Tests for mutagenic effects of ammoniated glycyrrhizin, butylated hydroxytoluene, and gum Arabic in rodent germ cells.

Ammoniated glycyrrhizin, butylated hydroxytoluene, and gum Arabic are "generally recognized as safe" (GRAS) substances that are used primarily as additives in foods. These substances were incorporated into rodent diets and fed to male rats and mice for 10 and 8 wk, respectively. The treated male mice and rats were then tested for dominant lethal effects. The mice were also tested for induced heritable translocation. Results of the rat studies indicated a statistically significant dominant lethal effect of each of the compounds tested; however, the biological significance of this response is not known. Results of the mouse dominant lethal and heritable translocation studies, on the other hand, indicated no adverse effects of the compounds tested.

Carcinogenicity of chloroform in drinking water to male Osborne-Mendel rats and female B6C3F1 mice.

The carcinogenic activity of chloroform administered at 0, 200, 400, 900, and 1800 mg/liter in drinking water was studied in male Osborne-Mendel rats and female B6C3F1 mice. A second control group was included in the study and was restricted to the water consumption of the high-dose group. Animals were maintained on study for 104 weeks. Group sizes were adjusted at low doses such that a detectable tumor response would result at the lowest dose if there was a linear relationship with dose, and the higher doses produced responses similar to previous carcinogenesis bioassays of chloroform. The primary finding was that chloroform increased the yield of renal tubular adenomas and adenocarcinomas in male rats in a dose-related manner. For the high-dose group, which corresponded to a time-weighted average dose of 160 mg/kg per day for 104 weeks, there was a 14% incidence of renal tubular adenomas and adenocarcinomas, vs 1% in the control group. This compares to a 24% incidence observed when 180 mg/kg per day of chloroform was administered for 78 weeks in earlier studies. In contrast, chloroform in the drinking water of mice failed to increase the incidence of hepatocellular carcinomas in female B6C3F1 mice. The highest dose group received a time-weighted average dose of 263 mg/kg for 104 weeks, resulting in a 5% combined incidence of hepatocellular adenoma and carcinoma relative to a 6% incidence in the control groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Dose-response study of chloroform carcinogenesis in the mouse and rat: status report.

Chloroform is being administered to male Osborne-Mendel rats and to female B6C3F1 mice at concentrations of 0 (negative control), 200, 400, 900 or 1800 ppm in the drinking water. Matched control groups of both species receive a volume of water identical to that consumed by the corresponding 1800 ppm groups. At this writing, the animals have completed 23 months on test. Negative control and CHCl3-treated rat groups have shown typical growth curves, with dose-related relative decrements in body weight evident throughout the study. Following decreases in CHCl3 groups during the first 8 weeks, rat water consumption values have continued to increase slowly, but persistent relative dose-related decrements are evident. No initial treatment-related decrements are evident. No initial treatment-related mortality was seen in the rats. Survival is 21, 41, 45, 76, 70 and 64% for the negative control, 200, 400, 900, 1800 ppm and matched control groups, respectively. Survival values for mice at three weeks were 99, 94, 74 and 76% for the 200, 400, 900 and 1800 ppm groups, respectively. Mortality was apparently related to markedly decreased fluid consumption among some of the treated mice. Subsequent mortality has been less than 15% for all mouse groups. Except for acclimation effects during the first 2-3 weeks, body weights for the treated mouse groups have been generally within 10% of negative control values. Tissue changes in decedents have been similar in treated and control groups, both in rats and mice. Terminal sacrifice and histologic evaluations will be initiated after completion of 24 months on test.

Toxicity of 1,4-dihexylpiperazine.

Attempts to synthesize the insect repellent, N,N'-dihexyl-N-carbomethoxyethylenediamine, led to an impurity which exhibited strong toxicity in the rabbit eye irritation test. Isolation of the impurity led to its identification at 1,4-dihexylpiperazine.