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CHAPTER I. INTRODUCTION
1 .1 Herbal Formulations
Herbs and products containing herb(s) have been in trade and commerce and are currently used for a variety of purposes.[1] The WHO defines an herb as being fresh or dried, fragmented or powdered plant material, which can be used in this crude state or further processed and formulated to become the final herbal product. Treatment of herbs by squeezing, steaming, roasting, decocting or infusing in water, extracting with alcohol, or sweetening and baking with honey can create „„herbal products‟‟ such as juices, tinctures, decoctions, infusions, gums, fixed oils, essential oils, and resins. These may be used medically or as the starting material for additional processing and as food ingredients. Depending on the sophistication of the „„herbal preparation,‟‟ these products may be subject to any number of physical, chemical, or biological processes, including pulverization, extraction, distillation, expression, fractionation, purification, concentration, or fermentation. Formulation of the „„final product‟‟ may require mixing one or more plant preparations with minerals or animal products and constituents isolated from herbal materials or synthetic compounds. These phytotherapeutic formulations may also be referred to as drugs or botanicals, or when taken orally to provide health benefits, they may be called dietary supplements or even food ingredients in some cases.[2] Herbal medicines are plant derived materials and preparations with therapeutic or other human health benefits, which contain either raw or processed ingredients from one or more plants, inorganic materials or animal origin. Herbal medicine preparations are developed and created drugs by the modern pharmaceutical industry. Nowadays, they are manufactured and sold most widely on the pharmaceutical market for curing diseases and promoting public health in India.[3] Of the 2, 50,000 higher plant species on earth, more than 80 ,000 are medicinal. India is one of the world‟s 12 biodiversity centres with the presence of over 45000 different plant species. India‟s diversity is unmatched due to the presence of 16 different agro-climatic zones, 10 vegetation zones, 25 biotic provinces and 426 biomes (habitats of specific species). Of these, about 15000 - 20000 plants have good medicinal value. However, only 7000 - 7500 species are used for their medicinal values by traditional communities. In India, drugs of herbal origin have been used in traditional systems of medicines such as Unani and Ayurveda since ancient times. The
Ayurveda system of medicine uses about 700 species, Unani 700, Siddha 600, Amchi 600 and modern medicine around 30 species.[4] India is sitting on a gold mine of well-recorded and traditionally well-practised knowledge of herbal medicine. This Country is perhaps the largest producer of medicinal herbs and is rightly called the botanical garden of the world. There are very few medicinal herbs of commercial importance which are not found in this country. India officially recognizes over 3000 plants for their medicinal value. It is generally estimated that over 6000 plants in India are in use in traditional, folk and herbal medicine, representing about 75% of the medicinal needs of the Third World countries.[5] Indian traditional medicine Ayurveda is a medical system primarily practiced in India that has been known for nearly 5000 years. It includes diet and herbal remedies, while emphasizing the body, mind and spirit in disease prevention and treatment (Morgan, 2 002). WHO has also issued Guidelines for the Assessment of Herbal Medicines (WHO, 1996 ). These guidelines defined the basic criteria for the evaluation of quality, safety and efficacy of herbal medicines with the goal of assisting national regulatory authorities, scientific organizations and manufacturers in assessing documentation, submissions and dossiers in respect of such products. It was recommended that such assessments take into account long-term use in the country (over at least several decades), any description in the medical and pharmaceutical literature or similar sources or documentation of knowledge on the application of a herbal medicine, and marketing authorizations for similar products. Although prolonged and apparently uneventful use of a substance usually offers testimony of its safety, investigation of the potential toxicity of naturally occurring substances may reveal previously unsuspected problems. It was also recommended that regulatory authorities have the authority to respond promptly to new information on toxicity by withdrawing or limiting the licenses of registered products containing suspect substances, or by reclassifying the substances to limit their use to medical prescription. The guidelines stressed the need for assessment of efficacy including the determination of pharmacological and clinical effects of the active ingredients, and labeling which includes a quantitative list of active ingredient(s), dosage, and contraindications. [6] Herbal medicines are being used by about 80 % of the world population primarily in the developing countries for primary health care. They have stood the test of time for their safety, efficacy, cultural acceptability and lesser side effects. The
used within the region and if sufficient knowledge about their safety and efficacy exists. 1.3.2 New herbal medicines Herbal medicines (single or mixture of herbs) can be considered “new herbal medicines” if never used within the community or region, used for only a short period of time, used to a very small extent (few uses in a small number of patients), or used in a new combination of herbal substances never combined before. 1.3.3 Phytotherapeutic agents or phytomedicines Phytotherapeutic agents or phytomedicines; are standardized herbal preparations consisting of complex mixtures of one or more plants, which are used in most countries for management of various diseases. According to the WHO definition, herbal drugs contain as active ingredients plant part or plant materials in the crude or processed state plus certain excipients, i.e. solvents, diluents or preservatives. The active principles responsible for their pharmacological actions are not usually known.[10]
1 .4 Quality – A Major Concern
Quality of herbs has become a major concern following reports of heavy metals in Indian herbs. Adulteration of plants is a serious problem. Some of the common adulterants are: botanicals, toxic metals, microorganisms, microbial toxins, pesticides, and fumigation agents. One study showed that 64% of Herbal Medicinal Products (HMP) samples collected in India contained significant amounts of lead (64% mercury, 41 % arsenic and 9 % cadmium). A recent Harvard Medical School study reported that 14 (20%) of 70 HMPs contained heavy metals. However, this problem is not unique to ayurvedic medicine. Other traditional medicines – Chinese, Middle East and South American-have also been implicated. Such contamination can lead to serious harm to patients taking such remedies and could also interfere with the assessment of safety in a clinical trial. Quality has to be assured at all stages – herbal raw materials, processing of herbals and finished herbal medicines. [11]
1 .5. Safety :
Doubts on safety of the herbal drugs is one of the most convenient weapon that comes into play in any event of fall out of ill effects of the herbal drugs, even when it could be due to misuse or unauthorized use/prescription. Citation of historical or traditional use is often cited as the basis of safety. However, in modern perspectives such a reference can only be of collateral corroboration and appears to lack any significance standalone. Rationally, the safety aspects have been less rigorously attended and emphasized in the literature. The therapeutic references on the herb have over-shadowed any effect as the therapeutic action appears to be the key focus and toxicity appears to have gone barley beyond tolerating (via co- administration of another herb) or specific linkage of the herb with food or drinks. Thus, a growing library of the epidemiological, toxicity data, co-effects, secondary effects etc. need to be appended to the information on historical/traditional use of the herb. Also, such growing database information would keep the potential consumers well educated and informed about the herb and forms an important platform for academic and investigative discussion. Particularly, sharing, documentation and publication of the negative (adverse effect) or null data is most important for rational conclusions to be drawn for the therapeutic action of the herbs. Similarly, a good placebo system needs to be evolved for herbs and herbal products for corroboration of the claimed benefits.[12] Fig.1.1. Frequency of occurrence of herbs in herbal formulation in India
clearly throws light towards the harvesting and production practices. The substance known as aflatoxins will produce serious side-effects if consumed along with the crude drugs.[13] Standardization of herbal formulations is essential in order to assess of quality drugs, based on the concentration of their active principles, physical, chemical, phyto- chemical, and standardization, and In-vitro, In-vivo parameters. The quality assessment of herbal formulations is of paramount importance in order to justify their acceptability in modern system of medicine. One of the major problems faced by the herbal industry is the unavailability of rigid quality control profiles for herbal materials and their formulations. In India, the department of Ayush, Government of India, launched a central scheme to develop a standard operating procedures for the manufacturing process to develop pharmacopeial standards for ayurvedic preparations. The subject of herbal drug standardization is massively wide and deep. There is so much to know and so many seemingly contradictory theories on the subject of herbal medicines and their relationship with human physiology and mental function. India needs to explore the medicinally important plants. This can be achieved only if the herbal products are evaluated and analyzed using sophisticated modern techniques of standardization.
Fig. 1.2.A schematic representation of herbal drug standardization
1 .7. Physical/physicochemical standardization
In the standardization of herbal material, physical and physico-chemical factors play an important role in the establishment of purity and quality. Ash values testify for the presence or absence of foreign matter like silica; extractive values indicate the extractable matters in a solvent and is an indication of possible exhausted material. Advantages of Herbal Medicine They have large amount of use. They have better patient tolerance as well as acceptance. The medicinal plants have renewable source of cheaper medicines. Improvements in the quality, efficacy and safety of herbal medicines with the development of science and technology. Fig. 1.2.A schematic representation of herbal drug standardization
1 .7. Physical/physicochemical standardization
In the standardization of herbal material, physical and physico-chemical factors play an important role in the establishment of purity and quality. Ash values testify for the presence or absence of foreign matter like silica; extractive values indicate the extractable matters in a solvent and is an indication of possible exhausted material. Advantages of Herbal Medicine They have large amount of use. They have better patient tolerance as well as acceptance. The medicinal plants have renewable source of cheaper medicines. Improvements in the quality, efficacy and safety of herbal medicines with the development of science and technology. Fig. 1.2.A schematic representation of herbal drug standardization
1 .7. Physical/physicochemical standardization
In the standardization of herbal material, physical and physico-chemical factors play an important role in the establishment of purity and quality. Ash values testify for the presence or absence of foreign matter like silica; extractive values indicate the extractable matters in a solvent and is an indication of possible exhausted material. Advantages of Herbal Medicine They have large amount of use. They have better patient tolerance as well as acceptance. The medicinal plants have renewable source of cheaper medicines. Improvements in the quality, efficacy and safety of herbal medicines with the development of science and technology.
variables like calcium oxalate, silica, carbonate, content of the crude drug affects total ash value. Ash value parameters include total ash value, acid-insoluble ash value and water soluble ash values. Acid insoluble ash value is used to determine the silica impurities, while the significance of total ash value lies in the determination of excess calcium oxalate or calcium carbonate crystals present. Water soluble ash is good indicator of either previous extraction of water soluble salts in drugs or incorrect preparation. 1.7.2 Extractive values- These are also useful for the evaluation of a crude drug and at the same time give idea about the nature of the chemical constituents present, which is helpful for the estimation of specific constituents, soluble in that particular solvent used for extraction. For this purpose we have to determine alcohol-soluble and water soluble extractives. Water soluble extractive value gives idea about presence of tannins, sugars, plant acids, mucilage and other water soluble phytochemicals. It also indicates about drug quality, adulteration and or incorrect processing. The alcohol soluble extractives are also indicatives of the same purpose and at the same time are best to determine the resin content of a drug. 1.7.3 Determination of ash The ash remaining following ignition of medicinal plant materials is determined by three different methods which measure total ash, acid-insoluble ash and water-soluble ash. The total ash method is designed to measure the total amount of material remaining after ignition. This includes both "physiological ash", which is derived from the plant tissue itself, and "non-physiological" ash, which is the residue of the extraneous matter (e.g. sand and soil) adhering to the plant surface. Acid-insoluble ash is the residue obtained after boiling the total ash with dilute hydrochloric acid, and igniting the remaining insoluble matter. This measures the amount of silica present, especially as sand and siliceous earth. Water-soluble ash is the difference in weight between the total ash and the residue after treatment of the total ash with water. The residue remaining after inceration is the ash content of the drug which simply represents inorganic salts, naturally in drug or adhering to it or deliberately added to it as a form of adulteration. Physiological ash is the total ash of the drug is inclusive of physiological as well as non physiological ash. Physiological ash is derived from the plant tissues, while non-physiological ash consist of residue of the extraneous matter (such as soil, sand etc) adhering to the herb itself .Many a time, the crude drugs are
admixed with various mineral substances like sand, soil, calcium oxalate, chalk powder or other drugs with the different inorganic contents for determining ash the powdered drug is incinerated so as to burn out all organic matter. Ash value is a criterion to judge the identity or purity of crude drugs. Total ash usually consists of carbonate, oxides, phosphate, silicates and silica. Acid insoluble ash, which is a part of total ash insoluble in dilute HCL, is also recommended for certain drugs. Adhering dirt and sand may be determined by acid insoluble ash. 1.7.4 Determination of Extractives:- The extracts obtained by exhausting crude drugs are indicative of approximate measures of their chemical constituents. Taking into consideration the diversity in chemical nature and properties of content of drugs various solvents are used for determination of extraction. The solvent used for extraction is in a position to dissolve appreciable quantities of substances desired. 1.Water soluble extractives:-This method is applied to drugs contain water soluble active constituents of crude drugs such as tannins, sugars, plant acids, mucilage, glycosides etc.
- Alcohol soluble extractives:- Alcohol is an ideal solvent for extraction of various chemicals like tannins, resins etc.Therefore this method is frequently employed to determine the approximate resin content of the drug. It is also used as an official method for assay in case of Myrrh and Asafoedtida. Generally 95 % ethyl alcohol is used for determination of alcohol soluble extractives. In some cases diluted alcohol may be used depending upon solubility of constituents of drugs.[21]
1 .8. Potential Toxic contaminants in herbal formulation
A World Health Organization survey indicated that about 7 0 – 80% of the world populations rely on non-conventional medicine mainly of herbal sources in their primary healthcare. In recent years, we have witnessed the increasing growth in popularity of over-the-counter (OTC) health foods, nutraceuticals, and medicinal products from plants or other natural sources in developed countries. This indirectly indicates that the public is not satisfied with their orthodox medical (OM) treatment. Such increase in popularity has also brought concerns and fears over the professionalism of practitioners, and quality, efficacy and safety of their treatment methods and products from herbal and natural sources available in the market. Over the past decade several news-catching episodes in developed communities indicated adverse effects, sometimes life threatening, allegedly arisen consequential to taking of OTC herbal products or traditional medicines from various ethnic groups. These OTC
comparison of traditional medicines with modern drugs with comparative efficacy has not been conducted for most of the drugs. [23]
1. 10. WHO Guidelines for Potential contaminants in Herbal
Formulations
Determination of heavy metals – e.g. cadmium, lead, arsenic, etc WHO, (199 8 ) mentions maximum permissible limits in raw materials only for arsenic, cadmium, and lead, which amount to 1.0, 0.3, and 10 ppm, respectively.. Pesticide residue – WHO and FAO (Food and Agricultural Organization) set limits of pesticides, which are usually present in the herbs. These pesticides are mixed with the herbs during the time of cultivation. Mainly pesticides like DDT, BHC, toxaphene, aldrin, and endosulfan cause serious side-effects in human beings if the crude drugs are mixed with these agents. Microbial contamination – usually medicinal plants containing bacteria and molds are coming from soil and atmosphere. Analysis of the limits of E. coli and molds clearly throws light towards the harvesting and production practices. Limits for Microbial Contamination Table 1.1. Limits for Microbial Contamination Microorganism Finished product Raw materials E. coli 101 104 Salmonella Total aerobic bacteria
Enterobacteria 103 - Aflatoxins should be completely removed or should not be present. Radioactive contamination – Microbial growth in herbals are usually avoided by irradiation. This process may sterilize the plant material but the radioactivity hazard should be taken into account. The radioactivity of the plant samples should be checked accordingly to the guidelines of International Atomic Energy (IAE) in Vienna and that of WHO.[24] There have been reports of acute and chronic intoxication resulting from the use of herbal remedies. Several researchers also reported that most herbal remedies comparison of traditional medicines with modern drugs with comparative efficacy has not been conducted for most of the drugs. [23]
1. 10. WHO Guidelines for Potential contaminants in Herbal
Formulations
Determination of heavy metals – e.g. cadmium, lead, arsenic, etc WHO, (199 8 ) mentions maximum permissible limits in raw materials only for arsenic, cadmium, and lead, which amount to 1.0, 0.3, and 10 ppm, respectively.. Pesticide residue – WHO and FAO (Food and Agricultural Organization) set limits of pesticides, which are usually present in the herbs. These pesticides are mixed with the herbs during the time of cultivation. Mainly pesticides like DDT, BHC, toxaphene, aldrin, and endosulfan cause serious side-effects in human beings if the crude drugs are mixed with these agents. Microbial contamination – usually medicinal plants containing bacteria and molds are coming from soil and atmosphere. Analysis of the limits of E. coli and molds clearly throws light towards the harvesting and production practices. Limits for Microbial Contamination Table 1.1. Limits for Microbial Contamination Microorganism Finished product Raw materials E. coli 101 104 Salmonella Total aerobic bacteria
Enterobacteria 103 - Aflatoxins should be completely removed or should not be present. Radioactive contamination – Microbial growth in herbals are usually avoided by irradiation. This process may sterilize the plant material but the radioactivity hazard should be taken into account. The radioactivity of the plant samples should be checked accordingly to the guidelines of International Atomic Energy (IAE) in Vienna and that of WHO.[24] There have been reports of acute and chronic intoxication resulting from the use of herbal remedies. Several researchers also reported that most herbal remedies comparison of traditional medicines with modern drugs with comparative efficacy has not been conducted for most of the drugs. [23]
1. 10. WHO Guidelines for Potential contaminants in Herbal
Formulations
Determination of heavy metals – e.g. cadmium, lead, arsenic, etc WHO, (199 8 ) mentions maximum permissible limits in raw materials only for arsenic, cadmium, and lead, which amount to 1.0, 0.3, and 10 ppm, respectively.. Pesticide residue – WHO and FAO (Food and Agricultural Organization) set limits of pesticides, which are usually present in the herbs. These pesticides are mixed with the herbs during the time of cultivation. Mainly pesticides like DDT, BHC, toxaphene, aldrin, and endosulfan cause serious side-effects in human beings if the crude drugs are mixed with these agents. Microbial contamination – usually medicinal plants containing bacteria and molds are coming from soil and atmosphere. Analysis of the limits of E. coli and molds clearly throws light towards the harvesting and production practices. Limits for Microbial Contamination Table 1.1. Limits for Microbial Contamination Microorganism Finished product Raw materials E. coli 101 104 Salmonella Total aerobic bacteria
Enterobacteria 103 - Aflatoxins should be completely removed or should not be present. Radioactive contamination – Microbial growth in herbals are usually avoided by irradiation. This process may sterilize the plant material but the radioactivity hazard should be taken into account. The radioactivity of the plant samples should be checked accordingly to the guidelines of International Atomic Energy (IAE) in Vienna and that of WHO.[24] There have been reports of acute and chronic intoxication resulting from the use of herbal remedies. Several researchers also reported that most herbal remedies
exhibit organ specific toxicity, hence the delay in manifestation of toxic effects. Lack of standardization is a major concern regarding use of medicinal herbal medicines. Herbal medicines are complex mixtures in which the active ingredient may not be known or may be only a small percent of the total product. Some are believed to achieve their beneficial effects through the combined actions of several ingredients. Little is known about chronic toxicities that might be associated with their prolonged use. Poor quality of herbal drugs may also be due to contamination with bacteria and fungi, microbial metabolites (i.e. aflatoxins), pesticides or heavy metals residues. Lead and mercury have been frequently found in Ayurvedic preparations: a case of lead poisoning is reported in a woman after consuming an herbal preparation to treat asthenia. Besides coming from air and soil pollution or manufacturing processes, heavy metals can be intentionally added in some Asian herbal preparations due to their alleged pharmacological properties. Many of the crude herbal drugs marketed in Italy come from extra-European countries and the Asiatic market is one of the most present ones. For the import of crude herbal material no quality control procedures are required in Italy; so a thorough purity check of marketed herbal drugs is of particular interest. Considering the growing interest in Western countries for herbal products of Chinese origin, it was decided to perform a set of purity assays on ten Chinese crude herbal drugs chosen among the most used in Italy. Samples were screened for contamination by foreign matter, inorganic residues, heavy metals and micro- organisms. [25] Today, to meet the needs of expanding herbal markets, many popular herbs are no longer totally wild-crafted. Depending on national laws, regulatory policies may control the amounts to be harvested from the wild, how they might be propagated for commercial harvest, or if a restriction of export of live material is allowed. Applying resource management to preserve rare or threatened medicinal species is a matter of concern for many countries where such taxa exist, and there is a need to rigidly enforce national regulations and international policies to ensure future availability. Guidelines for the Conservation of Medicinal Plants formulated by the WHO, the International Union for Conservation of Nature and Natural Resources (IUCN), and the World Wide Fund for Nature (WWF) (WHO/IUCN/WWF, 1993) is regularly updated (e.g., July 28, 2 004) and forms the basis for providing a framework for the conservation and sustainable use of plants in medicine.[26]
sources, such as volcanoes, and the rest comes from man-made sources. Due to natural geological contamination, high levels of arsenic can be found in drinking water that has come from deep drilled wells. This is particularly true for Bangladesh. Industrial processes such as mining, smelting and coal-fired power plants all contribute to the presence of arsenic in air, water and soil. Environmental contamination also occurs because it is used in agricultural pesticides and in chemicals for timber preservation. Arsenic occurs in different forms and some is transported between different parts of the environment where it may change its form. Arsenic in weathered rock or soil can be picked up and moved by the wind and water. Many arsenic compounds bind to soil and only move short distances when water percolates down through the soil. If arsenic is released into the atmosphere by industrial processes or volcanic activity, it attaches to particles that are dispersed by the wind and fall back to the ground. Microbes in soil and sediment also release substances containing arsenic into the atmosphere. These are then converted to other arsenic compounds that settle back onto the ground.[29] One is a rigorous procedure that has been employed in natural product chemistry and is appropriate for the identification of compounds of previously unknown structure. Arsenic species are separated from a large quantity of starting material, purified and isolated, and their structuresdetermined by X-ray crystallography, NMR spectroscopy, IR spectroscopy, mass spectrometry, UV-visible spectroscopy and elemental analysis. The method affords an unequivocal identification, but requires a rather large amount of arsenic compound and, usually, much time. This type of approach has been used to provide The other method is to combine a separation method with selective and sensitive detection methods. A typical method is a chromatographic separation with atomic absorption or emission spectrometric detection. These methods are selective and sensitive if appropriate combinations are made, and are suitable for both quantitative and qualitative analysis if standard arsenic compounds are available. [30] 1.12.1 Human Health Effects of Arsenic Arsenic may serve a useful function in the body, but only at very low levels. If there is a useful role, the amounts found naturally in foods are enough or more than is needed. Excessive exposure is clearly harmful. At very high dosages arsenic causes immediate (acute) effects including nausea, vomiting, and diarrhea. Ingestion of two grams or more may be lethal in a very short time. More commonly, arsenic exposure
involves much less than this, and may not cause any immediate or observable effects. Arsenic at low doses over a long period of time is known to cause skin changes that may lead to skin cancer. More recently arsenic has been found to cause other kinds of cancer including lung, colon and bladder cancers. It is classified as a Class A (known) human carcinogen by the US Environmental Protection Agency, and has also been associated with harmful effects on the heart and the circulatory system chronic exposure of animals to arsenic in water may also be harmful to them. Prolonged use of arsenic-rich water for irrigation can result in elevated soil arsenic levels that may become harmful to plants, animals and human beings in the area. [31]
1. 13 Cadmium
Cadmium is a toxic heavy metal, well known for its occupational health risk, and cadmium (as a pollutant of air and water) is an increasing public health concern. Inhalation of cadmium fumes or dust is the primary cause of cadmium exposure. Contamination of ground water (wells) and food are the other predominant sources of environmental pollution Cadmium accumulates in the human body a half-life every year. Though it is recognized as a neurotoxic and nephrotoxic metal in developed countries, there is not much awareness of its toxicity in developing countries. [32] 1.13.1 Human Health Effects of Cadmium The kidney is the critical target organ for the general population as well as for occupationally exposed populations. Cadmium is known to accumulate in the human kidney for a relatively long time, from 20 to 30 years, and, at high doses, is also known to produce health effects on the respiratory system and has been associated with bone disease. Most of the available epidemiological information on cadmium has been obtained from occupationally exposed workers or on Japanese populations in highly contaminated areas. Most studies have centered on the detection of early signs of kidney dysfunction and lung impairment in the occupational setting, and, in Japan, on the detection and screening for bone disease in general populations exposed to cadmium-contaminated rice. More recently, the possible role of cadmium in human carcinogenesis has also been studied in some detail. [ 33 ]
1. 14. Lead
Lead is a ubiquitous toxicant. Lead poisoning is an insidious disease that can result in developmental delays, behavioral disorders and irreversible brain damage. The major signs and symptoms of lead poisoning are pallor, gingival lead line, gastrointestinal disorder, and anemia, renal and neurological symptoms (peripheral
effects of lead than adults. Lead has been shown to be associated with impaired neurobehavioral functioning in children. Lead is known to cause proximal renal tubular damage, characterized by generalized aminoaciduria, hypophosphatemia with relative hyperphosphaturia and glycosuria accompanied by nuclear the reproductive effects of lead in the male are limited to sperm morphology and count. In the female, some adverse pregnancy outcomes have been attributed to lead. Lead is well known to inhibit the biosynthesis of heme, and consequently of hemoglobin and to decrease the life span of circulating red blood cells.[36] Iron deficiency and Pb toxicity can be synergistic and potentially devastating, upto 50% more Pb may be absorbed in children with iron deficiency.The developing fetus is at maximum risk of lead toxicity. Exposure of pregnant women can transfer significant amount of this metal to the developing fetus which may result in premature birth, low birth weight or even abortion. Infants born to mothers exposed to high level of Pb show significant signs of neurological deficits. In countries, where a major proportion of people are prone to anemia due to a variety of reasons, Pb exposure can be more serious. [37] The most common methods currently used for analysis of Pb in biological and environmental samples are flame atomic absorption spectrophotometry (AAS) and graphite furnace atomic absorption spectrophotometry (GFAAS), anode stipping voltametry (ASV), inductively coupled plasma atomic emission spectroscopy (ICP/AES), and inductively coupled plasma mass spectrometry(ICP/MS). For samples analysed by these methods, detection limits of 0.12mmoles Pb/l blood (2. 49 mg/dL) can be achieved. [38]
1. 15. Microbial Contamination
The microbial quality of pharmaceuticals is influenced by the environment and quality of the raw materials used during formulation. Some infectious outbreaks have been associated with the use of heavily contaminated raw materials of natural origin. The incidence of micro flora in non-sterile medicines generally is indicated by the nature of the ingredients the quality of the vehicle and the care and attitude of personnel involved in their handling. [39] Raw materials of herbal formulation are frequently carrier of numerous possibly pathogenic microorganisms which may cause serious infection .The permitted numbers of apathogenic bacteria in oral medicaments (1 0 3 bacteria/g) is very much lower than foodstuff. The limit in natural starting material should be 104 bacteria/g and 100 mould or yeast cell/g.The type and frequency of the tests depends
on the product. Some pharmacopoeial monograph demand absence of one or more indicator micro organism such as E.coli, salmonella species, Staphyllococus aureus and pseudomonas aeruginosa. Human or animal fecal contamination is always possible when the herbs have been harvested from small rural farms still using as fertilizer either„„night soil‟‟ or animal dung or when the workers themselves prepare the products under unsanitary conditions. Although survival of bacterial enteropathogens for any length of time is unlikely in dried material, these and other organisms have the potential of causing GI tract and nosocomial infections. [40] The WHO has specified total microbial contamination limits for contamination crude plant materials the limit adopted for untreated plant material harvested under acceptable hygienic condition. [41] 1.15.1 Pseudomonas aeruginosa This rod-shaped bacterium, Pseudomonas aeruginosa, is normally found in water, soil and other places that contain moisture. It is a pathogen that takes advantage of the weakened immune system of an ill person and causes different infections. Thus, these types of pathogen are called 'opportunistic pathogen'. 1.15.1.1. Health effect of Pseudomonas aeruginosa Infection The symptoms of pseudomonas aeruginosa infection, depends on the part of the body that is infected. Fever, muscle and joint pain are symptoms of pseudomonas bacteremia. The following list gives the respective symptoms of each infection, Bone infection: Swollen infected part, redness. Ear infection: Pain in the ear, reduced ability to hear, facial paralysis. Eye infection: Pain in the eye, reduced vision, swollen eyelids. Cystic fibrosis: Cough, reduced appetite, fast breathing, enlargement of abdomen. Skin infections: Ulcer that can result in bleeding. 1.15.2. Escherichia coli E. coli are a group of bacteria that can cause a variety of illnesses in humans, including, respiratory illnesses and other problems. There are also many types of E. coli bacteria that are harmless. One type of E. coli that often causes illness and outbreaks in humans is known as E. Coli O157. There are other strains of E. coli that cause illness as well, but O is the most notorious. on the product. Some pharmacopoeial monograph demand absence of one or more indicator micro organism such as E.coli, salmonella species, Staphyllococus aureus and pseudomonas aeruginosa. Human or animal fecal contamination is always possible when the herbs have been harvested from small rural farms still using as fertilizer either„„night soil‟‟ or animal dung or when the workers themselves prepare the products under unsanitary conditions. Although survival of bacterial enteropathogens for any length of time is unlikely in dried material, these and other organisms have the potential of causing GI tract and nosocomial infections. [40] The WHO has specified total microbial contamination limits for contamination crude plant materials the limit adopted for untreated plant material harvested under acceptable hygienic condition. [41] 1.15.1 Pseudomonas aeruginosa This rod-shaped bacterium, Pseudomonas aeruginosa, is normally found in water, soil and other places that contain moisture. It is a pathogen that takes advantage of the weakened immune system of an ill person and causes different infections. Thus, these types of pathogen are called 'opportunistic pathogen'. 1.15.1.1. Health effect of Pseudomonas aeruginosa Infection The symptoms of pseudomonas aeruginosa infection, depends on the part of the body that is infected. Fever, muscle and joint pain are symptoms of pseudomonas bacteremia. The following list gives the respective symptoms of each infection, Bone infection: Swollen infected part, redness. Ear infection: Pain in the ear, reduced ability to hear, facial paralysis. Eye infection: Pain in the eye, reduced vision, swollen eyelids. Cystic fibrosis: Cough, reduced appetite, fast breathing, enlargement of abdomen. Skin infections: Ulcer that can result in bleeding. 1.15.2. Escherichia coli E. coli are a group of bacteria that can cause a variety of illnesses in humans, including, respiratory illnesses and other problems. There are also many types of E. coli bacteria that are harmless. One type of E. coli that often causes illness and outbreaks in humans is known as E. Coli O157. There are other strains of E. coli that cause illness as well, but O is the most notorious. on the product. Some pharmacopoeial monograph demand absence of one or more indicator micro organism such as E.coli, salmonella species, Staphyllococus aureus and pseudomonas aeruginosa. Human or animal fecal contamination is always possible when the herbs have been harvested from small rural farms still using as fertilizer either„„night soil‟‟ or animal dung or when the workers themselves prepare the products under unsanitary conditions. Although survival of bacterial enteropathogens for any length of time is unlikely in dried material, these and other organisms have the potential of causing GI tract and nosocomial infections. [40] The WHO has specified total microbial contamination limits for contamination crude plant materials the limit adopted for untreated plant material harvested under acceptable hygienic condition. [41] 1.15.1 Pseudomonas aeruginosa This rod-shaped bacterium, Pseudomonas aeruginosa, is normally found in water, soil and other places that contain moisture. It is a pathogen that takes advantage of the weakened immune system of an ill person and causes different infections. Thus, these types of pathogen are called 'opportunistic pathogen'. 1.15.1.1. Health effect of Pseudomonas aeruginosa Infection The symptoms of pseudomonas aeruginosa infection, depends on the part of the body that is infected. Fever, muscle and joint pain are symptoms of pseudomonas bacteremia. The following list gives the respective symptoms of each infection, Bone infection: Swollen infected part, redness. Ear infection: Pain in the ear, reduced ability to hear, facial paralysis. Eye infection: Pain in the eye, reduced vision, swollen eyelids. Cystic fibrosis: Cough, reduced appetite, fast breathing, enlargement of abdomen. Skin infections: Ulcer that can result in bleeding. 1.15.2. Escherichia coli E. coli are a group of bacteria that can cause a variety of illnesses in humans, including, respiratory illnesses and other problems. There are also many types of E. coli bacteria that are harmless. One type of E. coli that often causes illness and outbreaks in humans is known as E. Coli O157. There are other strains of E. coli that cause illness as well, but O is the most notorious.
