Examining the regulatory value of multi-route mammalian acute systemic toxicity studies

Regulatory information requirements for pesticides call for submission of acute systemic toxicity data for up to three different exposure routes (oral, dermal, inhalation) for both active ingredients and formulated products. Similar multi-route testing is required in the European Union and elsewhere for industrial chemicals. To determine the value of acute toxicity testing by more than one route, oral-dermal and oral-inhalation concordances among regulatory classifications were examined for large data sets of chemicals and pesticide active ingredients. Across all sectors examined, oral acute toxicity classifications for pure/active substances were more severe than those derived from dermal data in more than 98% of cases, which calls into question the value of routine dermal route testing for acute toxicity. Oral classifications were equivalent to or more severe than for the inhalation route for 83% of industrial chemicals and for 48% of pesticides examined.JRC.I.2 - Validation of Alternative Method

Draft genome sequence of Pseudomonas syringae pathovar syringae strain FF5, causal agent of stem tip dieback disease on ornamental pear.

addresses: The Sainsbury Laboratory, John Innes Centre, Norwich, United Kingdom.notes: PMCID: PMC3393499types: Journal Article; Research Support, Non-U.S. Gov'tFree on Open AccessPseudomonas syringae FF5 causes stem tip dieback disease on ornamental pear (Pyrus calleryana). Its genome encodes a complete type III secretion system (T3SS) and HopAC1, HopM1, AvrE1, HopI1, HopAA1, HopJ1, HopAH2, HopAH1, HopAG1, and HopAZ1. Lacking detectable homologues of other T3SS effectors, it may encode novel, undiscovered effectors

Sequences of Learning Types for Organizational Ambidexterity

Ambidexterity involves strategies for effectively managing the inherent tensions between short-term stability and long-term investments, a challenge known as the exploitation-exploration paradox. Despite the acknowledged importance of learning in the context of ambidexterity, there is a limited understanding of how various forms of organizational learning are employed over time in projects focused on either exploitation or exploration. This gap in knowledge is significant because the timing and sources of knowledge acquisition that support innovation can significantly impact the success of an ambidextrous approach. In essence, ambidexterity not only requires balancing the conflicting demands of exploitation and exploration but also necessitates the integration of both internal and external knowledge sources.https://dc.suffolk.edu/ciclseries/1002/thumbnail.jp

An Uncertain Stability

Installation of 16 mixed media found object sculptures

Habitat characterization of Saskatchewan's Dakota skipper, Hesperia dacotae population

The Dakota skipper, Hesperia dacotae (Skinner, 1911) (Hesperiidae), is an at-risk butterfly species that inhabits the mesic mixed-grass prairie. The Dakota skipper is listed endangered under the federal Species at Risk Act. Loss of native prairie is the main factor driving declines in Dakota skipper habitat and species abundance is assumed to be declining. Currently, there is a knowledge gap pertaining to habitat associations and availability of Saskatchewan populations. This information is critical to construct a recovery plan to secure Dakota skipper populations. The first objective was to better understand the environmental associations of Dakota skipper habitat through landscape, vegetation, soil, climate, microclimate, and Hesperiidae butterfly species occupancy. Data collection was conducted in 2015 and 2016; of the 46 sites surveyed; nine were Dakota skipper positive (i.e., present) sites and 37 were negative (i.e., non-detect) sites. Results indicated that plant community composition was not a significant predictor of Dakota skipper presence, but three plant species were significantly associated with the species; Pediomelum argophyllum (Pursh) J.W.Grimes (Fabaceae), Zizia aptera (A.Gray) Fernald (Apiaceae), and Schizachyrium scoparium (Michx.) Nash (Poaceae). No soil or climate variables were significant predictors of Dakota skipper presence; however the species was significantly associated with steep slopes. Warmer maximum and average ground-level temperatures were also associated with Dakota skipper presence. The second objective was to determine Dakota skipper habitat suitability and distribution through a landscape-level habitat distribution model based on climate normal, soil, and landscape variables. Data were obtained from publically available Dakota skipper observation locations and in situ data collection within Saskatchewan. A total of 66 unique survey sites were obtained; 28 of these sites were Dakota skipper positive sites whereas the remaining 38 were negative sites. A habitat distribution map ranks the suitability of Dakota skipper habitat throughout southeastern Saskatchewan. Results indicated that although the Dakota skipper inhabits the mesic mixed-grass prairie region, only 11% of this region contains exceptional habitat (habitat probabilities 0.71-1) for this species. These areas contain a significantly lower mean diurnal temperature range and a higher ammonium soil content. I conclude that although the Dakota skipper inhabits the native mesic mixed-grass prairie region, environmental constraints including climate, soil, and landscape variables restrict this species to a more limited area of available habitat then initially thought. A landscape-level habitat suitability and distribution map complemented by habitat associations allows for more accurately targeted surveys, informs managers developing conservation and management plans, and allows for an overall better understanding of the Dakota skipper’s current situation in southeastern Saskatchewan. Findings indicate that additional Dakota skipper populations are likely in Saskatchewan and future targeted surveys will allow for a full evaluation of this species’ distribution and conservation status

Coalbed Methane Development in Indonesia: Design and Economic Analysis of Upstream Petroleum Fiscal Policy

Due to increasing demand for natural gas in Indonesia, the Government now promotes exploration for coalbed methane (CBM). Currently, Indonesia has 453 trillion cubic feet (TCF) of CBM reserves. However, CBM development in the country is still in the exploration phase, with significant under-investment. To attract investors, a tailored Production Sharing Contracts (PSC) regime is required. Based on a combination of Factor Analysis (FA), Discounted Cash Flows (DCF) and Parameter Sensitivity Analysis, the research explores an optimal scenario of a company’s share of revenue that optimised CBM development contracts. We find that a combination of 5 years straight line depreciation (SLD), 5% First Tranche Petroleum (FTP), 78% Contractor Share (CS) and 35% income tax best spreads the risk of CBM development and exploitation between the government and the contractor. This combination is a more suitable PSC regime for developing CBM in an early stage of the industry. Therefore, the Government must cede some taxes during exploration to incentivise CBM development. Three PSCs regimes are thus required to fully develop and exploit CBM, including exploration, transitional and exploitation phase PSCs which better match contractor risks and returns and ensure reasonable certainty of contractor cost recovery

A Modular One-Generation Reproduction Study as a Flexible Testing System for Regulatory Safety Assessment

The European Union’s Registration, Evaluation and Authorisation of Chemicals (REACH) legislation mandates testing and evaluation of approximately 30,000 existing substances within a short period of time, beginning with the most widely used “high production volume” (HPV) chemicals. REACH testing requirements for the roughly 3000 HPV chemicals specify three separate tests for reproductive toxicity: two developmental toxicity studies on different animal species (OECD Test Guideline 414) and a two-generation reproduction toxicity study (OECD TG 416). These studies are highly costly in both economic and animal welfare terms. OECD TG 416 is a fertility study intended to evaluate reproductive performance of animals in the P and F1-generations following repeated exposure to a test substance. It can also be used to detect adverse effects on structural and functional development. Thus, it has conventionally been preferred to the one-generation study (OECD TG 415). Recently, the Agricultural Chemical Safety Assessment (ACSA) Technical Committee of the ILSI Health and Environmental Sciences Institute (HESI) proposed that routine two-generation studies could in most cases be replaced with an “enhanced” one-generation study (Reuter et al. [1]). The flexible design proposed by HESI-ACSA allows for the addition of one or more specialised modules, if triggered (e.g. production of a second generation or the investigation of classical developmental toxicity or developmental neuro- or immunotoxicity). Significantly, however, the HESI-ACSA proposal was designed for use in the safety assessment of pesticidal, as opposed to industrial, chemicals. Thus for the purposes of REACH, a streamlined one-generation study that also examines structural development would be the most efficient means of addressing current information requirements for HPV chemicals. This study represents a flexible testing system that can be modified to meet regulatory needs in a variety of sectors