Adequacy of models for developmental toxicity; C 10, 29; Steroid disruptors: estrogen, androgen, progestin, corticoid; C 20, 21, 29; Thyroid, retinoid and other disruptors; C 10, 20, 21; Take Home Exam Questions Distributed

Adequacy of models for developmental toxicity

The best existing models for developmental toxicity use multiple generations to evaluate impacts on both the first and second generations following dosage of the parental generation (usually of either the male or female parent only so as to optimize the identification of the target of the actual insult). Evaluations of the first generation indicate direct effects of toxic insult on development. This may involve germline mutations in the parental generation if exposure took place in the parents prior to mating. It may involve genotoxic impacts involving the germline or embryonic F1 tissues. It may involve teratogenic insults derived from either mutational or epigenetic influences within the F1 embryo. More subtle impacts on the F1 generation may appear later in development or during aging, e.g., increased incidences of particular tumor types. Evaluations of the F2 generation primarily serve to demonstrate the integrity of the F1 generation's germinal and reproductive tract. The model organisms used might include common test species, but they may also include more rapidly reproducing animals such as zebra fish, a model for exploration of development within the laboratory. Explorations may also include evaluation of mRNA transcription or protein synthesis within specific tissues or cells within the developing test organism.

Note however that disruptions of many of the epigenetic influences on development (hormonal, nutritional) are not ascertained, or are observed only indirectly, in these tests. Tests that look at shorter test segments or isolated tissues are further blinded to the complexities of the developmental process which is actually a three body problem (father, mother, offspring). As environmental exposures of populations become more important with respect to developmental insults (see anti-estrogens and anti-androgens below) it will probably become important to include test designs that explore a variety of non-protein as well as protein hormones during the course of gestation and development. Moreover, it will also be important to explore the impacts of exposure of both parents on the developmental outcomes of the offspring.

Endocrine Disruption

As a topic of active interest currently and in the recent past there are many references that can be pointed to:

Silent Spring. R. Carson. Fawcett Crest: New York, NY. 1970. [Many other editions are available.]

Our Stolen Future. T. Colborn, D. Dumanoski, J.P. Myers. Penguin Books: New York, NY. 1997.

Out Stolen Future - an activist website

Hormonally Active Agents in the Environment. Committee on Hormonally Active Agents in the Environment, Board on Environmental Studies and Toxicology, Commission on Life Sciences, National Research Council. National Academy Press: Washington, D.C. 1999.

Endocrine and Hormonal Toxicology. P.W. Harvey, K.C. Rush, A. Cockburn. John Wiley & Sons Ltd.: Chichester, UK. 1999.

Generations at Risk: Reproductive Health and the Environment. T. Schettler, G. Solomon, M. Valenti, A. Huddle. The MIT Press: Cambridge, MA. 1999.

Hormonal Chaos: The Scientific and Social Origins of the Environmental Endocrine Hypothesis. S. Krimsky. Johns Hopkins University Press: Baltimore, MD. 2000.