Toxicants: VOC &

Thalidomide

Presented by:
Harshita Puthran
A-002
Pre-Ph.D. Biological Sciences

Volatile Organic Compound

They are a large group of carbon-based
chemicals that easily evaporate at RT
They have low boiling point, so large no of
molecules evaporate and enter the
surrounding air
VOCs are both natural and man-made

Sources
Two types of sources: Natural and Man-made
In natural, plants are the major source of VOCs
Ex: terpenes

Indoor sources
Text

Health effects and risks

Health effects (short term)

Eye, nose and throat irritation
Headaches
Nausea / Vomiting
Dizziness
Worsening of asthma symptoms
Long term health risks
Leukemia, lymphoma
Hepatotoxicity
Renaltoxicity
Central Nervous System depression

Trichloroethylene
An industrial solvent- harmful VOC
Believed to be highly contributing in smogs
and acid rain
Can be inhaled, orally ingested or dermally
contacted
Spillage by industries causing contamination
of drinking water
CYP 2E1 is considered to be the major
enzyme involved in the metabolism

Incident

In 1960s Woburn, Massachusetts industrial

suburb
TCE leached out of some industries into
ground water supplies causing health hazards
in locals
Dizziness, loss of coordination, blurred vision,
confusion, shortness of breath, miscarriages
were occurring
In children, birth defect and leukemia were
reported

Conclusion
Should try to avoid using
products which can emit
VOCs
If unavoidable should
minimize the consumption
of that product

Thalidomide
Effective tranquiliser and painkiller
Proclaimed a "wonder drug for insomnia,
coughs, colds and headaches
After its launch in 1954, it was found to be
effective antiemitic
Thousands of pregnant women took this drug to
get relieved from morning sickness

Thalidomide tragedy
During those days, scientists did not
believe that a drug can pass through
placental barrier and harm the fetus
Some gynecologists noticed that
using this drug leads to deformities
in babies

At the same time, peripheral neuritis was developed in

patients who took the drug for more than 18 months
After that, thalidomide was not provided over-thecounter

 Over 10,000 children born with

deformities were reported in 19591960 in 46 countries
Still in Canada they were sold till
1962

The most common form of birth defects from

thalidomide is shortened limbs, with the arms being
more frequently affected

Many possible birth defectsphocomelia, dysmelia, amelia,

bone hypo plasticity,
congenital heart disease;
ocular, intestinal, and renal anomalies;
malformations of the external and inner ears
were also involved

Mechanism
Thalidomide is an unstable molecule and it rise
to polar metabolites- derivatives of glutamine
and glutamic acid
An investigation on rabbit showed that, when
thalidomide and -phenyl-N-t-butylnitrone -PBN
(a radical scavenger), the teratogenic effect of
thalidomide were reduced

 The shift in redox potential was observed

which reduces binding of a key transcription
factor, NF-B, to its binding sites in DNA.
Binding of NF-B is required to turn on the
expression of the genes twist and FGF-10 in
the mesenchyme of the developing limb
In turn, absence of expression of these two
genes results in loss of FGF-8 expression in
the apical ectodermal ridge of the developing
limb bud

Conclusion
This tragedy has brought awareness of the
side effects of a drug on pregnant women and
her baby
It increased fear of the safety of drugs
Now to launch a drug in market rigorous
toxicity tests have to be approved by FDA

Thankyou