Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0153470 (Spleen)
 4,015 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This article addresses results from a single 4-h and repeated 1- and 4-wk inhalation exposure studies in Wistar rats with vapor and/or aerosol atmospheres of 4-ethoxyaniline (p-phenetidine). Groups of 10 rats/sex were exposed nose-only to mean analytical concentrations of 11.1, 86.2, and 882.6 mg p-phenetidine/m(3) using an exposure regimen of 6 h/day, 5 days/wk for 4 wk. Concentrations were selected based on results from a pilot study in which rats were exposed under identical conditions on 5 consecutive days for 6 h/day to mean analytical concentrations of 38.2, 133.0, and 1247.6 mg/m(3). In repeated exposure studies, the focus of endpoints was on hematotoxicity. The LC50 was not determined, but no rats died following a single 4-h exposure to 5085 mg/m(3) as a mixture of vapor and aerosol. No mortality was observed either in the 1- or 4-wk studies. Rats exposed to 882.6 mg/m(3) and above evoked characteristic signs of toxicity that included cyanosis, with no apparent progression of findings during the exposure period. Animals exposed to 86.2 mg/m(3) and above exhibited a concentration-dependent, significant increase in blood methemoglobin and reticulocyte counts as well as a significant decrease in hemoglobin, hematocrit, and red blood cell counts. Spleen weights were significantly increased in groups exposed to 133.0 mg/m(3) and above. Microscopic changes demonstrated an increased hematopoiesis (bone marrow smears) and splenic hemosiderosis at 86.2 and 882.6 mg/m(3) and a hepatic hemosiderosis only at 882.6 mg/m(3). These data suggest that the toxicity of p-phenetidine is similar to that of its structural analog aniline. Based on the erythrocytotoxicity occurring at 86.2 mg/m(3) and above, including the apparent reactive changes in bone marrow (increased erythropoiesis) and spleen (increased erythroclasia), the no-observed-adverse-effect level (NOAEL) of the 4-wk study was 11.1 mg/m(3) air and that of the 1-wk study was 38.2 mg/m(3) air. This difference in NOAELs is considered to be related to the selection of exposure concentrations rather than cumulative toxicity.
 ...
PMID:Inhalation toxicity of 4-ethoxyaniline (p-phenetidine): critical analysis of results of subacute inhalation exposure studies in rats. 1169 70

This article addresses results from a 4-wk inhalation exposure study in Wistar rats with the vapor and/or aerosol atmospheres of 2-chloro-4-toluidine. Groups of 10 rats/sex were nose-only exposed to mean analytical concentrations of 19.1, 115.1, and 702.3 mg/m3 using an exposure regimen of 6 h/day and 20-22 exposures within a time period of 4 wk. These concentrations were selected based on results from a repeated 5 x 6 h/day pilot study using concentrations of 27.1, 104.8, 381.6, and 1283.7 mg/m3. In a single 4-h exposure study at the maximum tested concentration of 7620 mg/m3, 1 of 10 female rats succumbed (no mortality in males), while no mortality occurred at 3293 mg/m3. In the 1- and 4-wk studies mortality occurred at 1283.7 and 702.3 mg/m3, respectively. Rats exposed for 4 wk to 702.3 mg/m3 displayed characteristic signs of toxicity that included cyanosis, respiratory distress, and significantly decreased body weights. Rectal temperatures were significantly decreased at 115.1 mg/m3 and above. Dark and enlarged spleens occurred at 702.3 mg/m3. At this concentration, prominent treatment-related effects included methemoglobinemia, reticulocytosis, red blood cells with Heinz bodies, decreased hemoglobin, hematocrit, and red blood cell counts. Borderline evidence of erythrocytotoxicty was noticed at 115.1 mg/m3 (based on a minimal increase in Heinz bodies). Spleen and liver weights were significantly increased at 702.3 mg/m3, whereas the thymus weight was decreased at 115.1 mg/m3 and above. Microscopic changes were found in the spleen (hemosiderosis) at 702.3 mg/m3. An atrophy of the olfactory epithelium in the nasal cavities occurred at 115.1 mg/m3 and above. Clinical pathology revealed changes pathognostic of hepatic effects, although microscopic examinations did not reveal any specific changes. The no-observed-adverse-effect level (NOAEL) of the 4-wk study was 19.1 mg/m3 and is based on the predominant atrophic changes of the olfactory epithelium and the minimal to borderline erythrocytotoxic effects at 115.1 mg/m3.
 ...
PMID:Subacute inhalation toxicity of 2-chloro-4-toluidine in rats. 1704 32