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Biomedical subjects

C S Weil

Publications and source records attributed to C S Weil.

At least 37 records · Page 2Linked to original sources

Economical LD50 and slope determinations.

Many regulatory standards and guidelines required LD50 determinations and dose-response curve slopes, using at least 5 animals per sex per dosage level and at least 3 levels. In contrast, the current trend is to use as few animals as necessary for toxicological studies. The moving average method for calculation of the LD50 has been available since 1947 but, as it does not involve curve fitting, has not been used to determine the slope. An accurate adaptation of this is presented so that both the LD50 and slope can be determined using very few animals and using levels with 0 or 100% kills; not usable with probit determinations.

Animals↗

Subchronic and reproductive toxicology studies on acrylic acid in the drinking water of the rat.

In the subchronic study acrylic acid was incorporated in the drinking water of Fischer 344 rats (15 per group) for three months at dosage levels of 0.75, 0.25, 0.083 or 0 g/kg/day. No deaths occurred during the study but several treatment-related effects were observed. At 0.75 g/kg/day dosage level, body weight gain was reduced as were food and water consumption. Changes in organ weights and clinical chemistry parameters were observed along with increases in urine specific gravity and protein concentration. Similar, though less profound, changes occurred at 0.25 g/kg/day. At 0.083 g/kg/day, the only effect was a reduction of water consumption by male rats. There were no significant treatment-related histopathologic changes. Many of the effects observed may have been the result of decreased water and food consumption rather than specific toxic effects of acrylic acid. In the reproduction study, the same dosages of acrylic acid were given to groups of 10 males and 20 females for 90 days after which the animals were mated. Treatment was continued throughout gestation and lactation. Treatment-related effects included decreased body weight gain, and reduced food and water consumption in F0 rats at the 2 highest dosage levels. Organ weight changes occurred in both F0 and F1 animals and reduced body weight gain was seen in the F1 pups at the highest level. No statistically significant changes in reproductive indices were observed, perhaps because of an atypical control group.

Acrylates↗

Statistical analysis and normality of selected hematologic and clinical chemistry measurements used in toxicologic studies.

The statistical comparison of hematological and clinical chemistry measurements of treated and control groups in toxicological studies has frequently, in the past, been done by methods that assumed, in the population of such values, normality of the data. This assumption was tested on pairs of concurrent control groups of rats from three long-term toxicological studies; two feeding and one inhalation routes of exposure were used. The normality of the data from three treated groups in one of these studies was also tested. The measurements examined were erythrocyte count, hemoglobin, white blood cell count, neutrophils, monocytes, urea nitrogen, and creatinine. In many cases significant skewness, kurtosis and deviation from normality as measured by the Kolmogorov-Smirnov test were present. The lack of consistency of normality versus nonnormality or, in some cases, direction of skewness, suggests that nonparametric statistical procedures be considered for use in the future for comparison of these types of data. Furthermore, the agreement of the data of the concurrent control groups as compared to the divergence of the values among the three studies affirms the importance of concurrent, in preference to historical, control data.

Animals↗

A critique of the collaborative cytogenetics study to measure and minimize interlaboratory variation.

A statistical reanalysis was performed on the data fecently reported on a 6-laboratory, collaborative cytogenetic study to measure and minimize interlaboratory variation. Three of the laboratories had mean values significantly different from the others on most of the 6 indexes of chemically-induced aberration; one laboratory with values higher and two with values lower. Furthermore, relative variability of the values around the means was consistently lower in one of the 6 participating laborabories. The results of the reanalysis of this collaborative study demonstrates that significant interlaboratory differences exist and that these should be adjusted or diminished before rat cytogenetic analysis can be an effective test system for evaluation of a compound for mutagenic potential.

Animals↗

Lymphocyte mitogen stimulation studies for patients with lung cancer: evaluation of prognostic significance of preirradiation therapy studies.

The responses of lymphocytes to stimulation by three common plant mitogens (PHA, Con A, and PWM) have been studied prior to irradiation treatment in 65 patients with bronchogenic carcinoma. The lymphocyte mitogen stimulation (LMS) responses of these patients were determined to be normal or abnormal based on data obtained from similar studies in healthy volunteers. The data for the patients with lung cancer were analyzed for correlations between the lymphocyte responses and (1) the stage of disease, (2) prognostic significance, and (3) period of survival. Statistically significant correlations were observed between the responses of lymphocytes and the stage of disease and the period of survival. However, this study indicates that these correlated responses will be of limited prognostic clinical value for individual patients.

Aged↗

Toxicology experimental design and conduct as measured by interlaboratory collaborative studies.

Interlaboratory variability in certain acute toxicological procedures was discussed. Three collaborative studies have been performed. One study concerned a determination of acute peroral toxicity and 2 collaborative studies have involved eye and/or skin irritation. All have indicated that, while the majority of the laboratories produced relatively consistent results, some were definitely outliers and others were quite variable. Recommendations were made to counteract and correct this interlaboratory variability; it was suggested that these be accomplished before standardization of techniques be promulgated. A brief discussion was presented on the faulty conclusions that can result from improperly planned and executed repeated-dose toxicological studies. Furthermore, the estimation of risk at the low-response end of a dose-response curve was discussed. The relative variability of the measurement of the slope of such a curve was compared to the variability of the measurement of the midpoint. The danger of extrapolation of animal dose-response results, using a constant slope, was deprecated.

Burns, Chemical↗