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Biomedical subjects

C S Weil

Publications and source records attributed to C S Weil.

At least 19 recordsLinked to original sources
PubMed1990

Safety of Sanguinaria extract as used in commercial toothpaste and oral rinse products.

This report represents the findings of an Expert Panel on the safety of Sanguinaria extract used in Viadent oral rinse and toothpaste products and represents an independent review of the Sanguinaria extract toxicologic data base. It is based on reviews and discussions of the data base by all members of the Expert Panel on Sanguinaria extract. The Panel concluded that the data base on Sanguinaria extract is substantial and indicates that Sanguinaria extract is safe in its present use in Viadent products based on a large margin of safety between levels of human exposure and levels found to produce minimum effect or to be without adverse effect in animals. The panel further concluded that published literature suggesting an association between human exposure to Sanguinaria extract and potential reproductive, cardiovascular, or ocular toxicity, or carcinogenicity is largely anecdotal, unfounded, and not corroborated by or consistent with the substantial data base that was subjected to peer review.

Alkaloids↗
PubMed1989

Dermal oncogenicity studies on two methoxysilanes and two ethoxysilanes in male C3H mice.

The dermal oncogenic potential of beta-(3,4-epoxycyclohexyl)ethyltrimethoxysilane (EEMS), gamma-glycidoxypropyltrimethoxysilane (GPMS), beta-(3,4-epoxycyclohexyl)ethyltriethoxysilane (EEES), and gamma-glycidoxypropyltriethoxysilane (GPES) was assessed by applying 25-microliters aliquots of acetone solutions to the skin of 40 male C3H/HeJ mice. The concentrations applied were 100, 25, 10, and 10% by volume for EEMS, GPMS, EEES, and GPES, respectively. Applications were made thrice weekly until the death of the animals. A negative control group received acetone (solvent) only. No treatment-related skin tumors were observed, nor was there evidence of increased incidence of any internal tumor in the groups that received GPMS, EEES, or GPES. In the group treated with EEMS, four mice were observed with squamous cell carcinomas of the treated skin and two mice had subcutaneous sarcomas outside of the treated area. No skin tumors were observed in the group treated with acetone, but two mice had subcutaneous sarcomas outside of the treated area. The mean survival times were 529, 482, 545, 492, and 502 days for the EEMS, GPMS, EEES, GPES, and acetone control groups, respectively. In no case was the mortality rate significantly different from that of the controls. The results indicate that only EEMS was oncogenic under the conditions of these studies.

Animals↗
PubMed1987

Dermal oncogenicity studies on various ethyleneamines in male C3H mice.

The dermal oncogenic potential of diethylenetriamine, high purity and commercial grades (DETA-HP and DE-TA-C), triethylenetetramine (TETA), tetraethylenepentamine (TEPA), and polyamine HPA No. 2 was assessed by applying 25-microliter aliquots of aqueous solutions to the skin of groups of 50 male C3H/HeJ mice. The concentrations applied were 5.0, 5.0, 5.0, 25.0, and 10.0% by volume for DETA-HP, DETA-C, TETA, TEPA, and HPA No. 2, respectively. Applications were made thrice weekly until the death of the animals. A negative control group received deionized water (solvent) only. All animals were individually housed. No treatment-related skin tumors were observed, nor was there evidence of increased incidence of any internal tumor. Twenty TEPA-treated mice had hyperkeratosis and 13 had necrosis of the epidermis, both indicative of skin irritation. Such lesions were absent or occurred very infrequently in the other groups of mice. The mean survival times were 587, 662, 627, 591, 601, and 626 days for the DETA-HP, DETA-C, TETA, TEPA, HPA No. 2, and water control groups, respectively. In no case was the mortality rate significantly different from that of the controls. The results indicate that none of these compounds was oncogenic under the conditions of these studies.

Administration, Topical↗
PubMed1986

Chronic toxicity and oncogenicity studies of ethylene glycol in rats and mice.

These studies were performed to assess the chronic toxicity and oncogenicity of ethylene glycol (EG) in rats and mice. Groups of 130 Fischer 344 rats and 80 CD-1 mice per sex were fed diets yielding approximate dosages of 1.0, 0.2, or 0.04 g/kg/day of EG. Two separate control groups in each study received no EG. Mortality rate was increased in high-dose male rats all of which died by 475 days. The following effects were also observed in high dose male rats: reduced body weight gain, increased water intake, increased blood urea nitrogen and creatinine, reduced erythrocyte count, reduced hematocrit and hemoglobin, increased neutrophil count, increased urine volume, reduced specific gravity and pH. Urinary calcium oxalate crystals and increased kidney weight were seen in all high-dose rats. Uric acid crystals were seen in the urine of high-dose female rats at 18 and 24 months. Histopathologic changes in high-dose male rats included tubular cell hyperplasia, tubular dilation, peritubular nephritis, parathyroid hyperplasia, and generalized soft tissue mineralization. Fatty change of the liver was seen in high- and intermediate-dose female rats. No clinical signs, or gross or microscopic evidence of toxicity was seen in mice at the dosages used. Water intake and clinical pathologic parameters were not measured in the mouse study. In these studies there was no evidence of an oncogenic effect of EG in rodents.

Animals↗
PubMed1986

Three-generation reproduction and dominant lethal mutagenesis studies of ethylene glycol in the rat.

To assess the possible effects of ethylene glycol (EG) on reproductive performance and mutagenesis, three-generation reproduction and dominant lethal mutagenesis studies were performed in the Fischer 344 rat. EG was included in the diet at approximate dosages of 1.0, 0.2, and 0.04 g/kg/day during three generations of reproduction. Each generation was bred once. In a dominant lethal mutagenesis study, the F2 males from the reproduction study were bred to three consecutive lots of untreated females at weekly intervals. Concomitantly, another group of untreated F2 males that received a single ip injection of 0.50 mg/kg triethylenemelamine (TEM) were bred similarly to serve as a positive control group. No evidence of reduced fertility or increased fetal death was observed in any of the groups receiving EG. Dominant lethal effects in the TEM group confirmed the susceptibility of the rats to a known mutagen. In conclusion, there were no reproductive or dominant lethal effects associated with the inclusion of as much as 1.0 g/kg/day of EG in the diet.

Animals↗
PubMed1986

Influence of housing conditions for mice on the results of a dermal oncogenicity bioassay.

Male C3H/HeJ mice were thrice weekly given 25 microliter applications of 0.25, 0.05, or 0.01% (w/w) benzo(a)pyrene (BaP) in acetone, or acetone alone, to clipped dorsal skin from 12 to 14 weeks of age for the remainder of their life spans. There were two groups of 40 mice for each treatment regimen, one group being housed in conventional stainless-steel wire mesh cages and the other in polycarbonate cages with wood shavings held in an enclosed ventilated cabinet. Under both housing conditions, tumor incidence was directly related and latency inversely related to BaP concentration. The time-adjusted incidence of epidermal neoplasms was significantly greater for the groups housed in polycarbonate cages. Mortality rates were directly related to BaP concentration and were significantly enhanced by the polycarbonate-cage housing conditions for the high and intermediate concentrations. Survival patterns for the two acetone control groups were similar. These findings indicate that differences in housing conditions can influence both the incidence and the latency of local neoplasms produced in response to the chronic application of a carcinogen in dermal oncogenesis bioassays.

Animals↗
PubMed1985

Dermal oncogenicity bioassays of monofunctional and multifunctional acrylates and acrylate-based oligomers.

Several important components of photocurable coatings were studied for dermal tumorigenic activity by repeated application to the skin of mice. The substances tested were 2-ethylhexyl acrylate (EHA) and methylcarbamoyloxyethyl acrylate (MCEA) (monomers); neopentyl glycol diacrylate (NPGDA), esterdiol-204-diacrylate (EDDA), and pentaerythritol tri(tetra)acrylate (PETA) (cross-linkers); and three acrylated urethane oligomers. For each bioassay, 40 C3H/HeJ male mice were dosed 3 times weekly on the dorsal skin for their lifetime with the highest dose of the test agent that caused no local irritation or reduction in body weight gain. Two negative control groups received acetone (diluent) only. A positive control group received 0.2% methylcholanthrene (MC). NPGDA and EHA had significant tumorigenic activity with tumor yields of eight and six tumor-bearing mice (three and two malignancies), respectively. The MC group had 34 mice with carcinomas and 1 additional mouse with a papilloma. MCEA had no dermal tumorigenic activity but resulted in early mortality. No skin tumors in the treatment area were observed in the other groups. Additional studies will be necessary to elucidate possible relationships between structure and tumorigenic activity for the acrylates.

Acrylates↗
PubMed1984

A two-year inhalation study of the carcinogenic potential of ethylene oxide in Fischer 344 rats.

Fischer 344 rats were exposed to 100, 33, 10, or 0 ppm of ethylene oxide vapor (EtO) by inhalation for 6 hr per day, 5 days per week, for approximately 2 years. Inhalation of EtO resulted in a significant depression of body weight gain in the 100- and 33-ppm exposure groups and a significant increase in mortality in the 100-ppm group. Through 18 months of exposure to EtO, no statistically significant increases in tumor incidence were observed. After 18 months, the incidence of primary brain tumors was increased for both sexes. Statistical evaluation indicated a treatment-related response, particularly for the male rats, in the 100- and 33-ppm exposure groups. After 24 months of exposure, histologic findings confirmed hematologic evidence that exposure to EtO resulted in an increased prevalence of mononuclear cell leukemia, which is a neoplasm that is common in aged Fischer 344 rats. This increase was dose related and increased for each of the three exposure concentrations. The percentage of female rats with multiple neoplasms was also greater in all three exposure groups than in controls. Furthermore, in both the 100- and 33-ppm exposure groups, the percentage of female rats with at least one malignant neoplasm was increased. An increased frequency of peritoneal mesothelioma was treatment related in the male rats exposed to 100 or 33 ppm of EtO. This study has shown biologically significant adverse effects at all concentrations tested. The incidences of mononuclear cell leukemia, peritoneal mesothelioma, and primary brain tumors in the air-control rats were similar to those reported in the literature. The possible contribution of a sialodacryoadenitis viral outbreak (which occurred during the 15th exposure month) to the EtO exposure-related tumors is unknown, though unlikely.

Animals↗
PubMed1984

A subchronic inhalation study on the toxicologic potential of ethylene oxide in B6C3F1 mice.

Four groups of B6C3F1 mice, each containing 30 per sex, were exposed to ethylene oxide (EtO) vapor at target concentrations of 250, 100, 50, 10, or 0 ppm which are equivalent to 450, 180, 90, 18, and 0 mg/m3, respectively. The actual mean chamber concentrations were 236, 104, 48, 10, and 0 ppm, respectively. After an exposure regimen of 6 hr per day, 5 days per week, for 10 weeks (males), or 11 weeks (females), urine and blood samples were taken for clinical pathologic evaluation and selected tissues were weighed and examined by light microscopy. Statistically significant findings that could be indicative of a toxic response were observed in the 250-ppm exposure group. These included minimal changes in certain erythroid parameters, increased liver weight, decreased testicular weight, and decreased spleen weight which was noted also in the 100-ppm group. However, there were no microscopic findings to support or explain any of these apparently treatment-related effects. Results of a neuromuscular screening test indicated that certain reflex responses and locomotor activities were altered in the EtO-exposed animals. A dose-related trend of response in the 250-, 100-, and 50-ppm exposure groups was noted in the evaluation of locomotor function; however, because of the small sample size, it was not possible to determine a threshold concentration for this effect. There were no accompanying histopathologic alterations in muscle and central or peripheral nervous tissue.

Animals↗
PubMed1984

Dermal oncogenicity bioassays of di-sec-butoxyacetophenone and diethoxyacetophenone.

Groups of 40 male C3H/HeJ mice were treated 3 times per week for their lifetime on the skin of the back with undiluted di-sec-butoxyacetophenone (DBAP), or with diethoxyacetophenone (DEAP), undiluted and as a 50% dilution in acetone. Approximate doses per application were 22.4 mg for DBAP, and 25.0 or 11.3 mg for DEAP. Two negative control groups received acetone only. Both DBAP and DEAP (undiluted) had weak tumorigenic activity. In the DBAP group, one mouse developed a squamous-cell papilloma, whereas one mouse in the high-dose DEAP group had a squamous-cell carcinoma, both tumors appearing in the treatment area. No skin tumors were observed in the other groups. Both DEAP-treated groups also had substantial incidences of hyperkeratosis, epidermal hyperplasia, and dermatitis. No significant reduction in survival was observed in the test groups. The occurrence of the skin tumors in the DBAP- and DEAP-treated groups is considered to be treatment-related and suggestive of oncogenic potential, because of the extremely low historical control incidence of skin tumors in similar studies.

Acetophenones↗
PubMed1984

Dermal oncogenicity bioassays of acrylic acid, ethyl acrylate, and butyl acrylate.

Male C3H/HeJ mice (40 per group) were treated with 25-microliter applications of undiluted ethyl acrylate, 1% acrylic acid, or 1% butyl acrylate on the dorsal skin 3 times weekly for their lifetime. A negative control group received acetone (diluent) only, and a positive control group received 0.1% 3-methylcholanthrene (MC). No epidermal tumors were observed in the animals that received any of the three test substances. In the positive control group, 39 animals had skin tumors, including 33 with confirmed squamous-cell carcinomas. Nonneoplastic skin changes such as dermatitis, dermal fibrosis, epidermal necrosis, and hyperkeratosis were observed in several mice that received ethyl acrylate. No statistically significant effects on survival were seen. Therefore, there was no evidence for local carcinogenic activity of acrylic acid, ethyl acrylate, or butyl acrylate under the conditions of these studies.

Acrylates↗
PubMed1983

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↗
PubMed1978

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↗
PubMed1977

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↗
PubMed1975

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↗