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Dr. Donald E. Stevenson obtained degrees in animal physiology and Veterinary Science from Liverpool University and his M.A., Ph.D at Cambridge University. He then joined the faculty of the Cambridge University School of Veterinary Medicine as a veterinary clinical pathologist. In 1960 he was recruited by Shell Research Ltd as Division Head in a new Toxicology Laboratory under construction at Sittingbourne, Kent, U.K. He was appointed Director of the Lab in 1972. Six years later he came to Shell Oil Co. on an assignment to establish a toxicology laboratory in Houston, Texas. Both laboratories are now closed because the major internal customers, the agrichemical businesses, were sold to other corporations. Don remained Director of Toxicology in Shell Oil Co. until his retirement in 1994. He was chairperson of the Scientific Committee of the American Industrial Health Council from 1986 to 1990. He is now an independent consultant with the Dermigen Consulting Group in Smithville, Texas.

As a physiologist, veterinarian and toxicologist, Don has been concerned with the responses of the whole animal. He is one of the founders of the Laboratory Animal Science Association and the British Laboratory Animal Veterinary Association. He has been particularly interested in the species differences in liver tumor responses to organochlorines and drugs and the comparative use of epidemiological information in health risk assessment. There are two broad topics which may be of interest to Belle members:

1. Recent collaborative studies with Jim Klaunig at the Indiana University Medical School have emphasized the importance of oxidative stress as a species specific mechanism of promotion in liver. This stress may be mediated through the P450 system, the induction of which is often one of the most sensitive indicators of exposure. Induction is accompanied by changes in several antioxidant systems. In guinea-pigs induction is ascorbic acid dependent and in those species which synthesize ascorbic acid, enzyme induction is associated with a large increase in it's synthesis and also urinary excretion. Glucaric acid synthesis (via the same enzyme system as ascorbic acid) is also increased and the urinary excretion rate has been used as a measure of enzyme induction in humans. Since both ascorbic and glucaric acids have protective properties for cancer and other endpoints, it may be that their increased production at low exposures is associated with a broader impact on health endpoints. The mouse liver tumor response is the sensitive to body weight, caloric restriction and diet composition, all of which may be far more important than low level environmental exposures in determining health outcomes in both animals and humans.

2. In collaboration with R. L. Sielken, Jr. it was realized that toxicologists and epidemiologists use entirely different mathematical models and the use of identical models on both kinds of data is now being investigated. A further problem is that the animal carcinogen dose response has been dominated by the regulatory assumption of linearity which has resulted in an ossification of comprehension of the properties of animal systems. Several evolving approaches have been explored. [a] Agencies do not adjust for species differences in background tumor rates even though this parameter is explicit in the linearized model. Background tumor rates are a key feature in developing prevention strategies [b] An analysis of the two-stage model for a restricted number of cell cycles has shown that the probability of a mutation is highly dependent on the background mutation rate and cell death rates. [c] the modeling of dose responses with epidemiological data involving individual exposure metrics. [d] the use of Gompertzian models for demonstrating dose response relationships and the presence of hormesis. The use of a residual to measure short-term deviations from model predictions. [e] the concept of an 'invaders - defenders' model in wich good health is regarded as a balance between protective and damaging factors, so that ill-health can reflect the loss of defense systems as much as an increase in exogenous exposures.

Recent publications:

1. The potential role of oxidative stress in nongenotoxic carcinogenesis in the mouse liver (Bachowski etal); Species Specificity of dieldrin- and phenobarbital-induced hepatocarcinogenesis (Stevenson et al) in: Growth Factors and Tumor Promotion - Implications for Risk Assessment. Eds R.M. McClain, T.J. Slaga, R.LeBoeuf and H Pitot. Wiley-Liss, 1995

2. Challenges to Default Assumptions Stimulate Comprehensive Realism as a New Tier in Quantitative Cancer Risk Assessment. R.L. Sielken,Jr. R.S. Bretzlaff and D.E. Stevenson. Reg. Tox. And Pharmacol. 21,270 280, 1995

3. Dose-Response Characterization of Life, Death and Hormesis. D.E. Stevenson, R.S. Bretzlaff, R.L.Sielken, Jr. and R.L. MacDonald. Comments Toxicology, 5,151-180, 1994





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