Prospective Power Calculations for the Four Lab Study of A Multigenerational Reproductive/Developmental Toxicity Rodent Bioassay Using A Complex Mixture of Disinfection By-Products in the Low-Response Region

In complex mixture toxicology, there is growing emphasis on testing environmentally representative doses that improve the relevance of results for health risk assessment, but are typically much lower than those used in traditional toxicology studies. Traditional experimental designs with typical sample sizes may have insufficient statistical power to detect effects caused by environmentally relevant doses. Proper study design, with adequate statistical power, is critical to ensuring that experimental results are useful for environmental health risk assessment. Studies with environmentally realistic complex mixtures have practical constraints on sample concentration factor and sample volume as well as the number of animals that can be accommodated. This article describes methodology for calculation of statistical power for non-independent observations for a multigenerational rodent reproductive/developmental bioassay. The use of the methodology is illustrated using the U.S. EPA’s Four Lab study in which rodents were exposed to chlorinated water concentrates containing complex mixtures of drinking water disinfection by-products. Possible experimental designs included two single-block designs and a two-block design. Considering the possible study designs and constraints, a design of two blocks of 100 females with a 40:60 ratio of control:treated animals and a significance level of 0.05 yielded maximum prospective power (~90%) to detect pup weight decreases, while providing the most power to detect increased prenatal loss

EFSA Panel on Food Contact Materials, Enzymes, Flavourings and Processing Aids (CEF) ; Scientific Opinion on Flavouring Group Evaluation 06, Revision 4 (FGE.06Rev4 ): Straight - and branched - chain aliphatic unsaturated primary alcohols, aldehydes, carboxylic acids and esters from chemical groups 1, 3 and 4

The Panel on Food Contact Materials, Enzymes, Flavourings and Processing Aids of the European Food Safety Authority was requested to evaluate 56 flavouring substances in the Flavouring Group Evaluation 6, Revision 4, using the Procedure in Commission Regulation (EC) No 1565/2000. This revision is made due to the inclusion of six additional flavouring substances, (-)-3,7-dimethyl-6-octen-1-ol [FL-no: 02.229], dec-4(cis)-enal [FL-no: 05.137], neral [FL-no: 05.170], trans-3,7-dimethylocta-2,6-dienal (geranial) [FL-no: 05.188], trans-3-hexenyl formate [FL-no: 09.562] and cis-3-hexenyl 2-methylbutanoate [FL-no: 09.854]. None of the substances were considered to have genotoxic potential. The substances were evaluated through a stepwise approach (the Procedure) that integrates information on structure-activity relationships, intake from current uses, toxicological threshold of concern and available data on metabolism and toxicity. The Panel concluded that the 56 substances [FL-no: 02.125, 02.138, 02.152, 02.170, 02.175, 02.176, 02.195, 02.201, 02.222, 02.229, 02.234, 05.061, 05.082, 05.137, 05.143, 05.170, 05.174, 05.188, 05.203, 05.217, 05.218, 05.220, 05.226, 08.074, 08.100, 08.102, 09.341, 09.368, 09.377, 09.562, 09.567, 09.569, 09.572, 09.575, 09.612, 09.638, 09.640, 09.643, 09.672, 09.673, 09.674, 09.831, 09.838, 09.854, 09.855, 09.871, 09.872, 09.884, 09.885, 09.897, 09.898, 09.928, 09.937, 09.938, 09.939 and 09.950] do not give rise to safety concern at their levels of dietary intake, estimated on the basis of the MSDI approach. Besides the safety assessment of these flavouring substances, the specifications for the materials of commerce have also been considered. Adequate specifications including complete purity criteria and identity for the materials of commerce have been provided for all 56 candidate substances

1950 Poultry disease diagnostic laboratory report, East Aurora, New York

Documentation of poultry disease by the Cornell University Department of Pathology and Bacteriology. These records included name and address of the owner, date of observation, accession number, description of tissue, procedure and results, and diagnosis of the problem