Antimicrobial resistance and biological governance: explanations for policy failure.

The paper reviews the state of policy on antimicrobial use and the growth of antimicrobial resistance (AMR). AMR was anticipated at the time of the first use of antibiotics by their originators. For decades, reports and scientific papers have expressed concern about AMR at global and national policy levels, yet the problem, first exposed a half-century ago, worsened. The paper considers the explanations for this policy failure and the state of arguments about ways forward. These include: a deficit of economic incentivisation; complex interventions in behavioural dynamics; joint and separate shifts in medical and animal health regimes; consumerism; belief in technology; and a narrative that in a 'war on bugs' nature can be beaten by human ingenuity. The paper suggests that these narratives underplay the biological realities of the human-animal-biosphere being in constant flux, an understanding which requires an ecological public health analysis of AMR policy development and failure. The paper suggests that effective policy change requires simultaneous actions across policy levels. No single solution is possible, since AMR is the result of long-term human intervention which has accelerated certain trends in the evolution of a microbial ecosystem shared by humans, animals and other biological organisms inhabiting that ecosystem. Viewing the AMR crisis today through an ecological public health lens has the advantage of reuniting the social-ecological and bio-ecological perspectives which have been separated within public health.

Testing methods for developmental neurotoxicity of environmental chemicals.

Human brain development is slow and delicate, involving many unique, though interrelated, cellular events. The fetus and child are often more susceptible to chemical toxins that alter the structure and/or function of the brain, although susceptibility varies for individual neurotoxicants. Early exposure to neurotoxins has been implicated in neurological diseases and mental retardation. Pesticide exposures pose a particular concern since many are designed to be neurotoxic to pests and can also affect humans. Acknowledging the potential for vulnerability of the developing brain, EPA recently began to "call in" data on developmental neurotoxicity (DNT) from manufacturers of pesticides already registered and considered to be neurotoxic-around 140 pesticides. Chemicals are to be tested following the DNT testing guideline (OPPTS 870.6300). This paper assesses whether tests performed according to this guideline can effectively identify developmental neurotoxicants. We found the testing guideline deficient in several respects, including: It is not always triggered appropriately within the current tiered system for testing; It does not expose developing animals during all critical periods of vulnerability; It does not assess effects that may become evident later in life; It does not include methodology for consideration of pharmacokinetic variables; Methodology for assessment of neurobehavioral, neuropathological, and morphometry is highly variable; Testing of neurochemical changes is limited and not always required. We propose modifications to the EPA testing guideline that would improve its adequacy for assessing and predicting risks to infants and children. This paper emphasizes that deficiencies in the testing methodology for developmental neurotoxicants represent a significant gap and increase the uncertainty in the establishment of safe levels of exposure to developing individuals.

Assessment of the U.S. Environmental Protection Agency methods for identification of hazards to developing organisms, Part I: The reproduction and fertility testing guidelines.

BACKGROUND: Successful reproduction depends on the coordination of many processes, particularly the normal development and subsequent maturation of the sexual organs. The Food Quality Protection Act of 1996 mandates that the U.S. Environmental Protection Agency must protect infants and children from the effects of toxins, including those that affect the reproductive system. Therefore, the Agency finds itself at a critical juncture to make sure that the methods it requires for toxicity testing, the Health Effects Test Guidelines or Series 870 Guidelines, are adequate to determine possible toxicity to children. METHODS AND RESULTS: We found that two testing protocols included in the core guidelines assess toxicological effects on developing animals. This article aims to provide a detailed analysis of the protocols included in the Reproduction and Fertility Effects Test Guideline. An accompanying article assesses the Developmental Toxicity Testing Guideline. We conducted this analysis on the basis of whether the test would yield the information needed to adequately determine risk to infants and children. CONCLUSIONS: Our analysis concludes that given the limitations inherent in testing for reproduction and fertility effects during development, it is necessary to include a safety factor during risk assessment of chemicals. This action will fulfill the mandate expressed in the FQPA to protect infants and children from environmental hazards.

Assessment of the U.S. Environmental Protection Agency methods for identification of hazards to developing organisms, Part II: The developmental toxicity testing guideline.

BACKGROUND: The effects of toxins on developing animals depend not only on the nature of the chemical but also on the timing of exposure and assessment of outcomes. This complicates the task of regulatory agencies such as the U.S. Environmental Protection Agency (EPA), which must comply with the 1996 Food Quality Protection Act to ensure that their standards and policies protect infants and children from environmental toxins. For this task, the Agency relies heavily on scientific data obtained by manufacturers of industrial chemicals and pesticides following protocols collected under EPA's Health Effects Test Guidelines. METHODS AND RESULTS: This article reviews the protocols included in the EPA guidelines to assess developmental toxicity, which are required for food-use pesticides under the core testing battery. We reviewed these protocols on the basis of their adequacy for identifying hazards to infants and children. Our analysis found limitations in the protocols that hinder their potential for identifying developmental hazards. CONCLUSIONS: Methods that the EPA currently depends upon to identify developmental toxicity of chemicals have limitations that impede obtaining complete and reliable data on which to base regulatory decisions that protect children. Other methodological approaches need to be explored as alternatives or supplements to the current protocols. Until more accurate testing protocols become available, it may well be necessary under existing laws to employ safety factors that are more protective of the health of children at all stages of development.