••• Chapter 63^ Reproductive Toxicology^635
❍ What are malformations, disruptions, and deformations?
A malformation is a defect that results from a developmental process, which has been abnormal from the
beginning of conception at very early in the life of the embryo. Its impact may be seen in a single or in multiple
developmental regions.
A disruption is a developmental defect that results from an intrinsic or extrinsic factor that interferes with the
originally normal development process. In the absence of the effects of this factor, the development would have
been normal. It cannot be inherited.
A deformation is an abnormal form, shape, or position of a part of the body due to the effect of mechanical force
acting on that area during development.
❍ What are the differences between a sequence, syndrome, and association?
A sequence is multiple anomalies resulting from a single known of presumed malformation, deformation, or
disruption.
A syndrome is multiple anomalies due to a single malformation.
An association is the occurrence of multiple anomalies associated with a known or unknown malformation in two
or more people.
❍ What steps are required to assess a person’s risk of an adverse reproductive outcome?
The first step is identifying whether the agent can cause a defect, and if so, the type of defect caused. The next step
is characterization of the hazard to assess the critical amount of an exposure needed to produce the result being
studied. Thirdly, the degree, type, and timing of the exposure are identified. Finally, how likely it is that the defect
resulted from the exposure being studied and not from other internal or external causes or from chance.
❍ What does the word teratogenesis mean?
Teratogenesis is a medical term, literally meaning monster-birth, which derives from teratology, the study of
the frequency, causation, and development of congenital malformations—misleadingly called birth defects.
Teratogenesis has gained a more specific usage for the development of abnormal cell masses during fetal growth,
causing physical defects in the fetus. The study of teratogenesis is called teratology.
❍ What are Wilson general principles of teratology?
The Six Principles of Teratology provides a framework for understanding how structural or functional teratogens act.
These principles were developed by James G. Wilson and are as follows:
(1) Susceptibility to teratogenesis depends on the genotype of the conceptus and the manner in which this
interacts with environmental factors.
(2) Susceptibility to teratogenic agents varies with the developmental stage at the time of exposure.
(3) Teratogenic agents act in specific ways (mechanisms) on developing cells and tissues to initiate abnormal
embryogenesis (pathogenesis);
(4) The final manifestations of abnormal development are death, malformation, growth retardation, and
functional disorder.
(5) The access of adverse environmental influences to developing tissue depends on the nature of the influences
(agent).
(6) Manifestations of deviant development increase in degree as dosage increases from the no-effect to the totally
lethal level.