Conservation of developmental

The paired box is another sequence motif that is very well conserved during evolution and is found in a number of genes known to be of developmental significance in lower organisms. The paired box encodes the 128-amino acid paired domain, which binds DNA(Chalapakis et al., 1991), and shows similarity, with a helix-tum-helix motif, to the homeodomain. 

Adjustments are often made in the NOAEL or BMD to account for the exposure scenario of concern. In the case of inhalation exposure, for example, if a study involved exposure to 500 parts per million (ppm) for 6 hours per day (h/ d), and there are no modifying pharmacokinetic data, the adjusted NOAEL or BMD for a continuous exposure would be calculated by multiplying by 6/24, yielding 125 ppm. Adjustment to account for the duration of exposure has not been applied routinely in assessments of developmental toxicity such an adjustment is made in the case of assessments for reproductive toxicity. The Subcommittee on Reproductive and Developmental Toxicology recommends that exposure duration should be considered in developmental and reproductive toxicity assessments alike. The reason for this recommendation is that adjusting for duration of exposure is likely to be more conservative with repeated exposures than with single exposures, even for developmental toxicity data (Weller et al. 1999). In the case of occupational exposure during a 6-8 h workday, this adjustment could be unnecessary. However, if pharmacokinetic data indicate accumulation with repeated exposure, an adjustment would be appropriate. 

Messenger RNAs that are expressed only at a specific stage in development and encode proteins involved in specific developmental timing events. See Pasqninelli, A.E., Reinhart, B.J., Slack, R. et al.. Conservation of the seqnence and temporal expression of let-7 heterochronic regnlatory RNA, Nature 408, 86-89,2000 Moss, E.G., RNA interference it s a small RNA world, Curr. Biol. 11, R772-R775, 2001. 

Berman, B. P., Pfeiffer, B. D Laverty, T. R., et al. (2004) Computational identification of developmental enhancers conservation and function of transcription factor binding-site clusters in Drosophila melanogaster and Drosophila pseudoob-scura. Genome Biol. 5, R61. 

IDENTIFICATION OF DEVELOPMENTAL ENHANCERS USING TARGETED REGIONAL ELECTROPORATION (TREP) OF EVOLUTIONARY CONSERVED REGIONS... 

The DNT study assesses a number of parameters in offspring. and to a limited extent in their dams, that could be utilized to provide a point of depanure for noncancer risk a.sse.ssmcnt calculations (Makris ei tiL, 1998), The study is not designed to identify the exact timing or duration of the exposure that results in an adverse developmental event. However, conservative assumptions are utilized in the absence of specific pharmacokinetic or experimental data that utilize limed dosing to examine specific critical windows of developmental susceptibility. These assumptions arc that adverse outcomes in the offspring could have... 

Sharman, A.C. and Holland, P.W.H. (1996) Conservation, duplication and divergence of developmental genes during chordate evolution , Netherlands Journal of Zoology, 46, 47-67. 

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