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Suggested Citation:"Summary." National Research Council. 2005. Mineral Tolerance of Animals: Second Revised Edition, 2005. Washington, DC: The National Academies Press. doi: 10.17226/11309.
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Suggested Citation:"Summary." National Research Council. 2005. Mineral Tolerance of Animals: Second Revised Edition, 2005. Washington, DC: The National Academies Press. doi: 10.17226/11309.
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Suggested Citation:"Summary." National Research Council. 2005. Mineral Tolerance of Animals: Second Revised Edition, 2005. Washington, DC: The National Academies Press. doi: 10.17226/11309.
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Page 11
Suggested Citation:"Summary." National Research Council. 2005. Mineral Tolerance of Animals: Second Revised Edition, 2005. Washington, DC: The National Academies Press. doi: 10.17226/11309.
×
Page 12
Suggested Citation:"Summary." National Research Council. 2005. Mineral Tolerance of Animals: Second Revised Edition, 2005. Washington, DC: The National Academies Press. doi: 10.17226/11309.
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Suggested Citation:"Summary." National Research Council. 2005. Mineral Tolerance of Animals: Second Revised Edition, 2005. Washington, DC: The National Academies Press. doi: 10.17226/11309.
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Summary • Increased feeding of recycled animal by-products and BACKGROUND wastes that contain high levels of certain minerals; Inorganic elements found in the Earth’s crust are often • Emergence of the aquaculture industry; referred to as minerals. Some minerals are essential for • Increased evidence for potentially toxic levels of mer- health and productivity of animals and have well-defined cury, cadmium, lead, and other minerals in the diet of hu- nutritional and biochemical roles. Many other minerals mans and companion animals; naturally occur at trace levels in the foods and tissues of • Refinements in the Recommended Dietary Allowances animals but are not typically suspected to play a useful nu- and the Tolerable Upper Intake Levels of minerals for hu- tritional purpose and are considered incidental contami- mans that permit more precise evaluation of potentially toxic nants. However, all minerals, whether essential or nones- mineral levels in foods of animal origin; sential, can adversely affect an animal when amounts in the • New appreciation of the impact of minerals on environ- diet and water become excessive, so the prevention of min- mental quality. eral toxicosis is a fundamental part of animal nutrition and management. Establishing the levels at which each mineral becomes toxic to animals aids nutritionists, veterinarians, Preventing adverse effects of minerals on the health of toxicologists, government regulators, and ranchers and other animals, consumers, and the environment requires the appli- animal owners to safeguard the feed that animals consume cation of appropriate nutritional and toxicological principles and the water that they drink to optimize animal health and to set limits on mineral exposure to animals. To address this minimize tissue residues. need, the Food and Drug Administration of the U.S. Depart- In 1980, the National Research Council published Min- ment of Health and Human Services asked the National eral Tolerance of Domestic Animals, which reviewed and Academy of Sciences to convene a committee of scientific evaluated the literature relating to mineral tolerance of do- experts to make recommendations on animal tolerances and mestic animals and set maximum tolerable levels of dietary toxic dietary levels. A subcommittee of the Committee on minerals in feeds. Since that time, there have been important Animal Nutrition undertook this task. The subcommittee developments in nutrition and toxicology that compel a re- consisted of nine scientists specializing in nutrition, toxicol- evaluation of mineral tolerances of animals. These develop- ogy, and veterinary medicine, with diverse expertise and ments include the following: perspectives on the impact of nutrition on the health of fish, poultry, livestock, companion animals, and humans. • Improvements in the sensitivity and specificity of analysis of mineral concentrations in feeds and animal tissues; COMMITTEE CHARGE AND APPROACH • New information on the bioavailability, homeostasis, The committee was given the following task: “An ad hoc and mechanism of toxicity of minerals; committee of the standing Committee on Animal Nutrition • New understandings of appropriate indices of animal will be convened to conduct a thorough review of the scien- health and well-being; tific literature on trace elements and macro minerals, includ- • Increased disposal of municipal and animal wastes on ing an analysis of the effects of exposure and toxic levels in crop lands and pastures, potentially resulting in greater ex- animal diets; provide recommendations on animal tolerances posure of animals to certain minerals; and toxic dietary levels, and identify elements that pose po- 1

2 MINERAL TOLERANCE OF ANIMALS tential human health concerns. The report will address re- mented to the diet: arsenic, boron, nickel, rubidium, silicon, cent research on tolerance and toxicity of minerals in animal and vanadium. However, specific biochemical functions diets including the following areas: general considerations; have not been identified for these six, and there is not a con- mineral sources, discrepancies and difficulties in methods of sensus among nutritionists that these minerals are essential. analyses and evaluation of biological status; metabolic min- eral interactions; assessments of form and species interac- EXPOSURE tions; supplementation considerations; bioavailability of dif- ferent mineral forms and sources; maximal tolerable levels; Animals may be exposed to toxic levels of minerals from and effects of diet composition, stressors, and animal physi- a wide variety of sources. Feedstuffs, especially those de- ological status on mineral utilization; and environmental rived from plants, are a common source of potentially toxic exposure considerations. The report will include all species levels of minerals. Molybdenum and selenium occur natu- for which adequate information is available—updating the rally in soils of some regions at concentrations sufficient to previous report, greatly expanding the topics covered, and cause certain plants to accumulate levels that can be toxic increasing the usefulness of the report. Recommendations for animals. High soil, and consequently plant, concentra- will be provided on maximum tolerable and toxic dietary tions of cadmium, lead, molybdenum, copper, and zinc are levels of minerals in animal diets. Potential for toxic expo- the primary minerals of concern from the application of sure, toxicosis, factors affecting toxicity, and essentiality of municipal wastes and other biosolids to the land. Mining, dietary minerals in various animal species will be discussed.” smelting, and other industries are often associated with local This report is based mostly on the primary literature of areas of mineral contamination to the water, soil, and air, peer-reviewed journal publications. The committee recog- and, ultimately, the plants grown in that area. Feedstuffs of nized that much of the information in the 1980 publication animal origin may also be sources of toxic levels of miner- was still relevant, but that this historic foundation needed to als. For example, some types of fishmeals may be high in be reevaluated in the context of newer information on the mercury because mercury bioconcentrates through the methods of mineral analysis, mechanisms of homeostasis and aquatic food chain. toxicity, and appropriate indices of animal health and well- Mineral supplements are commonly added to animal di- being. Consequently, a reanalysis of the historic literature is ets to correct deficiencies found in pastures, forages, and synthesized with the recent literature to form the recommen- other dietary ingredients. Some mineral supplements may dations in this report. In addition, this report considers a greater contain potentially toxic levels of contaminating minerals, breadth of animal species than the past edition and expands depending upon the source of the supplement and the method the coverage on the metabolism and mechanisms of toxicity of its processing. Toxic levels of minerals may accidentally of minerals, methods and problems in mineral analysis, and occur due to mistakes in feed formulation and manufactur- the relationships between mineral exposure of animals and the ing, or from contamination during storage or transportation. mineral levels in animal products destined for human con- Such accidental administration can result in very high min- sumption. New chapters provide additional focus on acid-base eral levels and cause acute toxicosis and death, whereas most balance, nitrates, water quality, and rare earth metals. other modes of introduction typically cause toxicosis only after chronic exposure. Surface water and occasionally even deep-well or domestic water supplies may contain excessive ESSENTIALITY levels of certain minerals due to naturally high levels in the The essential minerals are those that have well-defined bio- ground. Sulfur, sodium, manganese, selenium, and fluorine chemical roles and must be in the diet of vertebrates for opti- are among the minerals most likely to reach toxic levels in mum health and productivity. Minerals play many vital roles: natural water supplies. Minerals may also be introduced into for example, they activate many proteins including enzymes, water supplies from industrial wastes, pesticide contamina- maintain the ionic and pH balance, provide for the structural tion, and other sources of pollution. Finally, minerals such rigidity of bones and teeth, and serve as regulatory signals in as arsenic, bromine, bismuth, copper, lithium, magnesium, metabolic homeostasis. Inadequate dietary concentrations of silver, zinc, and some of the rare earths are sometimes added essential minerals compromise animal growth, reproduction, to feed or water as therapeutics or for growth promotion. and health. As shown in Table S-1, the committee identified Mistakes in use of these minerals have occasionally resulted in toxicoses. • Seventeen minerals that are required by vertebrates: calcium, chlorine, chromium, cobalt, copper, fluorine, io- TOXICITY dine, iron, magnesium, manganese, molybdenum, phospho- rus, potassium, selenium, sodium, sulfur, and zinc; The committee looked at two main aspects of the effects • Six additional minerals that may be required based on of toxicity on animals: the mechanisms of toxicity of each experiments that indicate beneficial effects when supple- mineral and the maximum tolerable level that will not impair

SUMMARY 3 animal health or performance. The individual chapters de- the mineral of concern to the diet or the water and measure scribe findings in each of these areas. Some general conclu- the impact on performance and pathological signs of toxico- sions are summarized below. sis. The duration of exposure to the test mineral markedly influences the level that causes toxicosis. The committee considered three exposure durations: a single dose, acute Mechanisms of Toxicity exposure, and chronic exposure. A single dose is defined as The adverse effects of minerals depend on the dietary exposure due to the consumption of a single meal or by a concentration and length of exposure and range from subtle single gavage of the mineral. Acute exposure is defined as effects on homeostatic processes, to impairments in animal an intake of 10 days or less. Chronic exposure is set as an growth or reproductive rates, to specific pathologies and exposure of 10 days or more but emphasis is given to the death. An understanding of the biochemical or physiological studies that had the longest durations of exposure. In this mechanism by which a mineral exerts its detrimental effect report, MTL recommendations for 38 minerals are provided, is useful in diagnosing toxicity problems and in designing which is seven more than included in the 1980 Mineral Tol- research to identify the level at which that mineral becomes erance of Domestic Animals. When information is available, toxic. Although the means by which minerals cause their MTL are given for fish, rodents, and companion animals, in toxic effects are diverse, several general mechanisms are addition to the poultry and livestock species considered in common. Some minerals cause oxidative damage to cellular the previous report. Research on mineral toxicities in do- macromolecules, either by their propensity to undergo redox mestic animals conducted during the past 25 years has re- reactions or by binding to and deactivating antioxidant mol- sulted in adjustments to many of the MTL provided in the ecules or enzymes. This property contributes to the toxicity 1980 report. The previous report adjusted the MTL for lead of arsenic, cadmium, chromium, copper, cobalt, lead, iron, and mercury in order to decrease tissue residues, but those mercury, nickel, selenium, and vanadium. recommendations were not based on animal health. Further- Many minerals antagonize chemically related minerals more, the rationale for those adjustments was not provided. that are nutritionally essential by impairing their absorption, The current MTL are based solely on considerations of ani- transport, excretion, or incorporation into active sites of mal health. As compared to the 1980 report, the recom- molecules. Aluminum, arsenic, bromide, cadmium, calcium, mended MTL based on indices of animal health were copper, lead, manganese, mercury, molybdenum, nickel, phosphorus, selenium, silver, strontium, sulfur, tin, tungsten, • Not changed appreciably for 8 minerals: boron, bro- and zinc antagonize the homeostasis of at least one other mine, iodine, silicon, silver, sulfur, tungsten, and vanadium; mineral. Minerals that exert toxic effects by disturbing acid- • Increased for 13 minerals: aluminum (nonruminants), base homeostasis include calcium, chloride, magnesium, barium, bismuth, cadmium, calcium (poultry), cobalt, fluo- phosphorus, potassium, sodium, and sulfur. Electrolyte bal- rine (cattle), lead (ruminants), magnesium, manganese (ru- ance can be disrupted by magnesium, potassium, sodium, minants and swine), molybdenum (swine), nickel (ruminants bromine, and chloride. The toxic effects of chromium and and swine), and selenium; vanadium are at least partly due to their ability to mimic or • Decreased for sodium chloride and 12 minerals: ar- potentiate the action of hormones. senic, calcium (ruminants), chromium, copper, iron (cattle Individuals are often most sensitive to toxicity during and poultry), lead (nonruminants), mercury, molybdenum embryonic development, growth, and periods of stress such (ruminants), phosphorus (cattle and swine), potassium, stron- as infections or trauma. Tolerance to minerals usually in- tium (swine and poultry), and zinc (poultry). creases with age. Healthy, mature animals are often most resistant to mineral toxicoses because they have passed im- The recommended MTL in this report do not include a portant developmental events, their homeostatic mechanisms built-in safety factor. Consequently, the recommended val- are well developed, and their relative rates of feed intake are ues should be adjusted according to their intended use, and low. However, cadmium and mercury are not easily excreted, each chapter contains relevant information on modifying fac- and they can accumulate during an animal’s lifetime result- tors for each mineral. Animals that are very young, old, re- ing in toxic effects in older animals. producing, sick, exposed to stressful environments, or con- suming nutritionally imbalanced diets may be especially sensitive to toxicoses, and each chapter provides additional Maximum Tolerable Levels information on the impact of these factors. In practice, the The “maximum tolerable level” (MTL) of a mineral is MTL is highly dependent upon the form of the mineral to defined as the dietary level that, when fed for a defined pe- which the animal is exposed. Important chemical factors that riod of time, will not impair animal health or performance). determine the bioavailability of the mineral sources include Tolerable mineral levels are typically distinguished from the solubility of a mineral compound in the digestive tract, toxic levels in experiments that use incremental additions of its valence state, and whether the mineral is in an organic,

4 MINERAL TOLERANCE OF ANIMALS metallic, or other inorganic form. For some minerals, such feed and water of animals. However, the maximum tolerable as silica, chromium, iron, tin, lead, aluminum, and barium, levels recommended in this report are based solely on indi- the MTL may vary by several orders of magnitude depend- ces of animal health and productivity. ing upon the chemical form of the mineral. The individual chapters provide further information on the bioavailabilities HUMAN HEALTH of common sources of minerals. Each chapter contains a table that summarizes the details on the levels, chemical Meat, milk, and eggs are an important part of the human form, duration, animal ages, and signs of toxicosis used in diet, in part, because they supply highly bioavailable forms the studies reviewed to establish the recommendations. In of minerals. Often animals can serve as an important buffer some cases, there is a wide interval between the MTL and for the high mineral concentrations found in some plants or the levels that are toxic because research is insufficient to supplements, thereby reducing human exposure to poten- make finer discrimination. The summary tables provided in tially toxic minerals. However, levels of some minerals may each chapter give insight into the level of uncertainty. accumulate in animal tissues intended for human consump- While all minerals can become toxic when exposure lev- tion to concentrations that might adversely affect human els are sufficiently high, the frequency that animals are ex- health, even when animals are exposed to safe levels (i.e., posed to excessively high levels differs greatly for each min- levels at or below their respective MTL). Consequently, ac- eral. As shown in Table S-1, the committee identified ceptable concentrations of minerals in feeds and water of animals raised for food must consider the health of the hu- • Some minerals where toxicosis is not normally of con- man consumer as well as the health of the animal itself. cern because levels in feed and water are unlikely to be ex- The committee identified minerals of concern for human cessive: aluminum, antimony, barium, bismuth, chromium, health by a three-step process. First, the amount of a mineral cobalt, germanium, iodone, lithium, magnesium, manganese, that accumulates in meat, milk, bone, and eggs in animals nickel, rare earth elements, rubidium, silicon, silver, stron- fed their MTL was estimated. Second, acceptable safety stan- tium, tin, titanium, tungsten, and uranium; dards for mineral intake by humans were identified. Third, • Eight minerals as being of occasional concern for ani- the maximum concentrations in animal tissues were com- mal toxicosis: arsenic, boron, bromine, calcium, iron, potas- pared to levels known to be safe for humans. Individual chap- sium, phosphorus, and zinc; ters in this report provide information on the dose–response • Sodium chloride and nine minerals as being of frequent relationship between feed mineral levels and tissue levels. concern for animal toxicosis: cadmium, copper, fluorine, The committee relied on recent recommendations by the lead, mercury, molybdenum (ruminants), selenium, sulfur Food and Nutrition Board of the National Academies and (ruminants), and vanadium (poultry). other national or international organizations. Recent data on food consumption trends in the United States were used to estimate daily intake of animal meat, milk, and eggs. It was ENVIRONMENTAL HEALTH assumed that all of the protein-rich foods consumed by an Although this report focuses predominantly on levels of individual came from animals consuming minerals at their minerals that are toxic for animals, there are some cases MTL. Using this process, the committee identified minerals where environmental factors may be the primary consider- for which levels that are tolerated by animals could result in ations that limit the acceptable levels of minerals in the feed unacceptably high mineral concentrations in tissues used for and water of animals. The concentration of some minerals in human foods. excreta is greater than that in the feed consumed, and this relationship is magnified by high dietary levels. In some situ- • Cadmium, lead, mercury, and selenium could accumu- ations, application of animal wastes to the land as fertilizer late to excessive levels in skeletal muscle. If it is assumed can reduce crop yields, result in high residue levels in crops, that 5 percent of meat was bone fragments (due to inappro- or cause environmental or human health concerns. priate processing), barium, and fluorine might also be exces- The committee identified 10 minerals that could be of sive in some cases. concern because of their potential effects on crop yields or • Cadmium, iodine, lead, and mercury might, in some the environment: cadmium, copper, iron, mercury, phospho- cases, become excessive in milk. rus, potassium, sodium, selenium, sulfur, and zinc. Of these, • Arsenic, cadmium, copper, lead, mercury, selenium, phosphorus is often the primary concern. and possibly iron could become excessive in liver. Depending upon manure management, location of dis- • Arsenic, bismuth, cadmium, chromium, cobalt, fluo- posal, and climate factors, environmental considerations may ride, lead, mercury, and selenium could become excessive in limit the levels of these minerals that can appropriately be kidney. fed to animals. In some regions, environmental issues should be considered along with levels that are tolerated by animals Establishing specific recommendations for mineral lev- in regulation of the concentrations of these minerals in the els in animal feeds that are safe for human health was be-

SUMMARY 5 yond the charge of the committee. However, for arsenic, reagent-grade, highly available forms. Research on the barium, bismuth, cadmium, chromium, cobalt, copper, fluo- bioavailability of minerals at dietary levels near the MTL ride, iron, lead, mercury, and selenium, the MTL in this would also permit refinement of the recommended MTL. report, while safe for animals, could result in unacceptably • The relationship between mineral concentrations in high levels of the mineral in some types of foods derived feed and water and the levels in meat, milk, and eggs is not from these animals. well characterized for most minerals, particularly at levels that are near the MTL of the animal. For most minerals, the available information was determined during relatively REMAINING QUESTIONS AND RESEARCH NEEDED short-term studies using unrealistically high levels of expo- Finally, the committee was charged with identifying gaps sure. Information on mineral accumulation in tissues follow- in knowledge that would benefit from further research. The ing lifetime exposure to minerals is needed to evaluate tissue individual chapters fairly consistently highlight three main residue levels and impacts on human health. areas across the minerals considered: • Relevant information for predicting the MTL of miner- als for aquatic and companion animals is relatively incom- • The bioavailability of minerals that animals commonly plete. Mineral absorption and excretion in aquatic animals is encounter in feedstuffs is not well characterized, especially often considerably different from that in terrestrial animals. when fed at concentrations near the MTL. Identifying the Studies designed specifically to determine the MTL in bioavailability of minerals in the form that animals would aquatic species are needed. Companion animals have long likely be exposed to and at moderately toxic levels is needed life spans and there are few studies on chronic mineral toxi- for nutritionists and veterinarians to use the MTL recom- coses in these species. mendations in this report. The MTL are often based on

6 MINERAL TOLERANCE OF ANIMALS TABLE S-1 Summary of Minerals Reviewed in This Report Required Concern for MTL Relative to 1980 Element Nutrienta Animal Health Recommendationsb Aluminum No Low Increased (nonruminants) c Antimony No Low New Arsenic Possibly Medium Decreasedc Barium No Low Increasedc Bismuth No Low Increasedc Boron Possibly Medium Similar Bromine No Medium Similar Cadmium No High Increasedd Calcium Yes Medium Decreased (ruminants)c Increased (poultry)c Chromium Yes Low Decreasedc Cobalt Yes Low Increasedc Copper Yes High Decreasedc Fluorine Yes High Increased (cattle)c Germanium No Low New Iodine Yes Low Similar Iron Yes Medium Decreased (cattle and poultry)c Lead No High Increased (ruminants)d Decreased (nonruminants)c Lithium No Low New Magnesium Yes Low Increasedc Manganese Yes Low Increased (ruminants, swine)c Mercury No High Decreasedc Molybdenum Yes Highe Decreased (ruminants)c Increased (swine)c Nickel Possibly Low Increased (ruminants, swine)c Phosphorus Yes Medium Decreased (cattle, swine)c Potassium Yes Medium Decreasedc Rare earths Possibly Low New Rubidium Possibly Low New Selenium Yes High Increasedc Silicon Possibly Low Similar Silver No Low Similar Sodium Chloride Yes High Decreasedc Strontium No Low Decreased (swine, poultry)c Sulfur Yes Highe Similar Tin No Low New Titanium No Low New Tungsten No Low Similar Uranium No Low New Vanadium Probably Highf Similar Zinc Yes Medium Decreased (poultry)c aPossibly: Indicates that circumstantial data indicate the possibility that the mineral is essential but mechanistic information is lacking. See specific chapters for supportive information. bSimilar: Recommended Maximum Tolerable Levels for poultry and livestock in this report are not appreciably different than in the 1980 report; Decreased: Recommendations in this report are lower than the previous recommendations; Increased: Recommendations in this report are higher than the previous recommendations; New: Mineral was not reviewed in 1980 or no recommendation was provided. cMTL changed due to new information. dMTL changed because the 1980 report was based on human health concerns and not on toxicity to animals. eRuminants. fPoultry.

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Excess minerals in the diet and water of animals can have an adverse effect on animal health, consumers, and the environment. Preventing unsafe mineral exposure is a fundamental part of animal nutrition and management. At the request of the Food and Drug Administration, the National Academies convened a committee to make recommendations on animal tolerances and toxic dietary levels, updating a 1980 report on mineral tolerance in domestic animals. Based on a review of current scientific data and information, the report sets a "maximum tolerable level" (MTL) for each mineral as it applies to the diets of farm animals, poultry, and fish. The report includes an analysis of the effects of toxic levels in animal diets, and it identifies elements that pose potential human health concerns. The report recommends research that includes a better characterization of animal exposure to minerals through feedstuffs; a better understanding of the relationship between mineral concentrations in feed and water and the levels in consumer products such as meat, milk, and eggs; and more research on the maximum tolerable level of minerals for aquatic and companion animals.

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