A Practical Approach, Second Edition=Ronald D. Ho.pdf

NONCLINICAL JUVENILE TOXICITY TESTING 295A: Prior to Fostering B: After FosteringDam ADam BDam CDam ADam BDam CA1 A2 A3 A4A5 A6 A7 A8B1 B2 B3 B4B5 B6 B7 B8C1 C2 C3 C4C5 C6 C7 C8B1 C2 D3 E4F5 G6 H7 I8C1 D2 E3 F4G5 H6 I7 A8D1 E2 F3 G4H5 I6 A7 B8Dam DDam EDam FDam DDam EDam FD1 D2 D3 D4D5 D6 D7 D8E1 E2 E3 E4E5 E6 E7 E8F1 F2 F3 F4F5 F6 F7 F8E1 F2 G3 H4I5 A6 B7 C8F1 G2 H3 I4A5 B6 C7 D8G1 H2 I3 A4B5 C6 D7 E8Dam GDam HDam IDam GDam HDam IG1 G2 G3 G4G5 G6 G7 G8H1 H2 H3 H4H5 H6 H7 H8I1 I2 I3 I4I5 I6 I7 I8H1 I2 A3 B4C5 D6 E7 F8I1 A2 B3 C4D5 E6 F7 G8A1 B2 C3 D4E5 F6 G7 H8Figure 8.14Fostering procedure. (A) Prior to fostering; a total of at least nine litters of eight pups on one dayare required for a fostering procedure that would create an entirely new litter. B. After fostering;no pups remain with original dams and no siblings are present in the fostered litter.then all the litters born on that day cannot be fostered. Therefore, careful planning must be usedto ensure efficient use of litters. Finally, fostering does not remove the effect of the litter entirely.Rather, the care provided by the foster dam is as important to the litter effect as that provided bythe birth dam. Thus, using the fostering approach does not entirely alleviate concerns of using thebetween-litter design, although genetic factors should be evenly distributed. The authors haveconducted several studies using the fostering design in rats and have observed that an environmentallitter effect was imposed on the fostered litter such that pups in the fostered litter gained weightat a similar rate. If the within-litter design is to be used, the fostering approach is not recommendedbecause it offers very little improvement in control of bias but increases the complexity of thestudy. Moreover, for logistical reasons, the fostering approach is not recommended for studies withlarge numbers of litters.4. One Pup per Sex per Litter DesignThe final organizational design that is used in juvenile toxicity studies is the selection of one pupper sex per litter. This design is the preferred approach for selecting a subset of offspring from apre- and postnatal development study. This approach eliminates the chance for cross-contamination(if the animals are group-housed) and avoids the large number of animals that would be dosed ina between-litter design.E. Potential Parameters for Evaluation1. Growth and DevelopmentThe FDA’s current draft guidance states that nonclinical juvenile studies should include appropriategrowth measurements, such as body weight, growth velocity, crown-rump length, tibia length, andorgan weights. 51 The utility of body weight and body weight change as sensitive measures oftoxicity has been previously described in other texts and therefore is not discussed in detail here.© 2006 by Taylor & Francis Group, LLC