Veterinary Medicine Commons^™

A Modular One-Generation Reproduction Study As A Flexible Testing System For Regulatory Safety Assessment, Richard Vogel, Troy Seidle, Horst Spielmann

Troy Seidle, PhD

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 …

Development And Evaluation Of A Replicon Particle Vaccine Expressing The E2 Glycoprotein Of Bovine Viral Diarrhea Virus (Bvdv) In Cattle, John Dustin Loy, Jill Gander, Mark Mogler, Ryan Vander Veen, Julia Ridpath, Delbert Hank Harris, Kurt Kamrud

John Loy

Background: Bovine viral diarrhea virus is one of the most significant and costly viral pathogens of cattle worldwide. Alphavirus-derived replicon particles have been shown to be safe and highly effective vaccine vectors against a variety of human and veterinary pathogens. Replicon particles are non-propagating, DIVA compatible, and can induce both humoral and cell mediated immune responses. This is the first experiment to demonstrate that Alphavirus-based replicon particles can be utilized in a standard prime/boost vaccination strategy in calves against a commercially significant bovine pathogen. Findings: Replicon particles that express bovine viral diarrhea virus sub-genotype 1b E2 glycoprotein were generated and …

The Future Of Teratology Research Is In Vitro, Jarrod Bailey, Andrew Knight, Jonathan Balcombe

Jonathan Balcombe, Ph.D.

Birth defects induced by maternal exposure to exogenous agents during pregnancy are preventable, if the agents themselves can be identified and avoided. Billions of dollars and manhours have been dedicated to animal-based discovery and characterisation methods over decades. We show here, via a comprehensive systematic review and analysis of this data, that these methods constitute questionable science and pose a hazard to humans. Mean positive and negative predictivities barely exceed 50%; discordance among the species used is substantial; reliable extrapolation from animal data to humans is impossible, and virtually all known human teratogens have so far been identified in spite …

The Future Of Teratology Research Is In Vitro, Jarrod Bailey, Andrew Knight, Jonathan Balcombe

Jonathan Balcombe, PhD

Birth defects induced by maternal exposure to exogenous agents during pregnancy are preventable, if the agents themselves can be identified and avoided. Billions of dollars and manhours have been dedicated to animal-based discovery and characterisation methods over decades. We show here, via a comprehensive systematic review and analysis of this data, that these methods constitute questionable science and pose a hazard to humans. Mean positive and negative predictivities barely exceed 50%; discordance among the species used is substantial; reliable extrapolation from animal data to humans is impossible, and virtually all known human teratogens have so far been identified in spite …

Cancerous Contradictions: The Mis-Regulation Of Human Carcinogens Based On Animal Data, Andrew Knight, Jarrod Bailey, Jonathan Balcombe

Jonathan Balcombe, PhD

The regulation of human exposures to potential carcinogens constitutes society’s most important use of animal carcinogenicity data. However, for environmental contaminants of greatest U.S. concern, we found that in most cases (58.1%; 93/160) the U.S. Environmental Protection Agency (EPA) considered the animal data inadequate to support a classification of probable human carcinogen or noncarcinogen.

The World Health Organisation’s International Agency for Research on Cancer (IARC) is a leading international authority on carcinogenicity assessments. For chemicals lacking human exposure data (the great majority), IARC classifications of identical chemicals were significantly more conservative than EPA classifications (p

Animal Carcinogenicity Studies: Implications For The Reach System, Andrew Knight, Jarrod Bailey, Jonathan Balcombe

Jonathan Balcombe, PhD

The 2001 European Commission proposal for the Registration, Evaluation and Authorisation of Chemicals (REACH) aims to improve public and environmental health by assessing the toxicity of, and restricting exposure to, potentially toxic chemicals. The greatest benefits are expected to accrue from decreased cancer incidences. Hence the accurate identification of chemical carcinogens must be a top priority for the REACH system. Due to a paucity of human clinical data, the identification of potential human carcinogens has conventionally relied on animal tests. However, our survey of the US Environmental Protection Agency’s (EPA’s) toxic chemicals database revealed that, for a majority of the …

Medical Training Using Simulation: Toward Fewer Animals And Safer Patients, Jonathan Balcombe

Jonathan Balcombe, PhD

This paper presents the current status of computer-based simulation in medicine. Recent technological advances have enabled this field to emerge from esoteric explorations in academic laboratories to commercially available simulators designed to train users to perform medical procedures from start to finish. Today, more than a dozen companies are producing virtual reality simulators and interactive manikins for training in endoscopy, laparoscopy, anaesthesia, trauma management, angiography, and needle insertion. For many of these procedures, thousands of animals are still being used in training. Yet simulation has many advantages that can transcend scientific, ethical, economic and logistical problems that arise when using …

Animal Carcinogenicity Studies: 1. Poor Human Predictivity, Andrew Knight, Jarrod Bailey, Jonathan Balcombe

Jonathan Balcombe, PhD

The regulation of human exposure to potentially carcinogenic chemicals constitutes society’s most important use of animal carcinogenicity data. Environmental contaminants of greatest concern within the USA are listed in the Environmental Protection Agency’s (EPA’s) Integrated Risk Information System (IRIS) chemicals database. However, of the 160 IRIS chemicals lacking even limited human exposure data but possessing animal data that had received a human carcinogenicity assessment by 1 January 2004, we found that in most cases (58.1%; 93/160), the EPA considered animal carcinogenicity data inadequate to support a classification of probable human carcinogen or non-carcinogen. For the 128 chemicals with human or …