Exposure, subacute

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). 

Villagra, R., Tchemitchin, N.N. and Tchernitchin, A.N., Effect of subacute exposure to lead and estrogen on immature pre-weaning rat leukocytes, Bull. Environ. Contam. Toxicol. 58, 190, 1997. 

Reiter LW, Kidd K. 1978. The behavioral effects of subacute exposure to Kepone or mirex on the weanling rat. Toxicol Appl Pharmacol 45 357. 

Eor the purpose of assessing the remaining interspecies uncertainty, Vermeire et al. (1999) collected and analyzed data for 184 chemicals tested in different species and via different exposure routes. NOAELs were selected from studies with mice, rats, and dogs exposed to the same chemical via the same exposure route and with the same duration of exposure. Two categories of exposure duration were defined, subacute and (sub)chronic, in order to increase the comparability of the different studies. The definition of these exposure categories is species specific, partly depending on their maximum lifetime. Subacute exposure was defined as 21-50 days for the mouse and rat, and as 28-90 days for the dog (sub)chronic exposure was defined as 90-730 days for the mouse and rat, and as 365-730 days for the dog. The oral NOAELs were adjusted to account for differences in metabolic size, i.e., by the caloric requirement approach (Section 5.3.2.3). 

Subacute exposure is repeated exposure for 1 month or less. 

Most reported cases of chronic cyanide poisoning involve workers with a mixture of repeated acute or subacute exposures, making it unclear whether symptoms resulted simply from multiple acute exposures with acute intoxication or from prolonged, chronic exposure. Some symptoms persisted after cessation of such exposures, perhaps because of the effect of anoxia from inhibition of cytochrome oxidase. Symptoms from chronic exposure are similar to those reported after acute exposures, such as weakness, nausea, headache, and vertigo. A study of 36 former workers in a silver reclaiming facility chronically exposed to cyanide demonstrated some residual symptoms 7 or more months after cessation of exposure frequent headache, eye irritation, easy fatigue, loss of appetite, and epistaxis occurred in at least 30% of these workers. ... 

Smialowicz RJ, Simmons JE, Luebke RW, et al. 1991. Immunotoxicologic assessment of subacute exposure of rats to carbon tetrachloride with comparison to hepatotoxicity and nephrotoxicity. Fund AppI Toxicol 17 186-196. 

The toxic effects associated with PCN exposures in humans and wildlife are, in general, characteristic of effects due to chlorinated hydrocarbons such as 2,3,7,8-TCDD. For instance, chloracne, vitamin A depletion, edema and liver damage have been observed in animals exposed to TCDD. The human toxicity and mechanistic relationship of PCNs to TCDD may be useful in understanding these classes of compounds. Particularly, acute and subacute exposures of humans and cattle to PCNs may provide important clues to the toxic effects at high levels for other dioxin-like compounds. 

Reiter L, Kidd K, Heavner G, et al. 1980. Behavioral toxicity of acute and subacute exposure to triethyltin in the rat. Neurotoxicology 2 97-112. 

The NOAEL for subacute exposure in rats ranged from 10,000 to 100,000 ppm (Kennedy 1979 Riley et al. 1979 Silber and Kennedy 1979b). Subchronic exposure using 1 hr/d snout-only exposure for rats and mice resulted in no effects at 50,000 ppm (Alexander and Libretto 1995) whole-body exposure of rats for 6 hr/d to 50,000 ppm also had no effect (Hext 1989 Collins et al. 1995). There were no effects in dogs when 120,000 ppm was administered by face mask for 1 hr/d (Alexander and Libretto 1995). In rats exposed chronically to HFC-134aby... 

Crook, J.W., P. Hott, E.J. Owens, E.G. Cummings, R.L. Farrand, and A.E. Cooper. 1983. The Effects of Subacute Exposures of the Mouse, Rat, Guinea Pig, and Rabbit to Low-Level VX Concentrations. Technical Report ARCSL-TR-82038, AD B086567L. Chemical Systems Laboratory, U.S. Army Armament Research and Development Command, Aberdeen Proving Ground, MD. 

Zabrodskii, P.F., Germanchuk, V.G., Kovalev, A.Yu., Kadushkin, A.M. (2007). Functional disturbance of T-lymphocyte subpopulations under subacute exposure to toxic chemical agents. Rossiyskii Khimicheskii Zhurnal [Russian Chemical Journal] LI(2) 98-100. (In Russian)... 

Chatteijee, D., Mukheijee, S., Smith, M.G., Das, S.K. (2004). Evidence of hair loss after subacute exposure to 2-chloroethyl ethyl sulfide, a mustard analog, and beneficial effects of N-acetyl cysteine. J. Biochem. Mol. Toxicol. 18 150-3. 

TCDD is the most toxic member of the 75 dioxins. It causes death in rats by hepatic cell necrosis. Death can follow a lethal dose by weeks. Acute and subacute exposure result in wasting, hepatic necrosis, thymic atrophy, hemorrhage, lymphoid depletion, chloracne. A by-product of the manufacture... 

Recent studies have shown that cyanide also inhibits the antioxidant defense enzymes (such as catalase, superoxide dismutase, and glutathione peroxidase) and stimulates neurotransmitter release. These effects of cyanide may also contribute to its acute toxicity. The prolonged energy deficit and the consequent loss of ionic homeostasis, which may result in activation of calcium signaling cascade and eventually cell injury, contribute to cyanide toxicity resulting from subacute exposure or in the postintoxication sequela. 

Hontela, A., C. Daniel and A.C. Ricard. Effects of acute and subacute exposures to cadmium on the interrenal and thyroid function in rainbow trout (Oncorhynchus mykiss). Aquat. Toxicol. 35 171-182,1996. 

Genetically modified mice have been useful to show the relationships between the key events in the PPARa MOA. PPARa-null mice provided critical evidence establishing the rodent MOA for PPARa activator-induced hepatocarcinogenesis. Evidence that a particular compound induces key events in wild-type mice but not in mice lacking PPARa would be considered strong support for a PPARa MOA for that particular compound. To date, three chronic bioassays have been conducted in these mice (Hays et al. 2005 Ito et al. 2007 Peters et al. 1997). A greater body of data exists in which precursor events for cancer have been assessed in wild-type and PPARa-nuU mice after acute or subacute exposures. 

Dudley HC, Miller JW. 1941. Toxicology of selenium. VI. Effects of subacute exposure to hydrogen selenide. Journal of Industrial Hygiene and Toxicology 23 470-477. 

Hoffman P, Klapperstiick M. 1990. Effects of carbon disulfide on cardiovascular function after acute and subacute exposure of rats. Biomed Biochem Acta 49(1) 121-128. 

It is common practice for toxicologists to differentiate exposure to chemicals based on the dose and the duration of exposure. Lour timeframes have been used to define duration of exposures acute, subacute, subchronic, and chronic. It is useful in light of today s interest in long-term, low-levef exposures to clarify these terms. Acute exposure is defined as exposure to a chemical for less than 24 h. Subacute exposure refers to an exposure of 1 month or less, subchronic for 1 to 3 months, and chronic for more than 3 months. These exposures can be by any route for most chemicals it is the oral route with the chemical given in the diet. However, the limited animal studies using nerve agents have usually employed parenteral administration... 

Adler, M., Maxwell, D., Foster, R.E., Deshpande, S.S., and Albuquerque, E.X., In vivo and in vitro pathophysiology of mammalian skeletal muscle following acute and subacute exposure to pyridostigmine. Studies on muscle contractility and cellular mechanisms. Proceedings of the Fourth Annual Chemical Defense Bioscience Review, 1984, 173. 

Crook, J. W, Hott, P-, Owens, E. J., Cummings, E. G, Fammd, R. L., and Cooper, A. E. (1983). The eft cci.s of subacute exposures of the mouse, rat, guinea pig, and rabbit to low-level VX concentration.s, Technical Report ARCSL-TR-82038. U.S. Army Armament Rc.scarch and Development CommaiKl, Chemical Sy.stems Laboratory, Aberdeen Proving Ground, MD. 

Subacute Involves mnltiple exposures with a period of time between exposures. The effect is actually less than an acute exposure. The theory is that as long as there are periods of time between exposures, there will be no ill effects. There are no cnmnlative effects of subacute exposure because of the time between exposures. This concept is similar to the time factor when dealing with radioactive materials. Personnel can be exposed to certain levels of radioactivity for short periods of time without any ill effects. 

Subacute exposure 1. Less than acute. 2. Of or pertaining to a disease or other abnormal condition present in a person who appears to be clinically well. The condition may be identified or discovered by means of a laboratory test or by radiologic examination. 

Hore, S.K., S.K. Maiti, and N. Gupta. 1999. Effect of subacute exposure to neem (Azadirachta indica) leaf extract in rats. Indian Vet. J. 76(11) 1011-1012. 

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