Erythrocytic effect

Nei, T. (1981). Mechanism of freezing injury to erythrocytes Effect of initial cell concentration on the post-thaw hemolysis. Cryobiol. 18, 229-237. 

Erythrocytic effect. Hydrogenated coconut oil, administered orally to healthy rats for 10 weeks, produced a significant effect on five of the six classes of erythrocytes identified. The proportion of cells in each class was dependent on the diet. There was no significant effect of diet on erythrocyte filterability index and no statistical correlation between erythrocyte filterability index and morphology " . 

Falcioni ML, PeUei M, GabbianeUi R. Interaction oftributyltin(IV) chloride and a related complex Bu3Sn(LSM)] with rat leukocytes and erythrocytes effect on DNA and on plasma membrane. Mutat Res. 2008 653 57-62. 

Quentin, M.J., F. Besson, F. Peypoux, and G. Michel Action of Peptidolipidic Antibiotics of the Iturin Group on Erythrocytes. Effect of Some Lipids on Hemolysis. Biochim. Biophys. Acta 684, 207 (1982). 

Wang, T.P., and J. Kagan Ageing of Human Erythrocytes Effects on Photosensitized Hemolysis. Chemosphere 19, 1345 (1990). 

Toxic Effects on the Blood-Forming Tissues Reduced formation of erythrocytes and other elements of blood is an indication of damage to the bone marrow. Chemical compounds toxic to the bone marrow may cause pancytopenia, in which the levels of all elements of blood are reduced. Ionizing radiation, benzene, lindane, chlordane, arsenic, chloramphenicol, trinitrotoluene, gold salts, and phenylbutazone all induce pancytopenia. If the damage to the bone marrow is so severe that the production of blood elements is totally inhibited, the disease state is termed aplastic anemia. In the occupational environment, high concentrations of benzene can cause aplastic anemia. 

In an erythrocyte undergoing glycolysis, what would be the effect of a sudden increase in the concentration of... 

Clinical studies, available only for entacapone and tolcapone, support preclinical findings. A dose-dependent (100-800 mg) inhibition of the COMT activity of the erythrocytes can be seen after nitrocatechols. However, effective and sufficient dose levels of both entacapone and tolcapone, given concomitantly with L-dopa and DDC inhibitors to patients with Parkinson s disease, appear to be 100-200 mg. However, the treatment strategies of entacapone and tolcapone differ entacapone is a short-acting compound that is given with each dose of L-dopa, and COMT activity may even... 

Hematological Effects. No information was found regarding hematological effects in humans following exposure to methyl parathion. Repeated oral exposure to methyl parathion resulted in decreased mean corpuseular volume in one study and decreased hematocrit and erythrocyte count in another study in rats. Chronic ingestion of methyl parathion induced reduction of mean hemoglobin, hematocrit, and erythrocyte eounts in rats. 

Neurological effects related to cholinesterase depression occurred in seven children acutely exposed to methyl parathion by inhalation as well as orally and dermally (Dean et al. 1984). The children were admitted to a local hospital with signs and symptoms of lethargy, increased salivation, increased respiratory secretions, and miosis. Two of the children were in respiratory arrest. Two children died within several days of each other. All of the children had depressed plasma and erythrocyte cholinesterase levels (Table 3-2). These effects are similar to those occurring in methyl parathion intoxication by other routes (see Sections 3.2.2.4 and 3.2.3.4). Three adults exposed in the same incident had normal plasma (apart from one female) and red blood cell cholinesterase, and urinary levels of 4-nitrophenol (0.46-12.7 ppm) as high as some of the ill children. 

Reductions in erythrocyte and plasma cholinesterase levels are considered biomarkers of neurological effects and not hematological effects as discussed in Sections 3.2.2.4 and 3.5.2. 

Following exposure of humans to organophosphates, but not specifically methyl parathion, restoration of plasma cholinesterase occurs more rapidly than does restoration of erythrocyte cholinesterase (Grob et al. 1950 Midtling et al. 1985). These findings are supported by studies of methyl parathion in animals. Erythrocyte cholinesterase levels are representative of acetylcholinesterase levels in the nervous system, and, therefore, may be a more accurate biomarker of the neurological effects of chronic low level exposure of humans to methyl parathion (Midtling et al. 1985 NIOSH 1976). 

Individuals with hereditary low plasma cholinesterase levels (Kalow 1956 Lehman and Ryan 1956) and those with paroxysmal nocturnal hemoglobinuria, which is related to abnormally low levels of erythrocyte acetylcholinesterase (Auditore and Hartmann 1959), would have increased susceptibility to the effects of anticholinesterase agents such as methyl parathion. Repeated measurements of plasma cholinesterase activity (in the absence of organophosphate exposure) can be used to identify individuals with genetically determined low plasma cholinesterase. 

EPA has derived an RfD of. 00025 mg/kg/day, based on a NOAEL of 0.025 for reduced hematocrit, erythrocyte counts, and hemoglobin (cholinesterase inhibition was also listed as a critical effect but the reason for this was not explained). This NOAEL appears to be from the same study as for the ATSDR chronic-duration oral MRL, although the study is referenced differently (IRIS 2001). 

Effects noted in study and corresponding concentrations No adverse effects were observed in the low-dose male and female rats. Mean hemoglobin, hematocrit, and erythrocyte counts were significantly reduced in the high-dose females at 6-24 months of treatment mean hematocrit and erythrocyte counts were significantly reduced in the mid- and high-dose males at 24 months of treatment. 

Other additional studies or pertinent information that lend support to this MRL An intermediate-duration gavage study in rats found decreased hematocrit and erythrocyte counts relative to before-treatment values (Galal et al. 1977), but this study had some limitations, including lack of a control group and disparities between text and tables. Another intermediate duration gavage study in male rats demonstrated dose-related significant decreases in mean corpuscular volume (Undeger et al. 2000). An effect on the erythrocyte is plausible because erythrocyte cholinesterase has a function in the control of erythrocyte permeability (Wills 1972). 

---