Developmental + Reproductive Toxicology

Standard ICH S5(R2) Studies

• Fertility and early embryonic development to implantation—
  Sec. 4.1.1, Segment I

• Embryo-fetal prenatal development—Sec. 4.1.3, Segment II

• Perinatal and postnatal development, including maternal function—
  Sec. 4.1.2, Segment III

  • Dose range-finding studies

  • Multigenerational dosing studies

• Toxicity to male fertility—ICH S5(R2) part 2

Fertility, Anti-fertility, and Contraception Studies

In Vitro Screens

• 3β-Hydroxysteroid dehydrogenase activity

• D5-3-Ketosteroid isomerase activity

• Progestagenic and anti-progestagenic activity

• Uterotrophic and anti-uterotrophic activity

• Androgen, estrogen, progesterone receptor binding

In Vivo Studies

• Spermatostatic contact

• Sperm motility and cytokine induction

• Clauberg-McPhail endometrial proliferation

• Androgenic assay

• Antigonadotropin assay

• Oocyte antimeiosis assay

• Sperm motility and morphology assay

Evaluation Endpoints

• Standard toxicology study routes and endpoints

• Fetal evaluations

• Spermatogenesis evaluations

• Neurobehavioral evaluations

• Sensorimotor evaluation in F1/F2 neonates and juveniles

• Pharmacokinetics, pharmacodynamics, toxicokinetics

• Immunogenicity/antibody levels

• Immunotoxicity

• Cytokine levels

• Drug levels in plasma, tissues, fetus, pups, milk

• DNA/RNA biodistribution, persistence, integration