Developmental and reproductive toxicity DART

Assessment of developmental and reproductive toxicity (DART) is commonly done in rodents (mice and rats) and in rabbits (mainly developmental toxicity). These evaluations use standardized experimental designs described in detail in the respective ICH guidelines (Table 18.1). The entire spectrum of DART... 

The endpoints measured in the developmental and reproductive toxicity (DART) study are consistent with studies conducted on small molecules and biotherapeutics. For further information, see FDA and International Conference on Harmonization (ICH) guidelines. Organs essential to the normal functioning of the immune system are not typically assessed in DART studies, and revisiting this should be considered as suggested by Holsapple et al.37... 

There are three principal ways for a chemical to be added to the Proposition 65 list. A chemical can be listed if either of two independent committees of scientists and health professionals finds that the chemical has been clearly shown to cause cancer or birth defects or other reproductive harm. These two committees are the Carcinogen Identification Committee (CIC) and the Developmental and Reproductive Toxicant (DART) Identification Committee, and both are part of OEHHA s Science Advisory Board. The committee members are appointed by the Governor and are designated as the State s Qualified Experts for evaluating chemicals under Proposition 65. When determining whether a chemical should be placed on the list, the committees base their decisions on the most current scientific information available. OEH-HA staff scientists compile all relevant scientific evidence on various chemicals for the committees to review. The committees also consider comments from the public before making their decisions. 

The DART Identification Committee evaluated each selected agent for male and female reproductive toxicity and developmental toxicity in humans and experimental animals. It also reviews other types of available toxicity data (e.g., acute and carcinogenicity) and pharmaco-kinetic data. 

DART provides bibliographic information and abstracts on reproductive and developmental toxicology studies. There is better coverage of developmental toxicity literature than reproductive toxicity literature. The studies cover a broad range of species and reproductive and developmental... 

In addition to DART, there are a number of additional sources of information that the Navy should consider using to evaluate the reproductive and developmental toxicity potential of agents. These sources are described in Appendix B. 

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