E-books, Collusion, and Antitrust Policy: Protecting a Dominant Firm at the Cost of Innovation

Amazon’s main rival, Apple, went to great lengths and took major risks to enter the e-book market. Why did Apple simply choose not to compete on the merits of its product and brand equity (the iPad and iBookstore) as it does with its other products? Why did Apple decide not to continue to rely on its earlier success of situating its products differently in the market than other electronics and working hard to be different and cutting-edge with its e-book delivery? This Note argues that the combination of Amazon’s 90% market share, network externalities, and an innovative technology market creates an environment that highly incentivizes a dominant firm to exclude potential rivals for as long as possible. Accordingly, when cases like United States v. Apple Inc. arise, there must be serious concern for not only price increases for consumers, but also diminished innovation in the market, which further harms consumers. This Note attempts to show that the market structure for e-books failed in some respects, which created an incentive for Apple—being a sophisticated and very large firm—to take highly risky steps to enter the e-book market. This Note also explores the theory that entry could not occur without an increase in price and, further, without entry, harm to innovation would result over time

E-books, Collusion, and Antitrust Policy: Protecting a Dominant Firm at the Cost of Innovation

Amazon’s main rival, Apple, went to great lengths and took major risks to enter the e-book market. Why did Apple simply choose not to compete on the merits of its product and brand equity (the iPad and iBookstore) as it does with its other products? Why did Apple decide not to continue to rely on its earlier success of situating its products differently in the market than other electronics and working hard to be different and cutting-edge with its e-book delivery? This Note argues that the combination of Amazon’s 90% market share, network externalities, and an innovative technology market creates an environment that highly incentivizes a dominant firm to exclude potential rivals for as long as possible. Accordingly, when cases like United States v. Apple Inc. arise, there must be serious concern for not only price increases for consumers, but also diminished innovation in the market, which further harms consumers. This Note attempts to show that the market structure for e-books failed in some respects, which created an incentive for Apple—being a sophisticated and very large firm—to take highly risky steps to enter the e-book market. This Note also explores the theory that entry could not occur without an increase in price and, further, without entry, harm to innovation would result over time

Proposed Occupational Exposure Limits for Non-Carcinogenic Hanford Waste Tank Vapor Chemicals

A large number of volatile chemicals have been identified in the headspaces of tanks used to store mixed chemical and radioactive waste at the U.S. Department of Energy (DOE) Hanford Site, and there is concern that vapor releases from the tanks may be hazardous to workers. Contractually established occupational exposure limits (OELs) established by the Occupational Safety and Health Administration (OSHA) and American Conference of Governmental Industrial Hygienists (ACGIH) do not exist for all chemicals of interest. To address the need for worker exposure guidelines for those chemicals that lack OSHA or ACGIH OELs, a procedure for assigning Acceptable Occupational Exposure Limits (AOELs) for Hanford Site tank farm workers has been developed and applied to a selected group of 57 headspace chemicals

International Frameworks Dealing with Human Risk Assessment of Combined Exposure to Multiple Chemicals

The development of harmonised terminology and frameworks for the human risk assessment of combined exposure to multiple chemicals (“chemical mixtures”) is an important area for EFSA and a number of activities have already been undertaken, i.e. in the fields of pesticides and contaminants. The first step prior to a risk assessment of combined exposure to multiple chemicals is problem formulation defining the relevant exposure, hazard and population to be considered. In practice, risk assessment of multiple chemicals is conducted using a tiered approach for exposure assessment, hazard assessment and risk characterisation. Higher tiers require increasing knowledge about the group of chemicals under assessment and the tiers can range from tier 0 (default values, data poor situation) to tier 3 (full probabilistic models). This scientific report reviews the terminology, methodologies and frameworks developed by national and international agencies for the human risk assessment of combined exposure to multiple chemicals and provides recommendations for future activities at EFSA in this area

Investigation of in vitro effects of ethephon and chlorpyrifos, either alone or in combination, on rat intestinal muscle contraction

A range of pesticides is widely used in pest management and the chances of exposure to multiple organophosphorus (OP) compounds simultaneously are high, especially from dietary and other sources. Although health hazards of individual OP insecticides have been relatively well characterized, there is lesser information on the interactive toxicity of multiple OP insecticides. The aim of this study is to elicit the possible interactions in case combined exposure of an OP pesticide chlorpyrifos (CPF) and a plant growth regulator ethephon (ETF) which are used worldwide. The ileum segments of 3 months old Wistar Albino male rats were used in isolated organ bath containing Tyrode solution. ETF and CPF were incubated (10−7 M concentration) separately or in combination with each other to ileum and their effects on acetylcholine-induced contractions were studied. The data obtained from this study show that, single and combined exposure to the agents caused agonistic interactions with regard to potency of ACh whereas they caused a decrease on Emax value of ACh. These findings suggest that exposure to these agents which have direct and indirect cholinergic effects, may cause developing clinical responses with small doses and earlier but the extent of toxicity will be lower

Genome-Wide Gene Expression Analysis in Response to Organophosphorus Pesticide Chlorpyrifos and Diazinon in C. elegans

Organophosphorus pesticides (OPs) were originally designed to affect the nervous system by inhibiting the enzyme acetylcholinesterase, an important regulator of the neurotransmitter acetylcholine. Over the past years evidence is mounting that these compounds affect many other processes. Little is known, however, about gene expression responses against OPs in the nematode Caenorhabditis elegans. This is surprising because C. elegans is extensively used as a model species in toxicity studies. To address this question we performed a microarray study in C. elegans which was exposed for 72 hrs to two widely used Ops, chlorpyrifos and diazinon, and a low dose mixture of these two compounds. Our analysis revealed transcriptional responses related to detoxification, stress, innate immunity, and transport and metabolism of lipids in all treatments. We found that for both compounds as well as in the mixture, these processes were regulated by different gene transcripts. Our results illustrate intense, and unexpected crosstalk between gene pathways in response to chlorpyrifos and diazinon in C. elegans

Evaluating Pharmacokinetic and Pharmacodynamic Interactions with Computational Models in Supporting Cumulative Risk Assessment

Simultaneous or sequential exposure to multiple chemicals may cause interactions in the pharmacokinetics (PK) and/or pharmacodynamics (PD) of the individual chemicals. Such interactions can cause modification of the internal or target dose/response of one chemical in the mixture by other chemical(s), resulting in a change in the toxicity from that predicted from the summation of the effects of the single chemicals using dose additivity. In such cases, conducting quantitative cumulative risk assessment for chemicals present as a mixture is difficult. The uncertainties that arise from PK interactions can be addressed by developing physiologically based pharmacokinetic (PBPK) models to describe the disposition of chemical mixtures. Further, PK models can be developed to describe mechanisms of action and tissue responses. In this article, PBPK/PD modeling efforts conducted to investigate chemical interactions at the PK and PD levels are reviewed to demonstrate the use of this predictive modeling framework in assessing health risks associated with exposures to complex chemical mixtures

Development of a Human Physiologically Based Pharmacokinetic (PBPK) Toolkit for Environmental Pollutants

Physiologically Based Pharmacokinetic (PBPK) models can be used to determine the internal dose and strengthen exposure assessment. Many PBPK models are available, but they are not easily accessible for field use. The Agency for Toxic Substances and Disease Registry (ATSDR) has conducted translational research to develop a human PBPK model toolkit by recoding published PBPK models. This toolkit, when fully developed, will provide a platform that consists of a series of priority PBPK models of environmental pollutants. Presented here is work on recoded PBPK models for volatile organic compounds (VOCs) and metals. Good agreement was generally obtained between the original and the recoded models. This toolkit will be available for ATSDR scientists and public health assessors to perform simulations of exposures from contaminated environmental media at sites of concern and to help interpret biomonitoring data. It can be used as screening tools that can provide useful information for the protection of the public

Review of Pesticide Urinary Biomarker Measurements from Selected US EPA Children’s Observational Exposure Studies

Children are exposed to a wide variety of pesticides originating from both outdoor and indoor sources. Several studies were conducted or funded by the EPA over the past decade to investigate children’s exposure to organophosphate and pyrethroid pesticides and the factors that impact their exposures. Urinary metabolite concentration measurements from these studies are consolidated here to identify trends, spatial and temporal patterns, and areas where further research is required. Namely, concentrations of the metabolites of chlorpyrifos (3,5,6-trichloro-2-pyridinol or TCPy), diazinon (2-isopropyl-6-methyl-4-pyrimidinol or IMP), and permethrin (3-phenoxybenzoic acid or 3-PBA) are presented. Information on the kinetic parameters describing absorption and elimination in humans is also presented to aid in interpretation. Metabolite concentrations varied more dramatically across studies for 3-PBA and IMP than for TCPy, with TCPy concentrations about an order of magnitude higher than the 3-PBA concentrations. Temporal variability was high for all metabolites with urinary 3-PBA concentrations slightly more consistent over time than the TCPy concentrations. Urinary biomarker levels provided only limited evidence of applications. The observed relationships between urinary metabolite levels and estimates of pesticide intake may be affected by differences in the contribution of each exposure route to total intake, which may vary with exposure intensity and across individuals