This topic discuss about major contaminants of herbal preparations and possible measures to get rid of them.

1. Potentially hazardous contaminants
and residues in herbal medicines
and its possible solutions
Deepak Basyal (M. Pharm)
Lecturer, CiST College, New Baneshwor

2. INTRODUCTION
• The use of herbs as medicine is the oldest form of healthcare
• Of about 2000 varieties of minor illnesses and serious diseases only
40% have cure using conventional orthodox pharmaceuticals
• About 25% of all modern medicines are directly or indirectly
derived from higher plants (WHO)
• Over 80% of the world population depends on herbal medicines and
product for healthy living (WHO)
• One of the impediments in its acceptance is the lack of standard
quality control profile
• Product quality standards are essential, whether you’re using herbs
or drugs

3. Herbal drugs
“herbal drugs” denotes plants or plant parts that have been
converted into phytopharmaceuticals by means of simple processes
involving harvesting, drying, and storage (EMEA, 1998)

4. Quality aspects of herbal drugs
 mixtures of many constituents
 in most cases active principle/s unknown
 Difficulty to get analytical methods or reference compounds
 Plant materials are chemically and naturally variable
 Chemo-varieties and chemo cultivars exist.
 The source and quality of the raw material are variable
 The methods of harvesting, drying, storage, transportation,
and processing (for example, mode of extraction and polarity
of the extracting solvent, instability of constituents, etc.)
 Toxic contaminants and residues

5. Layout: WHO Guidelines for QC of Herbal Medicine

6. Herbal Contamination
The undesired introduction of impurities of a chemical or
microbiological nature, or of foreign matter, into or onto a
starting material, Intermediate product or finished herbal
product during production, sampling, packaging, repackaging,
storage or transport.
(WHO technical report series: 908)

8. Sources of toxic contaminants in herbal
products
• Environmental and conditions that the medicinal plants are
grown
• The condition under which they are dried and processed
• The storage conditions and conditions during transport
• The manufacturing processs when ready-made medicinal
products are produced

9. Heavy metals
• ‘Heavy metal’ refers to any metallic chemical element that has a
relatively high density and is toxic or poisonous at low
concentrations. e.g. mercury (Hg), cadmium (Cd), arsenic (As) and
lead (Pb).
• Emissions from factories, leaded petrol, agrochemicals such as
cadmium-containing fertilizers, organic mercury, and arsenic-based
pesticides
• Furthermore, metals are sometimes intentionally added to Asian
herbal preparations, because the traditional Indian (Ayurvedic) and
Chinese medicine believe in their therapeutic properties

10. Heavy metals
• Not biodegraded but accumulate in the living system
• Causes various disease and disorders even at very low
concentration
• Soil residence time of thousand of years
• Negative impact on soil microflora

11. Heavy metals WHO limits (ppm)
Arsenic 10
Cadmium 0.3
Lead 10
Mercury 1

12. Country Herbal Drugs As Pb Cd Hg
Canada Finished 5 10 0.3 0.2
China Crude 2 10 1 0.5
Singapore Finished 5 20 - 0.5
Thailand Crude ,Finished 4 10 0.3 -
WHO Crude 10 10 0.3 1
EP Crude - 5 0.5 0.1
Comparison of Various National/Regional Limits (ppm)

13. Source: Caserett and Doull's Toxicology

14. Source: Caserett and Doull's Toxicology

15. Source: Caserett and Doull's Toxicology

16. Microbial Load
• Exerts an important impact on the overall quality of herbal
products and preparations
• Contamination of medicinal herbs and herbal products
with bacterial strains resistant to known antibiotics poses a
particular health risk
• An assessment of microbial contamination should take into
account the following:
o route of application (in eyes, nose, respiratory tract)
o nature of the product (the presence of substrate which could
promote the growth of microbes or preservatives)
o intended recipient (newborns, infants, debilitated patients)
o concomitant use of immunosuppressive agents and corticosteroids;
underlying disease, wound, or organ damage

17. Recommended microbial limits for herbal drugs (values in CFU/g)
Microbes USP EP WHO Brazilian P
Aerobic bacteria 105/104/102 107/105 * / 107 / 105 107 / 105 /
104
Mold and yeast 103/102/10 105/104 105 / 104 / 103 104 / 103 /
102
Enterobacteria and other
Gram negative bacteria
103/*/* */103 * / 104 / 103 104 / 103 /
102
E. coli Absent 103/Absent 104 / 102 / 10 Absent
Salmonella Absent */Absent * / Absent/
Absent
Absent
* Limits are not specified.

18. USP:
• The first value represents dried or powdered botanicals and botanicals to be treated with
boiling water before use
• The second value represents tinctures, powdered botanicals extracts, fluid extracts and
nutritional supplements with botanicals
• The third value represents infusions/decoctions
EP:
• the first value represents herbal medicinal products to which boiling water is added before
use
• The second value represents herbal medicinal products to which boiling water is not added
before use
WHO:
• The first value represents contamination of "crude" plant material intended for further
processing
• The second value represents for plant materials that have been pretreated (e.g. with boiling
water as used for herbal teas and infusions) or that are used as topical dosage forms
• The third value represents for other plant materials for internal use
Brazilian Pharmacopoeia:
• The first value represents herbal drugs to which boiling water is added before use
• The second value represents herbal drugs to which the extractive process made in cold
temperature
• The third value represents final products for oral use.

19. Residue solvents
These are the residues of organic solvents that are used during
manufacture or processing of herbal preparations/products.
Solvents are classified by ICH(CPMP/ICH 283/95) into three
classes
• Class 1: Solvents to be avoided e.g. Benzene
• Class 2: Limited toxic potential e.g. Methanol, Hexane
• Class 3: Low toxic potential e.g. Ethanol

20. Radioactive Contamination
• The environment may be contaminated with airborne radioactive
materials (Cs-134, Cs-137) which may deposit on plants
• Their activity concentration and type of radioactive contamination
should be measured
• No limits are proposed for radioactive contamination (Taking into
account the quantity of herbal medicine normally consumed by an
individual, is unlikely to be a health risk)
• Details of laboratory techniques are available from International
Atomic Energy Agency (IAEA)

21. Aflatoxins
Aflatoxins are highly toxic contaminants produced by certain
strains of the fungi Aspergillus flavus and A. parasiticus
Among 18 different types of aflatoxins identified, major members
are aflatoxin B1, B2, G1 and G2. Aflatoxin B1 is the most toxic and
most prevalent among this family.

22. • More than 25% of world agricultural crops are conatminated with
mycotoxins (FAO, 2004)
• The major target for the toxicity of aflatoxins is the liver. Causes
necrosis of liver cells, damage to mitochondria, and proliferation of
bile ducts
• Ochratoxin A (OTA) secreted by Aspergillus ochraceus is carcinogenic
(class 2B) according to the International Agency for
Research on Cancer (IARC)
• There is no specific antidote for toxicity of aflatoxins and OTA. Timely
administration of methionine (200 mg/kg) and sodium thiosulfate (50
mg/kg), at eight hour intervals, is proven to be of therapeutic value

25. Degradation Products
• Certain plant constituents are susceptible to chemical
transformation by contaminating micro-organisms
(Penicillium nigricans and P. jensi )
• Enhanced enzymatic activity transforms some constituents to
other metabolites not initially found in the herb
• These newly formed metabolites may then have adverse
effects

26. Pesticide residues
• Chemical compounds used to control or eradicate pests
(insecticides, fungicides, nematocides, herbicides, rodenticides)
• Derived from synthetic and natural sources and effective in small
concentrations against pest
• Accumulate from agricultural practices, such as spraying,
treatment of soils during cultivation, and administering of
fumigants during storage
• It may be desirable to test herbal drugs for broad groups in
general, rather than for individual pesticides.
• Many pesticides contain chlorine in the molecule, which, for
example, can be measured by analysis of total organic chlorine. In
an analogous way, insecticides containing phosphate can be
detected by measuring total organic phosphorus.

27. Classification of pesticides
1. Fungicides: prevents plant from diseases caused by phyto
pathogenic fungi
e.g. Parathion, Carboxins, Colloidal sulphur, Barium sulphide,
Dithiocarbamates
2. Herbicides: ‘weed killers’ which are used for destroying the
unwanted plants
e.g. Carbamates, Urea derivatives, Triazines , Quarternary
ammonium compounds
3. Insecticides: used to protect the crop from insects
e.g. Lead arsenate, Sodium fluoride, Nicotine, Pyrethrum D

28. Pesticide Limits (mg/kg) USP-2006 and EP (2007)
Aldrin 0.05
Chlropyrifos 0.2
Diazinon 0.5
Dichlorvos 1.0
Dithiocarbamate 2.0
Endosulfan 3.0
Endrin 0.05
Ethion 2.0
Malathion 1.0
Parathion 0.5
Permethrin 1.0
Phosalane 0.1
Pryethrin 2.0

31. Possible solutions to prevent contamination
Bioremedation: Using Hyper-accumulator Plants and certain
strains of degrading Bacteria and Fungus (Ecological engineering)
 Salix viminalis absorbs heavy metals(Ag, Cd, Pd, Cu, Zn,
Radioactive Ura)
 Indian mustard green absorbs/extracts heavy metals
 Deinococcus radioduran absorbs radioactive nuclei
 Yeast (Trichosporon mycotoxinivorans) and Mould(
Streptomyces spp.) can detoxify AF and OTA in Soil
 Use competitive non toxic strain of A. flavus (AF-36 and Alfa
Guard) to decrease the population of toxigenic A. flavus in soil
 Sunflower are grown at Chernobyl Nuclear site (Ukraine) and
Uranium plant at Ohio (USA) to absorb radioactive metals

32. Gamma-irradiation: fast, safe, convenient, eco-friendly
method to decrease microbial count. Also reduces the
reliance on chemical fumigants and preservatives
 Drying at high temperature decreases the total aerobic
microbial count (TAMC) in herbs
 Avoiding harvesting or collection in damp and cool weather
Assessing the potential sources of risk
To reduce heavy metals by plant pH of soil is adjusted to level
6.5 -7
Use of chelating agents(5mmol/kg of soil) to form complex
with heavy metals and decrease their bioavailability
Mapping of the contaminated soil sites

33. • Establish good agricultural, harvesting, and manufacturing,
processing, drying, storage, packaging and distribution practices for
herbal starting materials ensuring the safety of the global herbal
market
• Various government agencies should follow a more universal
approach to herbal quality by adopting the WHO guidelines and
also developing monographs using the various quality parameters

34. Selected References Concerning Quality of Herbal
 Quality control method for medicinal plant material
 Good agricultural and collection practice for medicinal plants
 International Pharmacopoeia
 Good manufacturing practice: Supplementary guidelines for
manufacture of herbal medicinal products
 Guide to good storage practice for pharmaceuticals
Good trade and distribution practices for pharmaceutical starting
materials
 General guidelines for methodology on research and evaluation of
traditional medicine
 Guidelines for assessment of herbal medicines
 WHO monograph on selected medicinal plants
 WHO pharmaceutical starting materials certification scheme

35. References
• AOAC (2005). Official Methods of Analysis of AOAC International, 18th edn.
AOAC International, Gaithersburg, MD.
• EMEA (1998). Quality of Herbal Medicinal Products. Guidelines. European
Agency for the Evaluation of Medicinal Products (EMEA), London.
• Wani MS (2007). Herbal medicine and its standardization. Pharma. Info. 1: 6.
• WHO (1999a). Quality Control Methods for Medicinal Plant Materials. World
Health Organization, Geneva.
• WHO (1996b). Guidelines for the Assessment of Herbal Medicines. WHO
Technical Report Series, World Health Organization, Geneva. 863.
• Curtis D. Klaassen: Caserett and Doull's Toxicology, The Basic Science of Poisons
(5th Ed.) 1996, McGraw Hill,New York
• B. Tangahu, S. Rozaimah. Review on heavy metal uptake by plants through
Phytoremedation. Int. J. Chem. Eng. 2011.

36. THANK YOU