Causation in risk assessment and management: models, inference, biases, and a microbial risk-benefit case study

Causal inference of exposure-response relations from data is a challenging aspect of risk assessment with important implications for public and private risk management. Such inference, which is fundamentally empirical and based on exposure (or dose)-response models, seldom arises from a single set of data; rather, it requires integrating heterogeneous information from diverse sources and disciplines including epidemiology, toxicology, and cell and molecular biology. The causal aspects we discuss focus on these three aspects: drawing sound inferences about causal relations from one or more observational studies; addressing and resolving biases that can affect a single multivariate empirical exposure-response study; and applying the results from these considerations to the microbiological risk management of human health risks and benefits of a ban on antibiotic use in animals, in the context of banning enrofloxacin or macrolides, antibiotics used against bacterial illnesses in poultry, and the effects of such bans on changing the risk of human food-borne campylobacteriosis infections. The purposes of this paper are to describe novel causal methods for assessing empirical causation and inference; exemplify how to deal with biases that routinely arise in multivariate exposure- or dose-response modeling; and provide a simplified discussion of a case study of causal inference using microbial risk analysis as an example. The case study supports the conclusion that the human health benefits from a ban are unlikely to be greater than the excess human health risks that it could create, even when accounting for uncertainty. We conclude that quantitative causal analysis of risks is a preferable to qualitative assessments because it does not involve unjustified loss of information and is sound under the inferential use of risk results by management.     

Arsenic geochemistry and health

Arsenic occurs naturally in the earth's crust and is widely distributed in the environment. Natural mineralization and activities of microorganisms enhance arsenic mobilization in the environment but human intervention has exacerbated arsenic contamination. Although arsenic is useful for industrial, agricultural, medicinal and other purposes, it exerts a toxic effect in a variety of organisms, including humans. Arsenic exposure may not only affect and disable organs of the body, especially the skin, but may also interfere with the proper functioning of the immune system. This paper, therefore, generally highlights the toxic effects of arsenic as well as its mobilization in the natural environment and possible controls. It also briefly attempts to outline the impact of arsenic on the immune system, whose alteration could lead to viral/bacterial infections.     

Atmospheric bulk deposition to the lagoon of Venice Part I. Fluxes of metals, nutrients and organic contaminants

First available data on atmospheric fall-out were provided by sampling monthly bulk depositions in four sites inside the Lagoon of Venice (550 km2). Sampling was carried out monthly during the period July 1998-July 1999, in one site near an industrial area (Porto Marghera; site D), another site in the city of Venice (site A), and the remaining two in the southern- and northernmost ends of the Lagoon (Valle Figheri, site C; Valle Dogà site B). The following determinations were carried out for each samples: pH, conductivity, grain-size, particulate load, and dissolved nutrients (N, P). Samples were then subdivided into soluble and insoluble fractions, and Al, Ca, Na, K, Mg, Si, Mn, Fe, Zn, Ni, Cr, Cu, Pb, Cd, As, Hg, Ti, V, S, P, Se and Sb were analysed on both fractions. Total organic micropollutants (PAH, PCB, HCB, DDT, PCDD/F) were measured. As regards particle size distribution, there was great variability among sampling sites. The percentage of the < or =2 microm grain-size fraction was higher in the southern and northern ends of the Lagoon. Small differences were found among sites for major elements, whereas higher variability was observed for inorganic and organic micropollutants, with standard deviations between 20% and 60% of the fluxes measured. Major differences in annual fluxes between the most polluted sites (mostly D and A) and background (site B) were seen for Cd (0.26 vs. 0.06 mg m(-2) year(-1)), Hg (41 vs. 15 microg m(-2) year(-1)), PCB ( approximately 2500 vs. approximately 500 ng m(-2) year(-1)) and HCB ( approximately 8000 vs. approximately 1000 ng m(-2) year(-1)). Comparisons with previous data, collected in the periods 1993-1994 and 1995-1997, were only available for a few trace metals. A definite decline in the annual Pb flux in the city of Venice was detected, from 18 to 13 mg m(-2) in 1996/1997 and 1995/1996 respectively, to approximately 5 mg m(-2) in the present study. Total annual deposition was calculated by means of two different methods, which gave very similar results: (i) the mean value of deposition in the four sites was multiplied by lagoon area (550 km2); (ii) the monthly rain isopleths were combined to normalize deposition values. The figures are: 15-34 kg of Hg and Sb, approximately 200 kg of As, approximately 100 kg of Cd and PAH, 0.7-1.3 tons of Cr, Ni and V, more than 2 tons of Cu and Pb, 17 of Zn, 55 of total P, approximately 200 of Al, and 3900 of DIN. Total fluxes of organics inside the lagoon were: PAH approximately 100 kg; HCB approximately 1 kg; DDT approximately 0.4 kg. PCB and PCDD/F fluxes were approximately 500 g and approximately 10 g, corresponding respectively to 0.1 and 0.4 g I-TE. The correlations between fluxes of inorganic micropollutants and grain-size were significant. Multivariate statistical analysis was applied to investigate more accurately relationships between the insoluble and dissolved fractions of inorganic micropollutants and grain-size fractions. In particular, significant correlations were highlighted between the dissolved fraction of As and the < or =1 mum particle size fraction. Relations between levels of SigmaPCDDF, SigmaPCDD, PCB and PAH congeners and grain-size revealed significant correlation coefficients for the remote sites (B, C), and none in the urban and industrial sites (A, D). In particular, significant correlations were highlighted between SigmaPCDDF, SigmaPCDD and particle size fraction < or =2 mum, and between benzo(a)pyrene and PCB 167 and particle size fraction 4-8 mum.     

Experience in quantitative analysis of floristic structure and diversity in Samarskaya Luka

Quantitative methods have been applied to the study of floristic structure and diversity in Samarskaya Luka. The results show that Samarskaya Luka is a floristically heterogeneous area in which six elementary floras can be distinguished. This area has been assessed as a floristically autonomous formation, and its floristic representativeness was estimated.     

Influence of air-sea fluxes on chlorine isotopic composition of ocean water: implications for constancy in delta37Cl--a statistical inference

The behaviors of chlorine isotopes in relation to air-sea flux variables have been investigated through multivariate statistical analyses (MSA). The MSA technique provides an approach to reduce the data set and was applied to a set of 7 air-sea flux variables to supplement and describe the variation in chlorine isotopic compositions (delta37Cl) of ocean water. The variation in delta37Cl values of surface ocean water from 51 stations in 4 major world oceans--the Pacific, Atlantic, Indian and the Southern Ocean has been observed from -0.76 to +0.74 per thousand (av. 0.039+/-0.04 per thousand). The observed delta37Cl values show basic homogeneity and indicate that the air-sea fluxes act differently in different oceanic regions and help to maintain the balance between delta37Cl values of the world oceans. The study showed that it is possible to model the behavior of chlorine isotopes to the extent of 38-73% for different geographical regions. The models offered here are purely statistical in nature; however, the relationships uncovered by these models extend our understanding of the constancy in delta37Cl of ocean water in relation to air-sea flux variables.     

Limits of thermoluminescence dosimetry using quartz extracted from recent building materials in urban settlements

The luminescence of quartz extracted from recently fired building material is known to detect doses of few mGy and can be successfully employed in the case of large scale radiation exposures due to nuclear accidents or terrorist acts. One brick and two tiles (50-80 years range) collected from an urban settlement were used to test the realistic minimum detectable dose limits of retrospective luminescence dosimetry. Independent methods like alpha counting, beta dosimetry, gamma spectrometry and flame photometry were used for the annual dose assessment. Two approaches were employed for the evaluation of the total accrued dose: regenerative dose and additive dose. The former allows the assessment of doses due to anthropogenic sources of radiation as low as approximately 12 mGy by using 10-year-old samples, but it can be applied only in samples showing no sensitisation. The latter can be applied to any sample, however, the related uncertainty is higher and minimum detectable anthropogenic dose in young samples amounts to 20 mGy.     

Anguilla anguilla L. Genotoxic responses after in situ exposure to freshwater wetland (Pateira de Fermentelos, Portugal)

Pateira de Fermentelos is a Cértima River enlargement, close to its river mouth (by the Agueda River), where the introduction of agricultural chemicals such as fertilisers and pesticides, domestic sewage, as well as heavy metals from electroplating industries, results in increased water pollution. The present research work concerns a 48 h in situ exposure of caged eels (Anguilla anguilla L.) at the Pateira de Fermentelos. Five exposure sites were selected, i.e., site A, site B, site C, site D and site E in order to study its water genotoxicity potential, measured in gill, blood, liver and kidney as DNA strand breaks. Eels were also exposed at a reference site by the Cértima River spring. Bottom water samples were collected for further physical-chemical analysis. Site A exposure, significantly decreased gill, blood and liver DNA integrity. Gill and liver DNA integrity was also significantly decreased at site B. At site C only blood DNA integrity was significantly decreased. The present field in situ study demonstrated that the three exposure sites close to the Pateira initial part, such as A, B and C are polluted by pro and/or genotoxic compounds. The genotoxic effects induced in A. anguilla L. suggest a different contamination of the exposure sites A, B and C, in genotoxic chemicals. Thus, according to its genotoxic potential the exposure sites A, B and C, may be ordered as follows site A>site B>site C. No genotoxic effects on A. anguilla L. were observed at site E as DNA strand breaks increase.     

Radionuclides in cigarettes may lead to carcinogenesis via p16 inactivation

It is widely accepted that tobacco smoke is responsible for the vast majority of lung cancers worldwide. There are many known and suspected carcinogens present in cigarette smoke, including α-emitting radioisotopes. Epidemiologic studies have shown that increased lung cancer risk is associated with exposure to ionizing radiation, and it is estimated that the majority of smoking-induced lung cancers may be at least partly attributable to the inhaled and deposited radiation dose from radioisotopes in the cigarette smoke itself. Recent research shows that silencing of the tumor suppressor gene p16^INK4a (p16) by promoter methylation plays a role in smoking-related lung cancer. Inactivation of p16 has also been associated with lung cancer incidence in radiation-exposed workers, suggesting that radionuclides in cigarette smoke may be acting with other compounds to cause smoking-induced lung cancer. We evaluated the mechanism of ionizing radiation as an accepted cause of lung cancer in terms of its dose from tobacco smoke and silencing of p16. Because both radiation and cigarette smoking are associated with inactivation of p16, and p16 inactivation has been shown to play a major role in carcinogenesis, ionizing radiation from cigarette smoke likely plays a role in lung cancer risk. How large a role it plays, relative to chemical carcinogens and other modes of action, remains to be elucidated.     

Study of the comparative dynamics of the incorporation of tissue free-water tritium (TFWT) in bulrushes (Typha latifolia) and carp (Cyprinus carpio) in the Almaraz nuclear power plant cooling reservoir

The Almaraz nuclear power plant (Spain) uses the water of Arrocampo reservoir for cooling, and consequently raises the radioactive levels of the aquatic ecosystem of this reservoir. From July 2002 to June 2005, monthly samples of surface water, bulrushes (Typha latifolia) and carp (Cyprinus carpio) were collected from this reservoir. They were analyzed to determine the temporal evolution of the levels of ³H in surface water and of its transfer from the surface water to free-water in the tissues (TFWT) of the aforementioned two organisms. The tritium levels in the surface water oscillate with a biannual period, with their values in the study period ranging between 53 and 433 Bq/L. The incorporation of tritium to bulrushes and carp was fairly similar, the respective mean concentration factors being 0.74 and 0.8 (unitless, as Bq/L tissue water per Bq/L reservoir water). The temporal evolution of the levels fairly closely followed that observed for the surface water tritium, although detailed analysis showed the dominant periodicity for the bulrushes to be annual. This difference reflects the influence on the incorporation of tritium to bulrushes of diverse environmental and metabolic factors, especially evapotranspiration and the seasonal growth of this plant.