Toxaphene, a complex mixture of polychloroterpenes and a major insecticide, is mutagenic.

Toxaphene, the most widely used chlorinated insecticide, is mutagenic in the Salmonella test without requiring liver homogenate for activity. This insecticide is a complex mixture (more than 177 polychloroterpenes) with carcinogenic activity in rodents. Some but not all of the mutagenic components are easily separated from the insecticidal ingredients.

Micronucleated erythrocytes as an index of cytogenetic damage in humans: demographic and dietary factors associated with micronucleated erythrocytes in splenectomized subjects.

Erythrocytes containing micronuclei serve as an indicator of genotoxic exposure in splenectomized individuals. Micronucleated erythrocytes, derived from cytogenetically damaged RBC precursors, are not selectively removed from peripheral blood in individuals who lack splenic function. The relationship between micronucleated cell frequencies and demographic, environmental, and dietary factors was examined in 44 subjects with previous splenectomy due to trauma. Their micronucleated cell counts fit a log-normal distribution, with geometric means of 3.3 micronucleus-containing cells/1000 reticulocytes and 2.7/1000 normochromatic erythrocytes. A multiple regression analysis showed that drinking five cups of coffee or tea/day (relative to none) was associated with an approximately 2-fold higher frequency of micronucleated cells. Weaker statistical associations were also noted with micronucleus frequency and the consumption of calcium supplements (associated with a higher frequency) and vitamins A, C, or E (lower frequency). An apparent trend of higher micronucleus counts with age was attenuated when other factors were considered in the regression. Cigarette smoking and decaffeinated coffee consumption were among the factors not associated with elevated micronucleated cell frequencies. Because the occurrence of micronuclei in reticulocytes reflects cytotoxic exposures within the past 3-8 days, it may be possible to test directly the relationship of these factors to micronucleus formation through intervention studies.

Ranking the potential carcinogenic hazards to workers from exposures to chemicals that are tumorigenic in rodents.

For 41 chemicals there exist both reasonable data on carcinogenic potency in experimental animals and also a defined Permissible Exposure Level (PEL), which is the upper limit of legally permissible chronic occupational exposure for U.S. workers. These 41 agents are ranked by an index that compares the permitted chronic human exposure to the chronic dose rate that induces tumors in 50% of laboratory animals. This index, the Permitted Exposure/Rodent Potency index, or PERP, does not estimate absolute risks directly, but rather suggests the relative hazards that such substances may pose. The PERP values for these 41 substances differ by more than 100,000-fold from each other. The PERP does not take into account the actual level of exposure or the number of exposed workers. Nevertheless, it might be reasonable to give priority attention to the reduction of allowable worker exposures to substances that appear most hazardous by this index and that some workers may be exposed to full-time near the PEL. Ranked by PERP, these chemicals are: ethylene dibromide, ethylene dichloride, 1,3-butadiene, tetrachloroethylene, propylene oxide, chloroform, formaldehyde, methylene chloride, dioxane, and benzene.

A carcinogenic potency database of the standardized results of animal bioassays.

The preceding paper described our numerical index of carcinogenic potency, the TD50 and the statistical procedures adopted for estimating it from experimental data. This paper presents the Carcinogenic Potency Database, which includes results of about 3000 long-term, chronic experiments of 770 test compounds. Part II is a discussion of the sources of our data, the rationale for the inclusion of particular experiments and particular target sites, and the conventions adopted in summarizing the literature. Part III is a guide to the plot of results presented in Part IV. A number of appendices are provided to facilitate use of the database. The plot includes information about chronic cancer tests in mammals, such as dose and other aspects of experimental protocol, histopathology and tumor incidence, TD50 and its statistical significance, dose response, author's opinion and literature reference. The plot readily permits comparisons of carcinogenic potency and many other aspects of cancer tests; it also provides quantitative information about negative tests. The range of carcinogenic potency is over 10 million-fold.

Synthesis of dopamine and octopamine in the crustacean stomatogastric nervous system.

The spiny lobster stomatogastric nervous system synthesizes dopamine and octopamine in vitro from exogenous [3H]tyrosine. Each amine accumulates with a specific distribution among 9 separately analyzed regions within the system. Synthesis of other catecholamines was not observed. [3H]Dopamine is found in nerves, ganglia, and identified commissural ganglion cell bodies in which catecholamine histofluorescence has been demonstrated. The biosynthetic and histochemical data together indicate that dopaminergic cells send axons from the commissural ganglia to the stomatogastric ganglion neuropil along the same pathway followed by fibers that activate the pylroic motor network. The results support the hypothesis that dopamine mediates activation of the pyloric system in vivo, as observed in vitro. [3H]Octopamine accumulates primarily in the commissural and stomatogastric ganglia, where it may modulate neuronal activity, but octopaminergic cells and release sites within the stomatogastric system have not been identified.

Mass spectrometry of derivatives of cyclopropene fatty acids.

Diketo fatty acids prepared by ozonization of cyclopropene fatty acids have been separated and purified by chromatographic techniques. Mass spectra of esters of these compounds and of methanethiol adducts of cyclopropene acid esters are reported and interpreted. Location of the ring from examination of mass spectra of these derivatives appears to be a straightforward matter.

Long-term carcinogenesis studies on 2,3,7,8-tetrachlorodibenzo-p-dioxin and hexachlorodibenzo-p-dioxins.

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) and 1,2,3,6,7,8- and 1,2,3,7,8,9-hexachlorodibenzo-p-dioxins (HCDDs) are among the most toxic and carcinogenic of "man-made" chemicals. These "dioxins," as well as many of the other polychlorinated dibenzodioxins (PCDDs) and dibenzofuran (PCDFs) derivatives, are chlorinated aromatic compounds which are chemically stable, insoluble in water, and highly soluble in fats and oils. TCDD acts as a complete carcinogen in several species, causing both common and uncommon tumors at multiple sites. It is a highly potent chemical carcinogen in chronic animal studies, producing carcinogenic effects in laboratory animals with doses as low as 0.001 micrograms/kg/day. In rats, TCDD induces neoplasms in the lung, oral/nasal cavities, thyroid and adrenal glands, and liver. In mice, TCDD induces neoplasms in the liver and subcutaneous tissue, thyroid gland, and thymic lymphomas. In hamsters, it induces squamous cell carcinomas of the facial skin. Tumors of the integumentary system are reported after oral (mice and rats), intraperitoneal (hamsters), and dermal (mice) administration. A mixture of HCDDS (defined as the mixture of the 1,2,3,6,7,8- and 1,2,3,7,8,9 isomers used in the NTP experiments) are potent liver carcinogens in mice and rats. Pharmacokinetic studies in laboratory animals indicate that 50-90% of dietary TCDD is absorbed. It concentrates in adipose tissue and the liver. In mammals, the TCDD present in the liver is slowly redistributed and stored in fatty tissue. Elimination of TCDD occurs via excretion of metabolites in the bile and urine and passively through the gut wall. Metabolism is slow: the biological half-life of TCDD varies from weeks (rodents) to years (humans), and is strongly dependent upon the rate of TCDD metabolism. Many of the toxic effects of TCDD, including teratogenicity, may arise by receptor-mediated mechanisms. The induction of cytochrome P-448 and related enzymes by TCDD occurs by such a mechanism, and is related to the binding of TCDD to the Ah receptor. The specific mechanism(s) by which TCDD exerts its carcinogenic effects is unclear: receptor-binding may be part of the story. The role of the Ah receptor has been indicated in a skin promotion assay. The evidence for mutagenicity is inconclusive. TCDD did not induce lethal mutations, chromosomal aberrations, micronuclei or sister chromatid exchanges in rodents treated in vivo, nor was it mutagenic to bacteria, but it did enhance transformation of mouse C3H 10T1/2 cells by N-methyl-N'-nitro-N-nitrosoguanidine and was mutagenic to mouse lymphoma cells.(ABSTRACT TRUNCATED AT 400 WORDS)