2. INTRODUCTION
‘XENOBIOTICS’ are the
foreign chemical substances found within an organism,
which are not normally naturally produced by an
organism or expected to be present within that organism.
It can also cover substances which are present in much
higher concentrations than are usual in any product.
5. HUMAN EXPOSURE TO DIFFERENT
XENOBIOTICS
Environment
al xenobiotics
Toxic foods
Drugs
Cosmetics
Others
E. Donner (2015). Centre for
Environmental Risk Assessment and
Remediation (CERAR)
9. II. TOXIC FOODS
Pesticides, herbicides, and growth hormones.
Infertility
Urinary tract infection
Food additives (MSG, artificial sweetners)
Immidiate effects- Headache, altered concentration
Long term effects- Risk of cancer and CVD
Bisphenol A and surfactants.
Hormonal Imbalance
Malabsoption syndrome
Heavy metals in water
Arsenic hands and foot
Tumours and cancers.
10. III. DRUGS
All drugs are not xenobiotics but drugs such as
antibiotics (Amikacin, Gentamycin, Sulphadiazine) are
harmful to human.
Effects:
Hypersensitivity: A set of undesirable reactions
produced by the normal immune system.
• Autoimmunity: An abnormal immune response of an
organism against its own cells and tissues.
Allergies
Atopic dermatitis
Rheumatoid
arthritis Celiac
sprue disease
Vitiligo
11. Infections: Invasion of an organism's body tissues by
disease causing agents, their multiplication, and the
reaction of host tissues to these organisms and the
toxins they produce.
Lymphoproliferative disorder: A Condition in which
lymphocytes are produced in excessive quantity.
Typically occur in people who have a weak immune
system and prefer excess medication
12. IV. COSMETICS
Effects of the ingredients present in beauty products, can
be more than just skin deep. Cosmetic industries who uses
thousands of synthetic chemicals (xenobiotics) in its products
right from lipstick and lotion to shampoo and shaving cream
are harmful to the body.
A recent study done at University of Berkeley in California
(2014) shows that many popular branded lipsticks (Lakme,
Revlon, and Maybelline) have high levels of aluminium, arsenic,
lead, chromium and other heavy metals in them. According to Dr.
Katharine Hammond, these heavy metals can cause many health
problems, if used for a long term.
14. Chemicals Product Possible causes
Phthalates Nail polish, perfumes Early puberty, Breast cancer, weak
estrogen production
Triclosan Antibacterial soaps, deodrants
toothpaste
Affects body’s immune system
1,4- dioxane Shampoo, bodywash, children’s bath
product
Carcinogenic
Parabens Creams, lotion, oinments, underarm
deodrants, eye products
Breast cancer, vision defects, endocrine
disruptor
Ethylene
oxide
Shampoo’s and body wash Carcinogenic
1,3 butadiene Shaving cream, sunscreen, foundations Carcinogen exposed through inhalation
Lead Contaminant in over 650 cosmetic
products like sunscreens foundation,
nail polish, lipstick, whitening tooth
paste
Neurotoxin linked to learning language
and behavioural problems, miscarriage,
reduced fertility, delays puberty.
Polycyclic
aromatic
hydrocarbons
Shampoo, lipstick Skin and breast cancer
National toxicology program , 2014
Adverse effects of cosmetics
15. V. XENOESTROGEN
A type of xenohormone that imitates endogenic estrogen.
They have estrogenic effects on a living organism even though
they differ chemically from the endogenic estrogen produced by
the endocrine system of any organism.
◦ Synthetic : Industrial compounds, such as Polychlorinated
Bisphynol and phthalates.
◦ Natural : Plant and animal derived xenoestrogens (Dietary
estrogen) Ex: Soyabean, red
meat, milk products.
Mycoestrogens/mycotoxins(estrogenic substances
from fungi)
17. Xenobiotic and human immune system
IMMUNOTOXICITY
Immunosupressi
on
Hypersensitivity
Immunostimulatio
n
Autoimmunity
Xenobiotics may interact with cellular immune
system which results in altered immune status which may
lead to immunotoxicity
18. Realm of xenobiotic activity in immune system
Xenobiotic
s
Xenobiotic related
health hazards
Autoimmunity/Hype
rsensitivity
Immune alteration
Oxygen free radical
generation
May act as antigen
Direct effect on immune
system resulting in
suppression and
stimulation
Indirect exerted
modulation through
hormonal imbalance
Effect on humoral
immune response
Effect on cell
mediateda immune
responseAltered suceptibility
to pathogens
Rao and Richardson
20. CHARACTERISTICS OF
XENOBIOTICS
Most xenobiotics are:
Lipophillic
Penetrate membranes by diffusion
Transported by lipoproteins in blood
Require chemical conversion to
facilitate excretion
21. ENTRANCE, DISTRBUTION AND
STORAGE OF XENOBIOTICS
Entrance to the body:
Ingestion ; Oral
Food contaminants
Gastrointestinal absorption
Inhalation ; Nasal cavities
Air pollutants
Pulmonary absorption
Skin ; Epidermis, dermis
Toxic chemicals
Dermal penetration
Other routs; injection, conjunctival instillation, suppositories
22. Distribution and storage:
Xenobiotics are distributed through peripheral tissues via blood,
lymph, cerebrospinal fluid (CSF) and than stored in:
Liver:
Food contaminants ( MSG, lead, Mycotoxins)
Drug deposites (Tetracycline, Doxycycline)
Body fat:
Pesticides (Dimethoate 30C, Phosalone 35EC, Quinalphos 25EC)
Organophosphate compounds (Plasticizers,herbicides, insecticide
DTT
Bone:
Fluoride
Lead
Cadmium
Radium
Plutonium
23. FATE OF XENOBIOTICS
Xenobiotics
Entrance to body
Ingestion Inhalation Dermal penetration
Absorption into blood stream
and
Distribution to body tissues and organs
Biotransformation
Conjugation
Toxicity
action
• Pharmacologic
• Cell injury
• Immunologic
• Carcinogenic
Storage
Outside body
Inside body
Outside body
Excretion
24. METABOLISM OF XENOBIOTICS
Till date more than 200,000 xenobiotics have been
identified, most of which are metabolized in the human
body (mainly in liver).
Understanding how xenobiotics are handled at the cellular
level is important for learning how to cope with the
chemical onslaught (attack).
25. PHASE I
BIOTRANSFORMATION OF XENOBIOTICS
Biotransformation is the metabolic modification of the
molecular structure of a compound, resulting in the loss or
alteration of some characteristic properties of the original
compound. It effects the solubility, mobility and toxicity of the
organic compound.
Xenobiotics are biotransformed through any of the
following reactions:
Oxidation (Drugs, heavy matels)
Reduction (Cosmetic chemicals, heavy metals)
Hydrolysis (Drugs)
(Parkinson A.2012)
26. OXIDATION
Oxidation of xenobiotic are carried out by a xenobiotic
biotransforming enzyme which play an important role in the
solubility and mobility of toxic producing molecules in its
major site- LIVER.
Cytochrome P450 enzyme
Parkinson A (2013) studied that cytochrome P450 enzyme
convert excess steroid hormones to water-soluble
metabolites that are excreted in urine or bile
27. REDUCTION
Certain xenobiotics containing aldehyde
ketone, disulfide, sulfoxide, quinone, azo, or nitro
groups are often reduced enzymatically or
nonenzymatically by interaction with some reducing
agents:
Xenobiotics Reducing
agents
Site
Parabens FAD Liver, skin
Lead FAD, FMN Intestinal microflora
Pthalates FMN Epidermis
Arsenic NADP, FMN Liver, Intestinal
microflora
28. HYDROLYSIS
This reaction involves the breakdown of any
bond in a molecule using water. Biotransformation of
xenobiotics through hydrolysis is done by certain hydrolytic
enzymes.
Xenobiotics Hydrolytic enzyme Site
Drugs
Procain Esterase Liver tissues, cystol
Procanamide Peptidase Endoplasmic
reticulum cystol
Spironolactone Epoxide
hydrolase
Mitochondria
Diisopropylfluorophosphat
e (DFP)
Esterase Endoplasmic
reticulum
29. PHASE II
CONJUGATION
The end products found from phase I reaction is
combined with some highly water soluble endogenous
metabolites such as:
Glucuronic acid
Sulphate
Glycine
This renders them even more water-soluble, and are
eventually excreted through urine or bile.
33. EXCRETION OF XENOBIOTICS
Urinary excretion
Biliary (fecal) excretion
Exhalation
Other secretions
Saliva
Sweat
Breast milk
34. Excretion via mammary route
Since milk is an emulsion in aqueous protein solution, a
variety of metabolites (both polar and non-polar) can be
excreted via this route.
- High polar metabolites such as alcohol, caffeine
- Medium polar compounds such as certain drugs
- Low polar or lipid-soluble compounds such as
pesticides/insecticides and industrial chemicals
An epidemiological survey in Lombardy
(Northern Italy) studied about presence of xenobiotics-
aflatoxins, ochratoxin A, lead and cadmium in human milk
and confirmed the presence of ochratoxin A (85.7% ), lead
(75.7% ), cadmium (87.4%) and aflatoxin (72%) in human
milk samples.
Patriarca M, Menditto A, Rossi B, Lyon TDB, Fell GS (2014)
Environmental exposure to metals of newborns, infants and young children. Microchemical
Journal-
35. CATEGORIES OF METABOLIZERS OF
XENOBIOTICS
Every human differs (more or less) in xenobiotics
metabolism depending on their metabolic activity. Three major
categories of metabolizers are classified as:
Extensive metabolizer – Normal enzyme activity.
Poor metabolizer - No or less enzyme activity
Very poor metabolizer - Decreased metabolism of
xenobiotics, needs medication or
therapies
36. FACTORS AFFECTING METABOLISM OF
XENOBIOTICS
Age: Metabolic activity tends to decrease with increase in
age.
Nutritional status: Poor nutritional status affects enzyme
activity in the liver.
Enterohepatic circulation
Pathological status: Liver diseases also affects metabolic
activity in the body.
Hepatoma
Jaundice
Hapatitis
Cirrosis
Wilson’s disease
37. DETOXIFICATION
A natural health recovery approach, used by traditional
herbalists, naturopaths and nutritionally trained chiropractors.
It is a specific active metabolic pathway throughout the
human body, that processes unwanted chemicals for elimination.
This pathway involves a series of enzymatic reactions that
neutralize and solubilise toxins, and transport them to secretory
organs (like the liver or kidneys), so that they can be excreted from
the body.
Detoxification usually includes one or more of the following:
◦ Colon cleansing
◦ Chelating therapy
◦ Detox foods
38. ◦ COLON CLEANSING: A type of colon therapy which
encompasses a number of alternative medical therapies,
claimed to remove "toxins" from the colon and intestinal
tract. Colon cleansing may also be branded as colon
hydrotherapy or colonic irrigation.
Enemas
Laxatives
Herbal therapies
Enzymes
39. Herbs used in colon cleansing
FLEX SEED, protects gut and intestinal flora
ALFA ALFA, soothes digestive tract during
cleanse
SPIRULINA, boosts oxygen and eliminate
toxins
ALOE VERA, heals and soothes intestinal
lining
40. YOGHURT, Excellent source of probiotics
MANGO, relieves constipation with its laxative
properties
PEPPERMINT, alleviates the intestine after
cleanse
FENNEL SEEDS, relieves lower abdominal
pain and enhance digestion
41. ◦ CHELATING THERAPY: Chemical process in which a
synthetic solution; EDTA (ethylenediaminetetraacetic acid)
is injected into the bloodstream to remove heavy metals or
minerals from the body.
It is used as a treatment for metal poisoning like:
Acute mercury
Iron
Arsenic
Lead
Uranium
Plutonium
The chelating agent may be administered intravenously
intramuscularly or orally, depending on the agent and the
type of poisoning
43. DETOX DIET
Water and water based drinks are one of the
simplest detox diets around.
Calcium-ions and magnesium found in hard water
helps to remove harmful toxins from our body.
It helps to promote a healthy carbohydrate
metabolism by burning calories fast.
WATER
44. Watermelon-lime-mint with water drink:
Watermelon, flush out toxins, due to presence of organic
compound citrulline, which helps our liver and kidneys to filter
and get rid of ammonia.
lime juice, stimulate and regulate our digestive track, it
thins out bile, which allows it to flow more freely.
Mint leaves, with refreshing flavor helps to digest even
more effectively, improving the flow of bile from the liver to
gallbladder then to small intestine, where it breaks down the
unwanted dietary fats.
Water based drinks:
45. Apple cinnamon detox drink:
Zero Calorie detox water.
Stimulates and cleanse our internal organs.
Water, honey and cinnamon detox drink:
Detoxify body.
Aids in weight loss.
Global healing centre 2015
Recent studies proved that rats fed at a diet
containing honey gained less weight compared to
rats fed with a diet rich in sugar.
47. FRUITS
Avocado, helps our body to produce certain antioxidants and
glutathione, which our liver needs to filter properly.
Papaya, contains papain similar to other types of enzymes in
the pancreas which helps to digest protein. But, those
enzymes need acid for activation and papain
can work even without the presence of acid.
48. Grapefruit: It is high in antioxidants and vitamin C.
grapefruit juice aids the liver in flushing carcinogens
and pesticides out of the body.
Indian gooseberry: Elimination of toxins relies on
healthy circulation, digestion, and elimination, and
amla supports all three of these functions with its rich
antioxidant content.
Pomegranate: Pomegranate boosts as a natural
detoxifier as these are packed with healthy and
healing antioxidants, flavonoids and polyphenols.
49. SUPPLEMENTS FOR REDUCING AND
ELIMINATING XENOBIOTICS
N-acetyl cysteine is a precursor to one of the body’s most
effective antioxidants – glutathione.
Green tea extract, quercetin, and alpha lipoic acid are
powerful antioxidants that assist in xenobiotic metabolism.
B vitamins, vitamin C, and vitamin E are cofactors in
metabolic processes that eliminate xenobiotics.
Calcium -gluconate assists in the metabolism and removal of
xenobiotics and xenoestrogens.
Human health specialist, 2015
50. TIPS TO AVOID EXPOSURE OF
XENOBIOTICS
Avoid all artificial colours, flavours, preservatives and
sweeteners.
Eat minimum processed foods; the closer a food is to its
natural state, the lower the toxin risk.
Eat organically grown food whenever possible,.
Carefully select body-care products, avoiding petroleum-
based cosmetics.
Avoid using chemical-based household cleaners, laundry
products and air fresheners. Toxin-free, biodegradable
products made with natural ingredients should be prefered.
Drink filtered or purified water.
51. FIVE WAYS TO REDUCE EXPOSURE TO
XENOBIOTICS
• Say “No” to plastic
◦ PVC; commonly found in condiment and salad dressing
bottles, and cheep baby toys.
◦ Used in Styrofoam coffee cups and containers.
◦ Unless it specifically states “BPA-free”.
• Wash your produce
Fruits or vegetables, contaminated with pesticides, herbicides,
and pathogenic microorganisms should be washed thoroughly.
• Pregnant Mothers should consult her physician before taking
any supplements
• Be volatile organic compounds (VOCs) free:
New paint, furnishings, and carpeting etc are some of the major
xenobiotic sources.
• Wise selection of cosmetics:
52. CONCLUSION
Prevention and cure of adverse health effects caused by
exposure to xenobiotics must be an integral part of protecting
public health. The ever increasing quantity and variety of
chemical compounds to which the public is inevitably exposed
to, makes it obvious for effective evaluation of health effects
caused due to these chemical mixtures. The classical
toxicological methods only focus on the toxicity of individual
chemicals. Hence In-depth mechanistic animal studies and
rationally designed clinical trials should be done to find the
modulating effects of food enzymes for detoxification.
53. We cannot free ourselves and the
environment from the toxic effects of
xenobiotics but we can atleast try our best
to avoid them with proper lifestyle and good
food.
“STAY WELL AND BE HEALTHY”
