Exposure interventions

Dioxin Dioxin in blood or lipid Biomarker to body burden and external dose in humans body burden and external dose to toxicity in animals Biomarker results can estimate human risk exposure intervention possible... 

Increase research emphasis on the low and high ends of the biomarker distribution to discover what leads to these tails and thus enhance the development of exposure interventions if warranted. 

During an accident or emergency, a source is often out of human control. This necessitates prompt action to mitigate a hazard or to prevent adverse consequences for human health and safety, quality of life, and condition of the environment. In addition, protective action should be taken in some chronic exposures. Intervention and action levels support the decisions regarding the introduction of different preventive procedures. 

In this review we concentrate on individual-based studies. In case-control studies, subjects with already existing disease are retrospectively compared with control persons with respect to previous exposure. In cohort studies, individual exposure is measured at baseline and the cohort is followed over time for newly diagnosed outcome variables. Both case-control and cohort studies estimate the (relative) risk associated with exposure. Intervention studies utilize an experimental design and are mostly double blind trials with a defined treatment or placebo assigned randomly. Results from intervention studies, followed by cohort studies, make the greatest contributions to obtaining evidence of a causal relationship. Case-control studies are liable to particular bias, which give their results less credibility. 

In some pharmacotherapy studies, psychotherapy exposure has been minimized, on the basis of concern that psychotherapy may produce a ceiling effect on improvement in drug or alcohol use, making medication effects difficult to detect. However, a recent meta-analysis revealed that psychosocial interventions, in fact, may enhance pharmacotherapeutic effects (Hopkins et al. 2002). In this review we have also noted instances where psychosocial and medication treatments have had beneficial additive effects. Minimization of psychotherapy in pharmacotherapy trials may be counterproductive, because psychosocial therapies that encourage the patient to remain engaged in treatment may positively affect patients adherence to the medication regimen, a factor that has an effect on alcohol treatment outcomes (Chick et al. 2000 Volpicelli et al. 1997). 

Intervention measures have been proposed, based on the relationships between ACHE inhibition levels and biological effects (ICOH, 1986 Zielhuis, 1972). An ACHE decrease of 30% or less from the baseline (or 50% or less from the average reference level) requires medical surveillance and examination of working conditions. A reduction of more than 30% from baseline (or 50% from the reference level) requires temporary removal from exposure and careful evaluation of the working conditions. 

Phytochemicals have been the subject of many studies evaluating their effects in relation to common chronic human illnesses such as cancer and cardiovascular diseases. These studies encounter difficulties in using this information to influence the dietary patterns of consumers because in the past they have used models or experiments with animals. However, in the last decade, researchers have moved away from animal studies in favour of human cell models or human intervention studies. Scientists still need to determine the likely incidence of illness from exposure to known amounts of a given natural compound in the diet and specifically in relation to the complex matrices of whole foods. Therefore, it is inevitable that some animal studies have to be continued for toxicological studies. 

Human toxicity data are limited to secondary citations. Because these citations provided no experimental details, they cannot be considered reliable. Deaths have occurred from aniline ingestion and skin absorption, but doses were unknown. Reviews of the older literature indicate that a concentration of 5 ppm was considered safe for daily exposures, concentrations of 7 to 53 ppm produced slight symptoms after several hours, a concentration of 40 to 53 ppm was tolerated for 6 h without distinct symptoms, a concentration of 130 ppm may be tolerated for 0.5 to 1 h without immediate or late sequalae, and 100 to 160 ppm was the maximum concentration that could be inhaled for 1 h without serious disturbance. In studies of accidents with unknown exposure concentrations, methemoglobin levels of up to 72% were measured. Recoveries occurred with a minimum of medical intervention following cessation of exposure. 

Levinsky et al. (1970) reported on three men exposed to an unknown concentration of arsine for an estimated, 2, 3, and 15 min. Signs and symptoms of exposure (malaise, headache, abdominal pain, chills, nausea, vomiting, oliguria/ anuria, hematuria, bronze skin color) developed within 1-2 h. All three individuals required extensive medical intervention to save their lives. Clinical findings were indicative of massive hemolysis and repeated blood exchange transfusions were necessary for the survival of these individuals. 

Pinto (1976) also reported similar characteristics regarding acute arsine poisoning. Although, an exposure concentration was unavailable, exposure to newly formed arsine for less than 1 h resulted in severe (likely fatal without medical intervention of exchange transfusion) signs and symptoms, including... 

Numerous cases of arsine poisoning have been reported (Elkins and Fahy 1967 DePalma 1969). However, these reports lack definitive exposure concentration data and usually lack exposure duration data as well. Some of the more recent and complete reports involving nonlethal consequences are described in the following section. These reports do not provide quantitative data suitable for AEGL derivations, but they do provide valuable insight into the nature and progression of arsine poisoning in humans. In most cases, the severity of the effects was usually sufficient to necessitate medical intervention to prevent lethality. Some of the more prominent reports and those with the best descriptive data have been summarized, but the overview is by no means exhaustive. 

A case report of acute arsine poisoning in which a 27-y-old man was exposed to arsine during chemical manufacturing was reported by Pinto (1976). The subject was exposed to arsine as a result of arsine production via a reaction between a galvanized bucket and an arsenic-containing sulfuric acid solution. The exposure (duration not specified) produced toxic effects characterized by abdominal cramping, thoracic discomfort, and hematuria. Over the next week, the patient s hematocrit declined from 42.5 to 27.1 and hemoglobin dropped from 14.1 to 9.5 g/dL even with medical intervention (blood transfusions and mannitol diuresis). Nine hours after exposure, blood arsenic was 159 g/dL and urinary arsenic was 1862 ug/L. 

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