1. Extent of the Problem Approximately 10% of couples are infertile.
Nearly half of all pregnancies do not result in the birth of a normal child.
One in 33 babies is born with a major birth defect.
An additional 15-25% of babies have minor defects or functional defects.
The effects of environmental agents are largely unknown, but may have some interaction with 3-50% of birth defects.

2. Causes of Reproductive Toxicity
Inhibition of spermatogenesis or oogenesis, maturation or motility.
Hormonal imbalance
Behavioral toxicity
Developmental toxicity

3. Male Reproductive Toxicity
Male germ cells are continuously produced, but take weeks to mature.
Toxicity to a single stage of developing sperm will only be picked up if breeding is followed over the period of maturation.
The number of sperm in rodents is much greater than in humans. Rodents can successfully breed with 70-90% decreases in sperm.
Humans have much less reserve and can suffer from infertility with smaller decreases,

9. EPIDIDYMIS
TRANSPORT
STORAGE
MATURATION
MOTILITY
FERTILIZING
ABILITY
NORMAL
DEVELOPMENT

10. Female Reproductive Toxicity
Females have all their germ cells at birth.
The ovulatory cycle is under hypothalamic control.
Reproductive senescence in humans arises from a lack of oocytes, whereas in rodents it is due to hypothalamic-controlled constant estrus or pseudopregnancy.

11. Reproductive Toxicity
Chemicals and drugs are tested for their ability to cause reproductive or developmental toxicity.
Segment I: Tests for effects on fertilization and implantation
Segment II: Evaluates effects on developmental toxicity
Segment III: Evaluates effects on parturation, birth, lactation and early development
Two Generation Study
Evaluates fertilization through early development of two generations

12. Developmental Toxicology
Altered survival (death)
Prenatal
Postnatal
Morphological alterations
Malformations
Variations
Developmental delays
Growth
Skeletal development
Neurodevelopment
Acquisition of developmental landmarks
Functional deficits
Biochemical
Sexual development
Behaviorial