© 2000 CRC Press LLC Section III Basic concepts in toxicology and environmental chemistry L1190 CH11 pgs Page 587 Friday, July 2, 1999 5:45 PM © 2000 CRC Press LLC chapter eleven General concepts 11.1Pesticide regulation Introduction In the U.S., pesticides are regulated by a myriad of laws and agency rules. No less than 14 different Federal Acts control some aspect of the manufacture, registra- tion, distribution, use, consumption, and disposal of pesticides. The bulk of pesticide regulation falls under the Federal Insecticide, Fungicide and Rodenticide Act (FIFRA). This legislation governs the registration, distribution, sale, and use of pes- ticides. The Environmental Protection Agency is responsible for the administration of this Act and for establishing rules and regulations consistent with the Act’s intent. Other Acts govern their presence in water and air, the clean-up of spills and releases, the concentrations of pesticide residues in raw and processed food, their impact on endangered species, their transportation, working conditions for manu- facturers and applicators, and their disposal. The three broad categories of concern with pesticide regulation focus on (1) the registration of new pesticides and the reregistration of existing pesticides; (2) the establishment and monitoring of pesticide levels in food products; and (3) the mon- itoring of pesticide levels in the environment, especially in ground and surface water. Pesticide registration New pesticides The EPA is responsible under FIFRA for registering new pesticides to ensure that, when used according to label directions, they will not pose unreasonable risks to human health or the environment. FIFRA requires the EPA to balance the risks of pesticide exposure to human health and the environment against the benefits of pesticide use to society and the economy. A pesticide registration will be granted if, after careful consideration of health, economic, social and environmental costs and benefits, the benefits of the pesticide’s use outweighs the costs of its use. Pesticide registration decisions are based primarily on the EPA’s evaluation of data provided by applicants. Depending on the type of pesticide, the EPA can require up to 70 different kinds of specific tests. For a major food-use pesticide, testing can cost the manufacturer many millions of dollars. Testing is needed to determine whether a pesticide has the potential to cause adverse effects on humans, wildlife, fish, and plants. Potential human risks, which are identified using the results of laboratory tests, include acute toxic reactions, such as poisoning and skin and eye irritation, as well as possible long-term effects like L1190 CH11 pgs Page 589 Friday, July 2, 1999 5:45 PM © 2000 CRC Press LLC cancer, birth defects, and reproductive system disorders. Data on “environmental fate” (how a pesticide behaves in the environment) are also required so that the EPA can determine, among other things, whether a pesticide poses a threat to ground or surface water. EPA may classify a product for restricted use if it warrants special handling due to its toxicity. Restricted Use Pesticides (RUPs) may be used only by or under the supervision of certified applicators trained to handle toxic chemicals, and this clas- sification must be shown on product labels. During registration review, the Agency may also require changes in proposed labeling, use locations, and application meth- ods. If the pesticide is being considered for use on a food or feed crop, the applicant must petition the EPA for establishment of a food tolerance. A brand-new active ingredient may need 6 to 9 years to move from development in the laboratory, through full completion of EPA registration requirements, to retail shelves. This time frame includes at least 2 or 3 years to obtain registration approval from the EPA. Since 1978, when the EPA began requiring more extensive data on pesticides than in the past, over 130 brand-new chemical active ingredients have been regis- tered; between 10 and 15 new pesticide active ingredients are registered each year. Reregistration of existing pesticides EPA is required by law to reregister existing pesticides that were originally registered before current scientific and regulatory standards were formally estab- lished. The reregistration process ensures that: 1.Up-to-date data sets are developed for each of these chemicals (or their reg- istrations will be suspended or canceled). 2.Modifications are made to registrations, labels, and tolerances as necessary to protect human health and the environment. 3.Special review or other regulatory actions are initiated to deal with any un- reasonable risks. Reregistration has proved to be a massive undertaking and has proceeded slowly. Under the 1988 FIFRA amendments, the EPA must accelerate the reregistration effort so that the entire process is completed by 1997. Many pesticides are being withdrawn from manufacture and sale rather than going through the lengthy and expensive reregistration process. Special review, cancellations, and suspensions New data on registered products sometimes reveal the existence of a problem or a potential for hazard that was not known at the time of registration. Congress and the EPA have developed various mechanisms to reach sound scientific decisions in these situations. Special Review: Under the law, if the EPA seeks to revoke the registration of a pesticide, the Agency must first announce its reasons and offer the registrant a formal hearing to present opposing evidence. Because the cancellation process can be very time and resource intensive, the EPA often will employ a more informal and often more productive process known as Special Review. Special Review offers opportunities for interested parties on all sides to comment and present evidence on the risks and benefits of a pesticide. In many cases, the L1190 CH11 pgs Page 590 Friday, July 2, 1999 5:45 PM © 2000 CRC Press LLC Special Review results in an agreement to modify the registration to sufficiently reduce risk so that a formal hearing is no longer necessary. Cancellation: If the Special Review process fails to resolve the issues, however, or if the EPA decides that the problem is severe enough to warrant cancellation, the EPA may issue a proposed notice of intent to cancel without holding a Special Review. The Agency is also required by FIFRA to send the proposed notice to the Scientific Advisory Panel and the U.S. Department of Agriculture (USDA), and must evaluate their comments before proceeding with a final Notice of Intent to Cancel Registration. If no hearing is requested within 30 days of the Notice, the pesticide’s registration is canceled immediately. If a hearing is requested, it is conducted in a trial-like manner before an EPA Administrative Law Judge, who issues a recommended deci- sion to the EPA Administrator. At the end of the cancellation process, which may take 2 years or more, the decision may still be challenged in a federal court of appeals. If there is no appeal to a decision to cancel, all pertinent registrations of the pesticide are automatically canceled, and the products may no longer be sold or distributed in the U.S. Suspension: During the entire cancellation process, the pesticide remains on the market and no regulatory restrictions are imposed on the pesticide or its use. In some cases, the EPA may believe that allowing the pesticide to stay on the market during a Special Review and/or a cancellation hearing would pose an unacceptably high risk. In such cases, the EPA may issue a suspension order that bans sale or use of the pesticide while the ultimate decision on the pesticide’s status is under review. In order to issue a suspension order, the EPA must find that use of the pesticide poses an imminent hazard. In most cases, the EPA must first offer the registrant an expedited hearing on the suspension issues. However, if the EPA finds that an emergency exists (i.e., that even during the time needed for a suspension hearing, use of the pesticide would pose unreasonable adverse effects), the Agency can ban the sale and use of a pesticide effective immediately. Under current law, even in an emergency suspension, the EPA must assess the benefits of the pesticide as well. This provision makes emergency suspension difficult to use, and the EPA has been able to make these findings for only three pesticides: ethylene dibromide (EDB), 2,4,5-T (Silvex), and dinoseb. Food safety and food tolerances The food supply of the U.S. is among the safest in the world. Although many of the foods we consume may contain low levels of pesticide residues as a result of their use, numerous safeguards are built into the regulatory process to ensure that the public is protected from unreasonable risks posed by eating pesticide-treated crops and livestock. The EPA regulates the safety of the food supply by setting tolerance levels, or maximum legal limits, for pesticides on food commodities and in animal feed avail- able for sale in the U.S. The purpose of the tolerance program is to ensure that consumers are not exposed to unsafe levels of pesticide residues in food. Pesticides may be registered by the EPA for use on a food or feed crop only if a tolerance (or an exemption from a tolerance) is first granted, under authority of the Federal Food, Drug and Cosmetic Act (FDCA) as amended by the Food Quality Protection Act of 1996. The EPA has approved about 300 pesticides for food uses; about 200 of them are in common use. L1190 CH11 pgs Page 591 Friday, July 2, 1999 5:45 PM © 2000 CRC Press LLC Setting pesticide tolerances on food To evaluate the risks posed by pesticides in the diet, the EPA follows standard risk assessment guidelines. The Agency uses different procedures for cancer risks and non-cancer risks. Under the new Food Quality Protection Act these tolerances must result in a reasonable certainty of no harm from aggregate exposure to the pesticide. In addition, this Act requires that safety for infants and children be explic- itly addressed in tolerance setting and also that the EPA develop and implement a screening program for pesticides that may be endocrine disruptors. Non-carcinogens For non-cancer effects, the EPA determines what the highest level of exposure to a pesticide is at which there are no observed adverse effects in animals (called the no adverse effect level, the NOEL). Then an “uncertainty factor” (usually about 100) is applied to that number to estimate the level of daily exposure to the pesticide that is acceptable for humans (that is, that would not cause any adverse effects). This level is called the Reference Dose (RfD). It was once known as the Acceptable Daily Intake (ADI). Next, the EPA estimates people’s exposure to pesticide residues in food, based on pesticide residue studies (how much residue is found on different crops after application) as well as studies of how much food people consume. This calculated value for potential human exposure to the pesticide from food is termed the theo- retical maximum residue contribution (TMRC). Then, using the information on both the chemical’s toxicity to humans (the RfD) and a person’s potential exposure (the TMRC), the Agency sets tolerance levels that will not pose significant dietary risks to the consumer. The EPA will usually deny a registration use if the anticipated exposure to humans from a proposed new use of a pesticide on a food crop, when added to estimated exposure from other food uses of that pesticide, exceeds the pesticide’s RfD. Carcinogens In cases where a food-use pesticide is a carcinogen (cancer-causing agent), the EPA uses a second approach in addition to the one discussed above. The EPA assesses the cancer risk associated with exposure to the pesticide in food over the course of a person’s lifetime. The EPA then determines whether that cancer risk can be con- sidered “negligible.” The EPA’s pesticide program defines a negligible risk as one- in-a-million or less chance of getting cancer as a direct result of a lifetime of exposure to a particular substance. In general, the EPA will grant a tolerance and register any pesticide that poses a negligible or no-cancer risk. For pesticide residues that pose a cancer risk greater than negligible (one in a million), the EPA may register the pesticide if the benefits of its use outweigh its risks. Monitoring residues Pesticide tolerances, set by the EPA, are enforced by the Food and Drug Admin- istration, which monitors all domestically produced and imported foods traveling in interstate commerce except meat, poultry, and some egg products. The FDA conducts a Total Diet Study, also known as a Market Basket Study, which measures the average American consumer’s daily intake of pesticide residues from foods that are bought in typical supermarkets and grocery stores, and prepared or cooked as L1190 CH11 pgs Page 592 Friday, July 2, 1999 5:45 PM © 2000 CRC Press LLC they would be in a household setting. The findings of the ongoing Total Diet Study show that dietary levels of most pesticides are less than 1% of the RfD. Imported foods receive special attention in the FDA’s monitoring program. Above-tolerance residues in 1987 and 1988 were found in less than 1% of import samples. Even so, the FDA has tightened its import policy in the last few years: if a single shipment from a given source is found to violate U.S. tolerance regulations, all shipments from the same source are subject to automatic detention. Monitoring meat and poultry products is conducted by the USDA’s Food Safety and Inspection Service (FSIS). Each year, the FSIS conducts 10,000 to 20,000 pesticide residue analyses. Currently, fewer than 1% of these tests show illegal residues, and the violation rate has been declining steadily over the last 2 decades. State regulatory agencies are also involved in monitoring the safety of the food supply; some states have their own pesticide residue regulations for food produced and sold within state boundaries. Environmental monitoring Historically, environmental contamination by pesticides has been subject to less regulatory scrutiny than food supply contamination. Registration and regegistration of pesticides require the thorough testing of the fate and movement of pesticides and the effects of pesticide exposure to non-target plant and animal species. However, until recently, little regulatory emphasis was placed on the monitoring and estab- lishment of specific levels of pesticides in the environment once a pesticide was registered for use. Requirements for monitoring are found in the Endangered Species Act, in the discharge limits for point-sources under the Clean Water Act, and in the Maximum Contaminant Levels (MCLs) in drinking water from both surface and groundwater sources. As part of this increased emphasis, the EPA undertook a major 5-year effort to determine the extent of pesticides in the drinking water supply on a national scale. 11.2Pesticide use in the United States Pesticides are chemical substances used by farmers, household residents, or industry to regulate and control various kinds of pests or weeds — boll weevils, gypsy moths, corn fungi, crabgrass, bull thistles, dandelions, and the like. There are three major types of pesticides: (1) herbicides, (2) insecticides, and (3) fungicides. Herbicides are chemicals used for killing weeds or inhibiting plant growth. Insecti- cides are chemicals or mixtures of chemicals intended to prevent or destroy any insects that may destroy crops or gardens. Fungicides are chemicals used to destroy or inhibit fungi, which usually cause plant diseases. The pesticide industry is very large; in 1992 within the U.S., $8.26 billion was spent on pesticides. Over 56.6% of the expenditures ($4.67 billion) was for herbicides; 30.0% ($2.48 billion) for insecticides; 6.4% ($525 million) for fungicides; and 7.0% ($579 million) was spent on various other pesticides. In addition to the economic cost of the pesticides, the amounts of pesticides produced are also very large. In 1992, over a billion pounds of pesticides were sold in the U.S. About 58.7% (647 million pounds) was herbicides; 23.2% (255 million pounds) was insecticides; 10.9% (120 million pounds) was fungicides; and 7.2% (80 million pounds) was other pesticides. L1190 CH11 pgs Page 593 Friday, July 2, 1999 5:45 PM © 2000 CRC Press LLC From 1983 to 1993, pesticide production fluctuated from year to year, but overall grew slowly from 975 million pounds in 1983 to 1152 million pounds of pesticides in 1993, a growth rate of about 18.2%. This corresponds to an average annual growth rate of 1.8% per year during the 10-year period. During this same period, there was moderately steady growth in herbicide production, from 587 million pounds in 1983 to 754 million pounds in 1993. The growth rate of 28.4% is nearly 50% more than the rate of overall pesticides produc- tion, corresponding to an average annual growth rate of 2.8% per year. The annual overall production of insecticides remained constant at approxi- mately 200 million pounds per year from 1983 to 1993. Lastly, the number of pounds of fungicides produced increased greatly from 43 million pounds in 1983 to 78 million pounds in 1993. This represents an overall growth rate of 81.4% and an average annual growth rate of 8.4% per year. Main uses of pesticides Pesticides are used mainly for three purposes: (1) agriculture, (2) industry, com- mercial establishments, and government, and (3) home and garden. Pesticide usage in agriculture The number of pounds of pesticides used by the agricultural sector has remained relatively constant from 1980 to 1992. In 1980, 79% (or 846 million pounds) of pesti- cides was used for agriculture; while in 1992, 76% (839 million pounds) of pesticide was used in the agricultural sector. Pesticide usage in industry, commercial establishments, and government The number of pounds of pesticides used by industry, commercial establish- ments, and government increased steadily from 147 million pounds in 1980 to 193 million pounds in 1992. The moderate increase in the amount of pesticides used was due to the increased usage of herbicides and fungicides. Pesticide usage in homes and gardens The number of pounds of pesticides used for home and gardens decreased slightly from 82 million pounds in 1980 to 71 million pounds in 1992. The decline was due to a reduction in the amount of insecticides used, from 42 million pounds in 1980 to 31 million pounds per year in 1992. Most commonly used pesticides A small number of active ingredients accounted for a large proportion of pesti- cide use. For example, the combined usage of the three most commonly applied herbi- cides, atrazine, metolachlor, and alachlor, in 1993 was 175 to 190 million pounds. This represented about 27 to 29% of all herbicides used in the U.S. The three most commonly used insecticides, as a group, were not as dominant as the top three herbicides. The combined usage of chlorpyrifos, diazinon, and malathion in 1993 was approximately 23 to 33 million pounds. This represents 9 to 13% of the total amount of insecticides used in the U.S. L1190 CH11 pgs Page 594 Friday, July 2, 1999 5:45 PM © 2000 CRC Press LLC Lastly, in 1993, the total usage of the top three fungicides combined, sulfur, chlorothalonil, and mancozeb, was approximately 49 to 60% of the total amount of fungicides applied in the U.S. Pesticides usage by crop The most common herbicides, triazine, metolachlor, and alachlor, were predom- inantly used in the planting of corn crops in the midwestern U.S., especially in the states of Illinois, Indiana, Iowa, Missouri, Nebraska, and Ohio. Insecticides such as chlorpyrifos were predominantly used on corn, peanuts, and wheat crops. Sulfur, the most commonly used fungicide, was primarily used on fruits, such as apples, grapes, and citrus, though it was also used extensively in peanuts in the southeastern region of the U.S. Chlorothalonil, another fungicide, was also used extensively on peanuts in the southeastern region of the U.S. as well as on tomatoes. Conclusion The usage of pesticides throughout the U.S. fluctuated slightly from 1983 to 1992, with an annual average growth rate of 1.8% per year, leading to an overall pesticide usage increase of approximately 18.2%. This growth in the pesticide volume resulted mostly from an increase in fungi- cide usage. Fungicide usage in 1992 was nearly 100% higher than that in 1983. Projecting the usage figures from 1983 to 1992 to the future, it is expected that pesticide usage will continue to increase slowly at a rate of about 1 to 2% per year. 11.3Dose-response relationships in toxicology “The right dose differentiates a poison and a remedy.” Paracelsus Introduction The science of toxicology is based on the principle that there is a relationship between a toxic reaction (the response) and the amount of poison received (the dose). An important assumption in this relationship is that there is usually a dose below which no response occurs or can be measured. A second assumption is that once a maximum response is reached, any further increases in the dose will not result in any increased effect. True allergic reactions do not show this type of dose-response relationship. Allergic reactions are special kinds of changes in the immune system and are not really toxic responses. The difference between allergies and toxic reactions is that a toxic effect is the direct result of the toxic chemical acting on cells. Allergic responses are the result of a chemical stimulating the body to release natural chemicals which are in turn directly responsible for the effects seen. Thus, in an allergic reaction, the chemical acts merely as a trigger, not as the bullet. For all other types of toxicity, knowing the dose-response relationship is a nec- essary part of understanding the cause-and-effect relationship between chemical exposure and illness. As Paracelsus once wrote, “The right dose differentiates a poison from a remedy.” Keep in mind that the toxicity of a chemical is an inherent L1190 CH11 pgs Page 595 Friday, July 2, 1999 5:45 PM © 2000 CRC Press LLC quality of the chemical and cannot be changed without changing the chemical to another form. The toxic effects on an organism are related to the amount of exposure. Measures of exposure Exposure to poisons can be intentional or unintentional. The effects of exposure to poisons vary with the amount of exposure, which is another way of saying “the dose.” Usually, when we think of dose, we think in terms of taking one vitamin capsule a day or two aspirin every 4 hours, or something like that. Contamination of food or water with chemicals can also provide doses of chemicals each time we eat or drink. Some commonly used measures for expressing levels of contaminants are listed in Table 11.1. These measures tell us how much of the chemical is in food, water, or air. The amount we eat, drink, or breathe determines the actual dose we receive. Concentrations of chemicals in the environment are most commonly expressed as ppm and ppb. Government tolerance limits for various poisons are often expressed using these abbreviations. Remember that these are extremely small quantities (see Table 11.1). For example, if you put 1 teaspoon of salt in 2 gallons of water, the resulting salt concentration would be approximately 1000 ppm, and it would not even taste salty! Dose-effect relationships The dose of a poison is going to determine the degree of effect it produces. The following example illustrates this principle. Suppose ten goldfish are in a 10-gallon tank and we add 1 ounce shot of 100-proof whiskey to the water every 5 minutes until all the fish get drunk and swim upside down. Probably none would swim upside down after the first two or three shots. After four or five, a very sensitive fish might. After six or eight shots, another one or two might. With a dose of ten shots, five of the ten fish might be swimming upside down. After fifteen shots, there might be only one fish swimming properly and it too would turn over after seventeen or eighteen shots. The effect measure in this example is swimming upside down. Individual sen- sitivity to alcohol varies, as does individual sensitivity to other poisons. There is a dose level at which none of the fish swim upside down (no observed effect). There is also a dose level at which all of the fish swim upside down. The dose level at which 50% of the fish have turned over is known as the ED 50 , which means effective dose for 50% of the fish tested. The ED 50 of any poison varies depending on the effect measured. In general, the less severe the effect measured, the lower the ED 50 for that particular effect. Obviously, poisons are not tested in humans in such a fashion. Instead, animals are used to predict the toxicity that may occur in humans. Table 11.1 Measurements for Expressing Levels of Contaminants in Food and Water Dose Abbreviation Metric equivalent Abbreviation Approx. amount in water Parts per million ppm Milligrams per kilogram mg/kg 1 teaspoon per 1000 gallons Parts per billion ppb Micrograms per kilogram µ g/kg 1 teaspoon per 1,000,000 gallons L1190 CH11 pgs Page 596 Friday, July 2, 1999 5:45 PM © 2000 CRC Press LLC One of the more commonly used measures of toxicity is the LD 50 . The LD 50 (the lethal dose for 50% of the animals tested) of a poison is usually expressed in milli- grams of chemical per kilogram of body weight (mg/kg). A chemical with a small LD 50 (like 5 mg/kg) is very highly toxic. A chemical with a large LD 50 (1000 to 5000 mg/kg) is practically nontoxic. The LD 50 says nothing about nonlethal toxic effects though. A chemical may have a large LD 50 , but may produce illness at very small exposure levels. It is incorrect to say that chemicals with small LD 50 values are more dangerous than chemicals with large LD 50 values; they are simply more acutely toxic. The danger, or risk of adverse effect of chemicals, is mostly determined by how they are used, not by the inherent toxicity of the chemical itself. The LD 50 values of different poisons may be easily compared; however, it is always necessary to know which specie was used for the tests and how the poison was administered (the route of exposure), since the LD 50 of a poison may vary considerably based on the animal species and the way exposure occurs. Some poisons may be extremely toxic if swallowed (oral exposure) and not very toxic at all if splashed on the skin (dermal exposure). If the oral LD 50 of a poison was 10 mg/kg, 50% of the animals who swallowed 10 mg/kg would be expected to die and 50% to live. The LD 50 is determined mathematically, and in actual tests using the LD 50 , it would be unusual to get an exact 50% response. In one test, the mortality might be 30% and in another 70%. Averaged out over many tests, the numbers would approach 50%, if the original LD 50 determination was valid. The potency of a poison is a measure of its strength compared to other poisons. The more potent the poison, the less it takes to kill; the less potent the poison, the more it takes to kill. The potencies of poisons are often compared using Signal Words or categories, as shown in the example in Table 11.2. The designation toxic dose (TD) is used to indicate the dose (exposure) that will produce signs of toxicity in a certain percentage of animals. The TD 50 is the toxic dose for 50% of the experimental subjects. The larger the TD, the less poison it takes to produce signs of toxicity. The TD does not give any information about the lethal dose because toxic effects (for example, nausea and vomiting) may not be directly related to the way that the chemical causes death. The toxicity of a chemical is an inherent property of the chemical itself. It is also true that chemicals can cause different types of toxic effects, at different dose levels, depending on the animal species tested. For this reason, when using the toxic dose designation, it is useful to precisely define the type of toxicity measured, the animal species tested, and the dose and route of administration. Table 11.2 Toxicity Rating Scale and Labeling Requirements for Pesticides Category Signal word(s) required on label LD 50 Oral (mg/kg) LD 50 Dermal (mg/kg) Probable oral label dose I DANGER — POISON <50 <200 A few drops to Highly toxic (skull and cross bones) a teaspoon II WARNING 51–500 200–2000 >1 teaspoon Moderately toxic to 1 ounce III CAUTION >5000 >20,000 >1 cup Slightly toxic IV None required Practically nontoxic L1190 CH11 pgs Page 597 Friday, July 2, 1999 5:45 PM [...]... the most convenient way to express this since metric units go by steps of ten, hundred, and thousand For example, a milligram is a thousandth of a gram, and a gram is a thousandth of a kilogram Thus, a milligram © 2000 CRC Press LLC L1190 CH11 pgs Page 600 Friday, July 2, 1999 5:4 5 PM is a thousandth of a thousandth, or a millionth of a kilogram A milligram is one part per million of a kilogram; thus,... deaths at all Figure 11. 1 Dose-response realationships A true assessment of chemical toxicity involves comparisons of numerous doseresponse curves covering many different types of toxic effects The determination of which pesticides will be Restricted Use Pesticides involves this approach Some © 2000 CRC Press LLC L1190 CH11 pgs Page 599 Friday, July 2, 1999 5:4 5 PM Restricted Use Pesticides have very...L1190 CH11 pgs Page 598 Friday, July 2, 1999 5:4 5 PM Toxicity assessment is quite complex, and many factors can affect the results of toxicity tests Some of these factors are temperature, food, light, and stressful environmental conditions Other factors related to the animal itself include age, sex, health, and hormonal status The NOEL (no observable effect... (low acute oral toxicity); however, they may be very strong skin or eye irritants and thus require special handling The knowledge gained from dose-response studies in animals is used to set standards for human exposure and the amount of chemical residue that is allowed in the environment As mentioned previously, numerous dose-response relationships must be determined in many different species Without this... five thousand milligrams (5000 mg) to make up one teaspoonful of a solid (such as salt) The unit of liquid volume, the liter, is very close to a quart Thus, a milligram per liter is about the same as a milligram per quart (See Table 11. 3.) Table 11. 3 Metric System Quantities For solids 1 kilogram (kg) so: 1 mg/kg 1 kilogram (kg) so: 1 µg/kg For liquids 1 liter (L) of water weighs exactly 1 kg so: 1 mg/L... chemical exposure, and work to minimize the risk to human health and the environment 11. 4 How much is a part per million? Introduction The health effects of any toxic substance are related to the amount of exposure, also known as the dose The greater the dose the more severe the effects Some chemicals can cause toxicity at very low doses, and thus it is important to be able to understand how these very... curve, which shows how fast the response increases at the dose increases Figure 11. 1 shows examples of dose-response curves for two different chemicals having the same LD50 Which of these chemicals is more toxic? Answer this question for doses below the LD50, and it is chemical A that is more toxic; at the LD50, they are the same, and above the LD50, chemical B is more toxic While the LD50 can provide some... encountered However, with the ability to detect even smaller amounts of contaminants, the terms part per billion and part per trillion are becoming more common In the metric weight system, a microgram is a thousandth of a milligram Since a milligram is a millionth of a kilogram, and the microgram is a thousand times smaller, it is equivalent to a billionth of a kilogram Microgram is abbreviated µg Thus, a part... based on their LD50 values, and base decisions about the safety of a chemical on this number This is an over-simplified approach to comparing chemicals because the LD50 is simply one point on the doseresponse curve that reflects the potential of the compound to cause death What is more important in assessing chemical safety is the threshold dose, and the slope of the dose-response curve, which shows... fish is about a million times higher © 2000 CRC Press LLC L1190 CH11 pgs Page 601 Friday, July 2, 1999 5:4 5 PM than the level of PCBs in drinking water However, we generally consume a lot more water than fish At the extreme, people might eat as much as a pound of fish a day or as little as one pound every 100 days (1/100 lb/day) On the other hand, people generally drink about 2 liters (equivalent to about . contamination. Registration and regegistration of pesticides require the thorough testing of the fate and movement of pesticides and the effects of pesticide exposure to non-target plant and animal species concepts in toxicology and environmental chemistry L1190 CH11 pgs Page 587 Friday, July 2, 1999 5:4 5 PM © 2000 CRC Press LLC chapter eleven General concepts 11. 1Pesticide regulation . bullet. For all other types of toxicity, knowing the dose-response relationship is a nec- essary part of understanding the cause -and- effect relationship between chemical exposure and illness. As Paracelsus