Integrated Assessment of Bioconcentration, Toxicity, and Hazards of Chlorobenzenes in the Aquatic Environment.

The evaluation of bioconcentration, toxicity, and hazard (BTH) of persistent lipophilic organic compounds (LOCs) are generally performed as separate rather than integrated assessments. There are adequate data sets in the literature for chlorobenzenes (CBs) consisting of (a) concentrations in aquatic biota (CB) and water (Cw) in the natural environment, (b) laboratory-derived bioconcentration factors (KB) and field concentration ratios (CR), the field equivalent factor of KB, (c) measured internal lethal concentrations (ILC50) and model estimated ILC50 calculated from KB and lethal concentrations (LC50), and (d) calculated hazard quotients in aquatic biota (HQB) and in water (HQW). However, there have been no integrated studies of those parameter values based on the respective lipid-based parameters (CBL, KBL, CRL, ILC50L, HQBL) performed. This study utilized the lipid-based parameters for CBs; a group of widely occuring, bioaccumulative, and toxic LOCs, and integrated those parameters into a bioconcentration-toxicity-hazard (BTHL) index. The values of the parameters were obtained from selected literature with known lipid contents of the aquatic biota. The results showed that the laboratory derived bioconcentration factors, KBLs, were comparable to the corresponding field based factors, CRLs, and the measured internal lethal concentrations, ILC50L, showed comparable values with the estimated ones. The integrated BTHL index was less than an order of magnitude or moderately acceptable for the assessment of variability, uncertainty, and predictive power of the index. This integrated assessment can be used to support decision making dealing with CBs in specific and LOCs in general, both in regional and global aquatic environments.

Accurate measures of changes in regional lung air volumes from chest x-rays of small animals.

Objective. To develop a robust technique for calculating regional volume changes within the lung from x-ray radiograph sequences captured during ventilation, without the use of computed tomography (CT).Approach. This technique is based on the change in transmitted x-ray intensity that occurs for each lung region as air displaces the attenuating lung tissue.Main results. Lung air volumes calculated from x-ray intensity changes showed a strong correlation (R2= 0.98) against the true volumes, measured from high-resolution CT. This correlation enables us to accurately convert projected intensity data into relative changes in lung air volume. We have applied this technique to measure changes in regional lung volumes from x-ray image sequences of mechanically ventilated, recently-deceased newborn rabbits, without the use of CT.Significance. This method is suitable for biomedical research studies,enabling quantitative regional measurement of relative lung air volumes at high temporal resolution, and shows great potential for future clinical application.

Experimental immune complex disease of the lung. The pathogenesis of a laboratory model resembling certain human interstitial lung diseases.

Membranous and/or proliferative pneumonitis, similar in certain features to human interstitial pneumonitis, developed in rabbits making hyperactive antibody response to daily injections of bovine serum albumin (BSA) administered in multiple large doses sufficient to maintain the state of relative antigen-antibody equivalence. The pulmonary lesions were associated with deposition in alveolar capillary walls and interstitium of antigen, host globulin and complement, presumably in immune complexes. In some rabbits chronic interstitial pneumonitis, characterized by thickening of alveolar capillary walls, interstitial fibrosis and deposition of fibrinogen, was observed. The production of immune complex pneumonitis seems to depend on the degree of the antibody response because rabbits developing chronic serum sickness with low doses of BSA, rabbits with acute serum sickness as well as nonresponders showed no pulmonary alterations. This observation is comparable to that described by Dixon in his studies on experimental immune complex glomerulonephritis. It is conceivable that the pulmonary pathology shown here is produced by formation of larger amounts of complexes which may persist longer at critical levels in the circulation than in rabbits immunized with a single daily injection of BSA. In conclusion this study suggests: first, that experimental chronic serum sickness can be used as a model, not only for glomerulonephritis, but also for experimental systemic disease, comparable to human systemic diseases produced by circulating antigen-antibody complexes; and second, that the pathogenesis proposed here offers an alternative to using antilung basement membrane pneumonitis for the experimental approach to the study of human lung immunopathology.

Degradation rate constants of steroids in sewage treatment works and receiving water.

Steroid estrogens are one of the most important groups of endocrine disrupting chemicals (EDCs) which can cause adverse effects on wildlife species and humans. Natural estrogens, including estrone (E1) and estradiol (E2), and synthetic estrogen 17alpha-ethinylestradiol (EE2) together contribute to most of the estrogenic activity in sewage effluents and receiving water. Degradation, particularly aerobic biodegradation was found to be the dominant removal mechanism in these environments. There are a number of factors such as temperature, pH, SRT, HRT and biomass concentration that can affect the rate of biodegradation. This paper reports the results of investigations in to the relationship between the equivalent biomass concentration and degradation rate constants for compounds E1, E2 and EE2 in various environments. It was found that a higher biomass concentration leads to higher rate constants, and relatively good linear correlations (R2 =0.73, 0.79 and 0.73) between the logarithm of the rate constants and the corresponding logarithm equivalent biomass concentration (EBC) values were obtained.

Evaluation of prediagnosis emergency department presentations in patients with active tuberculosis: the role of chest radiography, risk factors and symptoms.

INTRODUCTION: London has a high rate of tuberculosis (TB) with 2572 cases reported in 2014. Cases are more common in non-UK born, alcohol-dependent or homeless patients. The emergency department (ED) presents an opportunity for the diagnosis of TB in these patient groups. This is the first study describing the clinico-radiological characteristics of such attendances in two urban UK hospitals for pulmonary TB (PTB) and extrapulmonary TB (EPTB). METHODS: We conducted a retrospective cohort study using the London TB Register (LTBR) and hospital records to identify patients who presented to two London ED's in the 6 months prior to their ultimate TB diagnosis 2011-2012. RESULTS: 397 TB cases were identified. 39% (154/397) had presented to the ED in the 6 months prior to diagnosis. In the study population, the presence of cough, weight loss, fever and night sweats only had prevalence rates of 40%, 34%, 34% and 21%, respectively. Chest radiography was performed in 76% (117/154) of patients. For cases where a new diagnosis of TB was suspected, 73% (41/56) had an abnormal radiograph, compared with 36% (35/98) of patients where it was not. There was an abnormality on a chest radiograph in 73% (55/75) of PTB cases and also in 40% (21/52) of EPTB cases where a film was requested. CONCLUSIONS: A large proportion of patients with TB present to ED. A diagnosis was more likely in the presence of an abnormal radiograph, suggesting opportunities for earlier diagnosis if risk factors, symptoms and chest radiograph findings are combined.

A preliminary risk assessment of organochlorines accumulated in fish to the Indo-Pacific humpback dolphin (Sousa chinensis) in the Northwestern waters of Hong Kong.

The Indo-Pacific humpback dolphin is considered threatened due to several factors including pollution in Hong Kong and the risks due to consumption of fish tainted with polychlorinated biphenyls (PCBs) and organochlorine pesticides were assessed. Six species of fish Collichthys lucida, Pseudosciaena crocea, Johnius sp., Thryssa sp., Mugil sp. and Trichiurus sp., which comprise the main prey species of humpback dolphins were collected for analyses. Risks due to total PCBs, total TEQs, PCB 118 and the pesticides were assessed with the use of toxicity reference values as the threshold reference benchmarks. The calculated risk quotients (RQs) showed that the risks associated with organochlorines were generally low. The highest RQ was associated with total TEQs suggesting that dioxin-like PCBs may pose the highest risk to the dolphins. The HCHs, total PCBs and heptachlor had comparatively high RQs and thus they should also be the priority organochlorines that would require further investigation.

Trace organic contamination in biota collected from the Pearl River Estuary, China: a preliminary risk assessment.

The marine ecosystem of the Pearl River Delta, located on the southern coast of China, has been heavily exploited following the rapid economic growth that has occurred since the 1980s. This investigation aimed to elucidate trace organic contamination in marine biota inhabiting the Pearl River Delta area. Biota samples, including green-lipped mussels (Perna viridis), oysters (Crassostrea rivularis) and shrimp (Penaeus orientalis) were sampled from 16 stations fringing the Estuary. Elevated concentrations (on a dry weight basis) of polycyclic aromatic hydrocarbons (27.8-1041.0 ng/g), petroleum hydrocarbons (1.7-2345.4 microg/g), polychlorinated biphenyls (2.1-108.8 ng/g), DDTs (1.9-79.0 ng/g), and hexachlorocyclohexanes (n.d.-38.4 ng/g) were recorded. A human health risk assessment was conducted to estimate the risk to local residents associated with the consumption of biota collected from the Pearl River Estuary. The results indicated that PCBs were at levels that may cause deleterious health effects in populations that consume large amounts of seafood. However, it would be instructive to establish health criteria for trace organic contaminants that are specific to the local populations, in order to derive a more accurate and relevant health risk assessment.

Evaluation of serum inflammatory biomarkers as predictors of treatment outcome in pulmonary tuberculosis.

OBJECTIVE: To evaluate C-reactive protein (CRP), globulin and white blood cell (WBC) count as predictors of treatment outcome in pulmonary tuberculosis (PTB). METHODS: An observational study of patients with active PTB was conducted at a tertiary centre. All patients had serum CRP, globulin and WBC measured at baseline and at 2 months following commencement of treatment. The outcome of interest was requirement for extension of treatment beyond 6 months. RESULTS: There were 226 patients included in the study. Serum globulin 45 g/l was the only baseline biomarker evaluated that independently predicted requirement for treatment extension (OR 3.42, 95%CI 1.597.32, P 0.001). An elevated globulin level that failed to normalise at 2 months was also associated with increased requirement for treatment extension (63.9% vs. 5.1%, P 0.001), and had a low negative likelihood ratio (0.07) for exclusion of requirement for treatment extension. On multivariable analysis, an elevated globulin that failed to normalise at 2 months was independently associated with requirement for treatment extension (OR 6.13, 95%CI 2.2316.80, P 0.001). CONCLUSIONS: Serum globulin independently predicts requirement for treatment extension in PTB and outperforms CRP and WBC as a predictive biomarker. Normalisation of globulin at 2 months following treatment commencement is associated with low risk of requirement for treatment extension.

Risks posed by trace organic contaminants in coastal sediments in the Pearl River Delta, China.

Local marine environments in China's Pearl River Delta (PRD), the most rapidly developing region in one of the world's fastest growing economies, have been experiencing significant environmental stress during the past decades. This investigation was conducted to determine the status and trends of persistence organic pollutants (POPs) such as polycyclic aromatic hydrocarbons (PAHs), petroleum hydrocarbons (PHCs), polychlorinated biphenyls (PCBs), organochlorine (OC) pesticides and dioxin-related compounds in marine sediments collected from sixteen coastal stations in the Pearl River Delta (PRD) in March 2003. Elevated concentrations of PAHs (94-4300 ng/g), PCBs (6.0-290 ng/g), PHCs (14-150 microg/g), and DDTs (1.4-600 ng/g) were detected in sediment samples. In addition, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-like activities in the sediment samples were estimated to range from 0.3 to 440 pg TCDD-EQ/g. Sediments collected from Xiashan contained the greatest concentrations of trace organic contaminations amongst all the sampling stations in the present study. The degree of trace organic contamination was, in general, more severe at stations situated along the west shores of the PRD than their counterparts in the east. A preliminary assessment was performed to examine the probable risks to the marine ecosystem due to POPs. The results showed that OC pesticide contamination in the PRD was particularly serious and might pose a threat to the health of the marine inhabitants.

Quantitative structure-activity relationships for nasal pungency thresholds of volatile organic compounds.

A model was developed for describing the triggering of nasal pungency in humans, based on the partition of volatile organic compounds (VOCs) between the air phase and the biophase. Two partition parameters are used in the model: the water-air partition coefficient and the octanol-water partition coefficient. The model was validated using data from the literature, principally on alcohols, acetates and ketones. The model suggests that all test compounds, regardless of their chemical functional groups, bind to a common receptor site within the hydrophobic interior of the bilayer membrane of the trigeminal nerve endings. There is probably only a slight, non-specific interaction between the VOC molecule and the receptor molecule, whereas this type of non-specific interaction for the detection of odor is much stronger. In practical terms, the suggestion that all VOCs share a common irritation receptor site implies that nasal-pungency thresholds of individual VOCs may be additive. Quantitative structure-activity relationships (QSARs) for nasal-pungency thresholds were also developed from the model, which can be used to predict nasal-pungency thresholds of common VOCs. Although the present model does not offer additional precision over that of M.H. Abraham et al., 1996, Fundam. Appl. Toxicol. 31, 71-76, it requires fewer descriptors and offers a physiological basis to the QSAR. Another advantage of the present model is that it also provides a basis for comparison between the olfactory process and nasal pungency.

Comparison of the critical concentration and critical volume hypotheses to model non-specific toxicity of individual compounds.

The critical concentration and critical volume hypotheses for non-specific toxicity require the molar concentration (CC) and volume fraction (VF) of toxicant in target tissue to be constant. Thus these factors should be independent of the octanol-water partition coefficient (Kow) for individual compounds. CC and VF values were calculated based on acute sub-lethal, acute and chronic lethal toxicity data, Kow and pure component molar volume (MV) data. When these values were plotted against log Kow, the slopes of the regression equations were significantly different to zero but were not significantly different from each other. The observed slight increase in CC and VF with increasing log Kow was attributed predominantly, to the use of Kow values which overestimate the target tissue-water partition coefficient (Kow). An additional error associated with the volume fraction calculations was the use of the molar volume instead of partial molar volume. VF and CC values were calculated correcting for both these factors and regressed against log Kow. The resulting equation for VF had a gradient not significantly different from zero, while that for CC was, thus indicating the superiority of the critical volume hypothesis in modelling non-specific toxicity of individual compounds.

Prediction and monitoring of the carcinogenicity of polycyclic aromatic compounds (PACs).

Chemical carcinogenesis is a multistage process that includes initiation, promotion, and progression. Some carcinogenic PACs have been shown to activate proto-oncogenes and deactivate tumor-suppression genes in the carcinogenic process. The function of DNA repair processes appears to be changed in some cases by PACs. Many PACs are well known for their carcinogenic activity, but for this activity to be exerted, metabolic activation by microsomal enzymes must occur. The enzyme system responsible for PAC activation is the mixed-function oxidase system and, in particular, cytochrome P-450. In the case of PAHs, oxidation predominantly produces reactive diol-epoxides that can then be converted to carbonium ions as the reactive electrophiles that can then covalently bind to DNA. Regions of high activity exist in PAHs, namely, the "bay," "K," and "L" regions which are associated with pi electron distribution. The diol-epoxides can exist in either syn or anti forms, each of which has two enantiomers producing four stereoisomers in all. Energy considerations favor the formation of the anti form. Nitrogen-containing PACs can be metabolically activated in a manner similar to that for PAHs, or the nitrogen atom can be oxidized to form hydroxylamines. These reactive electrophiles can then form covalently bound DNA adducts. The monitoring of DNA adducts has been used in risk assessment for human exposure to PACs. This form of biomonitoring has advantages over the monitoring of external exposure or body levels of the chemicals in question. In the case of PACs, binding to DNA is an important step in the multistage carcinogenic process. The estimation of DNA adducts has been used in the monitoring of humans exposed to PAHs in a wide range of industrial situations. Recent research has shown a dose-response relationship between PAH adduct levels and human cancer, thus developing molecular epidemiology as a relevant science for the field of risk assessment. Techniques have been developed for the determination of DNA adducts and these include immunochemical, fluorescence spectroscopic, GC-MS, and 32P-postlabeling methods. The 32P-postlabeling assay is by far the most sensitive, with limits of detection being of the order of one adduct in 10(10) normal nucleotides. The use of HPLC for separation of adducted nucleotides in this postlabeling assay is becoming more common and gives better resolution of adducts than does the TLC technique used in the traditional assay. The detection of adducts on hemoglobin and other proteins has been used as a surrogate for DNA adduct estimation.(ABSTRACT TRUNCATED AT 400 WORDS)

The internal critical level concept of nonspecific toxicity.

The internal lethal concentration (ILC) can be an effective approach in describing the toxicity of a chemical to aquatic organisms that can complement the use of the external toxic concentration characteristic of the LC50. The ILC is an estimate of the toxicant concentration close to the target site and can be estimated from bioconcentration relationships and acute toxicity data. The observed ILC values were found to be consistent for organic compounds exerting the same mode of toxic action. The nonspecific toxicants have the lowest toxicity and the highest ILC values, whereas the chemicals exhibiting specific modes of action have lower concentrations and higher toxicity. There are some reports that the ILC value decreases with increasing exposure periods for various organic chemicals with aquatic organisms. The nonspecific toxicants possibly exhibit their toxic action at the target site by at least two different mechanisms depending on the toxicant concentrations. First, the toxicants bind directly to membrane proteins at relatively low concentrations, resulting in reversible toxic effect. Second, the toxicants inhibit the membrane proteins, and alterations in the lipid bilayers occur at toxicant concentrations sufficient to produce mortality of the organisms. The nonspecific toxicity expressed as acute and chronic toxicity measures are found to correlate well with log Kow. However, the relationship between the ILC and log Kow is less satisfactory because the values of ILC are relatively consistent compared to those of LC50.

Toxicology and risk assessment of freshwater cyanobacterial (blue-green algal) toxins in water.

The occurrence of cyanobacterial toxins affects aquatic organisms, terrestrial animals (both wild and domestic), and humans. Detrimental effects have been documented in the scientific literature during the past 50 years. Possible guideline values of some cyanobacterial toxins (microcystins, cylindrospermopsin, and anatoxin-a) are estimated, and they show that children and infants are more susceptible to cyanobacterial toxins than adults. Therefore, particular attention should be paid when cyanobacterial blooms occur, even at relatively low cell counts, to protect children and infants from possible risks. Based on these guideline values and the occurrence of the toxins, it can be concluded that chronic and subchronic exposure to cyanobacterial toxins does occur in some populations, particularly in developing countries where high proportions of the population consume untreated surface water directly, such as pond, ditch, river, or reservoir water. Because wildlife and domestic animals consume a large amount of untreated water daily, they are at higher risk than humans from cyanobacterial toxins. Calculated guideline values in Section X show that a relatively high risk posed by the toxins to these animals is likely to occur, even at low cell densities.

Risk to breeding success of fish-eating Ardeids due to persistent organic contaminants in Hong Kong: evidence from organochlorine compounds in eggs.

Eggs of two Ardeid species, the Little Egret (Egretta garzetta) and the Black-crowned Night Heron (Nycticorax nycticorax), were collected from two egretries located in the New Territories of Hong Kong with one located near the internationally acclaimed wetland reserve, the Mai Po Marshes, and the other in a remote site (A Chau). The eggs were analysed for organochlorine (OC) compounds including the DDTs, PCBs, hexachlorocyclohexanes (HCHs) and the chlordanes (CHLs). All of the OCs under investigation were detected in the eggs of both species with significantly higher levels in the Little Egret (DDTs, 560-2200; PCBs, 270-1700; CHLs, 81-470 ng g(-1) wet weight) than the Night Heron (DDTs, 210-1200; PCBs, 85-600; CHLs 59-75 ng g(-1) wet weight). The DDTs consisted mainly of DDE with levels ranging from 85% to 95% of the total. The HCHs were at about the same levels in both species (8.4-30 ng g(-1) wet weight). All of the OCs had linear concentration probability distributions on a log-normal basis which were used to evaluate exposure associated with these compounds as part of a probabilistic risk analysis. A linear dose/response relationship for the percentage reduction in the survival of young associated with DDE in eggs was developed. This probabilistic relationship was used to establish the threshold level (1000 ng g(-1) wet weight) at which there was a significant level of reduction in the survival of young above zero and the variability in DDE concentrations at this effect level. Using a threshold level of 1000 ng g(-1), the calculated Risk Quotient (RQ) had a 12.4% probability of RQ exceeding unity with the Night Heron, and 40.9% with the Little Egret. These results indicate that the DDTs in eggs would be expected to be associated with adverse effects on the survival of young of both species, particularly the Little Egret.

Prediction of the partition coefficient of lipophilic compounds in the air-mammal tissue system.

A theoretical bioconcentration model for predicting the air-mammal tissue partition coefficient of lipophilic compounds has been developed. The tissue was considered to consist of three compartments, i.e. lipid, protein and water, in different proportions depending on the tissue considered. The model is based on equilibrium partitioning of the chemicals between the compartments and the atmosphere and requires the octanol-water partition coefficient (K(ow)), Henry's Law Constant (H) and the phase composition of the animal tissue as input information. The model was evaluated using experimental partition coefficients for 19 volatile chlorohydrocarbons and aromatic hydrocarbons. Predicted partition coefficients (Kba) for human blood and olive oil systems are in good agreement with the experimentally determined values. The model gave a lower level of precision with rat blood, rat muscle and rat liver systems and fairly consistently underestimated the experimental values by 22-62%.

Mussel-based monitoring of trace metal and organic contaminants along the east coast of China using Perna viridis and Mytilus edulis.

Green lipped mussels, Perna viridis, and blue mussels, Mytilus edulis, were collected from seven locations along the east coast of China in September and October 2001. The mussel tissues were analyzed for metals (Ag, As, Cd, Cr, Ni, Pb, Se, Zn, Cu, Fe and Hg), and trace organic contaminants including organochlorine compounds (OCs), polycyclic aromatic hydrocarbons (PAHs; based on 24 individual PAHs), polychlorinated biphenyls (PCBs) and petroleum hydrocarbons (PHCs). Maximum concentrations of Ag, As, Cd, Cr, Ni, Pb, Se, Zn, Cu, Fe and Hg in the mussel tissues were 0.14, 26.76, 5.31, 15.72, 4.78, 2.93, 7.40, 231.0, 54.17, 1002 and 317.3 microg/g dry weight respectively. Levels of DDTs, PAHs, PCBs and PHCs in the mussel samples were 14-640, 456-3495, 1-13 ng/g and 621-2863 microg/g dry weight, respectively. Results of this study indicated that contaminant levels were, in general, higher or at least comparable to those reported in other local or regional studies. Mussel samples collected in Chongming Dao in Shanghai and Jiao Zhou Wan in Qingdao had significantly higher levels of metal and trace organic contaminants among the seven sampling stations. Examination of the contaminant profiles suggests that PHCs originated from petrogenic sources, while both petrogenic and pyrolytic sources were important for PAHs. The generally high levels of metals and organochlorine compounds are probably the result of increasingly intense industrial activities along the east coast of China. An assessment of potential risks to human health due to consumption of the mussels was undertaken for the metals, PCBs, DDTs and chlordanes, and the results indicated that all metals, except Ni, could pose a health risk to heavy seafood consumers, while Hg appears to be of concern even for low level consumers.

Internal lethal concentration and internal lethal volume fraction of chlorobenzenes in mosquito fish (Gambusia affinis).

The internal lethal concentration (ILC) and internal lethal volume fraction (ILVF) of a series of chlorobenzenes with mosquito fish (Gambusia affinis) were measured by a semistatic test approach in closed jars. Their variation with exposure times were also investigated with different aqueous chemical concentrations and different exposure periods, the measured ILC values on wet weight and lipid weight bases ranged from 3-12 mmol kg-1 and 46-208 mmol kg-1 lipid, respectively. Measured ILVF values covered a range from 0.008-0.025 (L toxicant L-1 lipid). These values are consistent with those found in literature. Generally ILC and ILVF values decreased with increasing exposure time with rate constants ranging from 0.03 to 0.33 day-1 (wet and lipid weight) for ILC and 0.03 to 0.31 day-1 for ILVF.

Concentrations of persistent lipophilic compounds in fish are determined by exchange across the gills, not through the food chain.

Uptake of persistent lipophilic toxicants in fish occurs via the food and by transfer across the body surface, notably the gills. Flux rates of most lipid soluble toxicants across the gills is rapid and the animal must eat at very high rates for feeding to have a significant effect on toxicant concentration in the body. The relative rates of uptake via feeding and transfer across the gills are analyzed from a theoretical and experimental standpoint. At the low feeding rates typical of fish, the uptake of toxicants in the food can be ignored when estimating toxicant body concentration.