To determine the effects of dichlorvos vapour on the tumour incidence in rats, 5 week old Carworth Farm E strain rats weighing between 94 and 150 g were exposed to 0, 0.05, 0.5 and 5.0 mg/m3 in a 2-year inhalation study. The growth rate of all treated rats was depressed, particularly in the males. There was increased survival of the rats exposed to 5 mg/m3. There were no consistent differences in food intakes, organ weights, haematological or blood chemistry estimations, except in cholinesterase activites, amongst the various groups of rats. No compound-related differences were seen in acetylcholine and choline estimations carried out on a small number of female rats' brain tissues after two years' exposure. There were no gross or microscopical compound-related changes in the rats' tissues. Ultrastructural examination of the respiratory tissues of the rats from the control and 5 mg/m3 group showed no changes attributable to dichlorvos. The results of a relative risk analysis of the tumour data showed that no dose-related increase in tumour risk was established for rats of either sex. These data confirm the results of earlier st.udies supporting the safety of insecticidal uses of dichlorvos.
Two mentally retarded adults with nonketotic hyperglycinemia had biochemical findings similar to those of the infantile form of the disease. Our patients differ from other adult patients and may represent the survival to adulthood of individuals with a mild form of infantile nonketotic hyperglycinemia.
Summary Twelve mineral oils, originating from naphthenic and paraffinic stocks and variously refined, were evaluated for their potential to induce cutaneous neoplasia in female CF1 mice. The oils were applied to the shorn dorsal skin for up to 78 weeks, using several different treatment regimes.The sole acid/earth refined naphthenic spindle oil was a moderately potent cutaneous carcinogen. By comparison, the 11 oils, processed by other refining routes, were less carcinogenic or non-carcinogenic to murine skin. Two of the 11 oils were weak cutaneous carcinogens viz, a naphthenic spindle oil refined only by mild hydrotreatment and a paraffinic spindle oil refined by mild solvent extraction and 'Ferrofining'. All 9 remaining oils had been solvent-extracted as part of the secondary refining process; none induced malignant tumours, although solitary benign tumours of the treated site were recorded after exposure to 3 oils.The cutaneous carcinogenic potential of the test oils did not correlate well with their potential to induce epidermal hyperplasia at the treated site. Consequently, hyperplasia caused after short term exposure is of little value for distinguishing between carcinogenic and non-carcinogenic oils.
Five experimental petroleum extracts were produced from luboil distillates derived from Middle East paraffinic crude by solvent extraction and severe hydrotreatment. The polycyclic aromatic content (PCA) of the extracts was determined by dimethyl sulphoxide extraction and ranged from 3.7-9.2% w/w. The five extracts were evaluated for their potential to induce cutaneous and systemic neoplasia in female mice derived from Carworth Farm No 1 strain (CF1). The test substances were applied undiluted (0.2 ml per application) to the shorn dorsal skin twice weekly for up to 78 weeks, with 48 mice in each treatment group and 96 in the untreated control group; two further groups, each of 48 mice, were similarly treated either with a non-hydrotreated commercial aromatic extract (PCA content, 19.7% w/v) or with a low dose of benzo(a)pyrene (12.5 micrograms/ml acetone). The mice were housed individually in polypropylene cages in specified pathogen free conditions. The incidence of cutaneous and systemic tumours was determined from histological analysis of haematoxylin and eosin stained tissue sections. The results were correlated with the PCA content of the extracts and compared with those from female mice exposed to a non-hydrotreated commercial aromatic extract. Four of the hydrotreated extracts were carcinogenic for murine skin; the two products with the lower PCA contents were less carcinogenic than the products with the higher PCA contents and all were less carcinogenic than the commercial extract. One extract with the lowest PCA content was non-carcinogenic. Thus refining by severe hydrotreatment was an effective method of reducing the carcinogenic potential of petroleum aromatic extracts. Although other physicochemical properties may influence the biological activity of oil products, the PCA content determined by dimethyl sulphoxide extraction may be a useful indicator of the potential of oil products to induce cutaneous tumours in experimental animals. There was no evidence that the commercial or hydrotreated extracts increased the incidence of systemic neoplasms when applied twice weekly to the dorsal skin.
This paper describes conditions wherein the serum peptides insulin and IGF1, which are typically associated with growth-promoting functions, can suppress in vitro immune responses. IL 2-induced proliferation of lymphocytes as well as in vitro antibody-producing cultures are suppressed by physiologic concentrations of IGF1 or by superphysiologic concentrations of insulin. Suppression of IL 2-induced proliferation is not overcome by increasing the IL 2 concentration and is mediated only during the first 24 to 48 hr of the 110-hr incubation period required to measure the proliferative response to IL 2. By analogy to other biologic systems, these effects of insulin and of IGF1 are probably mediated by occupancy of the IGF1-receptor, which is cross-occupied by insulin at superphysiologic concentrations. These data support the possibility of a novel function for these endocrine and endocrine-like peptides and also expands their range of biologic activities to within the immune system.
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