Exercises for the Technical Evaluation - Section (2) Understanding the Problem and Scope of Work, Soundness of Scientific Approach
For each of the two accompanying datasets:
- Clearly and completely describe the methods you used to analyze the data, in a manner suitable for an audience of statisticians and applied mathematicians.
- Show the results of the analyses.
- Describe the analytic methods and results in a manner appropriate for the researchers who collected the data.
In a feasibility study, blood was collected from untreated 28 day old male and female Harlan Sprague-Dawley rats. Up to 4 pups of each sex were sampled from each litter. Hematology parameters were measured as listed below. In addition, the thyroid gland was assessed for abnormalities. Do males and females differ from each other?
|Abbreviation||Description||Unit of Measure|
|RBC||Red blood cell count||× 1012 per liter|
|Hb||Hemoglobin||grams per deciliter|
|Spun HCT||Spun hematocrit||%|
|MCV||Mean cell volume||Femtoliters|
|MCH||Mean cell hemoglobin||Pictograms|
|MCHC||Mean cell hemoglobin concentration||grams per deciliter|
|MCHC (s)||Spun mean cell hemoglobin concentration||grams per deciliter|
|Ret||Reticulocyte count||× 109 per liter|
|WBC||White blood cell count||× 109 per liter|
|Neut||Segmented neutrophil count||× 109 per liter|
|Lymph||Lymphocyte count||× 109 per liter|
|Mono||Monocyte count||× 109 per liter|
|Eos||Eosinophil count||× 109 per liter|
|Baso||Basophil count||× 109 per liter|
|Plate||Platelet count||× 109 per liter|
Thyroid abnormality is indicated as Present or Absent.
In a study of the brominated flame retardant, 2-Ethylhexyl-2,3,4,5-tetrabromobenzoate (TBB), adult female Sprague Dawley rats were given a single oral gavage dose of 100 nmol/kg TBB.
At 1, 4, 8, 24 and 72 hours (h) post-dosing, four to five animals were sacrificed and the concentration of TBB was determined in a number of tissues (adipose, adrenal, brain, heart, kidneys, large intestines, liver, lung, muscle, ovaries, pancreas, skin, small intestines, spleen, stomach, thymus, thyroid, urine bladder, and uterus) of each animal.
In addition the concentration of TBB was determined in the contents of the stomach, small intestines and large intestines.
For each tissue and relevant contents, estimate the appropriate toxicokinetics parameters (e.g., Cmax, the maximum concentration; tmax, the time at which the maximum concentration occurred; t1/2, the half-life; etc.).
For the tissue concentration determinations, the limit of detection was 0.8 pmol and the limit of quantitation was 1.3 pmol. [Note: nmol = nanomoles, pmol = picomoles]