Subacute dose

Byard JL, Baumann CA. 1967. Selenium metabolites in the urine of rats given a subacute dose of selenite [Abstract], Fed F roc 26 479. 

Subacute dose — The doses are given between 24 h and 1 month. 

The aim of the research described herein is the determination of acute and subacute doses of mercury in static experiments with catfish exposed in aquaria at different concentrations. The accumulation of mercury in different organs and tissues has been... 

These results indicate that mercury concentration from 0.5 mg/1 to higher levels are able to induce acute toxicity in catfish after 96 h exposure. Lower doses of mercury (0.1,0.2 and 0.4 mg/1) resulted in accumulation but were subacute after 96 h exposure. These subacute doses of mercury were used for the determination of molecular parameters in catfish liver. Liver has been chosen because of its larger dimension in fact, it was possible to use a single liver for both mercury content measurements and glutathione and enzymes determinations. 

Other individuals who had also suffered intoxication following a subacute dose of pyridostigmine. In none of the cases studied was any abnormality of BuChE seen. The second mutation disrupts a probable glucocorticoid response element, but the consequences of this mutation arc yet to be elucidated however, there is surely some kind of effect. 

The pathological effects and clinical signs for many toxic materials can vary with the route and type (acute, single dose vs chronic, subacute doses) of exposure. For the trichothecene mycotoxins, however, a number of the toxic responses are similar, regardless of the route of exposure. As we discussed earlier in this chapter, once they enter the systemic circulation, trichothecene mycotoxins affect rapidly proliferating tissue regardless of the... 

Chronic exposure to subacute doses of trichothecene mycotoxins is not thought to be an effect of biological warfare. This type of exposure, however, was responsible for ATA toxicosis in humans and mycotoxicosis in domestic animals. In addition, chronic toxicity has been iatrogenically induced when repeated subacute doses of a trichothecene mycotoxin were administrated intravenously to cancer patients as a chemotherapy for colon adenocarcinoma. Alimentary Toxic Aleukia Toxicosis... 

Toxicity. Many /V-nitrosamines are toxic to animals and cells in culture (4,6—8,88). /V-Nitrosodimethy1amine [62-75-9] (NDMA) is known to be acutely toxic to the Hver in humans, and exposure can result in death (89). Liver damage, diffuse bleeding, edema, and inflammation are toxic effects observed in humans as a result of acute and subacute exposure to NDMA. These effects closely resemble those observed in animals dosed with NDMA (89,90). 

Scientific information for the process of establishing OELs may come from human or animal data obtained using different methods, from studies of acute, subacute, and chronic toxicity through various routes of entry. Human data, which is usually the best source, is not easily available, and frequently it is incomplete or inadequate due to poor characterization of exposure and clear dose-response relationships. Human data falls into one of the following categories ... 

Subacute and chronic toxicity of alcohol and alcohol ether sulfates has been extensively tested in several animals and sometimes humans. The duration of the tests was in some cases as long as 2 years. When administered below the toxic amount no specific damages were observed in any of the species tested [333]. No severe side effects were observed in the study by Swisher, carried out with volunteers who ingested considerable amounts of anionic and nonionic surfactants over long periods [348]. Similarly, the effects produced by the intake of daily doses of 1 g of alcohol sulfate per person over 8 weeks [349],... 

In initial ICC studies, animals were treated with MDA or MDMA using the protocol described by Ricaurte et al. (1985). Adult Sprague-Dawley rats (150 to 200 g) reeeived subcutaneous injections of racemic MDA or MDMA every 12 hours for 4 days. Each dose was equivalent to 20 mg/kg of the free base. The rats were sacrificed by intracardiac aldehyde perfusion 2 weeks after the final dose. In order to study subacute effects for evidence of degeneration, additional rats received MDA every 12 hours for 2 days and were sacrificed 24 hours after the last injection. Additional experimental details are described elsewhere (O Heam et al. 1986 O Heam et al. 1988). A series of animals treated identically and in parallel were analyzed for changes in 5-HT levels and density of uptake sites using paroxetine binding (Yeh et al. 1986 Battaglia et al. 1987). 

The combination of methotrexate and UVB seems to be synergistic responses may occur with lower cumulative doses of both methotrexate and UVB. However, stopping methotrexate may cause rebound21,33 and there is some concern about photosensitivity.21 Methotrexate and PUVA have been used together in patients refractory to other treatments however, there is additive carcinogenesis (especially increasing the risk of squamous cell cancer) and subacute phototoxicity.21... 

In toxicity studies, acute toxicity tests are usually carried out in the rat, mouse, cat, and dog. Subacute toxicity studies for IM products are performed by giving SC injections to rats and IM injections to dogs. In IV studies the rat tail vein or a front leg is used. Deliberate overdosing usually washes out metabolism differences between species. In dogs it is common to give an IV dose five times that intended for humans. In rats this is increased to 10 times. 

The single-dose toxicity studies were performed in two mammalian species, rat and mouse, by the route used in clinical practice, that is oral, as well as that ensuring adequate systemic exposure to the drug, that is intravenous. The subacute (3 months) toxicity studies were correctly carried out in the two animal species (rat, dog) in which also the pharmacokinetics was studied. Since in accordance with the International Conference on Harmonization (CPMP/ICH/286/95), 3-month toxicity studies support clinical trials for up to 1 month s duration (the longest duration of drug administration in clinical use), chronic toxicity studies have not been performed. 

In subacute toxicity studies only the highest rifaximin dose (i.e. 100 mg/kg, corresponding to 25 times the therapeutic dose in humans) induced mild toxic effects (like, for instance, acute gastroenteritis) connected to the topical GI action of the drug [59, 255], A dose-dependent increase of the total cholesterol value was recorded in female animals [255], most likely due to an alteration of biliary acid metabolism consequent to the antibiotic effect on gut flora [256]. 

For patients undergoing primary PCI, clopidogrel is administered as a 300-to 600-mg loading dose followed by a 75 mg/day maintenance dose, in combination with aspirin 325 mg once daily, to prevent subacute stent thrombosis and long-term cardiovascular events. 

A subacute study in rats treated intraperitoneally with deltamethrin showed testicular degeneration and an inhibition of spermatogenesis, which seemed to be mediated by an elevation of nitric oxide levels [148], Subcutaneous dosing also produced adverse testicular effects and reduced spermatogenesis [149],... 

Repeat-dose toxicity (subacute and chronic trials) ... 

Sato M, Miyagawa M, Honma T, et al. 1985. Subacute effects of methyl bromide dosed by inhalation exposure to rats. Ind Health 23 235-238. 

Oral toxicity. The approximate lethal dose of the dicyclo-hexyl-18-crown-6 polyether for ingestion by rats was 300 mg./ kg. In a 10-day subacute oral test, the compound did not exhibit any cumulative oral toxicity when administered to male rats at a dose level of 60 mg./kg./day. It should be noted that dosage at the approximate lethal dose level caused death in 11 minutes, but that a dose of 200 mg./kg. was not lethal in 14 days. 

The term repeated dose toxicity comprises the adverse general (i.e., excluding reproductive, genotoxic, or carcinogenic effects) toxicological effects occurring as a result of repeated daily dosing with, or exposure to, a substance for a part of the expected life span (subacute or subchronic exposure) or for the major part of the fife span, in case of chronic exposure (EC 2003). 

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