Phosphine toxicity: ethical questions.
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Chemical Industry↗
Biomedical subjects
Elizabeth L Anderson
Publications and source records attributed to Elizabeth L Anderson.
Rhinovirus illnesses during infancy predict subsequent childhood wheezing.
BACKGROUND: The contribution of viral respiratory infections during infancy to the development of subsequent wheezing and/or allergic diseases in early childhood is not established. OBJECTIVE: To evaluate these relationships prospectively from birth to 3 years of age in 285 children genetically at high risk for developing allergic respiratory diseases. METHODS: By using nasal lavage, the relationship of timing, severity, and etiology of viral respiratory infections during infancy to wheezing in the 3rd year of life was evaluated. In addition, genetic and environmental factors that could modify risk of infections and wheezing prevalence were analyzed. RESULTS: Risk factors for 3rd year wheezing were passive smoke exposure (odds ratio [OR]=2.1), older siblings (OR=2.5), allergic sensitization to foods at age 1 year (OR=2.0), any moderate to severe respiratory illness without wheezing during infancy (OR=3.6), and at least 1 wheezing illness with respiratory syncytial virus (RSV; OR=3.0), rhinovirus (OR=10) and/or non-rhinovirus/RSV pathogens (OR=3.9) during infancy. When viral etiology was considered, 1st-year wheezing illnesses caused by rhinovirus infection were the strongest predictor of subsequent 3rd year wheezing (OR=6.6; P < .0001). Moreover, 63% of infants who wheezed during rhinovirus seasons continued to wheeze in the 3rd year of life, compared with only 20% of all other infants (OR=6.6; P < .0001). CONCLUSION: In this population of children at increased risk of developing allergies and asthma, the most significant risk factor for the development of preschool childhood wheezing is the occurrence of symptomatic rhinovirus illnesses during infancy that are clinically and prognostically informative based on their seasonal nature.
Child, Preschool↗
Viral infections, cytokine dysregulation and the origins of childhood asthma and allergic diseases.
BACKGROUND: The origins of asthma and allergic disease begin in early life for many individuals. It is vital to understand the factors and/or events leading to their development. METHODS: The Childhood Origins of Asthma project evaluated children at high risk for asthma to study the relationships among viral infections, environmental factors, immune dysregulation, genetic factors, and the development of atopic diseases. Consequently wheezing illnesses, viral respiratory pathogen identification, and in vitro cytokine response profiles were comprehensively evaluated from birth to 3 years of age, and associations of the observed phenotypes with genetic polymorphisms were investigated. RESULTS: For the entire cohort, cytokine responses did not develop according to a strict T helper cell 1 or T helper cell 2 polarization pattern during infancy. Increased cord blood mononuclear cell phytohemagglutin-induced interferon-gamma responses of mononuclear cells were associated with decreased numbers of moderate to severe viral infections during infancy, especially among subjects with the greatest exposure to other children. In support of the hygiene hypothesis, an increased frequency of viral infections in infancy resulted in increased mitogen-induced interferon-gamma responses at 1 year of age. First year wheezing illnesses caused by respiratory viral infection were the strongest predictor of subsequent third year wheezing. Also, genotypic variation interacting with environmental factors, including day care, was associated with clinical and immunologic phenotypes that may precede the development of asthma. CONCLUSIONS: Associations between clinical wheezing, viral identification, specific cytokine responses and genetic variation provide insight into the immunopathogenesis of childhood asthma and allergic diseases.
Animals↗
Cytokine response patterns, exposure to viruses, and respiratory infections in the first year of life.
Daycare attendance and siblings are associated with viral-induced wheezing in children. Preexisting immunologic factors may influence the expression of viral infections in infancy, and in turn, recurrent infections may influence the development of immune responses. A total of 285 children were enrolled in the Childhood Origins of Asthma Project at birth and followed for at least 1 year. Cord blood and 1-year mononuclear cells were stimulated with phytohemagglutinin, and cytokine-response profiles were measured by enzyme-linked immunosorbent assay. Nasal lavage was performed for moderate to severe respiratory illnesses. Daycare attendance and/or siblings significantly increased the likelihood of contracting respiratory syncytial virus (1.5-1.6-fold increase) and rhinovirus (1.8-2.1-fold increase), and increased the risk of rhinovirus-induced wheezing (14-18% vs. 2%, p = 0.011). Cord blood IFN-gamma responses were inversely related to the frequency of viral respiratory infections (r(s) = -0.11, p = 0.05), and more significant for subjects with high exposure to other children (r(s) = -0.27, p = 0.028). The interval change in infantile IFN-gamma responses correlated positively with the frequency of viral infections in infancy (r(s) = 0.12, p = 0.047). These data suggest that neonatal IFN-gamma responses may influence antiviral activity, or may represent a marker of antiviral immunity maturation. Conversely, the frequency of viral infections in infancy can influence IFN-gamma responses.
Child Day Care Centers↗
The contrast between risk assessment and rules of evidence in the context of international trade disputes: can the US experience inform the process?
Risk assessment provides a formalized process to evaluate human, animal, and ecological responses associated with exposure to environmental agents. The purpose of risk assessment is to answer two related questions: - How likely is an (adverse) event to occur? - If it does, how severe will the impact be? In the United States, the science of risk assessment has evolved out of the necessity to make public health decisions in the face of scientific uncertainty. Its basic propositions have been established over the past three decades and its applications have impacted virtually every aspect of public health and environmental protection in many countries, including the United States. More recently, the World Trade Organization's (WTO) dispute-settlement process has provided additional incentive for the reliance on risk assessments internationally through the requirement that member countries be able to provide scientific justification, based on a risk assessment, for public health and environmental regulatory measures that are challenged. The purpose of this article is to review the history of risk assessment in the United States, emphasizing the development of both its scientific and policy aspects, as one example of the development of institutional capacity for risk assessment. This article discusses the importance of the social, political, and economic contexts of risk assessment and risk management in shaping the approaches taken while highlighting the reality that the analytic or risk assessment part of the decision-making process, in the absence of scientific data, can be completed only by inserting inferences, or policy judgments, which may differ among countries. This article recognizes these differences, and the consequent difference between risk assessment that incorporates public health protective assumptions and the rules of evidence that seek to answer questions of causality, and discusses implications for the WTO dispute-settlement process. It further explores the value of country-specific risk assessment guidelines to facilitate consistency within a country along with the appropriateness and feasibility of international risk assessment guidelines.
Animals↗
Worker exposure standard for phosphine gas.
The 1998 U.S. Environmental Protection Agency Office of Pesticide Programs (OPP) re-registration eligibility decision (RED) for phosphine fumigants has generated much interest in defining safe levels of exposure for workers and worker bystanders. This report summarizes the pertinent literature on phosphine toxicity, including animal inhalation studies and human epidemiology studies, and also describes a margin-of-exposure (MOE) analysis based on available worker exposure data. In addition, a safe occupational exposure limit is estimated using typical OPP assumptions, after determination of appropriate uncertainty factors, based on quality of data in the principal study and pharmacokinetic considerations. While a conservative 8-hour time-weighted average (TWA) of 0.1 ppm was calculated, the overall weight of evidence, from a risk-management perspective, supports a conclusion that an occupational TWA of 0.3 ppm provides adequate health protection. In addition, a 15-minute short-term exposure limit (STEL) of 3 ppm was estimated. Finally, in contrast to the MOE analysis described in the OPP's phosphine RED, the MOE analysis described herein does not indicate that fumigation workers are currently being exposed to unacceptable levels of phosphine. Collectively, these findings support the occupational exposure limits of 0.3 ppm (8-hour TWA) and 1 ppm (STEL) established in the updated applicator's manuals for phosphine-generating products, which recently received approval from OPP.
Administration, Inhalation↗
A framework and case study for exposure assessment in the Voluntary Children's Chemical Evaluation Program.
A conceptual framework is presented for conducting exposure assessments under the U.S. EPA's Voluntary Children's Chemical Evaluation Program (VCCEP). The VCCEP is a voluntary program whereby companies that manufacture chemicals of potential concern are asked to conduct hazard, exposure, and risk assessments for the chemicals. The VCCEP is unique in its risk-based, tiered approach, and because it focuses on children and requires a comprehensive consideration of all reasonably foreseeable exposure pathways for a particular chemical. The consideration of all potential exposure pathways for some commonly used chemicals presents a daunting challenge for the exposure assessor. This article presents a framework for managing this complicated process, and illustrates the application of the framework with a hypothetical case study. The framework provides guidance for interpreting multiple sources of exposure information and developing a plausible list of exposure pathways for a chemical. Furthermore, the framework provides a means to process all the available information to eliminate pathways of negligible concern from consideration. Finally, the framework provides guidance for utilizing the tiered approach of VCCEP to efficiently conduct an assessment by first using simple, screening-level approaches and then, if necessary, using more complex, refined exposure assessment methods. The case study provides an illustration of the major concepts.
Adolescent↗
Assessing the risks of terrorism: a special collection of perspectives articles by former presidents of the Society for Risk Analysis.
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Editorial↗