.97 (95% CI 0.85-1.10) and 1.01 (95% CI 0.80-1.27), respectively. Mortality due to all causes was higher for short-term workers (SMR 1.23, 95% CI 0.91-1.62) than long-term workers (SMR 0.92, 95% CI 0.80-1.06) and women had lower death rates than men. Analyses by latency and period of hire did not show any patterns consistent with an adverse impact of occupational exposures. CONCLUSIONS: The mortality experience of workers at the site was similar to the rest of New Zealand.

Evidence for the involvement of 5f orbitals in the bonding and reactivity of organometallic actinide compounds: thorium(IV) and uranium(IV) bis(hydrazonato) complexes.

Migratory insertion of diphenyldiazomethane into both metal-carbon bonds of the bis(alkyl) and bis(aryl) complexes (C(5)Me(5))(2)AnR(2) yields the first f-element bis(hydrazonato) complexes (C(5)Me(5))(2)An[eta(2)-(N,N')-R-N-N=CPh(2)](2) [An = Th, R = CH(3) (18), PhCH(2) (15), Ph (16); An = U, R = CH(3) (17), PhCH(2) (14)], which have been characterized by a combination of spectroscopy, electrochemistry, and X-ray crystallography. The two hydrazonato ligands adopt an eta(2)-coordination mode leading to 20-electron (for Th) and 22-electron (for U) complexes that have no transition-metal analogues. In fact, reaction of (C(5)H(5))(2)Zr(CH(3))(2) or (C(5)Me(5))(2)Hf(CH(3))(2) with diphenyldiazomethane is limited to the formation of the corresponding mono(hydrazonato) complex (C(5)R(5))(2)M[eta(2)-(N,N')-CH(3)-N-N=CPh(2)](CH(3)) (M = Zr, R = H or M = Hf, R = CH(3)). The difference in the reactivities of the group 4 metal complexes and the actinides was used as a unique platform for investigating in depth the role of 5f orbitals on the reactivity and bonding in actinide organometallic complexes. The electronic structure of the (C(5)H(5))(2)M[eta(2)-(N,N')-CH(3)-N-N=CH(2)](2) (M = Zr, Th, U) model complexes was studied using density functional theory (DFT) calculations and compared to experimental structural, electrochemical, and spectroscopic results. Whereas transition-metal bis(cyclopentadienyl) complexes are known to stabilize three ligands in the metallocene girdle to form saturated (C(5)H(5))(2)ML(3) species, in a bis(hydrazonato) system, a fourth ligand is coordinated to the metal center to give (C(5)H(5))(2)ML(4). DFT calculations have shown that 5f orbitals in the actinide complexes play a crucial role in stabilizing this fourth ligand by stabilizing both the sigma and pi electrons of the two eta(2)-coordinated hydrazonato ligands. In contrast, the stabilization of the hydrazonato ligands was found to be significantly less effective for the putative bis(hydrazonato) zirconium(IV) complex, yielding a higher energy structure. However, the difference in the reactivities of the group 4 metal and actinide complexes does not arise on thermodynamic grounds but is primarily of kinetic origin. Unfavorable steric factors have been ruled out as the sole influence to explain these different behaviors, and electronic factors were shown to govern the reactivity. For the actinides, both the C(5)H(5) and more realistic C(5)Me(5) ligands have been taken into account in computing the energy surface. The reaction profile for the C(5)Me(5) system differs from that with the C(5)H(5) ligand by a uniform shift of approximately 5 kcal/mol in the relative energies of the transition state and products. The insertion of a second diazoalkane molecule into the sole metal-carbon bond in the mono(hydrazonato) complexes involves a high energy barrier (approximately 20 kcal/mol) for the zirconium(IV) system, whereas the actinides can facilitate the approach of the diazoalkane by coordination (formation of an adduct) and its insertion into the An-C bond with a very low barrier on the potential energy surface.

Chlorinated dibenzo-p-dioxins, dibenzofurans, and biphenyl profiles of workers with trichlorophenol and pentachlorophenol exposures.

We examined the serum lipid adjusted levels of 2,3,7,8-substituted chlorinated dioxins and furans, and four coplanar PCBs for 98 workers. We found workers who worked only in the trichlorophenol units had mean lipid adjusted 2,3,7,8-TCDD levels of 36.8 ppt significantly higher (p<0.05) than 6.0 ppt in the reference group. Workers who worked only in the pentachlorophenol units had mean lipid adjusted levels for 123478-HxCDD of 14.8 ppt, 123678-HxCDD of 156.4 ppt,123789-HxCDD of 23.7 ppt, 1234678-HpCDD of 234.6 ppt, and OCDD of 2,778.2 ppt significantly higher (p<0.05) than the reference group levels for the same congeners of 7.5, 71.8, 8.0, 67.5, and 483.2 ppt, respectively. While we did find 12378-PeCDD levels higher than the reference group in trichlorophenol and pentachlorophenol workers, the differences are small, and could be attributed to normal variation. All furan levels among the trichlorophenol or pentachlorophenol only workers were not significantly different than the reference group. Workers with both trichlorophenol and pentachlorophenol exposures had mean dioxin levels consistent with complex chlorophenol exposures. Tradesmen who worked throughout the plant had congener profiles consistent with both trichlorophenol and pentachlorophenol exposures. PCB 169, 23478-PeCDF, 123478-HxCDF, and 123678-HxCDF levels were also significantly greater (p<0.05) in these tradesmen than in the reference group. We found distinct patterns of dioxin congeners many years after exposure among workers with different chlorophenol exposures. We were effectively able to distinguish past trichlorophenol exposures from pentachlorophenol exposures based on differing serum dioxin profiles among workers.

A sulphur and uranium fiesta! Synthesis, structure, and characterization of neutral terminal uranium(vi) monosulphide, uranium(vi) η2-disulphide, and uranium(iv) phosphine sulphide complexes.

Three new uranium species (C5Me5)2U([double bond, length as m-dash]N-2,6-iPr2-C6H3)([double bond, length as m-dash]S), (C5Me5)2U([double bond, length as m-dash]N-2,6-iPr2-C6H3)(η2-S2), and (C5Me5)2U([double bond, length as m-dash]N-2,6-iPr2-C6H3)(S[double bond, length as m-dash]PMe3) were synthesized and fully characterized by a combination of NMR, IR, and UV/vis-NIR spectroscopies, elemental analysis, and cyclic voltammetry. The solid state structures of (C5Me5)2U([double bond, length as m-dash]N-2,6-iPr2-C6H3)([double bond, length as m-dash]S) and (C5Me5)2U([double bond, length as m-dash]N-2,6-iPr2-C6H3)(η2-S2) were also determined. The compound (C5Me5)2U([double bond, length as m-dash]N-2,6-iPr2-C6H3)([double bond, length as m-dash]S) is the first neutral uranium complex with a terminal sulphido ligand, and (C5Me5)2U([double bond, length as m-dash]N-2,6-iPr2-C6H3)(S[double bond, length as m-dash]PMe3) is the first uranium compound with a coordinated phosphine sulphide ligand. The phosphine sulphide adduct, (C5Me5)2U([double bond, length as m-dash]N-2,6-iPr2-C6H3)(S[double bond, length as m-dash]PMe3), can be synthesized either by reaction of the uranium(iv) complex (C5Me5)2U([double bond, length as m-dash]N-2,6-iPr2-C6H3)(thf) with S[double bond, length as m-dash]PMe3 or by the reaction of the uranium(vi) terminal sulphido complex (C5Me5)2U([double bond, length as m-dash]N-2,6-iPr2-C6H3)([double bond, length as m-dash]S) with PMe3.