Toxicants: VOC & Thalidomide

Presented by:

Harshita Puthran

A-002Pre-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

SourcesTwo types of sources: Natural and Man-madeIn 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

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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 1960’s 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-the-counter

• Over 10,000 children born with deformities were reported in 1959-1960 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 defects-

• phocomelia, 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 α-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-κB, to its binding sites in DNA.

• Binding of NF-κB 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