72 research outputs found
Risk characterisation of chemicals in food and diet
No full textRisk characterisation of chemicals in food and diet. Renwick AG, Barlow SM, Hertz-Picciotto I, Boobis AR, Dybing E, Edler L, Eisenbrand G, Greig JB, Kleiner J, Lambe J, Muller DJ, Smith MR, Tritscher A, Tuijtelaars S, van den Brandt PA, Walker R, Kroes R. University of Southampton, Clinical Pharmacology Group, School of Medicine, Biomedical Sciences Building, Bassett Crescent East, SO16 7PX, Southampton, U
Cumulative risk assessment of pesticide residues in food
No full textThere is increasing need to address the potential risks of combined exposures to multiple residues from pesticides in the diet. The available evidence suggests that the main concern is from dose addition of those compounds that act by the same mode of action. The possibility of synergy needs to be addressed on a case-by-case basis, where there is a biologically plausible hypothesis that it may occur at the levels of residues occurring in the diet.
Cumulative risk assessment is a resource-intense activity and hence a tiered approach to both toxicological evaluation and intake estimation is recommended, and the European Food Safety Authority (EFSA) has recently published such a proposal. Where assessments have already been undertaken by some other authority, full advantage should be taken of these, subject of course to considerations of quality and relevance.
Inclusion of compounds in a cumulative assessment group (CAG) should be based on defined criteria, which allow for refinement in a tiered approach. These criteria should include chemical structure, mechanism of pesticidal action, target organ and toxic mode of action.
A number of methods are available for cumulating toxicity. These are all inter-related, but some are mathematically more complex than others. The most useful methods, in increasing levels of complexity and refinement, are the hazard index, the reference point index, the Relative Potency Factor method and physiologically based toxicokinetic modelling, although this last method would only be considered should a highly refined assessment be necessary.
Four possible exposure scenarios are of relevance for cumulative risk assessment, acute and chronic exposure in the context of maximum residue level (MRL)-setting, and in relation to exposures from the actual use patterns, respectively. Each can be addressed either deterministically or probabilistically. Strategies for dealing with residues below the limit of detection, limit of quantification or limit of reporting need to be agreed.
A number of probabilistic models are available, but some of there are geographically constrained due to the underlying datasets used in their construction. Guidance on probabilistic modelling needs to be finalised.
Cumulative risk assessments have been performed in a number of countries, on organophosphate insecticides alone (USA) or together with carbamates (UK, DK, NL), triazines, chloroacetanilides, carbamates alone (USA), and all pesticides (DE).
All identifiable assumptions and uncertainties should be tabulated and evaluated, at least qualitatively. Those likely to have a major impact on the outcome of the assessment should be examined quantitatively. In cumulative risk assessment, it is necessary, as in other risk assessments, for risk managers to consider what level Of Fisk would be considered "acceptable", for example what percentile of the population should be below the reference value.
Criteria for prioritising CAGs for cumulative risk assessment include frequency of detection in monitoring programmes, high usage, high exposure relative to the reference value, large number of compounds (e.g. five or more) in a group
Comparative physicochemical and pharmacokinetic profiles of inhaled beclomethasone dipropionate and budesonide
No full textComparative physicochemical and pharmacokinetic profiles of inhaled beclomethasone dipropionate and budesonide
No full textAbstractThe physicochemical and pharmacokinetic characteristics of BDP and budesonide are somewhat different, but the overall result is that both are well suited for use as inhaled corticosteroids. Both BDP and budesonide are metabolized primarily by the liver, with one of the metabolites of BDP, 17-BMP, having greater receptor affinity than either the parent compound or budesonide, which has no active metabolites. BDP has a lower water solubility than either 17-BMP or budesonide, which have similar water solubilities. Budesonide has lower oral bioavailability than BDP; however, it is generally reported to have a longer plasma half-life than either BDP or 17-BMP. The physicochemical and pharmacokinetic profiles of inhaled BDP and budesonide provide both compounds with a favourable ratio of topical to systemic effects and support their well-established role in the treatment of asthma. The device used to deliver an inhaled corticosteroid influences the lung deposition of the drug and selection of the device should be made with an understanding of the particular advantages and disadvantages of the device for each individual patient
Towards microbial fermentation metabolites as markers for health benefits of prebiotics
No full textAvailable evidence on the bioactive, nutritional and putative detrimental properties of gut microbial metabolites has been evaluated to support a more integrated view of how prebiotics might affect host health throughout life. The present literature inventory targeted evidence for the physiological and nutritional effects of metabolites, for example, SCFA, the potential toxicity of other metabolites and attempted to determine normal concentration ranges. Furthermore, the biological relevance of more holistic approaches like faecal water toxicity assays and metabolomics and the limitations of faecal measurements were addressed. Existing literature indicates that protein fermentation metabolites (phenol, p-cresol, indole, ammonia), typically considered as potentially harmful, occur at concentration ranges in the colon such that no toxic effects are expected either locally or following systemic absorption. The endproducts of saccharolytic fermentation, SCFA, may have effects on colonic health, host physiology, immunity, lipid and protein metabolism and appetite control. However, measuring SCFA concentrations in faeces is insufficient to assess the dynamic processes of their nutrikinetics. Existing literature on the usefulness of faecal water toxicity measures as indicators of cancer risk seems limited. In conclusion, at present there is insufficient evidence to use changes in faecal bacterial metabolite concentrations as markers of prebiotic effectiveness. Integration of results from metabolomics and metagenomics holds promise for understanding the health implications of prebiotic microbiome modulation but adequate tools for data integration and interpretation are currently lacking. Similarly, studies measuring metabolite fluxes in different body compartments to provide a more accurate picture of their nutrikinetics are needed
How to assess gastrointestinal health benefits of prebiotics: focusing on "microbial fermentation and metabolism"
No full textAvailable evidence on the toxicological, bioactive and nutritional properties of gut microbial metabolites has been evaluated in support of a more integrated view of how prebiotics might influence host health throughout life. The literature search targeted available evidence for the physiological and nutritional effects of metabolites like short chain fatty acids (SCFA), the possible toxicity of other metabolites and determined normal concentration ranges. We assessed the biological relevance of more holistic approaches including faecal water toxicity assays, metabolomics and the limitations of fecal measurements (production v absorption rates). Existing literature indicates that protein fermentation metabolites (phenol, p-cresol, indole, ammonia), typically considered as potentially harmful, occur at concentration ranges in the colon such that no toxic effects should be produced. The various end products of saccharolytic fermentation, SCFA, may have very different effects on colonic health, host physiology, lipoprotein metabolism and appetite. Measuring SCFA concentrations in faeces however is insufficient to assess the dynamic processes of their nutrikinetics. Existing literature is limited on the usefulness of genotoxicity measures of fecal water as indicators of cancer risk. In conclusion, at present there is insufficient evidence to use changes in faecal bacterial metabolite concentrations as markers of prebiotic effectiveness. Integration of results from metabolomics and metagenomics holds promise for understanding the health implications of prebiotic microbiome modulation but currently suitable tools for data integration and interpretation are lacking. Similarly, studies measuring metabolite flux in different body compartments to provide a more accurate picture of their nutrikinetics would be usefu
The significance of sample mass in the analysis of steroid estrogens in sewage sludges and the derivation of partition coefficients in wastewaters
No full textOptimization of an analytical method for determination of steroid estrogens, through minimizing sample size, resulted in recoveries >84%, with relative standard deviations <3% and demonstrated the significance of sample size on method performance. Limits of detection were 2.1–5.3 ng/g. Primary sludges had estrogen concentrations of up to one order of magnitude less than those found in biological sludges (up to 994 ng/g). However, partition coefficients were higher in primary sludges (except estriol), with the most hydrophobic compound (ethinylestradiol) exhibiting the highest Kp value, information which may be of value to those involved in modeling removal during wastewater treatment
Influence of operating parameters on the biodegradation of steroid estrogens and nonylphenolic compounds during biological wastewater treatment processes
No full textThis document is the unedited author's version of a Submitted Work that was subsequently accepted for
publication in Environmental Science & Technology, copyright © American Chemical Society after peer
review. To access the final edited and published work see http://pubs.acs.org/doi/abs/10.1021/es901612v.This study investigated operational factors influencing the removal of steroid estrogens and nonylphenolic compounds in two sewage treatment works, one a nitrifying/denitrifying activated sludge plant and the other a nitrifying/denitrifying activated sludge plant with phosphorus removal. Removal efficiencies of >90% for steroid estrogens and for longer chain nonylphenol ethoxylates (NP4−12EO) were observed at both works, which had equal sludge ages of 13 days. However, the biological activity in terms of milligrams of estrogen removed per day per tonne of biomass was found to be 50−60% more efficient in the nitrifying/denitrifying activated sludge works compared to the works which additionally incorporated phosphorus removal. A temperature reduction of 6 °C had no impact on the removal of free estrogens, but removal of the conjugated estrone-3-sulfate was reduced by 20%. The apparent biomass sorption (LogKp) values were greater in the nitrifying/denitrifying works than those in the nitrifying/denitrifying works with phosphorus removal for both steroid estrogens and nonylphenolic compounds possibly indicating a different cell surface structure and therefore microbial population. The difference in biological activity (mg tonne−1 d−1) identified in this study, of up to seven times, suggests that there is the potential for enhancing the removal of estrogens and nonylphenols if more detailed knowledge of the factors responsible for these differences can be identified and maximized, thus potentially improving the quality of receiving waters.Public Utilities Board (Singapore), Anglian Water Ltd, Severn Trent Water Ltd, Thames Water Utilities Ltd, United Utilities 393 Plc and Yorkshire Water Services
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