Toxicity synergistic

Safety/Toxicity Acute and subacute toxicity,"" carcinogenicity,"" environmental contaminants," estrogenicity," genotoxicity,"" hypersensitivity," mutagenicity,"" photoinduced toxicity,"" synergistic toxicity" ... 

Sesamex [51-14-9] (Sesoxane) (30) is a synergist oflow toxicity, acute oral LD q (rat) = 2000 2270 mg/kg, for pyrethrins and allethrin. 6,7-Dihydroxy 4-methylcoumarin has been offered as an antioxidant for phenoHcs and polymers, and as an anthelmintic. 2,4,5-Trihydroxybutyrophenone has been available as an antioxidant and light stabilizer for polyolefins, waxes, and foods. Isoflavones, eg (31), have been patented as components of antioxidant compositions for foods and cosmetics (qv) (97). 

Dactinomycin, an antineoplastic dmg, was discovered in 1943 and is made in rather pure form by StreptomjcesparvuUus. Dactinomycin has some bacteriostatic antibacterial and antifungal activity, but high toxicity limits its use to antineoplastic therapy. It may be used alone or with other antineoplastics, with or without surgery and synergistic x-ray therapy. Dose limiting bone marrow toxicity may result in low white cell and platelet count. Intestinal mucosal damage also occurs. Reviews of more detailed chemotherapeutic information are available (217—222). 

SYNERGISTIC When the combined effect, e.g. of exposure to a mixture of toxic chemicals, is greater than the sum of the individual effects. 

The edible parts of parsnips contain a chemical of insecticidal and strong synergistic nature. This chemical, present in a concentration of about 200 p.p.m., was isolated and identified as 5-allyl-l-methoxy -2, 3-methylene-dioxybenzene or myristicin. Its toxicity to various insects (fruit flies, etc.) was established and compared with pyrethrum and aldrin. A second chemical, identified as 2-phenylethyl isothiocyanate, was found in the edible parts of turnips and rutabaga, which also have been consumed for centuries by humans without obvious harm. 

Table V. Effect of Synergist on Toxicity to Vinegar Flies ...

Jasmolin II in pure form was nearly equal to cinerin II in toxicity to houseflies but much less when synergized. The synergistic factor of the synergized compounds is pyrethrum extract 9.6 jasmolin II, 7.0 cinerin II, 12.0. 

A number of synergists are used with pyrethrum to increase its toxicity. Most of the better ones, as far as flying insects are concerned, are of the methylene dioxyphenyl type. The best known of this type is piperonyl butoxide. 

Table III. Relative Toxicity of Four Constituents of Pyrethrum at Six Ratios of Synergist to Active Ingredient...

When Hie cholinesterase inhibitors are administered with the anticholinergic drugp, there is a potential decrease in activity of the anticholinergic drug. There is an increased risk of toxicity of theophylline when the cholinesterase inhibitors are administered with tacrine There is a synergistic effect when tacrine is administered with succinyl-choline, cholinesterase inhibitors, or cholinergic agonists (eg, bethanechol). 

There is an additive bone marrow depression when methimazole or propylthiouracil is administered with otiier bone marrow depressants, such as the antineo-plastic drugs, or witii radiation therapy. When methimazole is administered with digitalis, there is an increased effectiveness of the digitalis and increased risk of toxicity. There is an additive effect of propylthiouracil when the drug is administered with lithium, potassium iodide, or sodium iodide When iodine products are administered with litiiium products, synergistic hypotiiyroid activity is likely to occur. 

These drug s are contraindicated in those with a known hypersensitivity to any component of the preparation. The topical anesthetics are used cautiously in patients receiving Class I antiarrhytiimic drug s such as tocainide and mexiletine because the toxic effects are additive and potentially synergistic. 

Although it is possible to identify a group of particularly toxic components in venom, it should be noted that the venoms are complex mixtures of components, many of which are synergistic. Muscle damage is particularly severe if myotoxic activity is combined with hemorrhagic activity. In this case, muscle regeneration is impaired, because the regenerating tissue is rendered anoxic at a time of intense metabolic activity. 

Mitochondria-associated toxicities, such as pancreatitis, are frequently demonstrated in HlV/HCV-coinfected individuals, and may significantly influence treatment options (de Mendoza and Soriano 2005). Yet, no cell culture or animal models have been developed to predict nucleoside-induced pancreatitis. Nevertheless, an association of HCV replication and mitochondrial DNA depletion in primary human lymphocytes obtained from HIV/HCV-coinfected individuals under concomitant administration of HCV and HIV medications was demonstrated by de Mendoza and coworkers (de Mendoza et al. 2007). They claimed that the use of HCV medication together with certain antiretroviral agents seemed to enhance mitochondrial damage due to a synergistic deleterious interaction between the anti-HCV and anti-HIV drugs. In contrast, an improvement in mitochondrial content with effective... 

Selective toxicity is also important in relation to the development of resistance or tolerance to pollutants from two distinct points of view. On the one hand, there is interest among scientists concerned with crop protection and disease control in mechanisms by which crop pests, vectors of disease, plant pathogens, and weeds develop resistance to pesticides. Understanding the mechanism should point to ways of overcoming resistance, for example, other compounds not affected by resistance mechanisms or synergists to inhibit enzymes that provide a resistance mechanism. On the other hand, the development of resistance can be a useful indication of the environmental impact of pollutants. 

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