This document discusses cadmium, a heavy metal that exists in small particles in air as a byproduct of industrial processes like smelting. It is extremely toxic even in low concentrations and can bioaccumulate in organisms. Cadmium is primarily toxic to lungs and kidneys, and long-term exposure can cause cancers and skeletal effects like osteoporosis. Sources of cadmium exposure include tobacco smoke, contaminated food, and industrial pollution. The document examines cadmium poisoning symptoms, diagnosis, and treatments focusing on chelation therapy and reducing further exposure through diet and lifestyle changes.

1. Presented By
Shashi Shekhar Singh
SES,JNU New Delhi

2. INTRODUCTION
 Encountered in earth’s crust combined with chlorine (CdCl2),
oxygen (CdO),sulphur (CdS)
 Exists as small particles in air, result of smelting, soldering
or other high temp. industrial processes
 By-product of smelting of zinc, lead, copper ores
 Used mainly in metal plating, producing pigments,
batteries, plastics and as a neutron absorbent in nuclear
reactors

3. CADMIUM POISONING
 Caused by excessive exposure to cadmium
 No constructive purpose in the human body.
 Extremely toxic even in low concentrations, and
will bioaccumulation in organisms and ecosystems
 The McDonalds Shrek Glasses are contaminated
with Cadmium

4. EXPOSURE SOURCES
 Tobacco smoke (a one pack a day smoker
absorbs roughly 5 to 10 times the amount
absorbed from the average daily diet)
 Tobacco smoke is an important source of
cadmium exposure
 Cadmium a component of chuifong tokwan ,
sold illegally as a miracle herb in china.
 Low levels are found in grains, cereals, leafy
vegetables, and other basic foodstuffs

5. Toxicity
 Primary effects on lungs & kidneys
 Lung, Emphysema, Kidney, Calcium metabolism, Possible lung
carcinogen.
 Secondary effects on skeletal system
 Mechanisms
 Binds to sulfhydryl groups, displacing other metals from
metalloenzymes, disrupting those enzymes
 competing with calcium for binding sites (calmodulin)
 Kidney toxicity
 Free Cd binds to kidney glomerulus
 Proximal tubule dysfunction

6. Contd…
 Lung toxicity:
 Edema and Emphysema by killing lung macrophages
Skeletal effects:
 Osteoporosis and osteomalacia (pseudofractures)
 Cancer:
 Carcinogenic in animal studies
 Approx.8% of lung cancers may be attributable to Cd

7. A Model: Major mechanism involved in Cd+2 Carcinogenesis
Enhancement of DNA
Inhibition of DNA repair damage
DNA Gene
damage Mutation
Preneoplastic
Decrease of Antioxidants Oxidative stress
lesion
Cd+2 Activation of cellular Induction of Proto- Promotion of
signals Oncogenes proliferation
Inhibition of DNA
Methylation
Malignant
E-cadherin dysfunction Disruption Cell Adhesion Cancer
Cell damage Induction of Apoptosis

8. Cadmium epidemics/case studies
 Japan (1950s) “Itai-Itai” is Japanese for “ouch-ouch”-refers to
bone pain related to calcium loss
 Renal failure,Anemia, severe muscle pain
 River polluted with waste from factory, water used on rice fields
for many years
 Rice accumulated high level of Cd Community was poor (and
therefore malnourished with respect to calcium)

9. Metabolism, storage and excretion of cadmium in
human body
Journal of Occupational Medicine and Toxicology 2006

10. Mechanism
 Two mechanisms are involved in cadmium mutagenicity,
 Induction of reactive oxygen species and
 Inhibition of DNA repair
 Cystein is a precursor to the anti-oxidant protein glutathione and
is also required for metallothionein which is a protein that binds
to cadmium specifically
 Intracellular, cadmium binds to metallothionein
 Cadmium is released into the plasma after haemolysis or when
the erythrocytes lifetime has expired
 Cadmium is transported in blood plasma initially bound to
albumin
 Cadmium bound to albumin is preferentially taken up by the liver

11. Contd..
 In the liver, cadmium induces the synthesis of
metallothionein
 After a few days exposure metallothionein-bound
cadmium appears in the blood plasma
 Plasma metallothionein play an important role in
transport of cadmium
 Bound to sulfhydryl groups of cystein residues
 After chronic exposure, cadmium accumulates in the
liver then redistributed slowly to the kidney

12. Mechanism
Mechanism responsible for the selective accumulation of cadmium in proximal tubular cells

13. Cadmium-induced apoptosis involves two main
pathways
• Extrinsic pathway Fas- FADD caspase-8 pathway initiated by ligand-induced activation
of the death receptors (such as Fas) at the plasma membrane resulting in the
activation of caspase-8 or caspase-10
• Intrinsic pathway triggered by cellular stress signals (such as DNA damage) activating
caspase-9. Caspase-8 and caspase-9 cleave and activate the effector caspases
caspase-3 and caspase-7, which kill the cells by cleaving a wide range of protein
substrates
• cadmium induced cell death seems to be associated with caspase-8 activation (via
FAS receptor) followed by BID cleavage and induction of mitochondria caspase
cascade after release of cytochrome C .
• Apoptosis may also be induced by caspase-independent events after intoxication,
maybe by Ca2+-calpain coupled processes or by translocation to the nucleus of
apoptosis-inducing factor (AIF)

14. Cadmium-induced apoptosis involves two main pathways

15. Cadmium induces ROS production
 Cadmium exposure causes oxidative stress, which is not due to
direct involvement of cadmium in the production of ROS but
through indirect processes like decrease of cellular anti-oxidants
and exhalation of ROS from mitochondria
 Surprisingly, the activities of superoxide dismutase (SOD) and
glutathione peroxidase (GPx) are reduced after 4 h but increased
again after 8 h of intoxication
 The reduction of glutathione levels after cadmium administration is
also shown to occur in mice.
 The reduction of the activities of antioxidants may lead to the
production of ROS species like H202, OH and O2–. This
overproduction of ROS is partly responsible for the DNA damage.

16. Proposed pathways for ROS in Cd toxicology and carcinogenesis
following acute and chronic exposures

17. EFFECTS OF POISONING:

18. SYMPTOMS
 Food poisoning (ingestion)
 Bronchitis (inhalation)
 Interstitial pneumonitis (inhalation)
 Pulmonary edema (inhalation)
MEDICAL CONDITIONS
 Osteoporosis
 Osteomalacia
 Hyperuricemia
 Hypophosphatemia
 Itai-itai disease
 Renal failure

19. DIAGNOSIS
DIRECT EVALUATION
 24 hour urine cadmium – reflects exposure over time Blood
cadmium-estimated
INDIRECT EVALUATION
 Urinary ß 2 -microglobulin – evaluate urine levels > 300 g/g
creatinine
 Urinary retinol-binding protein(RBP)Urinary
 Metallothionein (MT)
 Critical levels:
 blood cadmium: 10 micrograms/l
 Urinary cadmium: 10 micrograms/g creatinine
 Urinary beta 2-microglobulin: 2000 micrograms/g creatinine
 Urinary retinol-binding protein: 200 micrograms/g creatinine

20. TREATMENT
 Elements like calcium and selenium are shown to
have protective effect against cadmium-induced
toxicity
 Adequate levels of zinc in the body helps to
displace cadmium from the tissues
 Potent antioxidants like Vitamin C, E,glutathione,
methionine, glycine, cysteine has great protective
efficiency.

21. TREATMENT:
 Smoking should be avoided and do check
your house products for compounds which
contain cadmium
 Render gastric lavage or make the infected
person vomit within an hour if the person has
consumed cadmium salts
 Chelation therapy

22. SMOKING IS INJURIOUS TO
HEALTH…..STOP SMOKING!!!: