Biomedical subjects

Mark Crane

Publications and source records attributed to Mark Crane.

At least 19 recordsLinked to original sources

PubMed2006

Chronic toxicity of tributyltin to development and reproduction of the European freshwater snail Lymnaea stagnalis (L.).

Chronic toxicity, growth and reproduction were measured in the freshwater gastropod Lymnaea stagnalis exposed to waterborne bis(tri-n-butyltin) oxide (TBTO) over a range of four nominal concentrations (0-10microg TBTl(-1)). Egg development was completely inhibited at 10microg TBTl(-1), whilst abnormal embryonic development was observed at 1microg TBTl(-1). For the solvent control and the 0.01microg TBTl(-1)treatment group, normal development of L. stagnalis was observed. Survivorship of hatchlings was significantly reduced by TBT at 1microgl(-1) while inhibition of shell growth of L. stagnalis was also observed at this concentration. The data were used to determine intrinsic growth rates (r) using two theoretical approaches (the Euler-Lotka equation and a Leslie Matrix). Both approaches showed that survival, fecundity and population growth rate were reduced at 1microg TBTl(-1). Interestingly, at 0.01microg TBTl(-1) snails showed a higher fecundity and growth rate than in the solvent control. The TBT concentration at which the r would equal zero (ECr(0)) and the population NOEC (No Observed Effect Concentration) were estimated. The population NOEC was defined as either the lower 95% confidence or lower 95% pointwise percentile limit of the ECr(0). Values obtained using the two different approaches were similar and thus a geometric mean was calculated to obtain a final representative population NOEC value for L. stagnalis of 2745ng TBTl(-1). The present data together with chronic toxicity TBT data for freshwater organisms, obtained from peer-reviewed literature, were used to construct a species sensitivity distribution (SSD). A predicted no effect concentration was then derived from the SSD (hazardous concentration at 5%, i.e., HC5 or 95% protection level). This SSD was compared with the SSD derived from saltwater species datasets. The HC5 value for saltwater species (3.55ng TBTl(-1); lower confidence limit: 1.93ng TBTl(-1)) was significantly lower than that for freshwater species (30.13ng TBTl(-1); lower confidence limit: 9.23ng TBTl(-1)), indicating that saltwater species are probably more susceptible to TBT than their freshwater counterparts.

Animals↗

PubMed2006

Chronic aquatic environmental risks from exposure to human pharmaceuticals.

This paper reviews current information on the chronic aquatic toxicity of human pharmaceuticals and how it should be measured. Chronic toxicity tests with Cyanobacteria are likely to be sensitive surrogates for both algae and other unicellular organisms, although possibly not for higher plants. In contrast, there is little evidence of a general need to perform chronic aquatic invertebrate tests for all human pharmaceuticals, although further acute-to-chronic ratio data are required for the main therapeutic classes and modes of action of pharmaceuticals before this issue can be fully resolved. Chronic fish tests may be necessary for some substances, but it is likely that these can be focused more accurately through use of information in mammalian toxicity datasets. For some substances and modes of action, life-cycle or partial life-cycle fish tests may be more relevant than reliance on early life-stage (ELS) tests, because the ELS test is unlikely to respond adequately to all pharmaceutical modes of action. Biomarkers may be useful in focusing research and testing efforts by identifying active substances and receptors of interest in aquatic species, and they may also be useful in field surveys for helping to establish possible cause and effect relationships. QSARs have been used by several authors to predict acute toxic effects, but predictions of chronic effects are currently hampered by the paucity of available chronic data to build predictive models. There seems to be no obvious reason why mixtures of pharmaceuticals in the environment should be treated in a different way to mixtures of other potentially hazardous substances. If mixture toxicity is considered to be an important environmental issue then all substances should be considered within an appropriate risk assessment framework.

Animals↗

PubMed2006

Bayesian and time-independent species sensitivity distributions for risk assessment of chemicals.

Species sensitivity distributions (SSDs) are increasingly used to analyze toxicity data but have been criticized for a lack of consistency in data inputs, lack of relevance to the real environment, and a lack of transparency in implementation. This paper shows how the Bayesian approach addresses concerns arising from frequentist SSD estimation. Bayesian methodologies are used to estimate SSDs and compare results obtained with time-dependent (LC50) and time-independent (predicted no observed effect concentration) endpoints for the insecticide chlorpyrifos. Uncertainty in the estimation of each SSD is obtained either in the form of a pointwise percentile confidence interval computed by bootstrap regression or an associated credible interval. We demonstrate that uncertainty in SSD estimation can be reduced by applying a Bayesian approach that incorporates expert knowledge and that use of Bayesian methodology permits estimation of an SSD that is more robust to variations in data. The results suggest that even with sparse data sets theoretical criticisms of the SSD approach can be overcome.

Animals↗

PubMed2006

Acceptability of pesticide impacts on the environment: what do United Kingdom stakeholders and the public value?

EU Directive 91/414/EEC requires there to be no unacceptable effects on the environment from the use of pesticides. This paper reports the views of direct stakeholder groups and results from an opinion survey of more than 2000 members of the general public on what in practice should constitute acceptable and unacceptable effects of pesticides. Stakeholders in focus groups were concerned with the potential effects of pesticides on animal and plant population viability and micro-organism function but recognized that a trade-off exists between the potential economic advantages of responsible pesticide use and the potential disadvantages of individual poisoning events. The public opinion survey showed that although pesticides are widely used in homes and gardens, their use on farm crops remains of concern to the public. Concerns are greatest on issues of human health and food quality but potential environmental effects are also an issue for a substantial number of people, particularly if attractive species could be affected.

Animals↗

PubMed2006

Does pesticide risk assessment in the European Union assess long-term effects?

Current methods would allow reasonable predictions of long-term effects of pesticide application if three changes were instituted. First, more population-based laboratory studies should be applied in predictive pesticide risk assessment. Second, ERA should include as much effort on collating and integrating ecological knowledge into the assessment in Tier 1 as is currently expended on gathering chemical and toxicological information on exposure and effects. Production of a formal conceptual ecological risk assessment model for each product or active substance for which authorization is sought would provide an appropriate framework for integrating and applying such knowledge. Third, in acknowledgment of the uncertainties in the predictive risk assessment process, more postauthorization monitoring should be done. The application of Occam's razor to pesticide risk assessment makes good sense, as it does in any other field of science. However, we must take care that simplicity in risk assessment process does not lead to oversimplification: Essentially all science is the study of either very small bits of reality or simplified surrogates for complex whole systems. How we simplify can be critical. Careless simplification leads to misleading simplistic conclusions. (Slobodkin 1994).

Environmental Pollutants↗

PubMed2004

Relationship between macroinvertebrate fauna and environmental variables in small streams of the Dominican Republic.

Field assessment methods for freshwater macroinvertebrates and water quality in tropical small-island states were assessed in the Dominican Republic. Macroinvertebrate samples were collected from 26 river sites within the Dominican Republic's Yaque del Norte river catchment. Environmental data on geographical, physical and chemical variables were also collected from each site. The Biological Monitoring Working Party score and total numbers of Ephemeroptera and Trichoptera were calculated for each site. Physico-chemical and biological data sets were ordinated by principal components analysis and non-parametric multi-dimensional scaling, and the biotic and abiotic data sets were correlated to determine the most influential factors determining site similarities. Macroinvertebrate assemblage structure was correlated with declining water quality: however, a high correlation between water quality and altitude confounded an unqualified interpretation of impairment.

Animals↗

PubMed2004

Risk characterisation in direct toxicity assessment of the River Esk and the Tees Estuary.

This paper illustrates the use of deterministic and probabilistic approaches to the ecotoxicological risk assessment of effluents through two simple examples taken from the UK Direct Toxicity Assessment Demonstration Programme. In this study, the direct protection objective for the River Esk in Scotland was the prevention of short-term lethal toxicity to invertebrates from exposure to effluent containing insecticides. Both a deterministic and a probabilistic risk characterisation show that such toxicity is very unlikely to occur. The protection objectives for the Lower Tees Estuary were more complex, due to a variety of discharges and potentially sensitive species. A deterministic risk assessment using the most sensitive species suggests that toxicity will be high at all times. In contrast, a probabilistic risk assessment suggests that, although acute toxicity is considerable, it is not likely to occur at all times or affect all species, and discharge scenarios do exist in which acute toxicity could be relatively low. These two case studies illustrate the use of probabilistic risk assessment in achieving more realistic assessments of effluent toxicity through use of all available data.

Animals↗

PubMed2004

Managing complex mixtures of chemicals--a forward look from the regulators' perspective.

The key findings to emerge from the successful Direct Toxicity Assessment Demonstration Programme are reviewed. At present, whole sample toxicity tests can identify and help control releases of complex mixtures that are likely to cause short-term toxic effects. Protection of aquatic organisms from the many hazardous chemicals that enter the environment, usually as complex mixtures, will require the introduction of new and improved techniques that are affordable and provide rapid turnaround of information. A number of bioassays were rigorously tested during the DTA programme. Further developments are suggested and other methods, including biosensors, biomarkers, and biological survey are briefly reviewed.

Animals↗

PubMed2003

Proposed development of Sediment Quality Guidelines under the European Water Framework Directive: a critique.

The Water Framework Directive is the most important piece of water legislation in Europe for many years and will substantially influence the environmental regulation of chemicals, including human and veterinary pharmaceuticals. The development of Sediment Environmental Quality Standards (EQSs) is called for by the Directive, and proposals have been made for achieving this. However, these proposals are technically controversial and could have considerable logistical consequences. This paper describes the background to the Directive and lists questions that must be answered before Sediment EQS derivation is undertaken. Possible answers to these questions are then provided. The main problems with current proposals to the EC are that mandatory 'pass/fail' standards assume that approaches for setting sediment standards are more reliable than is the case, and that suspended sediments are a more appropriate sampling medium than settled sediments for assessing the general risk of sediment-bound chemicals to wildlife.

European Union↗

PubMed2003

Environmental risk assessment of veterinary pharmaceuticals in the EU: reply to Montforts and de Knecht.

This paper is in response to a previous article in a Special Issue of Toxicology Letters. That article criticised the current regulatory framework in the European Union for the environmental risk assessment of veterinary medicinal products (VMPs) and feed additives (FAs), in particular the ongoing process of international harmonisation of guidance. This response addresses the concerns raised in relation to veterinary medicinal products and demonstrates that the VICH process has been brought within the scope of current EU regulatory processes for veterinary medicines and therefore is not separate to them. Consultation with stakeholders takes place throughout the VICH process, with an additional period of open public consultation before guidance is adopted and implemented.

Animal Feed↗

PubMed2003

Uptake and depuration of 4-nonylphenol by the benthic invertebrate Gammarus pulex: how important is feeding rate?

The major exposure and uptake route for soluble toxins by aquatic organisms is generally considered to be through the water column. In the case of hydrophobic chemicals, exposure and uptake through diet often take on greater importance as the chemicals adsorb onto organic sediments and food. A chemical that has recently come under close scrutiny because of its toxicity and possible endocrine disrupting effects in aquatic life is 4-nonylphenol (NP). It has been detected in environmental water and sediment samples and is a persistent and hydrophobic (log KOW = 4.48) contaminant in many aquatic systems. In this study, the relative importance of NP uptake through accumulation from diet and water was examined for the detritus-feeding freshwater shrimp Gammarus pulex. Using a bootstrap nonlinear regression technique, the level of toxin present in G. pulex at any time during or after initial exposure was estimated. Heterogeneity, together with assumptions on feeding rate, was shown to affect the determination of NP uptake substantially. Because of its lifestyle as a benthic organism, the main exposure route was at first assumed to be through sediments and food. However, the results suggest that major uptake may also occur through water. The statistical and modeling methodology may be applied to uptake and depuration assessments for any aquatic organisms exhibiting a variable feeding phase.

Amphipoda↗

PubMed2003

Estimating the effects of 17alpha-ethinylestradiol on populations of the fathead minnow Pimephales promelas: are conventional toxicological endpoints adequate?

Environmental benchmarks have recently been proposed for several steroids including the synthetic steroid, 17alpha-ethinylestradiol (EE2). These benchmarks are based on extrapolation from studies involving long-term exposure of various fish species to EE2. One of the critical studies was a complete life-cycle experiment performed with the fathead minnow Pimephales promelas over a 289 day exposure period. The lowest observed effect concentration (LOEC) and the no observed effect concentration (NOEC) for gonad histology were 4 and 1 ng L(-1) respectively. This was because no testicular tissue could be found in any fish exposed to 4 ng L(-1). In the present paper, the survival and reproduction data from that study are reanalyzed to determine the effects of EE2 on the intrinsic rate of population growth (r = In (lambda)), a parameter of demographic importance. We estimate critical threshold concentrations with respect to r and compare these with those previously derived from conventional toxicity test summaries. Further, we assess the influence of individual variability on threshold estimates using a combination of bootstrap and regression approaches, together with a suite of perturbation analyses. These yield ErC100 values (the concentration estimated to reduce intrinsic growth rate to zero) of 3.11 ng L(-1) (linear model) and 3.41 ng L(-1) (quadratic model), comparable with a maximum acceptable toxicant concentration (MATC) of 2 ng L(-1) for feminization of exposed fish calculated by Laenge et al. Our results indicate that reduction in population growth rate with increasing concentration occurred more through EE2 acting to reduce fertility than survival rates. The significance of these summary statistics when deriving environmental benchmarks for steroid estrogens is discussed in the context of affording protection to populations following long-term exposure.

Animals↗

PubMed2003

Evaluation of probabilistic risk assessment of pesticides in the UK: chlorpyrifos use on top fruit.

The use of probabilistic risk assessment (PRA) for examining chemical impacts has become an important area of debate within the European Union. This paper describes a case study on probabilistic techniques to assess pesticide risks in the UK aquatic environment. The main aim of this paper is to demonstrate both the potential strengths and weaknesses of PRA for assessing pesticides when compared with the conventional deterministic approach, and to examine whether PRA is useful within the European regulatory context. The organophosphate insecticide, chlorpyrifos, was selected as a model compound and toxicity exposure ratios calculated using Monte Carlo analysis and different distributions of spray drift and toxicity values following application to top fruit. Chlorpyrifos is highly toxic to arthropods but less toxic to fishes. Species sensitivity followed a log-normal distribution when fitted to all toxicity data. Toxicity data quantity had little influence on species sensitivity distribution model parameters when n was greater than 10 species. Below this, estimates were less accurate and precise, possibly because of the inclusion of data from many different sources. Estimates of chlorpyrifos exposure derived from the standard spray drift model differed substantially from measurements of chlorpyrifos in European surface waters. When a distribution based on measured concentrations was used in a PRA, the risk of acute fish mortality was low, and the risk of acute arthropod mortality was lower than in other scenarios, although not negligible. If PRA is used to assess pesticides, risk managers need further guidance on how to conduct a PRA and what constitutes 'unacceptable risk' under EC Directive 91/414/EEC, as judgement is required when simple trigger values are no longer used.

Animals↗

PubMed2003

Estimation of demographic toxicity through the double bootstrap.

Toxicity to organisms is usually expressed in terms of an observable effect on individuals from which a summary endpoint (such as the NOEC or ECx) is derived for risk assessment and environmental quality standards. However, toxicity evaluated in terms of a demographic endpoint may be more relevant to such regulatory applications. In this paper the effect of toxicity on population growth rate r is explored in tandem with a 'double bootstrap' to incorporate uncertainty. Exemplifying the approach with a set of individualized life table response data obtained for Daphnia magna exposed to zinc sulphate solution, the influence of increasing concentrations is assessed. A demographic-based metric for r, the ErCx (effect on r concentration percentage), is defined to permit alternative population level estimation of a 'safe effect' concentration.

Animals↗

PubMed2003

Induction of cytochrome P-450 activity in individual Chironomus riparius Meigen larvae exposed to xenobiotics.

Cytochrome P450 activity in individual Chironomus riparius larvae was measured using a microtiter plate adaptation of the ethoxyresorufin-O-deethylase (EROD) assay. The sensitivity of this biomarker was tested by exposing larvae to phenobarbital (0.5 and 1.0 mM) and permethrin (1 and 10 microg/g). Both chemicals induced EROD activity in C. riparius larvae by up to 1.58-fold with PB and 2.47-fold with permethrin. EROD induction was more pronounced after 48 h. The initially high EROD activity in the controls suggested that P450s are induced by stress. Feeding levels prior to exposure also had a significant effect on EROD activity. EROD activity compared to the control was highest when larvae were fed double the normal ration. These results indicate that EROD activity in individual C. riparius may be a useful biomarker to add to a suite of biomarkers for the detection of freshwater pollution.

Animals↗

PubMed2003

Haem peroxidase activity in Daphnia magna: a biomarker for sub-lethal toxicity assessments of kerosene-contaminated groundwater.

A novel biomarker was developed in Daphnia magna to detect organic pollution in groundwater. The haem peroxidase assay, which is an indirect means of measuring oxidase activity, was particularly sensitive to kerosene contamination. Exposure to sub-lethal concentrations of kerosene-contaminated groundwater resulted in a haem peroxidase activity increase by dose with a two-fold activity peak at 25%. Reproduction in D. magna remained unimpaired when exposed to concentrations below 25% for 21 days, and a decline in fecundity was only observed at concentrations above the peak in enzyme activity. The measurement of haem peroxidase activity in D. magna detected sublethal effects of kerosene in just 24 h, whilst offering information on the health status of the organisms. The biomarker may be useful in determining concentrations above which detrimental effects would occur from long-term exposure for fuel hydrocarbons. Moreover, this novel assay detects exposure to chemicals in samples that would normally be classified as non-toxic by acute toxicity tests.

Animals↗

PubMed2003

Toxicity of cadmium and zinc to the cercarial activity of Diplostomum spathaceum (Trematoda: Diplostomidae).

The toxicity of cadmium and zinc at concentrations ranging from 0.1 to 100 microg/l was investigated against the activity of Diplostomum spathaceum (Rudolphi, 1819) cercariae. Over a 24 h exposure period a significant reduction in cercarial activity occurred in solutions of cadmium, zinc, and a mixture of cadmium and zinc at all concentrations. Reduced cercarial activity also occurred in all toxicant solutions compared with controls after only 6 h exposure indicating that cercariae were vulnerable during the period of maximum cercarial infectivity (0-5 h). The mechanisms of metal toxicity and their importance to parasite transmission are discussed.

Animals↗

PubMed2003

Multivariate relationships between groundwater chemistry and toxicity in an urban aquifer.

Multivariate statistical methods were used to investigate the causes of toxicity and controls on groundwater chemistry from 274 boreholes in an urban area (London) of the United Kingdom. The groundwater was alkaline to neutral, and chemistry was dominated by calcium, sodium, and sulfate. Contaminants included fuels, solvents, and organic compounds derived from landfill material. The presence of organic material in the aquifer caused decreases in dissolved oxygen, sulfate and nitrate concentrations, and increases in ferrous iron and ammoniacal nitrogen concentrations. Pearson correlations between toxicity results and the concentration of individual analytes indicated that concentrations of ammoniacal nitrogen, dissolved oxygen, ferrous iron, and hydrocarbons were important where present. However, principal component and regression analysis suggested no significant correlation between toxicity and chemistry over the whole area. Multidimensional scaling was used to investigate differences in sites caused by historical use, landfill gas status, or position within the sample area. Significant differences were observed between sites with different historical land use and those with different gas status. Examination of the principal component matrix revealed that these differences are related to changes in the importance of reduced chemical species.

Animals↗