Policy, practice and decision making for zoonotic disease management: water and Cryptosporidium.

Decision making for zoonotic disease management should be based on many forms of appropriate data and sources of evidence. However, the criteria and timing for policy response and the resulting management decisions are often altered when a disease outbreak occurs and captures full media attention. In the case of waterborne disease, such as the robust protozoa, Cryptosporidium spp, exposure can cause significant human health risks and preventing exposure by maintaining high standards of biological and chemical water quality remains a priority for water companies in the UK. Little has been documented on how knowledge and information is translated between the many stakeholders involved in the management of Cryptosporidium, which is surprising given the different drivers that have shaped management decisions. Such information, coupled with the uncertainties that surround these data is essential for improving future management strategies that minimise disease outbreaks. Here, we examine the interplay between scientific information, the media, and emergent government and company policies to examine these issues using qualitative and quantitative data relating to Cryptosporidium management decisions by a water company in the North West of England. Our results show that political and media influences are powerful drivers of management decisions if fuelled by high profile outbreaks. Furthermore, the strength of the scientific evidence is often constrained by uncertainties in the data, and in the way knowledge is translated between policy levels during established risk management procedures. In particular, under or over-estimating risk during risk assessment procedures together with uncertainty regarding risk factors within the wider environment, was found to restrict the knowledge-base for decision-making in Cryptosporidium management. Our findings highlight some key current and future challenges facing the management of such diseases that are widely applicable to other risk management situations.

Is risk-based regulation feasible? The case of polybrominated diphenyl ethers (PBDEs).

The polybrominated diphenyl ethers (PBDEs) are a class of brominated flame retardants used extensively in an array of textiles and plastics. Initially viewed as inert and nontoxic, in recent years an emerging body of science has cast doubt on this perception. Consequently, the compounds have drawn sustained government, media, and lobby group focus in the United States and Europe, yet have taken contrasting trajectories in different risk regulation regimes. We present a longitudinal analysis of these pathways, examining the actions of legislatures, executives, courts, scientists, and pressure groups. We show that the emergence and resolution of PBDEs as a risk issue was strongly shaped by path dependency, political entrainment (inter-institutional conflict unrelated to PBDEs), and partisan lawmaking. This raises the question of whether risk-based principles are capable of being the foundation on which managing the potential for harm can be based--even when that harm is associated with specific objects like flame-retardant chemicals. We conclude by reflecting on the difficult normative issues that are raised.

Understanding the mismatch between the demands of risk assessment and practice of scientists--the case of Deca-BDE.

This review describes how a mismatch between the knowledge produced by scientists and the evidence demanded by regulators has emerged, and how society has struggled to find definitive answers to questions of safety, for an important flame retardant chemical in current use - Deca-BDE. This has involved two key disciplines: analytical chemistry and toxicology. Within the chemistry, a lack of standardized methodologies among scientists has resulted in a persistent yet largely undeclared failure to replicate results within the discipline. Within the toxicology, the quest for innovative, curiosity-driven research by university scientists in preference to using validated standard protocols, designed to promote consistency within the risk assessment process, has prompted questions about the credibility and relevance of scientific findings. Yet scientific laboratories have compelling reasons to do things the way they do in the cause of producing new knowledge, pointing to a sustained gap between the aims and practices of research scientists and those of risk management. A more rigorous scientific process that treats different elements of input data as discrete pieces of evidence is needed to ensure that science rather than politics will always define chemical safety.

Risk migration and scientific advance: the case of flame-retardant compounds.

It is a common experience that attempts to mitigate a risk lead to new risks, and that risks formerly thought to be of one kind become another kind as technical knowledge evolves. This phenomenon of risk migration suggests that we should take processes over time, rather than specific risks or specific technologies, as a unit of analysis. Several of our existing models of the social management of risks-such as that of social risk amplification-are process models of a kind but are still oriented around the playing out of a particular event or issue. A case study of risk in a group of flame-retardant compounds was used as the basis of a grounded, exploratory analysis of migration processes, the phenomena that influence them, and their consequences. This illustrated how migration naturally occurs from risks that are understood, in which risk bearers have at least some agency, to risks that are not understood and not capable of being influenced by risk bearers. It illustrated how the simultaneous improvement in measuring technology, which detects potential toxins at increasingly small concentrations, combines with intuitive models that ignore concentration to produce conditions likely to generate anxiety. And it illustrated how pressure groups and commercial interests exploit this effect. It also showed how migration makes precautionary action problematic, and how more generally it tends to undermine a society's capacity to cope with risk.

Inter-individual differences in the ability of human milk-fat extracts to enhance the genotoxic potential of the procarcinogen benzo[a]pyrene in MCF-7 breast cells.

Environmental factors are believed to play an important role in cancer aetiology. Whether environmental pollutants act in isolation or in combination within mixtures remains unclear. Four human milk-fat extracts (from resident U.K. women) were screened for levels of organochlorinated and brominated compounds prior to being tested (1-50 mg-equiv) for micronucleus (MN)-forming activity in MCF-7 cells. Using the cytokinesis-block micronucleus assay, micronuclei (MNi) were scored in 1000 binucleate cells per treatment. Cell viability (% plating efficiency) and immunohistochemical detection of p53 induction were also measured. The effects of treatment with 1 mg-equiv of extract in combination with benzo[a]pyrene (BP) were also examined. BP-DNA adducts were detected and quantified by 32P-postlabeling analysis. Dose-related increases in MNi independent of pollutant concentrations were induced by milk-fat extracts. All four extracts elevated the percentage of p53 positive cells, although not always in a dose-related fashion. Some combinations resulted in profound low-dose-induced increases in MNi and significant elevations in the percentage of p53 positive cells, which occurred without further reduction in cell viability or mitotic rate. When one particular extract was combined with BP, a 100-fold increase in BP-DNA adducts was detected as compared with the levels induced by BP alone; an effect not induced by other extracts. This adduct-enhancing extract was fractionated into 14 fractions that were subsequently tested (1 mg-equiv of original extract) in combination with 0.01 microM BP. Fraction 1, into which nonpolar pollutants mostly eluted, enhanced MN-forming activity with BP. Surprisingly, the more polar and less likely to contain fat-soluble pollutants fractions 5 and 8 also enhanced MN-forming activity. No identifiable pollutants were present in these fractions. The results suggest that different environmental pollutants present in human tissue may influence the susceptibility of target cells to initiating events.

Different levels of polybrominated diphenyl ethers (PBDEs) and chlorinated compounds in breast milk from two U.K. Regions.

Polybrominated diphenyl ether (PBDE) congeners are constituents of flame retardants, and there is growing concern regarding their persistence, bioaccumulation, and toxicity. We collected breast milk samples between late 2001 and early 2003 from 54 U.K.-resident mothers. Of these, 27 originated from southeast England (London), and the other 27 originated from northwest England (Lancaster). Analysis of milk-fat extracts by gas chromatography-mass spectrometry was performed to determine the levels of 15 PBDE congeners, 15 polychlorinated biphenyl (PCB) congeners, and other selected chlorinated compounds. PCB and organochlorine (OC) levels in southeast samples were consistently higher, and significant differences (p < 0.05) were observed. Sigma PBDE levels ranged from 0.3 to 69 ng/g lipid (geometric mean, 6.6 ng/g), and PBDE-47 was the most abundant congener. Sigma PCB levels ranged from 26 to 530 ng/g lipid (geometric mean, 150 ng/g) and were composed mainly of PCB-153 (26%), PCB-138 (20%), and PCB-180 (13%). OC levels for 1,1,1-trichloro-2,2-bis(p-chlorophenyl)ethane (p,p'-DDT) and its metabolites (Sigma DDX) ranged from 24 to 2,300 ng/g lipid (geometric mean, 160 ng/g);Sigma hexachlorocyclohexane levels ranged from 1.2 to 1,500 ng/g lipid (geometric mean, 16 ng/g). Using nuclear magnetic resonance-based metabonomics, samples (n = 7) containing the highest contaminant levels were compared with samples (n = 7) containing the lowest levels. Excellent separation along the first principal component implied that the chemical constituents of the two groups were significantly different. Although reasons for such differences remain obscure, lifestyle factors associated with a more heterogeneous London cohort could be responsible. Identifying primary routes of contaminant exposures and their biologic effects is of great importance. Key words: breast milk, flame retardants, gas chromatography-mass spectrometry, milk-fat extracts, organochlorines, PBDE-47, persistent contaminants, polybrominated diphenyl ethers, polychlorinated biphenyls, United Kingdom.

Low dose induction of micronuclei by lindane.

Environmental contaminants possessing hormonal activity have long been suspected of playing a role in cancer causation. What is unclear is whether such agents elicit their effects through genotoxic and/or epigenetic mechanisms. gamma-Hexachlorocyclohexane (gamma-HCH, lindane) was tested in the 10(-12)-10(-4) M range. Chromosomal damage in MCF-7 breast cells and PC-3 prostate cells was assessed using the cytokinesis block micronucleus assay. Micronuclei (MNi) were scored in 1000 binucleate cells per treatment. Cell viability and cell cycle kinetics were also assessed, along with immunocytochemical and quantitative gene expression analyses of CDKN1A (P21WAF1/CIP1), BCL-2 and BAX. Following 24 h treatment, lindane (10(-12)-10(-10) M) induced increases (up to 5-fold) in MNi in both cell lines. Increases in MNi occurred in the absence of DNA single-strand breaks or cytotoxicity and, compared with benzo[a]pyrene and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine, at low concentrations. Lindane induced more MNi than the alpha or beta stereoisomers of HCH. Low dose lindane (10(-12)-10(-10) M) significantly elevated the percentage of MCF-7 cells staining positive for Bcl-2 and of PC-3 cells staining positive for Bax. Only high dose lindane (10(-4) M) disrupted cell cycle kinetics with increases in percentage of cells in G1 and decreases in percentage of cells in G2/M. Despite a comparable high dose lindane induction of cell cycle arrest, marked increases in expression of P21WAF1/CIP1 were observed only in MCF-7 cells, although in PC-3 cells a significant increase (P < 0.0005) in the percentage of cells staining positive for p21Waf1/Cip1 was seen. These results suggest that 'environmental' concentrations of lindane can induce a number of subtle alterations in breast and prostate cells in the absence of cytotoxicity.

Understanding levels and trends of BDE-47 in the UK and North America: an assessment of principal reservoirs and source inputs.

Despite increasing interest in the occurrence of Polybrominated diphenyl ethers (PBDEs) in the environment, there has been only limited effort expended to identify principal source input reservoirs and pathways into the environment. Taking a single congener BDE-47, an important component of the penta commercial product, we have estimated principal contemporary reservoirs and emissions in two regions with very different historical use patterns. In North America, production and use of the penta-product has been rising steadily for the last 20 years, whilst in the UK, use has been restricted over the last 10 years, and most recently, there has been an EU ban on use. Mass balance models have been applied using our contemporary emission estimates to predict environmental levels. Results highlight that contemporary emissions to air can account for contemporary air concentrations but cannot account for measured concentrations in principal reservoirs such as soils and sediments. Future efforts are needed to improve our knowledge of the stocks of PBDEs in use, and emission factors from those stocks, to better understand/predict past and likely future trends.

Temporal and spatial trends of PCB congeners in UK gannet eggs.

Gannet (Sula bassana) eggs collected from Ailsa Craig, Western Scotland between 1977-1998 have been analyzed retrospectively for several PCB congeners. Concentrations of a range of congeners were determined in 8-10 eggs analyzed separately for several individual years. All congeners declined in concentrations throughout the time period, but the rates of decline differed for different congeners. Declines were first order and half-lives varied between 5.4 years for PCB-101 to 10.1 years for PCB-180. Egg concentrations reflect the maternal body burden, which itself is controlled by the birds rate of intake (principally via the diet) and losses (via metabolism and other clearance mechanisms). The declining concentrations in eggs, therefore, broadly reflect reductions in prey concentrations (principally herring and mackerel) and--in turn--water column concentrations. Rates of change in PCB concentrations from this study were similar to those noted in fish-eating birds from the Baltic Sea and North American Great Lakes, and ambient air in the UK. This provides indirect evidence that gannet eggs are broadly reflecting regional/global scale clearance/removal mechanisms which are controlling ambient PCB concentrations.

Using PCDD/F congener patterns to determine the source of elevated TEQ concentrations in cows milk: a case study.

PCDD/F congener profiles have been used to determine the source of elevated TEQ concentrations in cows' milk collected in the vicinity of several industrial sites. Principal components analysis and modelling of the air-to-milk transfer of individual PCDD/F congeners have shown that the milk fingerprint was related to that of sediment taken from the River Rother adjacent to the farm where the cows had grazed. It is suggested that sediment from the river had been washed onto the grazing land during periods of flooding, and this had been ingested by the grazing cows. This pathway could represent an important route of contaminant intake for livestock grazing on the regularly inundated floodplains of rivers containing contaminated sediments.