- Developmental toxicology examines detrimental effects of toxic substances on developing organisms. Currently, it is an exciting field that can improve understanding of how toxins disrupt normal development. - Congenital malformations are physical defects present at birth that can be caused by genetics or prenatal events. They occur when development of a structure is arrested or misdirected early in embryonic life. - Thalidomide caused limb malformations in thousands of infants in the 1950s before being withdrawn, resulting in new drug testing rules to prevent such outcomes.

1. Paracelsus
“All substances are
poisons;
there is none which is not
a poison.
The right dose
differentiates a poison
from a remedy.”
Paracelsus (1493-1541)

2. Developmental Toxicology
-Developmental is concerned with the investigation of
chemically induced teratogenic effects or birth defects.
-Studies involve examining any detrimental effect produced
following exposure of a developing organism during
development.
- Currently, developmental biology is one of the most exciting
fields of study which will facilitate a better understanding of
how toxic substances perturb the complex regulation patterns
required for normal development.

3. Congenital Malformation
- A physical defect present in a baby at birth, irrespective
of whether the defect is caused by a genetic factor or by
prenatal events that are not
genetic.
-In a malformation, the development of a structure is
arrested, delayed, or misdirected early in embryonic life
and the effect is permanent. These malformation can
include heart defects, cleft lip or palate, Down syndrome
spina bifida and limb defects.

4. Terms
 Monster – abnormal or strange animal or plant.
From Latin monstrum omen, from monere to
warn (abnormal infants reflect the future).
 Teratology – The study of malformations. From
the Greek word for monster – teras.

5. Human Reproductive Facts
• 50% of pregnancies end in miscarriage
or spontaneous abortion often before
pregnancy is recognized
• 15% of couples of reproductive age are
infertile

6. Phocomelia- A birth defect in which the upper portion of a limb is absent or
poorly developed, so that the hand or foot attaches to the body by a short,
flipperlike stump.

7. Reproductive Toxicants
 Endocrine disruptors
• DDT, Dioxin
 Heavy metals
• Lead (decreased sperm)
 Organic Solvents
• Toluene, benzene
 Drugs
• Alcohol

8. Thalidomide as sedative
 Introduced in 1956
(sleeping pill) and to reduce nausea
and vomiting during pregnancy
 Withdrawn in 1961
 Discovered to be a human teratogen causing
absence of limbs or limb malformations in
newborns
 5000 to 7000 infants effected
 Resulted in new drug testing rules

9. Methylmercury (MeHg)
 Mercury (quick silver) is converted to
methylmercury by bacteria
 Methylmercury accumulates in fish, which are
consumed by humans
 In 1950’s the developmental effects of MeHg
were first recognized in Minamata, Japan
 Across the world there a regulatory agencies set
limits the amount of mercury in fish that is safe
to consume

10. Life-Long Effects of MeHg

11. Iraq Infant - Effects of Mercury