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M J Hooper

Publications and source records attributed to M J Hooper.

At least 19 recordsLinked to original sources
PubMed2005

Case Study Part 1: How to calculate appropriate deterministic long-term toxicity to exposure ratios (TERs) for birds and mammals.

In the European Union, first-tier assessment of the long-term risk to birds and mammals from pesticides is based on calculation of a deterministic long-term toxicity/exposure ratio (TER(lt)). The ratio is developed from generic herbivores and insectivores and applied to all species. This paper describes two case studies that implement proposed improvements to the way long-term risk is assessed. These refined methods require calculation of a TER for each of five identified phases of reproduction (phase-specific TERs) and use of adjusted No Observed Effect Levels (NOELs) to incorporate variation in species sensitivity to pesticides. They also involve progressive refinement of the exposure estimate so that it applies to particular species, rather than generic indicators, and relates spraying date to onset of reproduction. The effect of using these new methods on the assessment of risk is described. Each refinement did not necessarily alter the calculated TER value in a way that was either predictable or consistent across both case studies. However, use of adjusted NOELs always reduced TERs, and relating spraying date to onset of reproduction increased most phase-specific TERs. The case studies suggested that the current first-tier TER(lt )assessment may underestimate risk in some circumstances and that phase-specific assessments can help identify appropriate risk-reduction measures. The way in which deterministic phase-specific assessments can currently be implemented to enhance first-tier assessment is outlined.

Animals↗
PubMed2005

Case Study Part 2: Probabilistic modelling of long-term effects of pesticides on individual breeding success in birds and mammals.

Long term exposure of skylarks to a fictitious insecticide and of wood mice to a fictitious fungicide were modelled probabilistically in a Monte Carlo simulation. Within the same simulation the consequences of exposure to pesticides on reproductive success were modelled using the toxicity-exposure-linking rules developed by R.S. Bennet et al. (2005) and the interspecies extrapolation factors suggested by R. Luttik et al. (2005). We built models to reflect a range of scenarios and as a result were able to show how exposure to pesticide might alter the number of individuals engaged in any given phase of the breeding cycle at any given time and predict the numbers of new adults at the season's end.

Animals↗
PubMed2005

A new interpretation of avian and Mammalian reproduction toxicity test data in ecological risk assessment.

The long-term risks of pesticides to wildlife in the EU currently are assessed by comparing the lowest no-observed-effect concentration (NOEC) determined from the suite of endpoints measured in existing avian and mammalian laboratory reproduction tests with estimated exposure concentrations by calculating Toxicity to Exposure Ratios (TERs). Regulatory authorities experience difficulties when assessing long-term risks because of the lack of accepted methods to improve the ecological realism of exposure and toxicity estimates and understand risks at a population level. This paper describes an approach for interpreting existing avian and mammalian toxicity test data that divides breeding cycles into several discrete phases and identifies specific test endpoints as indicators of direct pesticide effects possible at each phase. Based on the distribution of breeding initiation dates for a species of concern and the dates of pesticide applications, this approach compares the phase-specific toxicity endpoint with the expected pesticide exposure levels during each of the breeding phases. The fate of each breeding attempt is determined through a series of decision points. The cumulative reproductive response of individuals in a breeding population based on this decision framework provides a means of examining the estimated risks over the course of the breeding season and deriving an overall metric of the impact of the pesticide on reproduction. Research needed to further improve the approach is discussed.

Animals↗
PubMed2005

Risedronate prevents bone loss in early postmenopausal women: a prospective randomized, placebo-controlled trial.

OBJECTIVES: To assess the efficacy and tolerability of risedronate, a pyridinyl bisphosphonate, in preventing loss of bone mineral density (BMD) of the lumbar spine and proximal femur in early postmenopausal women. METHODS: A total of 383 patients were randomly assigned to receive risedronate 2.5 or 5 mg or placebo once daily for 24 months. All patients received 1 g elemental calcium daily. BMD was measured by dual X-ray absorptiometry at baseline and at 3, 6, 12, 18, and 24 months. RESULTS: Risedronate 5 mg significantly increased BMD at the lumbar spine and femoral neck and trochanter in early postmenopausal women. Significant results were observed as early as 3 months. In the control calcium-supplemented group, BMD decreased steadily at each site throughout the study. The mean percentage change from baseline in BMD in the risedronate 5 mg group was significantly different from that in the control group at each determination at each site. At 24 months, the differences were 4.5 +/- 0.45% at the lumbar spine, 3.3 +/- 0.49% at the femoral neck, and 4.3 +/- 0.67% at the femoral trochanter. Risedronate 2.5 mg maintained BMD at each site, although the effect was less pronounced than that of risedronate 5 mg. Risedronate was well tolerated and was not associated with an increased incidence of overall or upper gastrointestinal adverse events. CONCLUSIONS: Risedronate 5 mg prevents bone loss in early postmenopausal women, is well tolerated, and represents an effective choice to maintain bone mass and prevent osteoporosis.

Absorptiometry, Photon↗
PubMed2000

Contaminant exposure and biomarker responses in spectacled eiders (Somateria fischeri) from St. Lawrence Island, Alaska.

Effects of chemical contaminant exposure may be contributing to the decline of spectacled eiders (Somateria fischeri) nesting in coastal areas of western Alaska. We evaluated chemical exposure and potential effects in 20 male eiders collected near St. Lawrence Island, Alaska. Analytes included metals, trace elements, chlorinated organics, and (137)Cesium ((137)Cs). Effects of contaminant exposure were evaluated using histopathology and biochemical measures of porphyrin profiles, cytochrome P450 activities, and metallothionein (MT) concentrations. Copper, cadmium, and selenium concentrations were elevated in spectacled eiders when compared to literature values for other marine birds. Only a few samples had trace concentrations of chlorinated organic compounds. Muscle (137)Cs levels were all below the average minimum quantifiable concentration of 0.079 Bq/g. No histopathological lesions were associated with elevated contaminant concentrations in liver, kidney, or testes. Protoporphyrin was found in highest concentration in both the liver and kidneys, followed by coproporphyrin and uroporphyrin, respectively. Hepatic uroporphyrin concentrations correlated significantly to hepatic arsenic concentrations. Mean activities of hepatic EROD, MROD, BROD, and PROD were consistent with other avian species. Comparisons of cadmium/MT ratios from this study to published literature ratios in seven marine avian species suggest that, although adult male spectacled eiders have elevated liver concentrations of certain MT-inducing metals, their MT concentrations are not as strongly induced as would be predicted based on literature values. Despite elevated metal concentrations, the apparent good health of the St. Lawrence Island birds suggests that should these contaminants be a factor in population declines, they likely act by decreasing fecundity or survival of young rather than via direct health impacts on adult male spectacled eiders.

Alaska↗
PubMed1998

Rat brain acetylcholinesterase activity: developmental profile and maturational sensitivity to carbamate and organophosphorus inhibitors.

A growing body of evidence indicates that young animals exhibit an increased susceptibility to the lethal effects of cholinesterase (ChE)-inhibiting insecticides. Our laboratory is engaged in defining factors which may explain this age-related sensitivity. This report includes results from experiments designed to compare the developmental profiles, kinetic parameters and intrinsic (i.e. in vitro) sensitivity of developing male rat brain acetylcholinesterase (AChE) activity to carbamate and organophosphorus anticholinesterases. Total ChE activity in whole brain for each age was composed of about 90% AChE and 10% butyrylcholinesterase (BuChE) activity for the six ages examined. Brain AChE activity showed an age-related increase in Vmax until postnatal day 17 with no change in Km (average of all six ages approximately equal to 72 microM). Optimal substrate (acetylthiocholine) concentration for each age was 1 mM, and there was substrate inhibition (approximately 10%) at 2.5 mM. IC50s (the concentration of compound that inhibits 50% of the AChE activity in 30 min at 26 degrees C) defined concomitantly for postnatal day 4 and adult brain AChE using either aldicarb, carbaryl, chlorpyrifos-oxon or malaoxon were virtually identical at both ages with average IC50 values being: aldicarb = 2.4 microM, carbaryl = 1.7 microM, chlorpyrifos-oxon = 4.9 nM and malaoxon = 140 nM. In summary, AChE in young and adult brain differs mostly in specific activity while the Km(s), substrate profiles, and in vitro sensitivity to selected anticholinesterase insecticides are not different. Therefore, these data support the hypothesis that the greater sensitivity of the young animals to anticholinesterase pesticides is not due to the greater sensitivity of the target molecule AChE to these inhibitors.

Acetylcholinesterase↗
PubMed1998

Comparison of the in vitro sensitivity of rat acetylcholinesterase to chlorpyrifos-oxon: what do tissue IC50 values represent?

The toxicological literature is replete with studies which have attempted to correlate differences in in vivo sensitivity to anticholinesterases with a common in vitro measure: acetylcholinesterase (AChE) IC50 values. Generally, it is assumed that these IC50 values reflect the intrinsic sensitivity of the AChE molecule to the inhibitor. Our goal was to ascertain whether differences in AChe sensitivity to an organophosphate (i.e., IC50 values) are due to varying properties of the enzyme molecule (i.e., present assumption) or to extrinsic factors. Tissue samples were obtained from immature and adult Long-Evans rats. AChE IC50 values were determined by incubating tissue homogenates with chlorpyrifos-oxon (active metabolite of chlorpyrifos, a common organophosphate insecticide) for 30 min at 26 degrees C, and then measuring residual AChE activity. The following IC50 values were noted for postnatal day 4 and adult animals, respectively: brain, 10 nM for both ages; liver, 96 and 527 nM; plasma, 18 and 326 nm. Thus, the "apparent" sensitivity of AChe was prone to vary dramatically with age and tissue type. In contrast, when AChE was isolated from the same tissues by immunoprecipitation, there were no age- or tissue- related differences (IC50 approximately equal to 3 nM in every case). These data show clearly that IC50 values from a crude homogenate do not measure the true sensitivity of AChE to the inhibitor. Presumably, for chlorpyrifos-oxon, at least, the tissue IC50 values depend greatly on a tissue's propensity to sequester or hydrolyze chlorpyrifos-oxon.

Acetylcholinesterase↗
PubMed1996

Maturational differences in chlorpyrifos-oxonase activity may contribute to age-related sensitivity to chlorpyrifos.

Chlorpyrifos (CPF), a commonly used cholinesterase-inhibiting insecticide, is lethal at much lower doses to young animals than adults. To explain this higher sensitivity in younger animals, we hypothesized that young rats have less chlorpyrifos-oxonase (CPFOase) activity than adults. To test this hypothesis, CPFOase activity was measured in the brain, plasma, and liver of male, postnatal day 4 (PND4) and adult (PND90) Long-Evans rats. CPFOase is biochemically defined as a Ca(2+)-dependent A-esterase that hydrolyzes chlorpyrifos-oxon (CPFO), the active metabolite of CPE. No brain CPFOase activity was detected at either age. Plasma and liver CPFOase activities were markedly lower at PND4 compared to adult: PND4 plasma and liver CPFOase activities were 1/11 and 1/2 the adult plasma and liver activities, respectively. Because the Km of CPFOase activity was high (i.e., 210-380 microM), it was important to determine if this CPFOase activity could hydrolyze physiologically relevant concentrations (i.e., nM to low microM) of CPFO. This was accomplished by comparing the shifts in the tissue acetylcholinesterase (AChE) IC50 for CPFO in the presence or absence of CPFOase activity. One would expect an increase in the "apparent" IC50 if CPFOase hydrolyzes substantial amounts of CPFO during the 30 minutes the tissue is preincubated with the CPFO. In the adult, both plasma and liver AChE apparent IC50 values were higher in the presence of CPFOase activity, suggesting that the CPFOase in those tissues was capable of hydrolyzing physiologically relevant concentrations of CPFO within 30 minutes. In young animals, however, there was less of a shift in the IC50 curves compared to the adult, confirming that the young animal has less capacity than the adult to detoxify physiologically relevant concentrations of CPFO via CPFOase.

Acetylcholinesterase↗
PubMed1995

Multiple endocrine neoplasia type two B. A case report with light and electron microscopic and immunohistochemical correlation.

PURPOSE: To describe a case of multiple endocrine neoplasia type two B (MEN IIB) where ocular and systemic clinicopathological findings are correlated, in association with light and electron microscopic and immunohistochemical findings. METHODS: A 23-year-old man presented with mucosal neuromas of the lips, tongue and eyelids, a Marfanoid habitus and prominent corneal nerves. These findings led to the diagnosis of multiple endocrine neoplasia type two B. The patient subsequently developed phaeochromocytoma and metastatic medullary thyroid carcinoma (MTC) which led to his demise. Correlation of light and electron microscopic and immunohistochemical findings with the systemic and ocular findings is presented to emphasise the aggressiveness of MTC in MEN IIB. Clinicopathological correlation was obtained by examining the eyes post mortem. RESULTS AND CONCLUSIONS: Three new findings in MEN IIB have been established by this study. The enlarged corneal nerves can now be regarded as ganglioneuromas. Medullary thyroid carcinoma metastases were found in the choroid. Light and electron microscopic examination of the eye showed ganglioneuromas of the nerves in the limbus, trabecular meshwork, uveal tract and posterior ciliary nerves; this finding may account for the glaucoma occasionally seen in patients with MEN IIB.

Adrenal Gland Neoplasms↗
PubMed1995

Carbofuran poisoning in herons: diagnosis using cholinesterase reactivation techniques.

Exposure to the carbamate insecticide carbofuran was detected using brain cholinesterase (ChE) reactivation techniques in heron carcasses collected from a potential pesticide exposure incident. Great egrets (Nycticorax nycticorax), great blue herons (Ardea herodias), and black-crowned night herons (Casmerodius albus) were exposed to carbofuran (2,3-dihydro-2,2-dimethyl-7-benzofuranyl methylcarbamate) either by dermal exposure while wading or through ingestion of contaminated food items. Carcasses may have been in the field up to 5 days prior to collection. Brain ChE, substantially inhibited in most samples, increased 7.9-208% in the reactivation assay after 4 to 96 hours at 37 C, providing evidence of exposure to a carbamate pesticide. Crayfish (Procambarus clarkii) identified in the crops of some herons contained carbofuran residues of up to 0.6 parts per million wet weight, providing additional evidence of exposure. Reactivated brain ChE in several samples approached the range of control values.

Animals↗
PubMed1994

Single-day intravenous pamidronate in Paget's disease.

Although the efficacy of pamidronate (APD) in Paget's disease is established, the optimal dose and regimen are not known. In this article, further findings using a single-day intravenous infusion are reported, comparing the responses of 114 subjects treated with doses of 20 mg (n = 35), 30 mg (n = 26), 45 mg (n = 29), and 60 mg (n = 24). Assessments of clinical and biochemical response were made at 2, 4, 8, 12, and 24 weeks. Patients with persistent disease activity were retreated after 24 weeks. The single-day infusion of APD was followed by a rapid and sustained biochemical response, but in only 24% of patients did alkaline phosphatase (AP) levels normalize. Of patients in whom the serum AP level normalized, 93% had initial values less than three times the upper limit of normal. Although there was no significant difference in response between the lower dosage groups, there was a greater response in patients treated with a higher dose of APD. The percentage decrease in AP from baseline was similar after the first and second infusions. These findings show that a single-day infusion of APD is effective in the treatment of Paget's disease and that a dose-response relationship exists.

Adult↗
PubMed1994

Toxicological foundations of ecological risk assessment: biomarker development and interpretation based on laboratory and wildlife species.

Ecological risk assessments based on chemical residue analysis and species demographics tend to ignore the bioavailability and bioaccumulation of the chemicals of concern. This study describes the incorporation of mechanistically based biomarkers into an ecological risk assessment of a poly-cyclic aromatic hydrocarbon (PAH)-contaminated site. A combination of soil residue analysis, tissue residue analysis, biomarkers in one-site trapped animals and biomarkers in animals confined to enclosures was used. In particular, the use of captured deer mice (Peromyscus maniculatus) for these studies is compared to the use of laboratory-raised deer mice placed in enclosures. This study indicates that the higher degree of variability in the responses of wild deer mice make the use of enclosure studies advantageous. Positive control studies performed by dosing laboratory-raised deer mice with the same PAHs as found on the site were used to validate this approach. These studies indicate that immune suppression occurred at PAH concentrations an order of magnitude below those required for the induction of ethoxyresorufin-O-dealkylase activity.

Animals↗
PubMed1994

Cyclophosphamide effects on immune function of European starlings.

We developed and tested a battery of immune function assays on adult European starlings (Sturnus vulgaris) exposed to the immunotoxicant cyclophosphamide (CY). Starlings were injected intraperitoneally for three consecutive days with saline or 20 mg/kg CY. Cyclophosphamide did not affect body mass or packed cell volume. However, spleen to body mass ratios and the number of viable spleen cells were lower in CY-treated birds when compared to controls. Peripheral white blood cell numbers were reduced in CY-treated starlings, and the decrease affected all cell types. Phagocytic ability of macrophages cultured from peripheral blood monocytes was impaired in cells from CY-treated birds. Additionally, CY treatment resulted in decreased lymphocyte blastogenesis to the T-cell mitogen Concanavalin A. The hemagglutination response to sheep erythrocytes was lower in birds that had received CY. Thus, these immunological methods detected chemically-induced immune dysfunction in starlings.

Animals↗
PubMed1993

Development and optimization of reactivation techniques for carbamate-inhibited brain and plasma cholinesterases in birds and mammals.

Two biochemical assays were developed which promote and measure the induced reactivation of carbamate-inhibited cholinesterases in avian and mammalian brain and plasma samples. The effects of inhibitor concentration, temperature, and the extent of dilution on the achievement of a steady state equilibrium and the subsequent level and rate of recovery of brain cholinesterase activity were investigated. A similar procedure for reactivation of carbamate-inhibited plasma cholinesterase activity involved the removal of excess carbamate from a small sample volume (< 400 microliters). Both methods begin by measuring cholinesterase activity immediately following dilution and involve an incubation period during which conditions for spontaneous reactivation of the inhibited enzymes are maximized. Both assays are suitable for large-scale, rapid use and appear able to restore inhibited cholinesterase activity to levels closely approximating that of control values for each species tested. These methods will not only maximize the usefulness of cholinesterases in monitoring carbamate pesticide exposure but should prove to be extremely useful tools in the forensic assessment of carbamate exposure in human and wildlife pesticide incidents.

Aldicarb↗
PubMed1993

Porphyrin profiles in the nestling European starling (Sturnus vulgaris): a potential biomarker of field contaminant exposure.

Porphyrin patterns in avian and mammalian tissues and/or excreta have been proposed as qualitative and quantitative biomarkers of exposure to polyhalogenated hydrocarbons, heavy metals, and other environmental contaminants. However, no widely distributed terrestrial species has been characterized as a suitable model in which to assess porphyrin profiles in the evaluation of environmental contaminant exposure. The European starling, whose nests can be readily established and manipulated on contaminated sites, has many qualities that accommodate controlled field research and that suggest its suitability for such assessments. In the present studies, we measured the total and individual porphyrin concentrations in liver, kidney, and fecal-urate excreta of nestling starlings from a noncontaminated field site from day of hatch through d 17 of the nestling period. Total as well as individual 8-, 7-, 6-, 5-, 4-, and 2-carboxyl porphyrin concentrations in liver, kidney, and fecal-urate excreta were readily detectable by high-performance liquid chromatography (HPLC) spectrofluorometric techniques and displayed tissue-specific patterns throughout the developmental period. Liver and fecal-urate porphyrin patterns were established by d 4 subsequent to hatch and remained constant through d 17 of development, whereas renal porphyrin profiles were constant throughout the entire developmental period. In controlled field studies, nestling starlings were treated with either HgCl2 or hexachlorobenzene (HCB), and tissue and excreta porphyrins were extracted and evaluated. The findings suggest that the nestling starling may serve as a suitable model species in which to monitor the effects of field contaminant exposure to wildlife based on chemical-induced changes in tissue or excreta porphyrin levels.

Animals↗
PubMed1993

Age-dependent changes in plasma and brain cholinesterase activities of eastern bluebirds and European starlings.

Age-dependent changes in plasma and brain cholinesterase (ChE) activity were characterized in two altricial passerine species: eastern bluebirds (Sialia sialis) and European starlings (Sturnus vulgaris). Plasma acetylcholinesterase (AChE) activity declined rapidly immediately after hatching, while plasma butyrylcholinesterase (BChE) activity increased throughout the nestling period. These patterns continued after birds fledged, since the BChE: AChE ratio was higher in adult birds than fledglings. This is the first confirmation of age-dependent changes in plasma ChE activity in altricial species. Total plasma ChE activity increased with age in both species, which is the reverse of results previously reported for several precocial species. Brain ChE activity increased with age in both species, and did not reach asymptotic levels before young fledged. This corresponded with patterns previously documented in European starlings and three other altricial species. We propose that age and degree of precocity in young birds must be considered when examining sensitivity or evaluating field exposure of birds to ChE-inhibiting compounds.

Acetylcholinesterase↗