HEAVY METAL TOXICITY & THEIR MANAGEMENT IN ANIMALS
Animal husbandry is an age old practice and the livestock production system is an integral part of modern global economy. The production efficiency of animals is immensely influenced by their health status, which is often impacted by a range of infectious and noninfectious diseases. Globally, livestock losses due to diseases were averaged above 20% (Justin et al., 2017). Heavy metal poisoning is one of the major non-infectious causes of adverse impact on animal health and production. Heavy metals are one of the oldest known toxicants to man due to their prehistoric use for diverse purposes. The Ebers papyrus (circa 1500 BC) contains information pertaining to many recognized poisons, including metals such as lead, copper, and antimony (Gallo, 2008). However the risk of exposure to heavy metals has increased considerably in the modern world due to their multiple industrial, domestic, agricultural, medical and technological applications (Tchounwou et al., 2012). In an analysis of the information on the occurrence of poisoning in livestock and poultry in the Europe, heavy metals were reported to be the second most significant factor causing mortality factor in accidental poisoning which corresponds to 34.4% of total positive cases in Northern Greece (Guitart et al., 2010).
Heavy metals are naturally occurring elements that have a high atomic weight and density, at least five times greater than that of water and is toxic, highly toxic or poisonous at low concentrations. A heavy metal is a member of an ill-defined subset of elements that exhibit metallic properties, which would mainly include the transition metals, some metalloids, lanthanides, and actinides. They are commonly known as toxic metal. Heavy metals are widely dispersed in the environment. “Environmental Protection Agency” (EPA), the ‘Agency for Toxic Substances and Disease Registry’ (ATSDR) in Atlanta, Georgia (a part of the U.S. Department of Health and Human Services) reported that in a ‘Priority List for 2001’ called the ‘Top 20 Hazardous Substances’, As, Pb and Hg are at the 1st, 2nd and 3rd position, respectively in the list; while Cd is at the 7th place. Therefore, the “elements/heavy metals”, viz., As, Cd, Pb and Hg are considered most toxic to the humans, animals and environment . Heavy metals concentrations in animal and their product may increase very fast . Their ecosystem accumulation (water-soil-plant-animal) makes them very toxic and leads to undesirable consequences for live organisms . These heavy metals produce reactive oxygen species and bring many changes in the repair mechanism of DNA. Depending upon its chemical form, heavy metal (s) cause toxicity or harm the body even if its concentration is very small. Increased concentrations of heavy metals in body of domestic animals result in decreased production, reproduction problems, immunity decline and occurrence of cancerous and teratogenic diseases .
Heavy metals constitute a very heterogeneous group of elements widely varied in their chemical properties and biological functions. The term “heavy metals” defined as commonly held for those metals, which have specific weights more than 5g cm-3 (Holleman and Wiverd, 1985). Heavy metals are kept under environmental pollutant category due to their toxic effects in plants, human and food. Some of the heavy metalsi.e. arsenic (As), Cadmium (Cd), Lead (Pb), Mercury (Hg) are cumulative poison. These heavy metals are persistence, accumulate and not metabolized in other intermediate compounds and do not easily breakdown in environment. These metals are accumulating in food chain through uptake at primary producer level and than through consumption at consumer level. Metals are entering the human body either through inhalation or injection. Heavy metals such as Cd, Ni, As, Pb pose a number of hazards to humans. These metals are also potent carcinogenic and mutagenic. Copper and zinc serve either as cofactor as a activator biochemical reactions & enzymatic for information of enzyme/ substrate metal complex (Mildvan, 1970). The high concentration intake of cadmium cause itai itai disease and mercury intake lead to minamita disease and other heavy metals cause poisoning due to drinking water contamination. Heavy metals have largest availability in soil and aquatic ecosystem and to relatively smaller proportion in atmosphere at particular vapors. Metal toxicity to plants varies with plants species, specific metals, concentration, chemical form, soil composition, pH and many metals considered to be essential for plants growth.
Biological significance of heavy metals
Heavy metals are the naturally occurring elements that have a high atomic weight and density, at least 5 times greater than that of water (Tchounwou et al., 2012). Knowledge and multi-purpose use of heavy metals predate recorded history of mankind and these metals have made critical contribution to the progress and success of civilizations. Owing to their extensive use and natural occurrence, the heavy metals are ubiquitous in the human environment causing some level of exposure to man and animals. In addition, all life has evolved in the presence of metals and organisms have been forced to deal with these potentially toxic, yet omnipresent, elements (Liu et al., 2008). Heavy metals are both beneficial as well as harmful to the body and can be classified into four major groups based on their biological importance: essential, non-essential, less toxic and highly toxic heavy metals. Traces of heavy metals such as copper (Cu), cobalt (Co), manganese (Mn), iron (Fe), and zinc (Zn) are essential for many vital physiological activities notably including regulation and function of several enzyme systems, oxygen and electron transport, synthesis of hormones, antioxidant defense, immunity and fertility. Deficiency of the essential metals not only adversely affects growth and physiological processes, but also potentiates toxicity due to non-essential heavy metals. Nonetheless, even essential metals will become toxic with increasing exposure. Toxic heavy metals, such as lead (Pb), cadmium (Cd) and mercury (Hg) have no known beneficial biological role and are toxic even at very low concentrations (Anjulo and Mersso, 2015). Often the non-essential toxicant metals mimic essential metals and thereby gain access to, and potentially disrupt, key cellular functions. This can also account for bioaccumulation of toxic metals. Further, elemental nature of metals impacts their biotransformation and toxicity because detoxification mechanisms by destructive metabolism cannot break an atomic species into a subcomponent of less toxicity. In essence, being an element, metals are nonbiodegradable and this indestructibility along with bioaccumulation contributes to the high concern for metal as toxicant (Liu et al., 2008).
Toxic metals in livestock and livestock production system
Though heavy metals are neither created nor destructed by human endeavor, they are redistributed and concentrated into the environment from a range of anthropogenic activities mainly consisting of mining and metallurgy, foundries, burning of fossil fuel and vehicular emissions. Volcanic activity, metal evaporation from soil and water, metal corrosion, and sediment re-suspension, soil erosion, geological weathering are the natural sources of heavy metals exposure and toxicity to man and animals (He et al., 2005; Tchounwou et al., 2012). Increased distribution of metals and metal compounds in the environment, especially through anthropogenic activities, raises increasing concern for ecotoxicological effects including toxicities in domestic animals. Biological cycles moving metals include bio-accumulation and biomagnification by plants and animals and their incorporation into food cycles (Liu et al., 2008). Heavy metal contaminants enter the food chain primarily through industry and agriculture (Tunegova et al., 2016). The coefficients of the transition and accumulation of heavy metals in the links of the food chain showed a strict correlation of animal welfare and dairy quality with environmental condition (Volkov and Samigullin, 2020). Domestic animals share human environment and are exposed to heavy metals mainly via ingestion of contaminated vegetation, feed, water and soil and to some extent by inhalation of metal particles present in the air due to industrial and vehicular pollution. Pesticides, insecticides and fertilizers used in the agricultural field are the secondary source of heavy metal pollution for animals. Higher concentrations of heavy metals like copper and zinc have been reported in animal feeds which can be one of the major sources of these heavy metals to animals (Dweba et al., 2018). Once in the body, heavy metals generally conjugate with one or more bio-active ligands viz –OH, -COO- ,- OPO3 H- , >C=O, -SH, -S-S, NH2 and >NH that are essential for normal physiological function and activate several enzyme system and persist for considerable time (Klaassen, 1996). Persistence of heavy metals in animal body and surrounding environment has been recorded several weeks even after discontinuation of the exposure. Elevated levels of lead were detected in animal tissues up to 12-18 months after exposure had ceased. Higher blood lead burdens have been reported in animals including pets from urban localities and around polluting industrial units from various parts of India (Swarup et al., 2005). Further, the animals allowed to graze on or fed with contaminated pastures or fodders from industrial sources are continually exposed to toxic pollutants including heavy metals. Those animals can serve as the better indicator of the health impacts of toxic heavy metal pollution on human population than the toxicant-administered experimental subjects (Swarup et al., 2007).
Toxic effects of heavy metals on domestic animals
Toxic effects of heavy metals in animals depend on extent of exposure, type of heavy metal and its form, age, sex, physiological and nutritional status of exposed animal and route of poisoning. Most metals are concentrated in the vital organs including liver and kidney and cause clinical or subclinical toxicities or subtle effects like oxidative stress, immunotoxicity, cardiotoxicity teratogenicity, enzyme inhibition, reproductive defects and endocrine disruption (Swarup and Dwivedi, 2002). The precise chemical basis of metal toxicology is inadequately understood and there is no uniform mechanism for all toxic metals because of the great variation in chemical properties and toxic endpoints (Liu et al., 2008). It is true that being elements, heavy metals are nonbiodegradable. However, their forms may be changed to free metal ions thereby altering their biological availability, activity and consequently, toxicity (Hollenberg, 2010). Chemically, metals in their ionic form can be very reactive and can interact in biological systems with toxicological targets in a large variety of ways resulting in variety of toxic effects and damage to various organs including kidney, nervous system, liver, respiratory system, endocrine and reproductive systems and gastrointestinal tract. The targets of heavy metals are generally cellular molecules, macromolecules, membranes or organelles and the toxicity is initiated by interaction of free metal ions with these targets. Common mechanisms by which toxic metals may act include inhibition of enzymes, subcellular organelles, interaction with DNA leading to mutagenesis and carcinogenesis, covalent modification of proteins, displacement of other critical metals dependent proteins, and generation of free radicals (Hollenberg, 2010). On the basis of their toxic effects, Kozlowski et al. (2014) placed toxic metals in four groups metals (copper and iron) acting as Fenton reaction catalyst and participate in generation of free radicals and oxidative stress; carcinogenic metals (nickel, cadmium, and chromium); metals (aluminum, lead and tin) involved in neurotoxicity; generally toxic metals like mercury. However, there is growing volume of literature suggesting that majority of heavy metals are capable of inducing oxidative stress in different animal species including buffalo (Yeotikar et al., 2018) and affects the oxidative stress quotient (Roth, 2017; Abuelo, 2019). Overproduction of free radicals and oxidative stress, not only affect immunity, but also cause biological disorders resulting in many diseases via damaging biomolecules, subcellular compartments and even whole cell e.g. neurons (Kozlowski et al., 2014). Production and reproductive performance of farm animals is heavily influenced by oxidative stress which may be responsible for considerable economic losses. Toxic heavy metals potentially disrupt endocrine system and can influence production and reproductive performance of animals (Swarup et al., 2007). There are growing evidences that heavy metals can influence antibiotic resistance and heavy metal induced co-selection of antibiotic resistance genes (ARGs) has become an emerging environmental issue (Ding et al., 2019). Presence of heavy metals such as arsenic, copper and zinc even at low level in the environment has been found to enhance resistance of bacterium to tetracycline (Chen et al., 2015). Livestock and livestock production system are viewed as the large reservoir of heavy metals due to their use in feed as well as exposure to heavy metal contaminants in the environmental. As such cocontamination of heavy metals and antibiotics in the livestock environment can add to the rapidly growing concern of antibiotic resistance. The proven positive correlation of heavy metal resistance and coexisting methicillin-resistance Staphylococcus aureus (MRSA) highlights the vulnerabilities of both humans and animals as compounded resistance is particularly difficult to treat effectively (Dweba et al., 2018).
Source of contamination
Heavy metals pollution can originate from natural and anthropogenic sources. Activities such as mining & smelting operation and agriculture, have contaminated extensive area of world such as Japan, Indonesia, and China mostly such as Cd, Cu and Zn (Herawati et al., 2000) Cu and Pb in north Greece (Zantopoulos et al., 1999), Cu, Pb, Cu, Ni, Zn, and Cd in Austrilia (Smith et al., 1996). In animal body, metals are enter through animals feeds, green fodder, drinking water and pharmaceutical medicines etc. Other sources are accidental access to limed field, mineral supplements with high content of trace metal and licking of painted surfaced containing metallic pigments.
Heavy metal contamination of animal products and food safety concern
Heavy metals are usually nonbiodegradable and tend to accumulate in the food chain including edible animal products like meat and milk of exposed livestock populations. Significant amount of heavy metals can be transferred from contaminated soil, water and air to plants and grass, causing accumulation of these metals in grazing animals and subsequently their transfer to food chain via milk and meat. Thus accumulation of toxic metals in animals is not only associated with toxic effects in food producing animals, but also poses health risks to humans consuming milk and meat contaminated by the toxic metals. Milk is not the major route of excretion of lead and cadmium. However, milk lead concentration is exponentially related to blood lead. As such, milk from lactating animals reared around industrial sources is expected to contain higher concentration of lead with possible risk of public health hazard (Swarup et al., 2000). There are several reports from different parts of the world indicating higher concentration of heavy metals in milk of cows reared in the contaminated environment (Vromman et al., 2008; Cai et al., 2009; Gonzalez-Montana et al., 2012; Pilarczyk et al., 2013; Rahimi, 2013). In Iran, 1.9% of the bovine and 8.1% of the sheep milk samples were found to contain higher levels of lead than the newly established Codex Standard indicating its public health hazards (Rahimi, 2013). Presence of lead in edible animal products like milk (Swarup et al., 2005; Kambli et al., 2019), chevon (Kar et al., 2015) and poultry meat (Orisakwe et al., 2017) is also reported in India raising public health concern. There are also reports indicating the presence of arsenic in cow milk, particularly in arsenic affected parts of the country (Rana et al., 2008). Likewise, a study from the same area revealed high concentration of arsenic in poultry products like chicken and poultry eggs. Contamination of heavy metals like cadmium and mercury was pointed out by another study conducted in Haryana (http://epubs.icar.org.in/ejournal/ index.php/IJDS/article/view/87447). More information on this aspect is reviewed under the description of specific toxicities associated with toxic heavy metals. A comprehensive review providing information on toxic doses, concentration in tissues of poisoned animals and physiological effects, symptoms, diagnostic procedures and treatment for poisoning by cadmium, lead, copper, chromium, iodine, manganese, molybdenum, selenium and zinc in the animals has been published by Reis et al. (2010). It is noted that old, young, undernourished and stressed farm animals are more severely affected and overall impact depends on kind of toxic metal and extent of exposure. General aspects of toxicity caused by some heavy metals of veterinary importance are reviewed hereunder.
Classification of Heavy metal
Heavy metals can be classified into four major groups on their health importance. Essential: Cu, Zn, CO, Cr, Mn and Fe . These metal also called micronutrients (Reeves and Baker, 2000) and are toxic when taken in excess of requirements (Monni et al., 2000; Blaylock and Huang, 2000). The toxic limit and recommended or safe intake of heavy metal for human health is given in Table – 1 (Oliver, 1997) Non essential : Ba, Al, Li and Zr Less toxic : Sn and Al Highly toxic : Hg, Cd and Cd. Heavy metals are also called trace element due to their presence in trace (10mg Kg-1) or in ultratrace (1µg kg-1) quantities in the environmental matrices.
Cadmium (Cd):
Pure cadmium is a soft, silver-white metal. The physical property of cadmium is atomic number 48, atomic weight 112.411, electro-negativity 1.5, crystal ionic radius (Principal valence state) 0.97, ionisation potential 8.993, oxidation state +2, Electron configuration Kr 4d1 5S2 Density 8.64 g/cm3, Melting point 320.9°C and Boiling point 765°C at 100 kPa. It is usually found as a mineral combined with other elements such as oxygen (cadmium oxide), chlorine (cadmium chloride), or sulphur (cadmium sulphate, cadmium sulphide). Cadmium is a toxic to virtually every system in the animal body. It is almost absent in the human body at birth, however accumulates with age. An average men accumulates as about 30 mg cadmium in his body by the age of 50 years. Refined foods, water foods, water pipes, coffee, tea, coal burning and cigrates are all the most important source of Cd. Daily dietary intake of Cd ranges from 40-50 µg/ day (WHO, 1987). Cadmium accumulated with in the kidney and liver over long time (McLaughlin et al., 1999). It is interact with numbers of minerals mainly Zn, Fe, Cu and Se due to chemical similarities and competition for binding stage. It is also reported that Cd can affected Ca, P and bone metabolism in both industrial and people exposed to Cd in general environment (Jarup et al., 1998).
Lead (Pb):
Lead is a bluish or silvery grey soft metal with atomic number 82; atomic weight 207.19; specific gravity 11.34, melting point 327.5 o C and boiling point 17400C. It is the most common industrial metal that has become widespread in air, water, soil and food. Lead is slightly soluble in water and is transported mainly through the atmosphere. It behaves like calcium in body and accumulates in bone, liver, kidney and other tissues. The problem of lead poisoning in animals has widely been recognized which needs a special attention for the environmentalist and healthpersonnel. It is a cumulative tissue poison and gets stored in different parts of the body especially in bones, liver, kidney and brain. Besides, direct ingestion of lead leading to increased blood lead levels, accumulated lead in the body also acts as a significant source of blood lead burden (Swarup et al., 2005). Accumulated lead is mobilized from the storage sites with decreasing blood lead level or following treatment with chelator, thus enhancing the chelator blood lead level without the animal being exposed to lead in the immediate past. Chelation treatment sometimes leads to fatal outcome due to immediate surge of lead from the deposited site to blood causing severe damages to kidney and brain. Lead produces mainly acute or chronic poisoning. In acute lead poisoning case fatality in lead poisoning may go up to as high as 100%. In acute lead toxicity in cattle, there is sudden onset of signs and the animal at pasture may succumb within 24 hours.
Arsenic (As)
The organoarsenicals in food are one of the most poisoning in livestock now a days because of the displacement of arsenic form almost all phases of farming activities. The common of source of arsenic is in fluid used for dipping and spraying of animal to control ecto-parasites. Clinical signs of arsenic toxicity in cattle vary form gastrointestinal to nervous signs. Arsenic were killer including sodium or sodium arsenate, Arsenic pentaoxide and monosodium or disodium acid. It toxicity produces goiter in rats, thyroid antagonism in man and inhibited the growth of rumen bacteria in pure culture as well as reduces the fermentative activity. Chronic arsenic toxicity is mostly manifested in weight loss, capricious appetite, conjunctively and mucosal erythematic lesion including mouth ulceration and reduce milk yield. Acute toxic effects include abdominal cramping, hyperesthesia in extremities, abdominal patellar reflexes and abdominal electrocardiogram (Franzblau and Lilis, 1989). Such effects generally occur at the levels of exposure equal to 50µg/kg weight/day. However, chronic poisoning of As includes anemia, liver and kidney damage, hyper pigmentation and keratosis i.e. skin damage (Wu et al., 1989; ATSDR, 2000). It is reported that As toxicity produced goiter in rats, thyroid in man. Arsenic inhibited the growth of rumen bacteria in pure culture as well reduced the fermentative activity.
Mercury (Hg):
Mercury is considered a highly toxic contaminant. The toxicity of mercury depends on its chemical form methyl mercury being the most hazardous metal and stable form of mercury that has been attributed to the suffering of most avian and mammalian predators at the top of contaminated tropics. Industrial wastes and sewage water form the chloroalkali industry are a major source of mercury pollution. The symptoms of toxicosis in most species of animals include in coordination of movement, visual aberration and decline in awareness. Fishes containing more than 0.4 ppm Hg are unfit human consumption, the critical urinary concentration of Hg has been suggested as 1 to 2 µg/ml. Minimata disease is characterized by symptoms of fatigue, loss of memory and concentration, tremors’ constriction of visual field, cortical blindness etc. (Jarup, 2003). The intake of mercury as suggested by WHO is 43 µg (Krishnamurti, 1987). The animal consumed high mercury containing vegetation will be affected and will suffer from alopecia, neuropathy, visual and gastrointestinal tract disorder.
Compiled & Shared by- Team, LITD (Livestock Institute of Training & Development)
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