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PubMed1996

The effects of EDRF/NO releasers or calcium ionophore A23187 on cyanide toxicity in mice.

Cyanide (CN) is a well-recognized poison whose complete actions are unclear. It has been shown that a vasoactive role may be partially responsible for the toxic effects of CN. Sodium nitrite, a known methemoglobin former and vasodilator, has been used to treat CN toxicity. It is rapidly transformed to nitric oxide (NO) which is thought to be endothelium-derived relaxing factor (EDRF). Since the literature suggests that NO can influence the biological effects of CN, studies were undertaken to determine if compounds known to release EDRF/NO will modify CN toxicity. Mice were administered a series of compounds which act through EDRF/NO release. These substances included, platelet-activating factor (PAF), hydralazine, bradykinin, histamine, calcium ionophore A23187, carbachol, or substance P at 0.060, 98.7, 50.0, 125, 1.0, 2.26, and 1.0 mg/kg, respectively. As a control, NG-monomethyl-L-arginine (NMA) 70 mg/kg, which inhibits NO synthesis, was administered to mice iv (tail vein) in combination with each test compound. All test compounds and NMA were administered prior to NaCN: NMA, 5 min; carbachol, 0.5 min; hydralazine, 0.5 min; bradykinin, 1 min; histamine, 1 min; substance P, 4 min; PAF, 5 min; and A23187, 5 min. Dose-response relationships were analyzed by probit dose-response methods and protective ratios for each compound were computed. Results suggest (i) that a portion of the action of CN is affected by a particular EDRF/NO-releasing compound, suggesting that each drug specifically affects regional EDRF/NO receptor sites, and (ii) that NO can play a role as a component in CN intoxication. It is suggested that CN does not act uniformly on all EDRF/NO receptor sites to produce toxicity and site-specific EDRF/NO agents may be useful for treating CN.

Animals↗

PubMed1996

Pharmacokinetic optimisation in the treatment of gastro-oesophageal reflux disease.

Gastro-oesophageal reflux disease (GORD) is a very common disorder of upper gastro-intestinal motility, differing widely in severity and prognosis. Medical therapy of GORD has involved antacids, alginates, prokinetic agents and antisecretory compounds, primarily H2 receptor antagonists and proton pump inhibitors. Knowledge of the pharmacokinetics of these compounds is important, to optimise the therapeutic benefit in each patient. GORD patients are often elderly and pharmacokinetics are move variable in this group. Furthermore, they often suffer from other diseases needing medical therapy and may need a combination of drugs to heal reflux oesophagitis and relieve reflux symptoms. The ideal therapy for GORD will have linear pharmacokinetics, a relatively long plasma half-life (t1/2), a duration of action allowing once daily administration, and a stable effect independent of interactions with food, antacids and other drugs. Over-the-counter antacids and alginates are widely used, buy may affect absorption of H2 receptor antagonists like cimetidine and ranitidine. Aluminium-containing antacids may, over time, cause toxicity in patients with renal insufficiency. In the treatment of GORD, cisapride presents important advantages over earlier prokinetic compounds, with a longer plasma t1/2, low penetration of the blood-brain barrier and fewer adverse effects. The group of H2 receptor antagonists is still the most frequently use therapy for GORD. Linear pharmacokinetics make dose adjustments easy and safe. In individual patients, suppression of gastric secretion is related to the area under the plasma concentration-time curve (AUC), but there is wide interindividual variation in the effect of the same oral dose. Only with frequent administration and high doses will acid suppression approximate that of proton pump inhibitors. Tolerance, with loss of effect over time, however, is most pronounced in this situation. H2 receptor antagonists seem well suited for on-demand treatment of reflux symptoms, due to the rapid onset of effect and a decrease likelihood of the development of tolerance. Effervescent formulations provide more rapid absorption and almost immediate clinical effect. Cimetidine, however, causes interference with the metabolism of several other drugs in common use. In elderly patients elimination is delayed and in patients with renal insufficiency, dose reductions of all H2 receptor antagonists are recommended. The most effective medical therapy for any severity of GORD, particularly in severe oesophagitis, are the proton pump inhibitors. The substituted benzimidazoles (omeprazole, lansoprazole and pantoprazole), are prodrugs which once trapped and activated in the acid milieu of the gastric glands potently suppress gastric secretion of acid and pepsin. Their long duration of action, more related to the slow turnover of parietal cell H(+)-K+ ATPase molecules, allows once daily administration in most patients. Interindividual variation in bioavailability sometimes calls for higher doses or twice daily administration. Acid suppression is closely related to the AUC. Omeprazole is prone to interaction with the metabolism of other drugs, some of which may e be clinically important. Lansoprazole seems to have an earlier onset of action than omeprazole, ascribed to higher bioavailability during the first days of treatment. Proton pump inhibitors have a slow onset of action, which makes them unsuited for on-demand therapy. Clinical practice in GORD calls for the use of not one but several substances, according to the severity and symptom pattern of the patient. Pharmacokinetic optimisation in the treatment of GORD is a question of selecting the most suitable substances and administration schemes within each group. Cisapride is superior to other prokinetics in terms of longer plasma t1/2 and less toxicity. Amongst H2 receptor antagonists, the more long-acting compounds, ranitidine and famotidine, will improve acidity control througho

2-Pyridinylmethylsulfinylbenzimidazoles↗

PubMed1981

The effect of uraemic serum and plasma on proliferating cells in vitro.

Phytohaemagglutinin (PHA)-stimulated lymphocytes from healthy individuals and a malignant cell-line (K-562 cells) were cultured in a growth medium of 75 per cent RPMI 1640 (Gibco) supplemented with 25 per cent of uraemic serum or plasma obtained after systemic heparinization. Pooled human A Rh+ serum from 3 different donors served as controls. There was a depression of the DNA synthesis in both cell systems measured as uptake of methyl-3H-thymidine when the cells were cultured in uraemic milieu. Systemic heparinization markedly increased the depressive effect of uraemic plasma compared with controls. Heparin added to the growth media in concentrations much higher than those usually present in plasma after systemic heparinization had little effect on the cell proliferation. Systemic heparinization thus appears to induce production of toxic substances in plasma acting on proliferating cells.

Cell Division↗

PubMed1984

Suppression of spermatogenesis without inhibition of steroidogenesis by a 1,2,3-trihydroxypropane solution.

This study presents the first evidence that the non-hormonal, biological substance, 1,2,3- trihydroxypropane (THP) acts as a selective and potent antispermatogenic agent without any apparent toxic or endocrine side effects. The studies were done on 119 rats which were injected intratesticularly (50-200 microliter) with either sterile filtered distilled water (Control) or water/THP (3:7; Treated) and histological, biochemical and fertility determinations were made up to 11 weeks after the injections. The results show that within one week of a single injection with THP, the weights of testes and epididymides are significantly less than those of the Controls and the reduced weights persist for at least 11 weeks. The seminiferous tubules are largely depleted of spermatogenetic cells by 2 weeks and they remain devoid of dividing germ cells for the 11 week period. The Leydig cells have a normal appearance and histochemically show the same 3 alpha-hydroxysteroid dehydrogenase (3 alpha-HSD) and 3 beta-HSD activities as Controls. In vitro studies of the testes showed that the activities of the steroid enzymes 20 alpha-HSD, 17 beta-HSD, 17 alpha-hydroxylase and C17-20-lyase and the production of testosterone and androstenedione were not altered by the THP treatment. Similarly, serum levels of testosterone, LH, and FSH, measured by RIA, and weights of the prostate and seminal vesicles were the same as in Controls. Treated males showed the same degree of sexual behaviour and mating frequency as the Controls, but after the 3rd mating were 100% infertile for the duration of the experiments. The total number of sperm in epididymides of Treated rats was reduced by 99.99% after the 3rd mating.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed2002

Cross-linked hyaluronan for augmentation of the posterior pharyngeal wall: an experimental study in rats.

Velopharyngeal insufficiency can be treated in different ways. Augmentation injections of various space-filling materials have been tried, but a substance that has the ideal properties--easy to inject, non-toxic, and not immunogenic, and having a lasting effect--has not yet been found. Hylan b gel, a double cross-linked hyaluronan solution, is a new tissue augmentor that is not immunogenic and is easy to use. The purpose of this study was to evaluate the persistence of and the tissue reaction to hylan b gel injected into the posterior pharyngeal wall of 12 rats. Six rats acted as controls. A light immediate, and no late, inflammatory reaction developed in the pharyngeal mucosa after injection. Six months after injection, the gel was still present and the substance had been invaded by and surrounded by newly-formed, loose connective tissue. These results indicate that hylan b gel may be an appropriate substance in the augmentation of mild velopharyngeal insufficiency in man. However, further studies are needed to evaluate its long-term effects.

Animals↗

PubMed2001

The costly illusion of regulating unknowable risks.

Uncommon but alarming man-made toxic episodes have occasioned regulation to ensure the safety of novel and commonly used substances and foremost to control agents that may cause cancer. However, the safety or harm of novel entities has no durable record of human use, and hence is virtually unknown. Compelled to act, regulators have chosen animal tests to forecast human cancer risks. To this end, animal data are filtered through a series of preconceived assumptions that are presumed to overcome a host of human/animal differences of biology, exposure, and statistics-differences that in reality are insurmountable. Asked for authoritative opinion, the National Academy of Sciences repeatedly found this regulatory approach without factual or scientific justification and, by implication, arbitrary and irrational. On these grounds, such a regulatory process appears vulnerable to scientific, legal, and constitutional challenges. Although it cannot provide credible assurance that an agent may be safe or harmful, the process has been a prime reason for an annual regulatory burden that exceeds the combined after-tax profits of all U.S. industrial activity. It is argued here that better use of national resources would come from a rational approach based on trade-off considerations, where a substance would be regulated depending on its socio-economic utility and on scientific evidence of proved relevance to human safety.

Animals↗

PubMed1993

Current perspectives on anabolic-androgenic steroid abuse.

For the past 40 years anabolic-androgenic steroids have been used by a wide variety of athletes with the hope of improving their training, endurance and performance. Proponents of their use claim that the drugs increase muscle strength and mass, endurance, decrease recovery time between workouts and improve physique. Critics claim that these beneficial effects are due primarily to expectancy and other factors associated with training; many doctors also claim that their use is actually quite dangerous. Regardless of their efficacy, the use and abuse of anabolic-androgenic steroids has escalated such that in 1990 the US Congress enacted the Anabolic Steroids Control Act requiring that anabolic steroids be added to Schedule III of the Controlled Substances Act. This action placed compounds such as testosterone cipionate and nandrolone decanoate in the company of various opioid drugs, amphetamines and barbiturates. As chair of the American Society for Pharmacology and Experimental Therapeutics' Committee on Substance Abuse, Scott Lukas advocates continued research on the effectiveness, toxicity and natural history of anabolic-androgenic steroid abuse.

Anabolic Agents↗

PubMedDate not supplied

Gastrointestinal host defence: importance of gut closure in control of macromolecular transport.

An important adaptation of the gastrointestinal tract to the extrauterine environment is its development of a mucosal barrier against the penetration of harmful substances (bacteria, toxins and antigens) present within the intestinal lumen. At birth, the newborn infant must be prepared to deal with bacterial colonization of the gut, with formation of toxic byproducts of bacteria and viruses (enterotoxins and endotoxins) and with the ingestion of antigens (milk proteins). These potentially noxious substances if allowed to penetrate the mucosal epithelial barrier under pathological conditions can cause inflammatory and allergic reactions which may result in gastrointestinal and systemic disease states. To combat the potential danger of invasion across the mucosal barrier the infant must develop an elaborate system of defence mechanisms within the lumen and on the luminal mucosal surface which act to control and maintain the epithelium as an impermeable barrier to uptake of macromolecular antigens. These defences include a unique immunological system adapted to function in the complicated milieu of the intestine as well as other non-immunological processes such as a gastric barrier, intestinal surface secretions, peristaltic movement and natural antibacterial substances (lysozyme, bile salts) which also help to provide maximum protection for the intestinal surface. Unfortunately, during the immediate postpartum period, particularly for premature and small-for-dates infants, this elaborate local defence system is incompletely developed. As a result of the delay in the maturation of the mucosal barrier newborn infants are particularly vulnerable to pathological penetration by harmful intraluminal substances. The consequences of altered defence are susceptibility to infection and the potential for hypersensitivity reactions and for formation of immune complexes. With these reactions comes the potential for developing life-threatening diseases such as necrotizing enterocolitis, sepsis and hepatitis. Fortunately, 'nature' has provided a means for passively protecting the 'vulnerable' newborn against dangers of a deficient intestinal defence system, namely human milk. It is now increasingly apparent that human milk contains not only antibodies and viable leucocytes but many other substances which can interfere with bacterial colonization and prevent antigen penetration.

Animals↗

PubMed1990

Air toxics in the U.S.: magnitude of the problem and strategy for control.

Over the past several years, substantial concern has been expressed by some in Congress, environmental groups, and members of the public concerning the lack of progress in regulating toxic air pollutants by the U.S. Environmental Protection Agency (EPA). As a result, a number of amendments to the Federal Clean Air Act have been introduced to require EPA to regulate in a relatively rapid timeframe, a large number of potentially toxic pollutants that are released to the ambient air. This paper discusses EPA's current understanding of the magnitude and nature of the air toxics problem in the U.S., and the pollutants and source categories that pose the most significant risk to the public. The focus of the discussion is on routine releases, as opposed to catastrophic, accidental releases such as the one in Bhopal, India. The paper then discusses the strategy that EPA has put in place to deal with the problem and presents the status of a number of regulatory and non-regulatory activities under way to better understand the problem and to mitigate it. The strategy involves important roles for: (1) EPA to regulate national problems using a variety of Federal authorities in addition to the Clean Air Act, and (2) States to develop their own air toxic control programs to deal with unique local problems involving high risk point sources and multipollutant, multisource problems in large urban or industrialized areas.

Air Pollutants↗

PubMed1995

A step towards developing the expertise to control hunger and satiety: regulatory role of satiomem--a membrane proteoglycan.

Regulation of hunger and satiety is a complex process thought to be controlled by a complex interplay of neurotransmitters in the hypothalamic region of the brain. Reduced food intake or anorexia has also been observed under various disease or disorder conditions including AIDS and cancer. On the other hand, increased appetite because of some impairment of central mechanisms regulating the food intake could also cause/obesity. A large number of substances including neuropeptides, hormones, drugs, and synthetic peptides have been implicated in the regulation of appetite and food intake behavior in normal as well as disease or disorder conditions. Most of these substances are not directly involved in the regulation of normal hunger and satiety but exert their effect indirectly via other media. Some of them are involved under certain pathologic conditions and during the course they become involved directly or indirectly in the triggering of hunger and satiety regulatory mechanism. Recently, we have been able to isolate and purify an endogenous proteoglycan from membranes of animal and plant sources. This membrane anchored proteoglycan termed as 'Satiomem' reduces food intake without any rebound effects and has no apparent toxicity. It also fulfils all the criteria of a true satiety or anorexigenic substance. The release of satiomem from the cell surface could be mediated by a specific phospholipase-C. Satiomem seems to be involved in transducing activating signals and may also act as a source of second messenger for the regulatory mechanism of appetite. This article summarizes the regulatory aspects of hunger and satiety mechanisms controlled by endogenous substances with the emphasis on our present knowledge about satiomem.

Animals↗

PubMed2000

Potent preventive action of curcumin on radiation-induced initiation of mammary tumorigenesis in rats.

This investigation evaluated the preventive effect of curcumin on radiation-induced tumor initiation in rat mammary glands. Fifty-four female rats were mated and then divided into two groups at day 11 of pregnancy. As the control group, 27 rats were fed a basal diet during the experimental period. As the experimental group, 27 rats were fed a diet containing 1% curcumin between day 11 of pregnancy and parturition (day 23 of pregnancy). All rats of both groups received whole body irradiation with 1.5 Gy gamma-rays from a (60)Co source at day 20 of pregnancy and were then implanted with a diethylstilbestrol pellet 1 month after weaning. A high incidence (70.3%) of mammary tumorigenesis was observed in the control group. The tumor incidence (18.5%) was significantly reduced in the rats fed curcumin during the initiation stage. The appearance of the first palpable tumor was delayed by 6 months in the curcumin-fed group and the average latent period until the appearance of mammary tumors was 2.5 months longer in the curcumin-fed group than in the control group. By histological examination, the proportion of adenocarcinoma (16.7%) in total tumors in the curcumin-fed rats was found to be decreased to half that (32.1%) in the control group. Compared with the control rats, the body weight of rats in the experimental group was decreased slightly by administration of the curcumin diet from day 11 of pregnancy, in spite of a similar intake of diet, but had recovered to the level of the control by the end of the experiment. At the time of irradiation, curcumin did not have any effect on organ weight or on the development and differentiation of mammary glands of pregnant rats. In addition, the serum concentrations of fatty acids, thiobarbituric acid-reactive substances and ovarian and pituitary hormones, except LH, remained at the control level. Also, no change in litter size and body weight of pups born from curcumin-fed rats indicated no toxicity of curcumin. These results suggest that curcumin does not have any side-effects and is an effective agent for chemoprevention acting at the radiation-induced initiation stage of mammary tumorigenesis.

Animals↗

PubMed2006

Toxic effects of two pesticides, Imazalil and Triadimefon, on the early development of the ascidian Phallusia mammillata (Chordata, Ascidiacea).

Azole compounds are fungicides used in agriculture and in clinical area and are suspected to produce craniofacial malformations in vertebrates. Toxicity tests on sperm viability, fertilization and embryogenesis of the solitary ascidian Phallusia mammillata were performed to evaluate the effects of two azole derivatives, Imazalil and Triadimefon. Ascidian (Chordata, Ascidiacea) embryos and larvae could provide biological criteria for seawater quality standards because the larvae are lecitotrophic and have a short pelagic period, allowing to run the larval toxicity tests over a short period of time. Imazalil and Triadimefon proved to have strong consequences on P. mammillata. They could influence the reproductive rate of the animal exerting their effects at different levels: acting as spermiotoxic agents, inhibiting fertilization and impairing embryological development. Fertilization rate significantly decreased after 30min exposure of sperm to 25microM Imazalil (P<0.0001) and after exposure of both gametes to 50microM Imazalil (P<0.05) and 1mM Triadimefon (P<0.0001) as compared to controls. Malformations caused by exposure of embryos to both substances were dose dependent. Imazalil median teratogenic concentration (TC50 concentration, the concentration that resulted in 50% malformed larvae) value was 0.67microM and median lethal concentration (LC50, the concentration that resulted in 50% embryos dead before completing the development) value was 10.23microM while for Triadimefon TC50 value was 29.56 and LC50 value was 173.7microM. Larvae developed from embryos treated with Imazalil and Triadimefon showed alterations of the anterior structures of the trunk: papillary nerves and the anterior central nervous system failed to correctly differentiate, as showed by immunostaining with anti-beta-tubulin antibody. Comparing the anomalies caused by retinoic acid, reported in a previous study, it was possible to hypothesize that malformations induced by Imazalil and Triadimefon could be due to a perturbation of the endogenous retinoid content, as it has been proposed for mammals. Ascidians proved to be good models to study the toxic effects of pesticides since they offered both the convenience of working with an invertebrate species and the tissue sensitivity to chemical compound comparable to vertebrates.

Animals↗

PubMed2004

Effects of natural and chemically synthesized furanones on quorum sensing in Chromobacterium violaceum.

BACKGROUND: Cell to cell signaling systems in Gram-negative bacteria rely on small diffusible molecules such as the N-acylhomoserine lactones (AHL). These compounds are involved in the production of antibiotics, exoenzymes, virulence factors and biofilm formation. They belong to the class of furanone derivatives which are frequently found in nature as pheromones, flavor compounds or secondary metabolites. To obtain more information on the relation between molecular structure and quorum sensing, we tested a variety of natural and chemically synthesized furanones for their ability to interfere with the quorum sensing mechanism using a quantitative bioassay with Chromobacterium violaceum CV026 for antagonistic and agonistic action. We were looking at the following questions: 1) Do these compounds affect growth? 2) Do these compounds activate the quorum sensing system of C. violaceum CV026? 3) Do these compounds inhibit violacein formation induced by the addition of the natural inducer N-hexanoylhomoserine lactone (HHL)? 4) Do these compounds enhance violacein formation in presence of HHL? RESULTS: The naturally produced N-acylhomoserine lactones showed a strong non-linear concentration dependent influence on violacein production in C. violaceum with a maximum at 3.7*10-8 M with HHL. Apart from the N-acylhomoserine lactones only one furanone (emoxyfurane) was found to simulate N-acylhomoserine lactone activity and induce violacein formation. The most effective substances acting negatively both on growth and quorum sensing were analogs and intermediates in synthesis of the butenolides from Streptomyces antibioticus. CONCLUSION: As the regulation of many bacterial processes is governed by quorum sensing systems, the finding of natural and synthetic furanones acting as agonists or antagonists suggests an interesting tool to control and handle detrimental AHL induced effects. Some effects are due to general toxicity; others are explained by a competitive interaction for LuxR proteins. For further experiments it is important to be aware of the fact that quorum sensing active compounds have non-linear effects. Inducers can act as inhibitors and inhibitors might be able to activate or enhance the quorum sensing system depending on chemical structure and concentration levels.

4-Butyrolactone↗

PubMed1997

Poisonings associated with illegal use of aldicarb as a rodenticide -- New York City, 1994-1997.

Although rodenticides historically have been among the most toxic substances available to the public and have been implicated as agents in both unintentional and suicidal exposures, the anticoagulant agents currently in use, such as coumadin and their long-acting derivatives (e.g., brodifacoum), are relatively safe. In 1995, most persons who reported exposure to anticoagulant rodenticides did not develop symptoms or require specific therapy. However, during 1994-1997, the New York City Poison Control Center (NYCPCC) was consulted about 25 patients, primarily persons who had emigrated from the Dominican Republic, who had manifestations consistent with the cholinergic toxidrome, which is not characteristic of poisoning by the anticoagulant rodenticides, after ingesting a rodenticide known as Tres Pasitos ("Three Little Steps"). In each case, the product had been purchased at a neighborhood store for use as a household rodenticide. The Environmental Investigation Unit of the New York State Department of Environmental Conservation (NYDEC) investigated the poisoning incidents. Laboratory analysis indicated that the product contained the carbamate pesticide aldicarb (2-methyl-2-(methylthio)-propionaldehyde O-(methylcarbamoyl) oxime), which is not registered for use as a rodenticide in the United States. This report presents a detailed description of two of these cases and a summary of the remaining cases.

Adult↗

PubMed2003

A critical assessment of the OECD collaborative study to validate the uterotrophic assay for the detection of oestrogenic and anti-oestrogenic chemicals.

The design and execution of a recently completed validation study on the rat uterotrophic assay for detecting oestrogens and anti-oestrogens, managed by the OECD, are critically assessed with respect to internationally agreed criteria for the validation of new in vitro and in vivo toxicity test methods. It is concluded that, while the design of the study did not take account of several important criteria for validation, the uterotrophic assay appears to reliably detect the strong and weak oestrogenic substances used in the study, which act via binding to the oestrogen receptor in vivo. However, the reliability of the assay has not been substantiated for detecting anti-oestrogens that act as antagonists, due to the involvement of an insufficient number of experiments and test chemicals. Moreover, the data do not permit an assessment of the accuracy of the prediction of oestrogenicity, and the protocols have not been sufficiently optimised with regard to controlling variables. This problem has been exacerbated by a wish to introduce as much flexibility as possible into the protocols during the formal validation phase of the study, rather than during a separate prevalidation stage. In addition, the choice between surgically treated and/or immature animals, and details of housing and husbandry conditions that are necessary for increasing the sensitivity and efficiency of the assay, need to be clarified. The assay also lacks a well-defined prediction model by which the overall relevance of the data to toxicity, and especially to human hazard, can be assessed, and no performance criteria have been established. The results of this analysis of the study indicate that it would be premature to produce an OECD test guideline for the uterotrophic assay at this time, before some of the above issues have been satisfactorily resolved.

Animals↗

PubMed2005

Relating results of chronic toxicity responses to population-level effects: modeling effects on wild Chinook salmon populations.

Standard toxicity tests assess the physiological responses of individual organisms to exposure to toxic substances under controlled conditions. Time and space restrictions often prohibit the assessment of population-level responses to a toxic substance. Compounds affecting various toxicity endpoints, such as growth, fecundity, behavior, or immune function, alter different demographic traits and produce different impacts on the population. Chronic effects of immune suppression, reproductive impairment, and growth reduction were examined using life history models for Chinook salmon (Oncorhynchus tshawytscha). Modeled immune suppression acted through reductions in age-specific survival, with first- and second-year survival producing the greatest changes in the population growth rate (lamda). A 10% reduction in various reproductive parameters all produced a similar lamda, but different sensitivity and stable age distributions. Growth reduction models incorporated effects to both survival and reproduction and produced additive effects. Overall, model output indicated that for Chinook salmon, alteration of first-year survival has the greatest relative impact on lamda. Results support the importance of linking toxicity endpoints to the demographic traits that they influence and help generate toxicity tests that are more relevant for the species. Life history modeling provides a useful tool to develop testable hypotheses regarding specific and comparative population-level impacts.

Animals↗

PubMed2004

Environmental pediatrics and its impact on government health policy.

Recent public recognition that children are different from adults in their exposures and susceptibilities to environmental contaminants has its roots in work that began >46 years ago, when the American Academy of Pediatrics (APA) established a standing committee to focus on children's radiation exposures. We summarize the history of that important committee, now the AAP Committee on Environmental Health, including its statements and the 1999 publication of the AAP Handbook of Pediatric Environmental Health, and describe the recent emergence of federal and state legislative and executive actions to evaluate explicitly environmental health risks to children. As a result in large part of these efforts, numerous knowledge gaps about children's health and the environment are currently being addressed. Government efforts began in the 1970s to reduce childhood lead poisoning and to monitor birth defects and cancer. In the 1990s, federal efforts accelerated with the Food Quality Protection Act, an executive order on children's environmental health, the Agency for Toxic Substances and Disease Registry/Environmental Protection Agency Pediatric Environmental Health Specialty Units, and National Institute of Environmental Health Sciences/Environmental Protection Agency Centers of Excellence in Research in Children's Environmental Health. In this decade, the Children's Environmental Health Act authorized the National Children's Study, which has the potential to address a number of critical questions about children's exposure and health. The federal government has expanded efforts in control and prevention of childhood asthma and in tracking of asthma, birth defects, and other diseases that are linked to the environment. Efforts continue on familiar problems such as the eradication of lead poisoning, but new issues, such as prevention of childhood exposure to carcinogens and neurotoxins other than lead, and emerging issues, such as endocrine disruptors and pediatric drug evaluations, are in the forefront. More recently, these issues have been taken up by states and in the international arena.

Congenital Abnormalities↗

PubMedDate not supplied

[Applicability of the new law of State and Regional Agreement on management of swimming pools].

The Authors carried out a survey on private and public managers of 80 Italian swimming pools to evaluate the hygienic aspects and safety of the swimming pools. Participants were submitted to a set of questions about the modifications recently brought to the Act on management of the swimming pools during 2003. The study showed a poor knowledge about the hygienic-safety parameters, in particular of chlorine doses, range of temperature and frequency of daily turnover of the swimming pool water. The respect of chemical-physical parameters is necessary not only to assure an adequate microbial control of the water, but also to reduce the production of irritant and potentially toxic substances. The Authors pointed out the need of greater attention to hygienic aspects in order to reduce health risks, deriving from an uncorrected application of the laws, and to provide a greater comfort to the users of swimming pools.

Chlorine↗