myers - Does'the dose make the poison Extensive results...

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April 30, 2007 Does 'the dose make the poison?' Toxicology testing assumes 'the dose makes the poison.' Photograph from Retha Newbold , NIEHS. Measuring how much of a compound, called its dose, produces a response, usually some kind of health effect, is difficult and time consuming. To understand how dose and effects are linked, toxicologists expose animals, tissues, or cells to pollutants. They then examine how the subject responds to the exposure. The "dose makes the poison" is a common adage in toxicology. It implies that larger doses have greater effects than smaller doses. That makes common sense and it is the core assumption underpinning all regulatory testing. When "the dose makes the poison," toxicologists can safely assume that high dose tests will reveal health problems that low dose exposures might cause. High dose tests are desirable because, the logic goes, they not only will reveal low dose effects, they will do so faster and with greater reliability. Greater reliability and speed also mean less cost. by Pete Myers, Ph.D. and Wendy Hessler While exposure in the womb to 100 parts per billion of the estrogenic drug diethylstilbestrol (DES) causes mice to become scrawny as adults, exposure to a much lower amount, 1 ppb, causes grotesque obesity. This photograph compares a control animal (left) to an animal exposed to a very small amount of DES in the womb (right). The trouble is, some pollutants, drugs and natural substances don't adhere to this logic, as can be seen in the photograph above. Instead, they cause different effects at different levels, including impacts at low levels that do not occur at high doses. Sometimes the effects can even be precisely the opposite at high vs . low. Because all regulatory testing has been designed assuming that "the dose makes the poison," it is highly likely to have missed low dose effects, and led to health standards that are too weak. Extensive results challenge a core assumption in toxicology 1 of 6
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In standard toxicology, as the dose increases, so does the effect. Conversely as dose decreases, so does its impact. This relationship is called a monotonic dose-response curve because effects are either increasing or decreasing. In a monotonic curve, they never reverse direction. It is akin to a dimmer switch and a lightbulb. The more electricity you let through by turning the knob, the brighter the bulb gets. The diagrams to the right present idealized forms of monotonic (left) andnon-monotonic (right) dose- response curves. Monotonic can either be linear ornon- linear. The key point is that the direction of the curve never changes from positive to negative or vice-versa. A monotonic curve can flatten, i.e., reach an asymptote. Non-monotonic curves, in contrast, change direction.
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This note was uploaded on 02/10/2012 for the course PHY 495 taught by Professor Hess during the Summer '11 term at Alabama.

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myers - Does'the dose make the poison Extensive results...

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