Characterization of Organophosphate Pesticides in Urine and Home Environment Dust in an Agricultural Community

Thesis (Master's)--University of Washington, 2016-06

Influence of body iron store status and cigarette smoking on cadmium body burden of healthy Thai women and men

The influence of cigarette smoking, body iron store status and gender on cadmium (Cd) body burden was examined in a group of 197 healthy Thais with overall mean age of 30.5 year (19-47 year). The lowest, geometric mean, and the highest urinary Cd excretion rate was 0.04, 0.46 and 3.84 mug/g creatinine, respectively. The prevalence of low iron stores (serum ferritin

Parental occupation and Ewing's sarcoma: Pooled and meta-analysis

Etiologic data on Ewing's sarcoma family of tumors (ESFT) are limited, with only 5 case-control studies reported. Interesting associations, particularly related to parental occupation, have been noted, but results are somewhat inconsistent. We conducted a pooled analysis of 3 case-control studies to assess the overall associations between parental occupation and ESFT. The pooled analysis provided data on parental occupational exposure on 199 cases of ESFT and 1,451 controls. The pooled odds ratio for the periconception and gestation periods were 2.3 (95% CI = 1.3-4.1) for children whose fathers had worked on farms and 3.9 (95% CI 1.6-9.9) for those whose mothers had farmed. For the periconception and gestation periods, there was a 3.5-fold increased risk for those with both parents having farmed and a doubling of risk for those with at least one parent having farmed; pattern of increasing risk with increasing number of years of postnatal parental exposure to farms was seen. No other occupational group (or more narrowly defined occupations) had other than minor inconsistent associations with the occurrence of ESFT. In addition, we conducted a meta-analysis of farm occupation (a main risk factor) including all 4 case-control studies that collected required information to consider parental occupation. Results of the meta-analysis were consistent with those from the pooled analysis. This collaborative analysis of available individual data on parental occupation and ESFT in the offspring provides evidence supporting the hypothesis of an association between ESFT and parental occupation in farming. © 2005 Wiley-Liss, Inc.

Genotoxicity of inorganic lead salts and disturbance of microtubule function

Lead compounds are known genotoxicants, principally affecting the integrity of chromosomes. Lead chloride and lead acetate induced concentration-dependent increases in micronucleus frequency in V79 cells, starting at 1.1 μ M lead chloride and 0.05 μ M lead acetate. The difference between the lead salts, which was expected based on their relative abilities to form complex acetato-cations, was confirmed in an independent experiment. CREST analyses of the micronuclei verified that lead chloride and acetate were predominantly aneugenic (CREST-positive response), which was consistent with the morphology of the micronuclei (larger micronuclei, compared with micronuclei induced by a clastogenic mechanism). The effects of high concentrations of lead salts on the microtubule network of V79 cells were also examined using immunofluorescence staining. The dose effects of these responses were consistent with the cytotoxicity of lead(II), as visualized in the neutral-red uptake assay. In a cell-free system, 20-60 μ M lead salts inhibited tubulin assembly dose-dependently. The no-observed-effect concentration of lead(II) in this assay was 10 μ M. This inhibitory effect was interpreted as a shift of the assembly/disassembly steady-state toward disassembly, e.g., by reducing the concentration of assembly-competent tubulin dimers. The effects of lead salts on microtubule-associated motor-protein functions were studied using a kinesin-gliding assay that mimics intracellular transport processes in vitro by quantifying the movement of paclitaxel-stabilized microtubules across a kinesin-coated glass surface. There was a dose-dependent effect of lead nitrate on microtubule motility. Lead nitrate affected the gliding velocities of microtubules starting at concentrations above 10 μ M and reached half-maximal inhibition of motility at about 50 μ M. The processes reported here point to relevant interactions of lead with tubulin and kinesin at low dose levels. Environ. Mal. Mutagen. 45:346-353, 2005. © 2005 Wiley-Liss, Inc.

Cadmium-induced nephropathy in the development of high blood pressure

In recognition of a central role of the kidney in long-term blood pressure control, we undertook an in-depth analysis of the relationship between blood pressure and kidney damage caused by environmental exposure to the common pollutants cadmium and lead. The subjects were 200 healthy Thais, 16 and 60 years of age (100 female non-smokers, 53 male non-smokers, and 47 male smokers). None of these subjects had been exposed to Cd or Pb in the workplace and their urinary Cd concentrations ranged from 0.4 to 37 nM, whereas their urinary Pb concentrations ranged from 0.1 to 30 nM. The prevalence of high blood pressure was 2%, 8% and 19%, respectively in subjects with low, average and high Cd-burden (linear trend chi(2) = 6.4, P = 0.01). Multiple regression analysis revealed a significant positive association between Cd-burden and blood pressure in male nonsmokers (adjusted beta = 0.31, P = 0.02) and an inverse association between blood pressure and urinary Pb excretion rate in male smokers (adjusted beta = -0.38, P = 0.005). Associations between Cd-burden and nephropathies were evidenced by increases in urinary excretion of beta 2-microglobutin (P = 0.02) and N-acetyl-beta-D-glucosaminidase (P = 0.005) in subjects with high Cd-burden, compared with the subjects with average Cd-burden. In addition, an association between Cd-related nephropathy and high blood pressure was evidenced by a 20% increase in the prevalence of high blood pressure in people with NAG-uria (linear trend chi(2) = 4.3, P = 0.04). Our present study provides first evidence for a possible link between renal tubular damage and dysfunction caused by environmental Cd exposure and increased risk of high blood pressure. (c) 2005 Elsevier Ireland Ltd. All rights reserved.

Dosing of gentamicin in patients with end-stage renal disease receiving hemodialysis

The aim of this study was to evaluate dosing schedules of gentamicin in patients with end-stage renal disease and receiving hemodialysis. Forty-six patients were recruited who received gentamicin while on hemodialysis. Each patient provided approximately 4 blood samples at various times before and after dialysis for analysis of plasma gentamicin concentrations. A population pharmacokinetic model was constructed using NONMEM (version 5). The clearance of gentamicin during dialysis was 4.69 L/h and between dialysis was 0.453 L/h. The clearance between dialysis was best described by residual creatinine clearance (as calculated using the Cockcroft and Gault equation), which probably reflects both lean mass and residual clearance mechanisms. Simulation from the final population model showed that predialysis dosing has a higher probability of achieving target maximum concentration (C-max) concentrations (> 8 mg/L) within acceptable exposure limits (area under the concentration-time curve [AUC] values > 70 and < 120 mg.h/L per 24 hours) than postdialysis dosing.

Asma, abitudini e stile di vita "Analisi retrospettiva di un campione di pazienti asmatici seguito in ambulatorio di terzo livello"

Growing evidence suggest the importance of different environments in promoting the pathogenesis and/or exacerbation of asthma. Indoor air pollution is a major contributor to human exposure, since people spend up to 90% of their day indoors. Apart from active smoking, indoor pollution is considered one of the major preventable risk factors of chronic respiratory diseases. The professional activity can also be dangerous because it exposes the subject to environments that can promote the onset of asthma or worsening of the latter in those already affected. Even bad habits such as incorrect diet, lead to more difficulty in controlling their disease. However asthma is a multifactorial disease in nature so it is not easy to distinguish the role of occupational exposure, pollution and normal habits such as smoking, nutrition, sports, etc. This retrospective study was conducted on a sample of asthma patients residing in the metropolitan area of Parma. 116 patients were selected among those who are followed up at least two years at the Asthma outpatient Clinic of Parma University Hospital. The sample in question is therefore closely controlled and monitored; it comes to patients who are well educated on the control of their disease, are able to take appropriate measures to minimize the symptomatology. With this tight approach is proposed to minimize the effect of confounding and then traced with greater certainty the possible cause of the failure to control the disease. For this purpose, each patient was subjected to regular checkups; we took as a reference the period of time between April and October 2015. During each visit, in addition to general data for each patient, we were collected personal information about their habits and way of life through a validated questionnaire delivered and completed by the patient during the visit in the presence of the permanent staff. The questionnaire covers mainly the qualification of the patient, its possible occupational exposure, his home, with information about nearby traffic, time spent outside, physical activity (place and time), exposure to chemicals, exposure to various fumes (fireplace or stove) and cigarette smoke, comorbidities and any drugs taken during the visits considered. Regarding the respiratory conditions of patients during every examination we were considered: Asthma Control Test (a test performed by patients to assess the state of the disease during the month preceding the test), the measurement of exhaled nitric oxide (FeNO) as an index of airways inflammation, measuring the resistance level of small airways (R5-R20) and some spirometric values observed in experiment; in particular the forced vital capacity (FVC), forced expiratory volume in the first second (FEV 1), FEV1/FVC ratio, forced expiratory flow rate over the middle 50% of the FVC (FEF25–75) and FEF25-75/FVC were recorded. The sample has been studied considering both the changes of the respiratory parameters for every patient in their examinations, and the respiratory parameters of all the examinations took as a whole in relation with the variables considered. From the results obtained, the patients are clinically stable; their adopted lifestyle and the exposure to possible sources of outdoor pollution, seems not affect the overall control of their disease. Some findings of our study are of interest. First, the subjects who carry a steroid therapy show a clinical worst, as revealed by the decrease of most spirometric indices, particularly FEF25, FEF75, FEF25-75 and R5-R20; also, the presence of comorbidities and the subsequent intake of other drugs, in addition to normal therapy for asthma, seem to be conditions associated with poorer performance in the functional respiratory parameters in particular FEV1/FVC, FEF75 and FEF25-75. Spirometric indexes that are down are mainly those related to obstruction imposed on small airways; this suggests a neglect to the latter on the contrary should be further explored and treated accordingly. It is also observed that both patients are overweight than those living on the lower floors and/or who have the most windows exposed to traffic, showed a decrease of pulmonary function, especially those relate to an obstruction at the small airways level. In conclusion, our results provided the evidence that a most appropriate therapy, specific to reach the small airways, associated with a healthy lifestyle, can help improve the management of asthma.

Cadmium in the environment and high risk population groups

Cadmium has been widely used in various industries for the past fifty years, with current world production standing at around 16,755 tonnes per year. Very little cadmium is ever recycled and the ultimate fate of all cadmium is the environment. In view of reports that cadmium in the environment is increasing, this thesis aims to identify population groups 'at risk' of receiving dietary intakes of cadmium up to or above the current Food and Agricultural Organisation/World Health Organisation maximum tolerable intake of 70 ug/day. The study involves the investigation of one hundred households (260 individuals) who grow a large proportion of their vegetable diet in garden soils in the Borough of Walsall, part of an urban/industrial area in the United Kingdom. Measurements were made of the cadmium levels in atmospheric deposition, soil, house dust, diet and urine from the participants. Atmospheric deposition of cadmium was found to be comparable with other urban/industrial areas in the European Community, with deposition rates as high as 209 g ha-1 yr-1. The garden soils of the study households were found to contain up to 33 mg kg-1 total cadmium, eleven times the highest level usually found in agricultural soils. Dietary intakes of cadmium by the residents from food were calculated to be as high as 68 ug/day. It is suggested that with intakes from other sources, such as air, adventitious ingestion, smoking and occupational exposure, total intakes of cadmium may reach or exceed the FAO/WHO limit. Urinary excretion of cadmium amongst a non-smoking, non-occupationally exposed sub-group of the study population was found to be significantly higher than that of a similar urban population who did not rely on home-produced vegetables. The results from this research indicate that present levels of cadmium in urban/industrial areas can increase dietary intakes and body burdens of cadmium. As cadmium serves no useful biological function and has been found to be highly toxic, it is recommended that policy measures to reduce human exposure on the European scale be considered.

Caracterização do material particulado e avaliação do risco ocupacional e mecanismos moleculares associados à queima artesanal da castanha de caju

Brazil is among the largest cashew nut producers of the world. However, the roasting process is still carried out artisanally, especially in the Brazilian semiarid region. In face of this occupational problem, the aim of this study was to perform a physical-chemical characterization of the particulate matter (PM) emitted by the roasting of cashew nuts, as well as to determine the occupational risk and molecular mechanisms associated. The most evident PM characteristics were the prevalence of fine particles, typical biomass burning morphologies such as tar ball and the presence of the elements K, Cl, S, Ca and Fe. In addition, atmospheric modeling analyses suggest that these particles can reach neighboring regions of the emission source. Polycyclic aromatic hydrocarbons (PAHs) with carcinogenic potential, such as benzo[a]pyrene, dibenz[a,h]anthracene, benzo[a]anthracene, benzo[b]fluoranthene, chrysene, benzo[k]fluoranthene, indeno[1,2,3-c,d]pyrene and benzo[j]fluoranthene were the most abundant PAHs found in the two air monitoring campaigns. Among the identified oxy-PAH the benzanthrone (7H-benz[d,e]anthracen-7-one) had the highest concentration and the evaluation of lifetime cancer risk showed an increase of 12 to 37 cases of cancer for every 10,000 exposed people. Chemical analysis of roasted cashew nuts identified the PAHs: phenanthrene, benzo[g,h,i]perylene, pyrene and benzo[a]pyrene, besides the 3-pentadecilfenol allergen (urushiol analogue) as prevalent. Occupational exposure to PAHs was confirmed by the increase of urinary 1-hydroxypyrene levels and genotoxic effects were evidenced by the increase on micronuclei and nuclear bud frequency in exfoliated buccal mucosa cells among the exposed workers. Other biomarkers of effects such as karyorrhexis, pyknotic, karyolytic, condensed chromatin and binucleated cells also have their frequencies increased when compared to an unexposed control group. The investigation of the molecular mechanisms associated with the PM organic extract showed cytotoxicity in human lung cell lines (A549) at concentrations ≥ 4 nM BaPeq. Using non-cytotoxic doses the extract was able to activate proteins involved in the DNA damage response pathway (Chk1 and p53). Moreover, the specific contribution of the four most representative PAHs in the cashew nut roasting sample showed that benzo[a]pyrene was the most efficient to activate Chk1 and p53. Finally, the organic extract was able to increase persistently the mRNA expression involved in the PAHs metabolism (CYP1A1 and CYP1B1), inflammatory response (IL-8 and TNF-α) and cell cycle arrest (CDKN1A) for DNA repair (DDB2). The high PM concentrations and its biological effects associated warn of the serious harmful effects of artisanal cashew nut roasting and urgent actions should be taken to the sustainable development of this activity.

Caracterização do material particulado e avaliação do risco ocupacional e mecanismos moleculares associados à queima artesanal da castanha de caju

Brazil is among the largest cashew nut producers of the world. However, the roasting process is still carried out artisanally, especially in the Brazilian semiarid region. In face of this occupational problem, the aim of this study was to perform a physical-chemical characterization of the particulate matter (PM) emitted by the roasting of cashew nuts, as well as to determine the occupational risk and molecular mechanisms associated. The most evident PM characteristics were the prevalence of fine particles, typical biomass burning morphologies such as tar ball and the presence of the elements K, Cl, S, Ca and Fe. In addition, atmospheric modeling analyses suggest that these particles can reach neighboring regions of the emission source. Polycyclic aromatic hydrocarbons (PAHs) with carcinogenic potential, such as benzo[a]pyrene, dibenz[a,h]anthracene, benzo[a]anthracene, benzo[b]fluoranthene, chrysene, benzo[k]fluoranthene, indeno[1,2,3-c,d]pyrene and benzo[j]fluoranthene were the most abundant PAHs found in the two air monitoring campaigns. Among the identified oxy-PAH the benzanthrone (7H-benz[d,e]anthracen-7-one) had the highest concentration and the evaluation of lifetime cancer risk showed an increase of 12 to 37 cases of cancer for every 10,000 exposed people. Chemical analysis of roasted cashew nuts identified the PAHs: phenanthrene, benzo[g,h,i]perylene, pyrene and benzo[a]pyrene, besides the 3-pentadecilfenol allergen (urushiol analogue) as prevalent. Occupational exposure to PAHs was confirmed by the increase of urinary 1-hydroxypyrene levels and genotoxic effects were evidenced by the increase on micronuclei and nuclear bud frequency in exfoliated buccal mucosa cells among the exposed workers. Other biomarkers of effects such as karyorrhexis, pyknotic, karyolytic, condensed chromatin and binucleated cells also have their frequencies increased when compared to an unexposed control group. The investigation of the molecular mechanisms associated with the PM organic extract showed cytotoxicity in human lung cell lines (A549) at concentrations ≥ 4 nM BaPeq. Using non-cytotoxic doses the extract was able to activate proteins involved in the DNA damage response pathway (Chk1 and p53). Moreover, the specific contribution of the four most representative PAHs in the cashew nut roasting sample showed that benzo[a]pyrene was the most efficient to activate Chk1 and p53. Finally, the organic extract was able to increase persistently the mRNA expression involved in the PAHs metabolism (CYP1A1 and CYP1B1), inflammatory response (IL-8 and TNF-α) and cell cycle arrest (CDKN1A) for DNA repair (DDB2). The high PM concentrations and its biological effects associated warn of the serious harmful effects of artisanal cashew nut roasting and urgent actions should be taken to the sustainable development of this activity.

Advanced Aerogel Composites for Oil Remediation and Recovery

Oil spills in marine environments often damage marine and coastal life if not remediated rapidly and efficiently. In spite of the strict enforcement of environmental legislations (i.e., Oil Pollution Act 1990) following the Exxon Valdez oil spill (June 1989; the second biggest oil spill in U.S. history), the Macondo well blowout disaster (April 2010) released 18 times more oil. Strikingly, the response methods used to contain and capture spilled oil after both accidents were nearly identical, note that more than two decades separate Exxon Valdez (1989) and Macondo well (2010) accidents.

The goal of this dissertation was to investigate new advanced materials (mechanically strong aerogel composite blankets-Cabot® Thermal Wrap™ (TW) and Aspen Aerogels® Spaceloft® (SL)), and their applications for oil capture and recovery to overcome the current material limitations in oil spill response methods. First, uptake of different solvents and oils were studied to answer the following question: do these blanket aerogel composites have competitive oil uptake compared to state-of-the-art oil sorbents (i.e., polyurethane foam-PUF)? In addition to their competitive mechanical strength (766, 380, 92 kPa for Spaceloft, Thermal Wrap, and PUF, respectively), our results showed that aerogel composites have three critical advantages over PUF: rapid (3-5 min.) and high (more than two times of PUF’s uptake) oil uptake, reusability (over 10 cycles), and oil recoverability (up to 60%) via mechanical extraction. Chemical-specific sorption experiments showed that the dominant uptake mechanism of aerogels is adsorption to the internal surface, with some contribution of absorption into the pore space.

Second, we investigated the potential environmental impacts (energy and chemical burdens) associated with manufacturing, use, and disposal of SL aerogel and PUF to remove the oil (i.e., 1 m3 oil) from a location (i.e., Macondo well). Different use (single and multiple use) and end of life (landfill, incinerator, and waste-to-energy) scenarios were assessed, and our results demonstrated that multiple use, and waste-to-energy choices minimize the energy and material use of SL aerogel. Nevertheless, using SL once and disposing via landfill still offers environmental and cost savings benefits relative to PUF, and so these benefits are preserved irrespective of the oil-spill-response operator choices.

To inform future aerogel manufacture, we investigated the different laboratory-scale aerogel fabrication technologies (rapid supercritical extraction (RSCE), CO2 supercritical extraction (CSCE), alcohol supercritical extraction (ASCE)). Our results from anticipatory LCA for laboratory-scaled aerogel fabrication demonstrated that RSCE method offers lower cumulative energy and ecotoxicity impacts compared to conventional aerogel fabrication methods (CSCE and ASCE).

The final objective of this study was to investigate different surface coating techniques to enhance oil recovery by modifying the existing aerogel surface chemistries to develop chemically responsive materials (switchable hydrophobicity in response to a CO2 stimulus). Our results showed that studied surface coating methods (drop casting, dip coating, and physical vapor deposition) were partially successful to modify surface with CO2 switchable chemical (tributylpentanamidine), likely because of the heterogeneous fiber structure of the aerogel blankets. A possible solution to these non-uniform coatings would be to include switchable chemical as a precursor during the gel preparation to chemically attach the switchable chemical to the pores of the aerogel.

Taken as a whole, the implications of this work are that mechanical deployment and recovery of aerogel composite blankets is a viable oil spill response strategy that can be deployed today. This will ultimately enable better oil uptake without the uptake of water, potential reuse of the collected oil, reduced material and energy burdens compared to competitive sorbents (e.g., PUF), and reduced occupational exposure to oiled sorbents. In addition, sorbent blankets and booms could be deployed in coastal and open-ocean settings, respectively, which was previously impossible.

Influence of serum levels of vitamins A, D, and E as well as vitamin D receptor polymorphisms on micronucleus frequencies and other biomarkers of genotoxicity in workers exposed to formaldehyde

Background/Aim: Formaldehyde is classified as carcinogenic to humans, making it a major concern, particularly in occupational settings. Fat-soluble vitamins, such as vitamins A, D, and E, are documented as antigenotoxic and antimutagenic and also correlate with the cell antioxidant potential. This study investigates the influence of these vitamins on genotoxicity biomarkers of formaldehyde-exposed hospital workers. Methods: The target population were hospital workers exposed to formaldehyde (n = 55). Controls were nonexposed individuals (n = 80). The most used genotoxicity biomarkers were the cytokinesis-block micronucleus assay for lymphocytes and the micronucleus test for exfoliated buccal cells. Vitamins A and E were determined by high-performance liquid chromatography with a diode array detector (HPLC-DAD) and vitamin D receptor (VDR) polymorphisms by real-time PCR. Results: Significant correlations were found between genotoxicity biomarkers and between vitamins A and E in controls. Multiple regression showed that vitamin A was significantly associated with a higher mean of nucleoplasmic bridges (p < 0.001), and vitamin E was significantly associated with a decreased frequency of nuclear buds (p = 0.045) in the exposed group. No effect of vitamin D was observed. The VDRBsmI TT genotype carriers presented higher means of all the genotoxicity biomarkers; however, we found no significant associations. Conclusions: The study suggests that vitamin levels may modulate direct signs of genotoxicity.