► We studied 256 men to see if PFOA and PFOS impacted semen quality or hormones. ► Blood and semen were analyzed for PFAs and reproductive and thyroid hormones. ► Semen quality was assessed using ...standard clinical methods. ► Neither PFOA nor PFOS was significantly associated with functional semen parameters. ► LH, but not FSH, was positively correlated with plasma PFOA and PFOS.
A total of 256 men were studied to evaluate whether serum concentrations of perfluorooctanoate (PFOA) and perfluorooctane sulfonate (PFOS) impacted semen quality or reproductive hormones. Blood and semen were collected and analyzed for perfluorochemicals and reproductive and thyroid hormones. Semen quality was assessed using standard clinical methods. Linear and logistic modeling was performed with semen profile measurements as outcomes and PFOS and PFOA in semen and plasma as explanatory variables. Adjusting for age, abstinence, and tobacco use, there was no indication that PFOA or PFOS was significantly associated with volume, sperm concentration, percent motility, swim-up motility and concentration, and directional motility (a function of motility and modal progression). Follicle-stimulating hormone was not associated with either PFOA or PFOS. Luteinizing hormone was positively correlated with plasma PFOA and PFOS, but not semen PFOS. Important methodological concerns included the lack of multiple hormonal measurements necessary to address circadian rhythms.
A total of 331 different VOCs and fixed gases from swine facilities in North Carolina were identified by gas chromatography and mass spectrometry (GC/MS). Of these, 203 were found in air samples ...adsorbed onto Tenax
®, 112 were found in air samples adsorbed onto cotton material, and 167 different compounds were identified in the lagoon samples. The compounds identified were diverse, and included many acids, alcohols, aldehydes, amides, amines, aromatics, esters, ethers, fixed gases, halogenated hydrocarbons, hydrocarbons, ketones, nitriles, other nitrogen-containing compounds, phenols, sulfur-containing compounds, steroids, and other compounds. The vast majority of these compounds were present at concentrations below published odor and irritation thresholds. Yet human assessments indicated that odors (and irritant sensations) in the immediate vicinity of the swine houses (and even at distances beyond 1000
ft) were strong. Comparison of the findings from chemical and human assessments points to the importance of the cumulative effects of hundreds of compounds in producing odor and irritation downwind of swine operations. Many GC peaks from the samples were too small to allow identification of the compounds, but their presence may also contribute significantly to the odor and irritation. Several methodological difficulties were associated with the human odor assessments. Odorous air evaluated in the field was simultaneously collected in Tedlar
® bags for evaluation in the laboratory; however, intensity ratings in the field were higher than those in the laboratory. This is due to the fact that organic dust (dried fecal material and feed) adheres to Tedlar
® bags and the tubing of collection/delivery systems; therefore, only VOCs from the vapor phase (but not the dust) reach the nose of the panelists in sniffing air samples obtained in Tedlar
® bags. Future collection and measurement techniques need to be developed that can evaluate odors from dust and vapor phases simultaneously in the laboratory. Dispersion models also need to be developed that account accurately for odor intensities downwind of animal operations. Finally, safety standards for odor exposures need to be determined that consider the risk of simultaneous exposure to hundreds of low level compounds.
A subset of private pesticide applicators in the Agricultural Health Study (AHS) epidemiological cohort was monitored around the time of their agricultural use of 2,4-dichlorophenoxyacetic acid ...(2,4-D) and O,O-diethyl-O-3,5,6-trichloro-2-pyridyl phosphorothioate (chlorpyrifos) to assess exposure levels and potential determinants of exposure. Measurements included pre- and post-application urine samples, and patch, hand wipe, and personal air samples. Boom spray or hand spray application methods were used by applicators for 2,4-D products. Chlorpyrifos products were applied using spray applications and in-furrow application of granular products. Geometric mean (GM) values for 69 2,4-D applicators were 7.8 and 25 microg/l in pre- and post-application urine, respectively (P<0.05 for difference); 0.39 mg for estimated hand loading; 2.9 mg for estimated body loading; and 0.37 microg/m(3) for concentration in personal air. Significant correlations were found between all media for 2,4-D. GM values for 17 chlorpyrifos applicators were 11 microg/l in both pre- and post-application urine for the 3,5,6-trichloro-2-pyridinol metabolite, 0.28 mg for body loading, and 0.49 microg/m(3) for air concentration. Only 53% of the chlorpyrifos applicators had measurable hand loading results; their median hand loading being 0.02 mg. Factors associated with differences in 2,4-D measurements included application method and glove use, and, for hand spray applicators, use of adjuvants, equipment repair, duration of use, and contact with treated vegetation. Spray applications of liquid chlorpyrifos products were associated with higher measurements than in-furrow granular product applications. This study provides information on exposures and possible exposure determinants for several application methods commonly used by farmers in the cohort and will provide information to assess and refine exposure classification in the AHS. Results may also be of use in pesticide safety education for reducing exposures to pesticide applicators.
The recent emergence of an apparently new form of chronic kidney disease of unknown aetiology (CKDu) has become a serious public health crisis in Sri Lanka. CKDu is slowly progressive, irreversible, ...and asymptomatic until late stages, and is not attributable to hypertension, diabetes, or other known aetiologies. In response to the scope and severity of the emerging CKDu health crisis, the Sri Lanka Ministry of Health and the World Health Organization initiated a collaborative research project from 2009 through 2012 to investigate CKDu prevalence and aetiology. The objective of this paper is to discuss the recently published findings of this investigation and present additional considerations and recommendations that may enhance subsequent investigations designed to identify and understand CKDu risk factors in Sri Lanka or other countries.
Polybrominated diphenyl ethers (PBDEs) are used commercially as additive flame retardants and have been shown to transfer into environmental compartments, where they have the potential to ...bioaccumulate in wildlife and humans. Of the 209 possible PBDEs, 2,2′,4,4′-tetrabromodiphenyl ether (BDE-47) is usually the dominant congener found in human blood and milk samples. BDE-47 has been shown to have endocrine activity and produce developmental, reproductive, and neurotoxic effects. The objective of this study was to develop a physiologically based pharmacokinetic (PBPK) model for BDE-47 in male and female (pregnant and non-pregnant) adult rats to facilitate investigations of developmental exposure. This model consists of eight compartments: liver, brain, adipose tissue, kidney, placenta, fetus, blood, and the rest of the body. Concentrations of BDE-47 from the literature and from maternal–fetal pharmacokinetic studies conducted at RTI International were used to parameterize and evaluate the model. The results showed that the model simulated BDE-47 tissue concentrations in adult male, maternal, and fetal compartments within the standard deviations of the experimental data. The model's ability to estimate BDE-47 concentrations in the fetus after maternal exposure will be useful to design in utero exposure/effect studies. This PBPK model is the first one designed for any PBDE pharmaco/toxicokinetic description. The next steps will be to expand this model to simulate BDE-47 pharmacokinetics and distributions across species (mice), and then extrapolate it to humans. After mouse and human model development, additional PBDE congeners will be incorporated into the model and simulated as a mixture.
Several sample preparation techniques were investigated to maximize the efficiency of arsenic species extraction from food composites. The optimized method includes lyophilization of food followed by ...prewashing with acetone and extraction by sonication with 50/50 methanol/water. Six arsenic species were separated and quantitated using an ammonium carbonate buffer system by ion exchange chromatography coupled to inductively coupled plasma mass spectrometry. The performance of the method for speciated arsenic components was evaluated using a matrix containing high fat food composite fortified with arsenic species. A certified reference material, dogfish muscle, was used to evaluate extraction methods for total arsenic content in food composites. More than 200 food composite samples were analyzed during an 18 month period, demonstrating the reliability of the analytical method over a long time period. Keywords: Food; extraction; ion chromatography; liquid chromatography; plasma mass spectrometry; arsenic speciation; IC-ICP-MS
Six arsenic species arsenate, arsenite, arsenocholine, arsenobetaine, monomethyl arsonic acid, and dimethyl arsinic acid present in human urine were determined using ion-exchange chromatography ...combined with inductively coupled plasma mass spectrometry (IC-ICP-MS). Baseline separation was achieved for all six species as well as for the internal standard (potassium hexahydroxy antimonate V) in a single chromatographic run of less than 30 min, using an ammonium carbonate buffer gradient (between 10 and 50 mM) at ambient temperature, in conjunction with cation- and anion-exchange columns in series. The performance of the method was evaluated with respect to linearity, precision, accuracy, and detection limits. This method was applied to determine the concentration of these six arsenic species in human urine samples (n = 251) collected from a population-based exposure assessment survey. Method precision was demonstrated by the analysis of duplicate samples that were prepared over a 2-year analysis period. Total arsenic was also determined for the urine samples using flow injection analysis coupled to ICP-MS. The summed concentration of the arsenic species was compared with the measured arsenic total to demonstrate mass balance.
Celotno besedilo
Dostopno za:
BFBNIB, DOBA, IZUM, KILJ, NMLJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Complaints of health symptoms from ambient odors have become more frequent in communities with confined animal facilities, wastewater treatment plants, and biosolids recycling operations.
The most ...frequently reported health complaints include eye, nose, and throat irritation, headache, nausea, diarrhea, hoarseness, sore throat, cough, chest tightness, nasal congestion, palpitations, shortness of breath, stress, drowsiness, and alterations in mood. Typically, these symptoms occur at the time of exposure and remit after a short period of time. However, for sensitive individuals such as asthmatic patients, exposure to odors may induce health symptoms that persist for longer periods of time as well as aggravate existing medical conditions. A workshop was held at Duke University on April 16-17, 1998 cosponsored by Duke University, the Environmental Protection Agency (EPA), and National Institute on Deafness and Other Communication Disorders (NIDCD) to assess the current state of knowledge regarding the health effects of ambient odors. This report summarizes the conclusions from the Workshop regarding the potential mechanisms responsible for health symptoms from ambient odors. Methods for validation of health symptoms, presence of odor, and efficacy of odor management techniques are described as well.
Risk assessments often must consider exposures that vary over time or for which the exposure duration of concern differs from the available data, and a variety of extrapolation procedures have been ...devised accordingly. The present experiments explore the relationship(s) between exposure concentration (C) and time (t) to investigate procedures for assessing the risks of short-term solvent exposures. The first hypothesis tested was that the product of C × t would produce a constant health effect (Haber’s rule). The second hypothesis tested was that exposure conditions produce effects in proportion to the tissue concentrations created. Awake, adult, male Long-Evans (LE) rats were exposed to trichloroethylene (TCE) vapor in a head-only exposure chamber while pattern onset/offset visual evoked potentials (VEPs) were recorded. Exposure conditions were designed to provide C × t products of 0 ppm/h (0 ppm for 4 h) or 4000 ppm/h created through four exposure scenarios: 1000 ppm for 4 h; 2000 ppm for 2 h; 3000 ppm for 1.3 h; or 4000 ppm for 1h (n = 9–10/concentration). The amplitude of the VEP frequency double component (F2) was decreased significantly by exposure; this decrease was related to C but not to t or to the C × t product, indicating that Haber’s rule did not hold. The mean amplitude (± SEM in μV) of the F2 component in the control and treatment groups measured 4.4 ± 0.5 (0 ppm/4 h), 3.1 ± 0.5 (1000 ppm/4 h), 3.1 ± 0.4 (2000 ppm/2 h), 2.3 ± 0.3 (3000 ppm/1.3 h), and 1.9 ± 0.4 (4000 ppm/1 h). A physiologically based pharmacokinetic (PBPK) model was used to estimate the concentrations of TCE in the brain achieved during each exposure condition. The F2 amplitude of the VEP decreased monotonically as a function of the estimated peak brain concentration but was not related to the area under the curve (AUC) of the brain TCE concentration. In comparison to estimates from the PBPK model, extrapolations based on Haber’s rule yielded approximately a 6-fold error in estimated exposure duration when extrapolating across only a 4-fold change in exposure concentration. These results indicate that the use of a linear form of Haber’s rule will not predict accurately the risks of acute exposure to TCE, nor will an estimate of AUC of brain TCE. However, an estimate of the brain TCE concentration at the time of VEP testing predicted the effects of TCE across exposure concentrations and durations.
The effect of trans-1,2-dichloroethylene (DCE), an inhibitor of cytochrome P450 (P450) 2E1, on the catalytic activities and total content of hepatic P450 was determined in vivo and in vitro. Hepatic ...microsomes were prepared from groups of rats prior to dosing and at 2, 5, 12, and 24 h postdosing, and total P450 content and the activities of P450 1A2, P450 2A1, P450 2B, P450 2C6, P450 2C11, P450 2D1, P450 2E1, and P450 3A were determined. The lowest dose of DCE that yielded maximal inactivation of P450 2E1 was found to be 100 mg/kg. Significant decreases in total content of P450 or the activities of P450 1A2, P450 2A1, P450 2B, P450 2C6, P450 2C11, P450 2D1, and P450 3A were not observed during the 24 h following administration of DCE (100 mg/kg ip), but P450 2E1 activity was diminished about 65% at 2 and 5 h after DCE treatment and returned to control levels at 24 h. Additionally, there was little or no significant effect on the activities of hepatic cytosolic alcohol dehydrogenase or mitochondrial or microsomal aldehyde dehydrogenases 5 h postdosing. DCE showed the same selectivity for P450 inactivation in vitro, and P450 2E1 activity was inhibited by >80% without affecting the other isozymes. However, DCE (5 mM) also proved to be a good competitive inhibitor of the probe activities of P450 1A2 and P450 2C6. The in vivo inhibition of P450 2E1 was accompanied by decreases in the levels of the immunoreactive protein, and an additional immunoreactive band appeared at ca. 30 kDa in the Western blot of microsomes from DCE-treated rats, possibly arising from proteolytic degradation of P450 2E1 protein after covalent modification by the inhibitor. DCE is an effective, relatively nontoxic inhibitor of P450 2E1 in vivo and in vitro that has greater selectivity than other agents currently used.
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