Developmental toxicity approaches

Narotsky MG, Kavlock RJ. 1995. A multidisciplinary approach to toxicological screening 11. Developmental toxicity. J Toxicol Environ Health 45 145-171. 

Hewitt M, Ellison CM, Enoch SJ, Madden JC, Cronin MTD (2010) Integrating (Q)SAR models, expert systems and read-across approaches for the prediction of developmental toxicity. Reprod Toxicol 30(1) 147-160... 

NOAEL, the BMD concept, and the limitations of its applicability are addressed in Section 4.2.5. Attention is brought to the fact that the BMD approach has been studied most widely in the contexts of developmental toxicity endpoints (Falk Filipsson et al. 2003). 

Dourson et al. (1996) noted that if data are only available from one chronic study on which to base the estimation of a sub-threshold dose, the question could be asked whether data from chronic studies in other species or data from different types of bioassays (e.g., reproductive or developmental toxicity) would yield lower NOAELs. The uncertainty related to this issue must therefore be addressed and, according to the authors, the default approach to address this uncertainty is to apply a 3- or 10-fold UF, based on the assumption that the critical effect can be discovered in a reasonably small selection of toxicity studies. With a reference to some analyses performed within this area, the authors suggested the use of a UF to account for missing bioassays however, the quantification of this UF was considered to require additional work. 

Factorial designs, in which n chemicals are tested at x dose levels (x treatment groups) have been suggested by the US-EPA (US-EPA 1986) as a statistical approach for risk assessment of chemical mixmres. A 2 factorial design has been used to describe interactions between the carcinogenic activity of five polycyclic aromatic hydrocarbons at two dose levels (Nesnow 1994) and a 5 design to identify nonadditive effects of three chemicals on developmental toxicity at five dose levels (Narotsky et al. 1995). 

Weinbauer GF et al (2008) Reproductive/ developmental toxicity assessment of biopharmaceuticals in nonhiunan primates. In Cavagnaro JA (ed) Preclinical safety evaluation of biopharmaceuticals. A science-based approach to facilitating clinical trials. Wiley, New Jersey, pp 379-397... 

Daston GP, Chapin RE, SciaUi AR et al (2010) A different approach to validating screening assays for developmental toxicity. Birth Defects Res B Dev Reprod Toxicol 89(6) 526-530... 

This chapter has addressed some of the critical issues and questions for computational approaches to understanding, modeling, and predicting developmental toxicity. Recent advances in computing power allow for the integration and correlation of vast amounts of data. This greatly extends our ability to identify and understand... 

Hurtt ME, Cappon GD, Browning A (2003) Proposal for a tiered approach to developmental toxicity testing for veterinary pharmaceutical products for food producing animals. Food Chem Toxicol 41 611-619... 

Knudsen TB, Kavlock RJ, Daston GP, Stedman DB, Hixon M, Kim J (2011) Developmental toxicity testing for safety assessment, new approaches and technologies. Birth Defects Res B Dev Reprod Toxicol 92 413-420... 

Due to the specificity of toxicogenomic signatures, compounds may be classified based on common genes (or pathways) disrupted. In developmental toxicity testing, approaches may be used for classification between (1) toxic and nontoxic exposures and/or (2) classes of chemical compounds. To date, most classification studies have been conducted in alternative developmental systems (i.e. stem cells, zebrafish, whole embryo culture) due to the size of material and experimental groups needed. In a series of studies by... 

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