RESUMO
Inhibition of the enzyme acetylcholinesterase (AChE) using a carbamate compound was measured in 30 Crl: CD(R)BR Sprague Dawley rats. Erythrocyte, plasma, and brain tissues were analyzed using modifications of the Ellman technique(1) on two different clinical chemistry analyzers. Both EDTA and heparin anticoagulated whole blood were used for the erythrocyte and plasma tests. Results demonstrated similar inhibition of the enzyme in all three tissues between the control and dosed groups using the two technique modifications and instruments. Final inhibition of plasma and erythrocyte AChE for the control vs. treated groups (males and females combined) was 89.5% vs. 82% and 39% vs. 38% for the Technicon AutoAnalyzertrade mark vs. the Boehringer Mannheim Hitachitrade mark 704, respectively. Inhibition of the left and right brain segments for the control vs. treated groups (males and females combined) was 35% vs. 39% and 33.2% vs. 29% for the Technicon and the Hitachi, respectively. All inhibitions were significant at the 5% level using two tailed Dunnett's t-Test. Hemolysates prepared from EDTA whole blood packed cells gave more consistent results on the Hitachi 704.
RESUMO
As a component to the risk assessment process for para-nonylphenol (NP; CASRN 84852-15-3), a 90-day study was conducted in rats following U.S. EPA TSCA guidelines and Good Laboratory Practice regulations. NP was administered to four groups of rats at dietary concentrations of 0, 200, 650, or 2000 ppm which corresponded to approximate dietary intakes of 0, 15, 50, or 150 mg/kg/day, respectively. There were 25 rats/sex/group in the control and high-dose groups and 15 rats/sex/group in the low- and middose groups. Ten of the 25 rats/sex in the control and high-dose groups were designated as recovery animals and were maintained on control diets for 4 weeks after completion of the 90-day exposure period to assess the reversibility of any effects which might be observed. To evaluate for the possible weak estrogen-like activity that has been reported for NP in a number of screening assays, estrous cyclicity was monitored using vaginal cytology during Week 8 of the study, and sperm count, motility, and morphology were evaluated at termination. In-life effects from NP exposure were limited to small decreases in body weight and food consumption in the 2000-ppm dose group. Postmortem measurements at Week 14 indicated a dose-related kidney weight increase in males and a decrease in renal hyaline globules/droplets in males from the high-dose group. The kidney weights showed complete recovery following the 4-week postdosing recovery period. Due to the small magnitude of the changes (i.e., all weights were within or near laboratory historical control values) and the lack of correlating clinical or histopathological changes, the kidney weight alterations were not considered toxicologically significant. The biological significance of reduced hyaline in the kidneys of male rats from the high-dose group is uncertain. Renal tubular hyaline is associated with the rat-specific protein, alpha-2u-globulin, and, therefore, this finding was not considered toxicologically relevant to humans. No other effects attributable to NP were observed. No changes were observed for estrous cycling, sperm evaluations, or effects on endocrine organs. NP, therefore, did not manifest any estrogen-like activity as measured in these parameters at dietary concentrations as high as 2000 ppm, the maximum dose administered in this study. Based on the minor findings for the 2000-ppm dose group, the NOAEL (no-observed-adverse-effect level) for NP in this study is considered to be 650 ppm in the diet, corresponding to an approximate intake of 50 mg/kg/day.