Dose-response Equations Research Articles

Integrating microbial source tracking with quantitative microbial risk assessment to evaluate site specific risk based thresholds at two South Florida beaches.

Quantitative microbial risk assessment (QMRA) can be used to evaluate health risks associated with recreational beach use. This study developed a site-specific risk assessment using a novel approach that combined quantitative PCR-based measurement of microbial source tracking (MST) genetic markers (human, dog, and gull fecal bacteria) with a QMRA analysis of potential pathogen risk. Water samples (n = 24) from two recreational beaches were collected and analyzed for MST markers as part of a broader Beach Exposure And Child Health Study that examined child behavior interactions with the beach environment. We report here the measurements of fecal bacteria MST markers in the environmental DNA extracts of those samples and a QMRA analysis of potential health risks utilizing the results from the MST measurements in the water samples. Human-specific Bacteroides was enumerated by the HF183 Taqman qPCR assay, gull-specific Catellicoccus was enumerated by the Gull2 qPCR assay, and dog-specific Bacteroides was enumerated by the DogBact qPCR assay. Derived reference pathogen doses, calculated from the MST marker concentrations detected in recreational waters, were used to estimate the risk of gastrointestinal illness for both children and adults. Dose-response equations were used to estimate the probability of the risk of infection (Pinf) per a swimming exposure event. Based on the QMRA simulations presented in this study, the GI risk from swimming or playing in water containing a mixture of human and non-human fecal sources appear to be primarily driven by the human fecal source. However, the estimated median GI health risk for both beaches never exceeded the U.S. EPA risk threshold of 32 illnesses per 1,000 recreation events. Our research suggests that utilizing QMRA together with MST can further extend our understanding of potential recreational bather risk by identifying the source contributing the greatest risk in a particular location, therefore informing beach management responses and decision-making.

Weathering of materials at Notre-Dame from changes in air pollution and climate in Paris, 1325–2090

Notre-Dame, as with much historic architecture in Paris, has been exposed to the ravages of changing pollution and climate. Estimates of historic temperature, precipitation and relative humidity and concentrations of key atmospheric pollutants SO2 NO2, O3 and PM10 have been combined with projections under Intergovernmental Panel on Climate Change scenarios RCP2.6 and RCP8.5 to estimate long term soiling, recession and corrosion. The Lipfert function and dose response equations from the International Co-operative Programme on Effects on Materials were used to estimate long-term damage. The picture reveals that the effect of pollution is apparent from around 1700, though it increases notably after 1850; then most pollutant concentrations decreased through the latter half of the 20th century. The soiling predicted for sheltered surfaces follows this trend, although changes in wind direction and washing by rain can also alter the dark and light patterns. Buildings facades are likely to be cleaner over the present century, so we may well be sensitised to other changes that architectural surfaces undergo, e.g. changing patterns and forms of biological growth and parallel changes in colour, especially if surfaces remain wet for substantial periods. In the coming century, decreasing snow fall and longer times of wetness could enhance recession and corrosion rates. While metals in general are likely to corrode less in future compared to the 20th century, some such as copper would be sensitive to any increases in ozone concentrations. Lead used as new roofing for Notre-Dame can be mobilised, increasing heavy metal concentrations in the local environment.

Atmospheric corrosion models

Abstract A number of damage functions or dose-response equation, which are compared to the atmospheric corrosion of metals with environmental parameters, have been determined in field programs ISOCORRAG, UN ECE ICP Materials Exposure Programme and Multi-Assess. The all of these dose-response equations are derived on field exposure results performed during period 1986-1995 where the SO2 level was relative high at urban and very high at industrial test sites. Several exposure programmes, national and international, of structural metals’ atmospheric corrosion were conducted since the 1970s on Czech atmospheric test sites including on-site measurement of environmental data. All data from these exposure programs were compared with prediction models.

Biological Toxicity of Five Metal Ions on Marine Algea

Internationally validated methods (ISO standards) for the determination of toxic effects were used in this study to evaluate the toxicity of metals [i.e. Hg, Cu, Zn, Pb and Cd] to a kind of marine algae, namely Chlorella autotrophica. In the test, the no observable effect concentration (NOEC) and the effective concentration for 50% of test algae (EC50) were obtained after 96-h of incubation at 25±1°C, by comparing the growth of the Chlorella autotrophica in the test samples and in the control. Among the 5 metal ions, mercury (Hg) was found to be the most toxic metal in the test (EC50=1.04 mmol/L), while cadmium (Cd) was the least toxic (EC50=151.37 mmol/L). The results from the Chi-square test of each dose-response equations showed that 96h-EC50s calculated were all precise and credible. According to both NOEC and 96h-EC50, the toxic sequence of these metals from high to low on the inhibition of Chlorella autotrophica’s growth was Hg2+, Cu2+, Zn2+, Pb2+ and Cd2+.

Root growth of Arabidopsis thaliana (L.) Heynh. treated with humic acids isolated from typical soils of Rio de Janeiro state, Brazil

Humic substances isolated from soil organic matter had been used as stimulators of plant metabolism. Arabidopsis thaliana (L.) Heynh. with only five chromosomes, short cycle and size, is an important model to evaluate the physiological effects of these substances, which are qualitatively and quantitatively influenced by morphogenesis, mineralogy and chemistry of soils. The objective of this study was to evaluate the ambience effects on bioactivity of humic acids. A and B horizons of four typical soils of the North Fluminense were sampled. After isolation and purification, humic acids were applied to plants in increasing concentrations. The number and length of lateral roots and main root length were evaluated and, subsequently, the concentrations of maximum stimulation were determined by dose-response curves and regression equations. The results showed that more stable humic acids isolated from soil in less advanced stages of weathering, high activity clay and high base saturation resulted in better physiological stimulants for Arabidopsis.

In vitro characterisation of the antimicrobial activity of selected essential oil components and binary combinations against the pig gut flora

The antimicrobial activity of selected essential oil (EO) components against the major culturable components of the pig gut flora has been characterised by means of an in vitro incubation model simulating the fermentation in different sections of the pig gastrointestinal tract (GIT). In a first study 7 components were screened for their antimicrobial properties. Dose–response equations were established for the 4 components with the highest potential in a second study. Binary combinations were tested as well, and the interaction effects were evaluated following the isobole method. The results of both studies indicated that carvacrol, thymol, eugenol and trans-cinnamaldehyde give opportunities to modulate the flora and fermentation pattern of the GIT of pigs. Eucalyptol, terpinen-4-ol and trans-anethole were found not to have interesting effects on the growth of the pig gut flora. The minimum concentration for carvacrol, thymol, eugenol and trans-cinnamaldehyde in jejunal simulations to reduce the number of total anaerobic bacteria compared to control with a probability of 99.7% was 255, 258, 223 and 56 mg/L respectively. This strong activity of trans-cinnamaldehyde was due to its progressively increasing effect against coliform bacteria; a dose of 104 mg/L gave a reduction of 1 log 10 CFU/mL vs. 371, 400 and 565 mg/L for carvacrol, thymol and eugenol respectively. However, trans-cinnamaldehyde showed clearly less inhibitory activity towards lactobacilli than carvacrol and thymol. Therefore, the use of trans-cinnamaldehyde (for example 100 mg/L) and to a lesser extent eugenol could result in a shift in the microbial ecology in favour of lactic acid producing bacteria and reducing the number of coliform bacteria. Carvacrol and thymol showed very similar and non-selective antimicrobial properties. Their effect was more pronounced in acidic media and demonstrated a rapidly increasing bactericidal effect from a certain concentration on (400–500 mg/L in jejunal simulations). The inhibition of the production of total short chain fatty acids (SCFA) in jejunal simulations by these 4 candidates was related to their effect against coliform bacteria, however they did not alter the lactic acid and ammonia concentrations. Few combinations demonstrated synergism; most mixtures showed zero interaction or antagonism. Carvacrol + thymol (ratio ≥1) was synergistic against total anaerobic bacteria in jejunal simulations, however this effect was rather small. In caecal simulations, carvacrol, thymol and trans-cinnamaldehyde were equally effective while eugenol had an effect only on coliforms. These data on the in vitro antimicrobial activities of EO components give support for a better control of the gastrointestinal bacterial community and the design of alternative growth promoters. Their in vivo potential is also discussed.

In vitro dose–response of carvacrol, thymol, eugenol and trans-cinnamaldehyde and interaction of combinations for the antimicrobial activity against the pig gut flora

Abstract In vitro simulations of the gastric and small intestinal fermentation with varying doses of carvacrol, thymol, eugenol and trans-cinnamaldehyde and binary combinations thereof were carried out to calculate dose–response equations for the antimicrobial effect against the main pig gut flora components. Interaction effects were evaluated following the isobole method. In gastric simulations eugenol and trans-cinnamaldehyde showed clearly less inhibitory activity towards lactobacilli than carvacrol and thymol, which could also be observed in the small intestinal simulations. The minimum concentration for carvacrol, thymol, eugenol and trans-cinnamaldehyde in small intestinal simulations to reduce the number of total anaerobic bacteria compared to control with a probability of 99.7% was 255, 258, 223 and 56 mg/l respectively. This strong activity of trans-cinnamaldehyde was due to its effect against coliform bacteria; a dose of 104 mg/l gave a reduction of 1 log CFU/ml vs. 371, 400 and 565 mg/l for carvacrol, thymol and eugenol respectively. Few combinations demonstrated synergism; most mixtures showed zero interaction or antagonism. Only carvacrol + thymol was slightly synergistic.

Mapping of critical loads and levels for pollution damage to building materials in the United Kingdom

The United Kingdom National Materials Exposure Programme was initiated in 1986 to study the effects of acid deposition on building materials. The output data in the form of empirical dose-response equations (described elsewhere) have been incorporated into a geographical information system (GIS). In addition, data for the stock at risk of building materials has also been used. The dose-response relations indicate a dominance of dry deposition of sulphur dioxide in the decay process. Critical level/load maps have been determined for a number of materials. General pollution and meteorological data sets are also included in the mapping process. Maps give ‘exceedence squares’ on a 20 km square grid basis, indicating the unprotected areas or those still at risk for a given scenario for SO2 reduction in the context of the UNECE protocol for sulphur. In order to derive maps of areas sensitive to pollutants in the future a model, HARM 7.2, is used for the prediction of distribution of emissions of pollutants in the UK. A series of maps has now been produced for different materials at 70% and 80% scenarios for the reduction of SO2. Studies of the sensitivity of the exceedence maps to the accuracy or variation of the components in the dose-response equations have been undertaken. Results from the mapping programme and the sensitivity analysis are presented together with discussion of the concept of critical loads of materials.

Sensitivity of hyperthermia trial outcomes to temperature and time: Implications for thermal goals of treatment

Purpose : In previous work we have found that the cumulative minutes of treatment for which 90% of measured intratumoral temperatures (T 90) exceeded 39.5°C was highly associated with complete response of superficial tumors. Similarly, the cumulative time for which 50% of intratumoral temperatures (T 50) exceeded 41.5°C was highly associated with the presence of > 80% necrosis in soft tissue sarcomas resected after radiotherapy and hyperthermia. In the present work we have calculated the time for isoeffective treatments with T 90 = 43°C and T 50 = 43°C, respectively, using published thermal isoeffective dose formulae. The purpose of these calculations was to determine the sensitivity of treatment outcome to variations in thermal isoeffective dose. Methods and Materials : The basis for the calculations were the thermal parameters and treatment outcomes in three patient populations: 44 patients with moderate or high grade soft tissue sarcoma treated preoperatively with hyperthermia and radiation; 105 patients with superficial tumors treated with hyperthermia and radiation, and 59 patients with deep tumors treated with hyperthermia and radiation. Results : The thermal dose values calculated are strongly associated with outcome in multivariate logistic regression analysis. Simple dose-response equations result from the analysis, and we use these equations to assess the sensitivity of outcome upon variations in thermal dose. This information, in turn, allows us to estimate the number of patients required in Phase II and III trials of hyperthermia and radiation therapy. Conclusions : For regimens of 5 to 10 hyperthermia treatments, improvements in median T 90 (superficial tumors) and T 50 (deep tumors) parameters by 1.2 – 1.5°C could result in response rates high enough (compared to radiotherapy alone) to justify Phase III trials. A similar improvement in response rates would require an increase in overall duration of treatment by a factor of 3 to 5. This would be difficult to achieve while also avoiding thermal tolerance induction. Achieving these temperature goals may be possible with improvements in hyperthermia technology. Alternatively, there may be ways to increase the sensitivity of cells to temperatures that can be achieved currently, such as pH reduction or chemosensitization.

The Comparative Tumorigenic Effects of Fission Neutrons and Cobalt-60 g Rays in the B6CF 1 Mouse

In the period from 1971 to 1986, both sexes of the B6CF1 (C57BL/6 x BALB/c) mouse were exposed at 110 +/- 7 days of age to single, 24 once-weekly or 60 once-weekly doses of fission neutrons or 60Co gamma rays. A small group of males was also exposed to gamma rays for 22 h/day, 5 days/week, for either 23 or 59 weeks, the elapsed times for the 24 and 60 once-weekly series. All mice were followed for their natural lifetimes. A gross pathology report is available on 32,000 animals, and a histopathology record is available on about 19,000. About 85% died with or from one or more neoplastic diseases. The principal tumors observed at death were of lymphoreticular (45-60%), vascular (20%), or pulmonary (35-50%) origin. From 4 to 10% died with fibrosarcomas, hepatocellular tumors, ovarian tumors, and tumors of the Harderian, adrenal, and pituitary glands. Dose-response equations (linear and linear-quadratic) were fitted to the data for deaths from and occurrences of eight different individual or groups of tumors. Equations were constrained through the control intercepts and fitted separately for the two sexes, the two radiation qualities, and all exposure patterns for the two intervals of 600-799 days and 800-999 days from first exposure. RBE values were derived from the ratios of linear coefficients of dose-response curves. RBE values increased as dose was protracted, largely due to the reduced effectiveness of protracted gamma irradiation; however, about 28% of the increase can be attributed to the increase in neutron-induced injury caused by dose protraction. Highest RBE values were seen for tumors of epithelial tissue origin and the lowest for tumors of connective tissue origin. The range for significant values was from about 2 to over 50. Nonneoplastic diseases accounted for about 5% of all deaths, and 10% were classified as from unknown causes. Neither category responded to differences in radiation quality or exposure patterns.

Growth and yield responses of processing tomato ( Lycopersicon esculentum Mill.) cultivars to ozone

Dose-response equations relating exposure to an air pollutant with yield losses in crops are essential elements in economic assessments of the impacts of air pollution on agriculture. However, dose-response equations for some crop species, such as tomato ( Lycopersicon esculentum Mill.), are based upon research with a single cultivar, which may or may not represent the response of the species as a whole. This experiment was conducted to determine the relative susceptibility to yield losses of four cultivars of processing tomato plants exposed to ozone (O 3) and to determine if physiological characteristics of the cultivars could be used to predict cultivar responses to O 3. Four field-grown tomato cultivars were exposed in open-top chambers to charcoal-filtered air (CF), non-filtered air (NF), and NF plus 1.5 times ambient O 3 (NF150) from July to October in Riverside, CA. Results showed that ambient levels of O 3 had relatively little effect on vegetative growth or yields of these tomato cultivars, but that 1.5 times ambient O 3 concentrations reduced yields from 17% in cv. “UC204C” to 54% for cv. “Hybrid 31”. However, the cultivar-by-O 3 interaction term in the ANOVA of yield data was not statiscally significant, indicating that in this experiment the cultivars responded relatively uniformly to O 3. Rates of stomatal conductance were also relatively uniform among the cultivars, and conductance rates were not correlated with cultivar responses to O 3. The hypothesis that differences in cultivar responses to O 3 could be predicted by measurements of rates of maximum stomatal conductance was not confirmed by this study.

The Role of Variability of Dose in Dose-Response Relationships for Alpha Emitting Radionuclides

Radiation protection requires predictions of the effects of radiation at low mean organ doses. Since epidemiological data are restricted to moderate to high doses, extrapolation functions must be developed. The present paper derives such a function from theoretical considerations of the ability of radiation to initiate, promote and kill cells. The resulting function, however, is unable to account for the continued increase in cancer incidence amongst uranium miners and 224Ra cases at mean organ doses of several tens of grays. This failure is ascribed to the use of mean organ dose as an appropriate variable in dose-response equations. By an explicit incorporation of variability in cellular doses, the model developed here is shown to display the general features of the epidemiological data when model parameters are made consistent with findings from cellular radiobiology. This indicates that variability of cellular dose may play an essential role in determining the shape of epidemiologically based dose-response curves.

Predicting ozone-induced soybean losses: Sensitivity to model form and inputs

In this study, alternative dose-response equations for assessing the effects of O 3 on soybeans ( Glycine max (L.) Merr.) were established. For each of three soybean cultivars, three models (linear, quadratic, and Weibull) were fitted to relate different measures of O 3 dose, during the soybean flowering maturity period, to the soybean yield. The dose measures were 7-h (9:00 a.m. to 4:00 p.m.) and 12-h (7:00 a.m. to 7:00 p.m.) means, 7-h and 12-h total doses, and the 90th and 75th percentile O 3 concentrations. Using data for primarily rural and small city O 3 monitoring sites, county-level O 3 doses were calculated, and soybean losses due to O 3 were predicted for Illinois, Kentucky, and Virginia. The sensitivity of O 3-induced soybean loss predictions to model forms and inputs was determined with regard to: (1) inter-year differences in ambient O 3, (2) differences among the six dose measures, (3) differences among the three different model forms, (4) the impact of the agricultural practice of double-cropped soybean production, and (5) variance in response to O 3 among three different soybean cultivars.

Effects of Chronic Doses of Ozone on Field-Grown Loblolly Pine: Seedling Responses in the First Year

A study was designed to examine responses of loblolly pine (Pinus taeda) to chronic exposure to ozone (O/sub 3/) in the field. Seedlings of four full-sib families of loblolly pine were planted in a field near Raleigh, NC, and exposed daily (May 27 to October 24, 1985) in open-top chambers to O/sub 3/ ranging from 0.5 to 1.96 times the O/sub 3/ concentration in non-filtered (NF) air. One-fourth of the plants in each plot were removed during each of two harvest (August and October) to measure effects of O/sub 3/ on plant growth. Plants of each family exhibited foliar symptoms characteristic of O/sub 3/ injury after five months of exposure to any greater-than-ambient O/sub 3/ concentration, and one family exhibited symptoms after five months of exposure to NF air. Ozone dose-plant response relationships were quantified by regression for stem height, stem diameter, biomass, and other plant morphological and yield characteristics. All relationships were linear for three families, but one family exhibited no significant growth response relationship of O/sub 3/ dose. Dose-response equations suggest a maximum growth suppression of 10 percent for NF air compared to charcoal-filtered air in the first season of exposure.

Effect of Estrogen Implants on Hepatic Lipid Deposition in Chicks Fed Different Isonitrogenous and Isocaloric Diets

Two experiments were conducted to determine if differences in response of livers to estradiol administration in male broiler chicks would be observed if fed isonitrogenous and isocaloric diets of different composition. A polymethylsiloxane tube filled with estradiol dipropionate was implanted under the neck skin to ensure a constant release of hormone. Different tube sizes were implanted in two- or three-week-old chicks fed a basal corn-soybean meal (CS) diet or a diet containing fish meal, alfalfa meal, and torula yeast (FAY) or distiller's dried grains with solubles (DDGS). Body weight gains were significantly reduced by the highest level of estradiol in chicks fed the CS diet but not in chicks fed FAY or DDGS. Liver weight, deposition of lipid in liver and plasma lipid were markedly increased in proportion to the size of estradiol tube in chicks fed all diets. Increase of liver weight and lipid deposition by the highest level of estradiol in chicks fed the CS diet was significantly greater than that in chicks fed the FAY diet. Liver weight and the liver lipid response to estradiol in chicks fed the CS diet were significantly greater than that in chicks fed the FAY diet when dose response equations were compared among diets. These data show that the response on deposition of lipid in liver to estrogen administration was modified by the type of ingredients included in diets with similar energy and nutrient profiles.estrogen liver lipid growing chicks