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comparisons among groups of people, usually contrasting
                     a group known to have been exposed to some hazard and a
                     group that has not. Epidemiologists track the fate of all people
                     in the study for a long period of time (often years or decades)
                     and measure the rate at which deaths, cancers, or other health
                     problems occur in each group. The epidemiologist then ana-
                     lyzes the data, looking for observable differences between the
                     groups, and statistically tests hypotheses accounting for dif-
                     ferences. When a group exposed to a hazard shows a signifi-
                     cantly greater degree of harm, it suggests that the hazard may
                     be responsible. For example, epidemiologists have tracked
                     asbestos miners for evidence of asbestosis, lung cancer, and
                     mesothelioma (cancer of the cells that line the body’s internal
                     organs). Survivors of the Chernobyl and Fukushima nuclear
                     disasters have been monitored for thyroid cancer and other
                     illnesses (pp. 580–581). Canadian epidemiologists are now
                     tracking people for impacts of bisphenol A exposure.
                        The epidemiological process is akin to a natural experi-
                     ment (p. 30), in which the experimenter studies groups of sub-
                     jects made possible by some event that has occurred. A similar
                     approach was followed by anthropologist Elizabeth Guillette,   Figure 14.15 Animal testing is used to study toxic sub-
                     who happens to be married to alligator biologist Louis Guillette   stances in the laboratory. Tests with specially bred strains of
                     (see The Science behind The STory, pp. 396–397). The advantages   mice, rats, and other animals allow researchers to study the toxic-
                     of epidemiological studies are their realism and their ability   ity of substances, develop safety guidelines, and make medical
                     to yield relatively accurate predictions about risk. Drawbacks   advances in ways they could not achieve without these animals.
                     include the need to wait a long time for results and an inability
                     to address future effects of new hazards, such as products just
                     coming to market. In addition, participants in epidemiological   effects. The data are plotted on a graph, with dose on the x
                     studies encounter many factors that affect their health besides   axis and response on the y axis (Figure 14.16a). The resulting
                     the one under study. Epidemiological studies measure a statis-  curve is called a dose-response curve.
                     tical association between a health hazard and an effect, but they   Once they have plotted a dose-response curve, toxicolo-
                     do not confirm that the hazard causes the effect.    gists  can  calculate  a  convenient  shorthand  gauge  of  a  sub-
                        To establish causation, manipulative experiments are   stance’s toxicity: the amount of the substance it takes to kill
                     needed.  However,  subjecting  people  to  massive  doses  of   half the population of study animals used. This lethal dose for
                     toxic substances in a lab experiment would clearly be unethi-  50% of individuals is termed the lD . A high LD  indicates
                                                                                                                  50
                                                                                                       50
                     cal. This is why researchers have traditionally used nonhu-  low toxicity, and a low LD  indicates high toxicity.
                                                                                               50
                     man animals as test subjects. Foremost among these animal   If the experimenter is interested in nonlethal health
                     models have been laboratory strains of rats, mice, and other   effects, he or she may want to document the level of toxicant
                     mammals (Figure 14.15). Because of shared evolutionary his-  at which 50% of a population of test animals is affected in
                     tory, the bodies of all mammals function similarly, so sub-  some other way (for instance, the level of toxicant that causes
                     stances that harm mice and rats are reasonably likely to harm   50% of lab mice to lose their hair). Such a level is called the
                     us. Some people feel the use of animals for testing is unethi-  effective-dose-50%, or ED .
                                                                                              50
                     cal, but animal testing enables scientific and medical advances   Some substances can elicit effects at any concentration,
                     that would be impossible or far more difficult otherwise. Still,   but for others, responses may occur only above a certain dose,
                     new techniques (with human cell cultures, bacteria, or tissue   or threshold. Such a threshold dose (Figure 14.16b) might be
                     from chicken eggs) are being devised that may soon replace   expected if the body’s organs can fully metabolize or excrete
                     some live-animal testing.                            a toxicant at low doses but become overwhelmed at high con-
                                                                          centrations. It might also occur if cells can repair damage to
                                                                          their DNA only up to a certain point.
                     Dose-response analysis is a mainstay                    Sometimes a response may decrease as a dose increases.
                     of toxicology                                        Toxicologists are finding that some dose-response curves are
                                                                          U-shaped, J-shaped, or shaped like an inverted U (Figure 14.16c).
                     The standard method of testing with lab animals in toxicol-  Such counterintuitive curves contradict toxicology’s traditional
                     ogy is dose-response analysis. Scientists quantify the toxic-  assumption that “the dose makes the poison.” These unconven-
                     ity of a substance by measuring the strength of its effects or   tional dose-response curves often occur with endocrine disrup-
                     the number of animals affected at different doses. The dose   tors, likely because the hormone system is geared to respond to
                     is the amount of substance the test animal receives, and the   minute concentrations of substances (normally, hormones in the
                     response is the type or magnitude of negative effects the ani-  bloodstream). Because the endocrine system responds to minus-
                     mal exhibits as a result. The response is generally quantified   cule amounts of chemicals, it may be vulnerable to disruption
             394     by measuring the proportion of animals exhibiting negative   by contaminants that are dispersed through the environment and







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