Degree Type

Thesis

Date of Award

2017

Degree Name

Master of Science

Department

Animal Science

Major

Toxicology

First Advisor

Steve M. Ensley

Second Advisor

Aileen F. Keating

Abstract

Diagnosing pine needle abortion (PNA) has proven challenging for veterinary diagnosticians. Naturally induced cases of PNA in cattle classically occur in the second and third trimester following consumption of foliage from the Ponderosa pine (Pinus ponderosa) and other toxic gymnosperms that contain the causative compound. A labdane diterpene acid (LDA), isocupressic acid (ICA), has been identified as an abortifacient compound, the causative agent of PNA, and ICA is present in multiple species of abortifacient gymnosperms. When LDAs are consumed multiple sequential steps transform isocupressic acid to a group of isocupressic acid metabolites. This body of work provides evidence that:

1) isocupressic acid metabolites are biomarkers of PNA,

2) isocupressic acid metabolites can be consistently observed in diagnostic specimens from the fetus in cases of PNA,

3) THAA, a metabolite of ICA, has been demonstrated in a wide variety of specimens from the fetus and placenta suggestive of a wide distribution,

4) LDAs, including ICA, are present at toxic levels in more species of gymnosperm trees than previously reported in any review manuscripts on the topic,

5) risk management of PNA requires hazard identification, which is lacking on a global scale,

6) risk communication requires meaningful context including economic impact and likelihood of exposure, and

7) North America toxicologists and diagnosticians lack the adequate experience to confidently and consistently provide test selection, diagnosis, and/or risk communication in cases of PNA (unpublished data).

The aim of this manuscript is to provide clarity and resources to empower the veterinary diagnostician to provide routine and consistent diagnostic interpretation of probable cases of intoxication suspected to be representative of PNA. The manuscript as a whole presents a multidimensional understanding of PNA. Whenever possible, core principles of toxicology are highlighted to demonstrate understanding and foster the reader’s connection between those principles and the findings reported during diagnostic investigations. The underlying theory and general conceptual framework supporting subtopics presented herein include hazard identification, risk assessment, risk management, and risk communication. More specifically, risk communication guided the diagnostic investigations establishment of case definition, prevention of PNA, diagnostic interpretation relative to exposure, and communicating diagnostic information. The format discussed further under thesis organization, provides a literature review of multiple subtopics, and three other manuscripts (i.e. a case control study, a case report, and review) in various stages of the peer-review publication process.

The literature review was designed to provide background and a general overview of PNA to set the stage to address key issues. Therefore, the literature review contains a brief history of PNA, the causative agent and accepted toxic principle, dose response, pathophysiology in the context of the bovine placenta, general diagnostic testing for detection of causative agents, range management for cattle, and tree species associated with PNA. Each subtopic in literature review was constructed to read somewhat independently of the next topic thereby addressing key features of each. The manuscript as a whole presents a multidimensional understanding of PNA including nuances of circumstances and rationale for improved surveillance of cattle reproduction complications. More specifically, hazard identification and range management for livestock are areas of focus.

The objective of our diagnostic investigations and reports are to determine whether the toxic principle found in pine needles or its metabolites can be detected in samples commonly submitted to diagnostic laboratories following an outbreak of abortion in cattle. The research focused on the principle of PNA, hazard identification and risk communication, and assessing and managing danger of PNA.

The first original manuscript (Chapter 3) describes the circumstances, methodology, and findings from an investigation of a naturally occurring case of PNA from Nebraska in context of a case control study. New information was provided for use by diagnosticians to aid diagnostic interpretation and guide test selection. This manuscript was published in the Journal of Veterinary Diagnostic Investigation. The second original manuscript (Chapter 4) confirms classically purported risk factors of PNA and findings from an investigation of a naturally occurring case of PNA from Montana. New information was provided for use by diagnosticians to guide diagnostic sample selection. This manuscript was prepared for publication in Veterinary Record. The third original manuscript (Chapter 5) characterizes hazard identification, risk assessment, and risk management towards prevention of PNA. New information was provided by curated data for review, review of hazard identification, hazard characterization, risk assessment, risk communication, and risk management on the subject of PNA. This manuscript was prepared for publication in Livestock Science.

Keywords: AA, agathic acid, biomarker, bovine, cattle, cow, dam, DHAA, dihydroagathic acid, dose response, fetal fluids, fetal tissues, fetal tissue juices, hazard identification, ICA, isocupressic acid, IMB, imbricataloic acid, pine needle abortion, placenta, range management, risk assessment, risk communication, risk management, sera, serum, tetrahydroagathic acid, THAA

DOI

https://doi.org/10.31274/etd-180810-5233

Copyright Owner

Douglas Byron Snider

Language

en

File Format

application/pdf

File Size

228 pages

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