Toxicity tests group size

Not only is it difficult to detect effects on male fertility because of group-size considerations, effects on male fertility mediated by decreased sperm production are also difficult to detect because of the normally huge excess of sperm included in a rat ejaculate. Sperm production can be decreased by up to 90% without effect on fertility (either pregnancy rate or litter size) in the rat. This is not the case for men, so the sperm excess in the rat represents a serious flaw in the rat model (see Working, 1988). To address this deficiency and improve the sensitivity of the model, it is advisable to determine the effects of the test agent on testes weights, testicular spermatid counts, and histopathology of the testes (preferably plastic sections) in the male fertility study and/or the 14-week toxicity study. In some cases, these parameters may be more predictive of possible effects on male fertility in humans than the fertility rate in rats. 

A Guidance Document on Acute Inhalation Toxicity Testing is being developed and presently exists as a draft (OECD 2004b). The document recommends the Acute Toxic Class (ATC) Method with a group size of three animals per sex, if the objective of the test is solely related to hazard classification. Limits for particle-size distribution of aerosolized test substances are suggested. The preferred mode of exposure is the nose-only, head-only, or head/nose-only exposure technique, because this mode of exposure minimizes exposure or uptake by noninhalation routes. 

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... 

The power of the statistical test is a quantitative measure of the ability to differentiate accurately differences in populations. The usual case in toxicity testing is the comparison of a treatment group to control group. Depending on the expected variability of the data and the confidence level chosen, an enormous sample size or number of replicates may be required to achieve the necessary discrimination. If the sample size or replication is too large, then the experimental design may have to be altered. 

Dibutyl sebacate was tested for reproductive toxicity in a dietary study with Sprague-Dawley rats 6.25% (approximately 5.6 g/kg/d) in the diet for 10 wk prior to breeding (Smith 1953). No effect on fertility, litter size, or pup survival was found. However, pups from treated dams weighed less than pups from the control group. 

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