Hematocrit, rats

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. 

ATSDR has derived a chronic-duration oral MRL of. 0003 mg/kg/day for methyl parathion based on a NOAEL of 0.025 mg/kg/day for reduced hematocrit and erythrocyte counts in rats (Suba 1984). 

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). 

The data from the only available animal study (Prigge and Greve 1977) indicate that inhaled lead is not teratogenic. However, it impaired heme synthesis in both rat dams and fetuses. In this study, dams were exposed to 1, 3, or 10 mg lead/m3 (chemical species not provided) throughout gestation (days 1-21). Maternal and fetal ALAD were inhibited at all exposure levels in a dose-related manner, and fetal (but not maternal) hematocrit and body weight were decreased at the 10-mg/m3 lead level. These results suggest that the fetuses were more sensitive to lead-induced toxicity than were the dams. 

Effects at even lower external and internal exposure levels were reported by Hayashi (1983). Lead acetate at 0.7 mg lead/kg/day in the drinking water of rats for the first 18 or 21 days of pregnancy resulted in decreased ALAD activity in the fetal and maternal erythrocytes and increased ALAD activity in fetal but not maternal liver. Fetal, but not maternal, hematocrits and hemoglobin levels were decreased in the group treated for 21 days. Fetal PbB levels were 27 pg/dL and 19 pg/dL in the 18-day and the 21-day treated groups, respectively. Maternal PbB levels were approximately 4 pg/dL in treated and control groups. The study is limited by the use of one dose level, which precluded assessment of dose response. 

In rats exposed at concentrations of 30 or 50 ppm for 8 h for up to 5 d, methemoglobin levels returned to control values after overnight recovery (10 ppm was identified by the authors as a no-effect level), whereas in the groups exposed at 150 ppm for 8 h or 50 or 150 ppm for 12 h for a maximum of 4 d, methemoglobin levels increased with increasing days of exposure. Hematocrit levels, measured 1 w after the start of exposure, were reduced at concentrations of >30 ppm. Signs of aniline intoxication either did not occur or were not reported. 

Consistent with the human responses to arsine exposure, observations in several animal species (rats, mice, and hamsters) indicated hematologic involvement. Cumulative exposures of 540-1,800 ppm-min produced decreases in hematocrit levels, RBC counts, packed cell volumes, and increases in absolute and relative spleen weights (consistent with erythrocyte damage). For acute exposures, the exposure-response curve is steep generally less than a 10-fold difference between no-effect and lethality exposures. 

Uncertainty Factors/Rationale Total uncertainty factor 30 Interspecies 10—The 10-min LC50 value for the monkey was about 60% of the rat value and one-third the rabbit value. The mouse data were used to calculate the AEGL levels, because the data exhibited a good exposure-response relationship and the endpoint of decreased hematocrit levels can be considered a sensitive indicator of arsine toxicity. In addition, arsine has an extremely steep dose-response relationship, allowing little margin in exposure between no effects and lethality. 

Treated rats had 1000 mg/kg FW liver (vs. 4.7 in controls) lowered hemoglobin, hematocrit, and red cell counts mean survival time of 67 days hepatic and renal histopathology Dose-time-dependent increase in copper concentrations in liver, spleen, and lung little accumulation in muscle and skin. Reduced growth at 2.5 and 3.75 mg/kg BW daily reduced survival at 3.75 mg/kg BW. Maximum copper concentrations recorded, in mg/kg FW (vs. saline controls,) were 710 in liver (<5), 212 in kidney (<10), 7 in lung (<1.5), 27 in spleen (<2.0) 6 in bone (<2.0) and 2.2 in testes (<1.6) Increased serum ceruloplasmin and white blood cell number... 

Signs of nickel deficiency in the laboratory white rat (Rattus sp.) include retarded growth, anemia, a reduction in hematocrit and hemoglobin values, decreased enzyme activities (malate dehydrogenase, glucose-6-phosphate dehydrogenase, alpha amylase), a reduction in liver total lipids... 

SP produces a pronounced (4-fold) increase in the histamine content of the venus outflow of the perfused rat hindquarters [91] and, when injected intravenously in intact animals, it produces a significant increase in the level of plasma histamine and in the hematocrit and a pronounced fall in systemic blood pressure [102], In these experiments, pretreatment with the steroid, dexamethasone, reduced the SP-induced elevations in plasma histamine and hematocrit neurotensin and compound 48/80 were found to be similarly... 

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