Cumulative risk assessment of the exposure to organophosphorus and carbamate insecticides in the Dutch diet.

We report the acute cumulative exposure to organophosphorus insecticides (OPs) and carbamates in the Dutch population and young children (1-6 years) via the diet. Residue data were derived from Dutch monitoring programmes performed during 2003-2005, and food consumption levels from the Dutch National Food Consumption Survey 1997/1998. The relative potency factor (RPF) approach was used to cumulate the exposure to OPs and carbamates using acephate and oxamyl as index compound respectively. The exposure was estimated using the probabilistic approach, including unit variability and processing effects. We demonstrate that about 3% of the composite samples analysed for OPs and 0.2% for carbamates contain combinations of these pesticides. The P99.9 of exposure to OPs and carbamates in the total Dutch population equals 23 and 0.64microg/kg BW/d respectively. For young children the corresponding exposure levels are 57 and 1.47microg/kg BW/d. When comparing the P99.9 of exposure with the ARfD, 50 and 9microg/kg BW/d for acephate and oxamyl respectively, there is only a possible health risk for young children. Spinach contributed most to the exposure to OPs in both age groups, followed by orange and mandarin. For carbamates apple (sauce) was the main product determining the exposure.

Long-term cannulation of the vena cava of rats for blood sampling: local and systemic effects observed by histopathology after six weeks of cannulation.

A cannulation system with fixation by a metal cuff around the tail was used for blood sampling. The cannula was guided subcutaneously and positioned in the vena cava after entering the body via the femoral vein. Histopathology was performed after long-term cannulation of up to 35 and 45 days. The presence of the cannula in the vena cava induced endothelial hypertrophy and hyperplasia accompanied by stromal hypertrophy. The endothelial activation was not limited to the vena cava but was also observed in both the cannulated vena iliaca and the contralateral control vena iliaca, the latter showing only minor alterations. In the lung, thrombi were noted in the larger lung arteries; and foreign body emboli, probably situated in the alveolar septi, could be detected occasionally. Inflammatory reactions in the tail at the site of cuff fixation consisted of a mixture of acute and chronic inflammatory responses. The chronic inflammation extended into the tail muscles, as shown by the presence of fibrous tissue associated with muscle degeneration. In conclusion, prolonged venous cannulation in rats resulted in local alterations in the veins, small emboli in the lungs and a moderate to marked inflammation in the tail. However, the procedure itself was well tolerated by the animals.

Subchronic mild noise stress increases HRP permeability in rat small intestine in vitro.

Recently we reported an increased trans- and paracellular protein permeability in rat small intestine after acute cold restraint stress. In the present study, we applied randomized 95- or 105-dB white noise pulses during 45 min/h, 12 h/day, duration 8 days, as a milder, but more chronic stressor to male rats. At 8 days before the noise experiments, 50% of the animals were cannulated in the vena cava for blood sampling during the experimental period. The other 50% of the animals were sacrificed at Day 9, segments of ileum were mounted in Ussing chambers and perfused at 37 degrees C. Horseradish peroxidase (HRP) was added mucosally, serosal appearance was detected enzymatically and tissues were fixed for electron microscopy. In the animals exposed to 95-dB noise, plasma corticosterone levels were enhanced twofold compared to controls, and ileal HRP flux was enhanced twofold. Electron micrographs of tissue from stressed or control animals showed no detectable paracellular staining of HRP. Quantification of HRP-containing endosomes in enterocytes revealed a twofold increase in endosome number in the animals exposed to 95-db noise indicating that the increased HRP permeability was primarily due to increased endocytosis. In contrast to the animals exposed to 95-dB noise, rats exposed to 105-dB noise showed no increase in corticosterone levels and ileal HRP fluxes were not significantly different from controls. We conclude that mild subchronic noise stress may cause a decrease in intestinal barrier function by increased transcytosis of luminal antigens.

Crossing the river stone by stone: approaches for residential risk assessment for consumers.

Consumer products may contain constituents that warrant a risk analysis if they raise toxicological concern. Risk assessments are performed a priori, e.g. for pesticides and biocides, and a posteriori, to diagnose risks of contaminants. An overview is presented of residential exposure assessment and risk characterization. For exposure assessment, predictive models are used to estimate exposure concentrations. The available data on product use are used to quantify the intensity of exposure. Often, both exposure concentration and product use show high variability. Worst case assessments cope with variability and uncertainty in data poor situations by selecting 'worst case' values for exposures and exposure factors. Probabilistic models may be used to quantify and model variability and uncertainty when appropriate data is available. The Margin Of Safety approach to characterize risk is discussed. Many biocides handled by consumers are used now and then and (sub)acute exposure and toxicology will be most relevant. Users and children are generally seen as critical groups during the application and post-application phases of exposure, respectively. Still, the diversity of consumer products requires consideration of the merits of each case. We conclude that residential risk assessment is still searching for methods, data and models. Probabilistic methods appear to be useful tools, but a major challenge is to integrate them in regulatory frameworks.

Hormonal status and the neuroendocrine response to a novel heterotypic stressor involving subchronic noise exposure.

Despite a number of studies on noise-induced health effects, it is still unclear to what extent different neuroendocrine pathways are affected by noise exposure. Male Wistar rats were housed in sound-attenuated rooms isolated for noise from outside. Three groups of chronically cannulated rats were exposed to either background noise (+/-64 dB) only or irregular experimental white noise (90 dB, 2-22 kHz). Two protocols, with approximately the same total amount of noise but with different densities, were used: protocol N1 (180 min random noise per day for 18 days) or protocol N2 (540 min random noise per day for 8 days). Basal levels of circulating hormones (ACTH, corticosterone, prolactin and catecholamines) and plasma glucose were measured. In control animals, no significant changes in any of these parameters were observed over 18 days. Except for plasma prolactin, N1 did not induce a significant elevation in basal hormonal levels. N2 however induced significant elevation in basal prolactin, corticosterone and noradrenaline levels. At the end of the exposure period, all animals were subjected to a novel heterotypic stressor (restraint stress) to monitor differences in neuroendocrine activation (ACTH, corticosterone and prolactin). Compared to nonexposed control animals, N1 animals showed a normal ACTH and an enhanced corticosterone response, whereas N2 animals showed an increased ACTH but a normal corticosterone response. The prolactin response of both N1 and N2 animals was significantly decreased. Adrenal cell suspension experiments revealed that in noise-exposed rats both basal- and ACTH-stimulated corticosterone production were significantly increased as compared to control animals. These results indicate that chronic noise exposure at mild intensities induces subtle but significant changes in hormonal regulation.

Time-dependent differential changes of immune function in rats exposed to chronic intermittent noise.

Noise is a highly relevant environmental and clinical stressor. Compared to most other experimental stressors, noise is a modest activator of neuroendocrine pathways that mimic the situation in human health where neuroendocrine activation by environmental stressors is often absent or difficult to establish. Little is known about the effects of noise exposure on the immune system. In the present work, the effects of a low-intensity chronic intermittent unpredictable noise regimen on various parameters of immune function was studied. Male wistar rats were exposed to a randomized noise protocol (white noise, 85 dB, 2-20 kHz) for 10 h per day, 15 min per h over a total period of 3 weeks. Control animals were exposed to ambient sound only. Immune function was monitored after 24 h, 7 days, and 21 days of noise exposure. Noise induced several significant changes in immune function in a time-dependent differential pattern involving both immunosuppression and immunoenhancement. After 24 h, serum IgM levels were increased and peripheral phagocytic activity was decreased. Splenic lymphocytic proliferation to mitogens was significantly decreased after 7 days, but slightly elevated after 3 weeks. The activity of splenic NK cells was increased significantly after 24 h and 7 days, but suppressed after 3 weeks. These results show that various parameters of immune function are affected differentially over time in a period of chronic mild noise stress, possibly due to sequential activation of different physiological mechanisms.

Noise stress and airway toxicity: a prospect for experimental analysis.

People are exposed to a mixture of chemicals, noise, bad smells and other factors. Little is known about the possible interactions between these various contaminants. Although research on the effects of chemical mixtures has been initiated, the combination of chemical and non-chemical factors has received little attention. This paper summarizes the possible effects of combined exposure to noise and the air pollutant ozone, which are both factors with a high prevalence in the Western society. A series of animal experiments are presented to evaluate the possible combined effects of noise and air pollution.

Behavioral strategy and the physiological stress response in rainbow trout exposed to severe hypoxia.

In higher vertebrates, two opposite behavioral coping strategies can be distinguished that are associated by a typical neuroendocrine pattern. Little is known about the individual variation in the stress response in lower vertebrates such as teleosts. In the present study, rainbow trout were fitted with an indwelling aortic catheter for repeated blood sampling and exposed to severe hypoxia and subsequent recovery and their behavior was characterized semiquantitatively during hypoxia. Blood levels of catecholamines, cortisol, glucose, FFA, lactate, and electrolytes were measured. About 60% of the fish survived the experiment whereas the others died during the recovery period. Behavioral strategy appeared to be highly related to survival since nonsurviving fish displayed strenuous avoidance behavior involving burst type activity whereas surviving fish did not panic and remained quiet. These behavioral differences were associated with marked differences in plasma catecholamine levels, which were 4- to 5-fold higher in nonsurviving fish as compared to survivors whereas the cortisol response tends to be lower in nonsurviving fish. Plasma lactate levels in nonsurvivors were 4- to 5-fold higher as compared to survivors while a severe hyperkalemia developed during recovery indicating the loss of intracellular homeostasis. The individual differences in behavioral concepts and neuroendocrine activation observed in rainbow trout during stress show great similarity with the active and passive coping strategies distinguished in higher vertebrates and may be determinant for survival during hypoxia.

Effect of arterially infused catecholamines and insulin on plasma glucose and free fatty acids in carp.

Common carp (Cyprinus carpio L.), kept at 20 degrees C, were fitted with an indwelling PE-50 cannula in the dorsal aorta. Hormones dissolved in Ringer saline were arterially infused at a rate of 1 microgram.kg-1.min-1 for epinephrine (Epi), 2 micrograms.kg-1.min-1 for norepinephrine (NE), and 1.33 micrograms.kg-1.min-1 for insulin. INfusion of bovine insulin in carp resulted in a long lasting (24 h) decrease of plasma free fatty acids (FFA; -0.41 +/- 0.06 mM) and glucose levels (-3.14 +/- 0.25 mM) compared with preinfusion levels at t = 0. Both Epi and NE induced a marked hyperglycemia although Epi was more potent (+8.2 +/- 0.9 and +6.9 +/- 0.8 mM, respectively). Plasma FFA levels increased by 0.25 +/- 0.03 mM compared with preinfusion levels on Epi infusion. In contrast, during NE infusion, plasma FFA levels decreased significantly by -0.21 +/- 0.03 mM. Plasma insulin titers did not significantly change during infusion of NE or Epi. It is concluded that the ratio of NE to Epi is the major factor that determines the effect of catecholamines on plasma FFA levels in carp. These results may explain species-dependent different effects of hypoxia on FFA metabolism in fish.