Oral and dermal absorption of chlorpyrifos: a human volunteer study. (57/8052)

OBJECTIVES: To determine the kinetics of elimination of urinary dialkylphosphate metabolites after oral and dermally applied doses of the organophosphate pesticide chlorpyrifos to human volunteers and to determine whether these doses affected plasma and erythrocyte cholinesterase activity. METHOD: Five volunteers ingested 1 mg (2852 nmol) of chlorpyrifos. Blood samples were taken over 24 hours and total void volumes of urine were collected over 100 hours. Four weeks later 28.59 mg (81567 nmol) of chlorpyrifos was administered dermally to each volunteer for 8 hours. Unabsorbed chlorpyrifos was washed from the skin and retained for subsequent measurement. The same blood and urine sampling regime was followed as for the oral administration. Plasma and erythrocyte cholinesterase concentrations were determined for each blood sample. The concentration of two urinary metabolites of chlorpyrifos--diethylphosphate and diethyl-thiophosphate--was determined for each urine sample. RESULTS: The apparent elimination half life of urinary dialkylphosphates after the oral dose was 15.5 hours and after the dermal dose it was 30 hours. Most of the oral dose (mean (range) 93% (55-115%)) and 1% of the applied dermal dose was recovered as urinary metabolites. About half (53%) of the dermal dose was recovered from the skin surface. The absorption rate through the skin, as measured by urinary metabolites was 456 ng/cm2/h. Blood plasma and erythrocyte cholinesterase activity did not fall significantly during either dosing regime. CONCLUSION: An oral dose of chlorpyrifos was readily absorbed through the skin and almost all of the dose was recovered as urinary dialkylphosphate metabolites. Excretion was delayed compared with the oral dose. Only a small proportion of the applied dose was recovered during the course of the experiment. The best time to collect urine samples for biological monitoring after dermal exposure is before the shift the next day. The amounts of chlorpyrifos used did not depress acetyl cholinesterase activity but could be readily detected as urinary dialkylphosphate metabolites indicating that the urinary assay is a more sensitive indicator of exposure.  (+info)

Mineral fibre analysis and routes of exposure to asbestos in the development of mesothelioma in an English region. (58/8052)

OBJECTIVES: To compare the concentrations of inorganic fibres in the lungs in cases of mesothelioma and controls: to determine whether concentrations of retained asbestos fibres differ with the different exposures identified from interview; and to investigate the existence of a cut off point in concentrations of asbestos fibres that indicates occupational exposure. METHODS: Case-control study; 147 confirmed cases of mesothelioma and 122 controls identified from deaths occurring in four districts of Yorkshire between 1979 and 1991. Surviving relatives were interviewed to determine lifetime exposure history to asbestos. Mineral fibre analysis was carried out on lung tissue from postmortem examinations. RESULTS: Odds on high concentrations of retained asbestos fibres were greater in cases than controls. After excluding subjects with occupational and paraoccupational exposure, the odds on high concentrations were still greater in cases than controls, but only significantly so for amphiboles. There was only a weak relation between probability of occupational exposure to asbestos and concentrations of retained asbestos fibres, and no significant difference in fibre concentrations was found between subjects who had been exposed to asbestos through different routes: these comparisons were only based on small groups. There was considerable overlap in concentrations of retained asbestos fibres between cases and controls with and without histories of occupational exposure. CONCLUSIONS: The study has confirmed previous results of higher concentrations of asbestos fibres in cases than controls, and has shown that this is still found in subjects with little evidence of occupational and para-occupational exposure. The overlap in concentrations of retained asbestos for different groups of subjects did not suggest a clear cut of value.  (+info)

Etiology and pathogenesis of airway disease in children and adults from rural communities. (59/8052)

Asthma is the most common chronic disease of childhood and affects nearly 5 million children. The prevalence and severity of childhood asthma have continued to increase over the past decade despite major advances in the recognition and treatment of this condition. A comparison of urban and rural children suggests that the etiology of airway disease is multifactorial and that unique exposures and genetic factors contribute to the development of asthma in both settings. The most important environmental exposure that distinguishes the rural environment and is known to cause asthma is the organic dusts. However, animal-derived proteins, common allergens, and low concentrations of irritants also contribute to the development of airway disease in children and adults living in rural communities. A fundamental unanswered question regarding asthma is why only a minority of children who wheeze at an early age develop persistent airway disease that continues throughout their life. Although genetic factors are important in the development of asthma, recurrent airway inflammation, presumably mediated by environmental exposures, may result in persistent airway hyperresponsiveness and the development of chronic airway disease. Increasing evidence indicates that control of the acute inflammatory response substantially improves airflow and reduces chronic airway remodeling. Reducing exposure to agricultural dusts and treatment with anti-inflammatory medication is indicated in most cases of childhood asthma. In addition, children with asthma from rural (in comparison to urban) America face multiple barriers that adversely affect their health e.g., more poverty, geographic barriers to health care, less health insurance, and poorer access to health care providers. These unique problems must be considered in developing interventions that effectively reduce the morbidity and mortality of asthma in children from rural communities.  (+info)

A theoretical basis for investigating ambient air pollution and children's respiratory health. (60/8052)

Acute respiratory health effects in children from exposure at current ambient levels of ozone are well documented; however, evidence for acute effects from other criteria pollutants such as nitrogen dioxide and respirable particles is inconsistent. Whether chronic effects result from long-term exposure to any of these pollutants during childhood is an important unresolved question. Establishing whether acute or chronic effects result from childhood exposure and identifying sensitive subgroups may require integration of biologic mechanisms of lung defenses, injury, and response into the study design and statistical models used in analyses. This review explores the theoretical basis for explaining such adverse effects in light of our contemporary understanding of mechanisms of lung injury and response at the cellular and molecular levels. The rapidly evolving understanding of the effects of air pollution on cellular and molecular levels presents an opportunity to develop and refine innovative biologically based hypotheses about the effects of childhood exposure. We hypothesize that children with low fruit and vegetable intake, low antioxidant levels, high polyunsaturated fat intake, or who have inherited certain alleles for genes involved in lung defenses and immune response regulation may be at increased risk for adverse effects. Because responses to air pollutants of interest are complex and involve a number of pathophysiologic processes, the magnitude of main effects of dietary factors, genes, and gene-environment interactions may be modest for individuals; however, each may make an important contribution to the population burden of preventable respiratory diseases.  (+info)

Exposures of children to organophosphate pesticides and their potential adverse health effects. (61/8052)

Recent studies show that young children can be exposed to pesticides during normal oral exploration of their environment and their level of dermal contact with floors and other surfaces. Children living in agricultural areas may be exposed to higher pesticide levels than other children because of pesticides tracked into their homes by household members, by pesticide drift, by breast milk from their farmworker mother, or by playing in nearby fields. Nevertheless, few studies have assessed the extent of children's pesticide exposure, and no studies have examined whether there are adverse health effects of chronic exposure. There is substantial toxicologic evidence that repeated low-level exposure to organophosphate (OP) pesticides may affect neurodevelopment and growth in developing animals. For example, animal studies have reported neurobehavorial effects such as impairment on maze performance, locomotion, and balance in neonates exposed (italic)in utero(/italic) and during early postnatal life. Possible mechanisms for these effects include inhibition of brain acetylcholinesterase, downregulation of muscarinic receptors, decreased brain DNA synthesis, and reduced brain weight in offspring. Research findings also suggest that it is biologically plausible that OP exposure may be related to respiratory disease in children through dysregulation of the autonomic nervous system. The University of California Berkeley Center for Children's Environmental Health Research is working to build a community-university partnership to study the environmental health of rural children. This Center for the Health Assessment of Mothers and Children of Salinas, or CHAMACOS in Monterey County, California, will assess (italic)in utero(/italic) and postnatal OP pesticide exposure and the relationship of exposure to neurodevelopment, growth, and symptoms of respiratory illness in children. The ultimate goal of the center is to translate research findings into a reduction of children's exposure to pesticides and other environmental agents, and thereby reduce the incidence of environmentally related disease.  (+info)

Pesticides and inner-city children: exposures, risks, and prevention. (62/8052)

Six million children live in poverty in America's inner cities. These children are at high risk of exposure to pesticides that are used extensively in urban schools, homes, and day-care centers for control of roaches, rats, and other vermin. The organophosphate insecticide chlorpyrifos and certain pyrethroids are the registered pesticides most heavily applied in cities. Illegal street pesticides are also in use, including tres pasitos (a carbamate), tiza china, and methyl parathion. In New York State in 1997, the heaviest use of pesticides in all counties statewide was in the urban boroughs of Manhattan and Brooklyn. Children are highly vulnerable to pesticides. Because of their play close to the ground, their hand-to-mouth behavior, and their unique dietary patterns, children absorb more pesticides from their environment than adults. The long persistence of semivolatile pesticides such as chlorpyrifos on rugs, furniture, stuffed toys, and other absorbent surfaces within closed apartments further enhances urban children's exposures. Compounding these risks of heavy exposures are children's decreased ability to detoxify and excrete pesticides and the rapid growth, development, and differentiation of their vital organ systems. These developmental immaturities create early windows of great vulnerability. Recent experimental data suggest, for example, that chlorpyrifos may be a developmental neurotoxicant and that exposure in utero may cause biochemical and functional aberrations in fetal neurons as well as deficits in the number of neurons. Certain pyrethroids exert hormonal activity that may alter early neurologic and reproductive development. Assays currently used for assessment of the toxicity of pesticides are insensitive and cannot accurately predict effects to children exposed in utero or in early postnatal life. Protection of American children, and particularly of inner-city children, against the developmental hazards of pesticides requires a comprehensive strategy that monitors patterns of pesticide use on a continuing basis, assesses children's actual exposures to pesticides, uses state-of-the-art developmental toxicity testing, and establishes societal targets for reduction of pesticide use.  (+info)

The environment and asthma in U.S. inner cities. (63/8052)

The prevalence and severity of asthma has increased in the last 20 years, and the greatest increase has been seen among children and young adults living in U.S. inner cities. The reasons for this increase are obviously complex, but include environmental exposures to allergens and pollutants, changing patterns of medication, and the psychosocial stresses of living in poor inner-city neighborhoods. This paper presents an overview of environmental, immunologic, and genetic factors associated with asthma morbidity and mortality. This overview can be used to provide a framework for designing an interdisciplinary research program to address the complexities of asthma etiology and exacerbation. The strongest epidemiologic association has been found between asthma morbidity and the exposure of immunologically sensitive asthmatic patients to airborne allergens. Our current understanding of the process of sensitization suggests that there is a strong genetic predisposition to form IgE to allergenic proteins on airborne particles. Much of this work has been conducted with animal models, but in a number of instances, specific confirmation has been reported in humans. Sensitized individuals respond to inhaled exposure with immediate mast-cell dependent inflammation that may be augmented by pollutant particles, especially diesel exhaust particles. Relatively little is known about the methods of assessing exposure to airborne pollutants, especially biologically active particulates. However, to examine the relationship of morbidity in genetically predisposed individuals, it will be important to determine the most relevant method of making this assessment.  (+info)

Introduction and summary: workshop on children's health and indoor mold exposure. (64/8052)

To evaluate the health consequences for children of indoor exposure to molds, an international workshop was organized with 15 scientists from eight countries. The participants agreed that exposure to molds may constitute a health threat to children resulting in respiratory symptoms in both the upper and lower airways, an increased incidence of infections, and skin symptoms. Allergy, either to molds or to other indoor agents, also presents a health risk. At very high exposure levels to specific molds, nose bleeding, hemoptysis, and pulmonary hemorrhage have been documented. Pediatricians and allergists need to obtain information about mold and dampness in the home environment when examining children with chronic respiratory symptoms, recurrent infections, or persistent fatigue and headache. Measurement techniques are available to determine exposure. Most important, the source of dampness must be eliminated and the indoor environment must be thoroughly cleaned of molds.  (+info)