The prenatal developmental toxicity study (also known as embryo-fetal developmental study, teratology study, or Segment II study) is undertaken to identify chemicals that may pose a risk to the developing fetus if pregnant women are exposed. The results of well-conducted animal studies are used by regulatory agencies to help set human exposure guidelines. The experimental protocols, in general, are outlined by EPA Health Effects Test Guidelines OPPTS 870.3700.
Chemicals are tested in pregnant animals such as mice, rats, or rabbits for their potential to cause birth defects (malformations) and other signs of toxicity during embryo-fetal development. Pregnant females are usually exposed to the test agent from implantation of the embryo in the uterus (gestation day 6 in the rodent) to the day before delivery. However, they may be exposed to the chemical throughout pregnancy. This testing paradigm can also be used within a larger study (See Modified One-Generation design) to assess multigenerational responses.
The test agent may be administered by different routes, approximating what may happen in humans. For example, pregnant animals may be administered the test agent by adding the chemical to their food or water, or by introducing the test agent into the stomach through a tube. The females are monitored throughout the study for signs of maternal toxicity. Upon necropsy, fetal toxicity is determined by evaluating the total number of implants (live and resorbed conceptuses) relative to eggs ovulated (pre-implantation loss), and number of viable fetuses relative to total number implants (post-implantation loss). Fetal weight is measured as an indicator delayed development. Fetuses are evaluated for externally visible malformations (permanent and rare changes that impact function) and variations (common, non-permanent changes), as well as malformations and variations of the internal organs and skeleton. The resulting data are compared to the data for unexposed fetuses, as well as the findings obtained from other unexposed fetuses from previous studies conducted in the test laboratory.
Since the effect of a chemical exposure on a pregnant animal can be different from the effect on a non-pregnant animal, a preliminary study is conducted to determine the doses to be used in each developmental toxicity study. Ideally, doses are selected so that a no adverse effect level (NOAEL) and a lowest adverse effect level (LOAEL) can be determined for maternal toxicity and fetal toxicity.