Regulatory Forum Opinion Piece: New testing paradigms for reproductive and developmental toxicity - The NTP Modified One generation study and OECD 443

摘要

The NTP has developed a new flexible study design, termed the modified one generation reproduction (MOG) study. The MOG study will encompass measurements of developmental and reproductive toxicity parameters as well as enable the setting of appropriate dose levels for a cancer bioassay through evaluation of target organ toxicity which is based on test article exposure that starts during gestation. This study design is compared and contrasted with the new OECD 443 test guideline, the extended one generation reproduction study. The MOG study has a number of advantages, with a focus on F1 animals, the generation of adequately powered, robust datasets which include both pre-and postnatal developmental toxicity information, and the measurement of effects on reproductive structure and function in the same animals. This new study design does not employ the use of internal triggers in the design structure for the use of animals already on test and is also consistent with the principles of the 3R’s.