Environmental Problems, Their Causes, and Sustainability 1

Table 9-1 Toxicity Ratings and Average Lethal Doses for HumansLD50 (milligrams perToxicity Rating kilogram of body weight)* Average Lethal Dose † ExamplesSupertoxic Less than 0.01 Less than 1 drop Nerve gases, botulism toxin, mushroom toxins,dioxin (TCDD)Extremely toxic Less than 5 Less than 7 drops Potassium cyanide, heroin, atropine, parathion,nicotineVery toxic 5–50 7 drops to 1 teaspoon Mercury salts, morphine, codeineToxic 50–500 1 teaspoon to 1 ounce Lead salts, DDT, sodium hydroxide, sodiumfluoride, sulfuric acid, caffeine, carbontetrachlorideModerately toxic 500–5,000 1 ounce to 1 pint Methyl (wood) alcohol, ether, phenobarbital,amphetamines (speed), kerosene, aspirinSlightly toxic 5,000–15,000 1 pint to 1 quart Ethyl alcohol, Lysol, soapsEssentially nontoxic 15,000 or greater More than 1 quart Water, glycerin, table sugar*Dosage that kills 50% of individuals exposed†Amounts of substances in liquid form at room temperature that are lethal when given to a 70.4-kilogram (155-pound) humanThe most widely used method for determining toxicityis to expose a population of live laboratory animals(especially mice and rats) to measured dosesof a specific substance under controlled conditions.Animal tests take 2–5 years and cost $200,000 to$2 million per substance tested. Such tests also kill orharm and can be painful to the test animals. The goalis to develop data on the response of the test animalsto various doses of a chemical (called a dose-responsecurve). But estimating the effects of low doses isdifficult.Animal welfare groups want to limit or ban use oftest animals or ensure that experimental animals aretreated in the most humane manner possible. Morehumane methods for carrying out toxicity tests areavailable. They include computer simulations and usingtissue cultures of cells and bacteria, chicken eggmembranes, and measurements of changes in the electricalproperties of individual animal cells.These alternatives can greatly decrease the use ofanimals for testing toxicity. But many scientists contendthat some animal testing is needed because thealternative methods cannot adequately mimic thecomplex biochemical interactions of a live animal.Acute toxicity tests are run to develop a doseresponsecurve, which shows the effects of variousdosages of a toxic agent on a group of test organisms(Figure 19-6). Such tests are controlled experiments inwhich the effects of the chemical on a test group arecompared with the responses of a control group of organismsnot exposed to the chemical. Care is takenthat organisms in both groups are as identical as possiblein age, health status, and genetic makeup, and thatall are exposed to the same environmental conditions.Fairly high dosages are used to reduce the numberof test animals needed, obtain results quickly, andlower costs. Otherwise, tests would have to be run onmillions of laboratory animals for many years, andmanufacturers could not afford to test most chemicals.For the same reasons, scientists usually use mathematicalmodels to extrapolate the results of high-doseexposures to low-dose levels. Then they extrapolatethe low-dose results on the test organisms to humansto estimate LD50 values for acute toxicity (Table 19-1).According to the nonthreshold dose-response model(Figure 19-6, left), any dosage of a toxic chemical orionizing radiation causes harm that increases with theEffectNonlineardose-responseLinear doseresponseDoseNo thresholdEffectThresholdlevelDoseThresholdFigure 19-6 Two types of dose-response curves. The linearand nonlinear curves in the left graph apply if even the smallestdosage of a chemical or ionizing radiation has a harmful effectthat increases with the dosage. The curve on the right applies ifa harmful effect occurs only when the dosage exceeds a certainthreshold level. Which model is better for a specific harmfulagent is uncertain because of the difficulty in estimating theresponse to very low dosages.414 CHAPTER 19 Risk, Toxicology, and Human Health