Association of azinphos-methyl with rat erythrocytes and hemoglobin.
To investigate whether hemoglobin might serve as a biomarker of exposure to azinphos-methyl (AZM) encountered by agricultural workers, we exposed rats to [14C]azinphos-methyl ([14C]AZM). We administered single doses of 1.5 mg/kg, 3 mg/kg, or 6 mg/kg of [14C]AZM by gavage to rats and collected blood 3 days later. We found a dose-dependent association between radioactivity and erythrocytes and hemoglobin (measured by liquid scintillation spectrometry). In another experiment, we administered a single dose of 3 mg/kg [14C]AZM by gavage to rats and collected blood 3, 11, 15, and 22 days after administration. Radioactivity continued to be associated with erythrocytes and hemoglobin at all time-points. Brain and plasma acetylcholinesterase (AChE) activities were not significantly inhibited, nor did we observe signs of acute toxicity in any of the treated animals. Loss of radioactivity associated with erythrocytes and hemoglobin over the study period was consistent with the expected kinetics of erythrocyte turnover, indicating adduct stability. Approximately 0.49%, 0.43%, 0.39%, and 0.32% of the original radioactivity was recovered in the hemoglobin 3 11, 15, and 22 days, respectively, after administration. These data support our hypothesis that AZM may form a hemoglobin adduct and may be useful as a biomarker of AZM exposure.
Bailey
B J
BJ
Environmental and Molecular Toxicology Department, Oregon State University, Corvallis 97331, USA.
Jenkins
J J
JJ
D000110:Acetylcholinesterase / Q000378:metabolism; D000818:Animals; D001387:Azinphosmethyl / Q000378:metabolism*; D015415:Biomarkers; D001921:Brain / Q000187:drug effects / Q000201:enzymology; D002250:Carbon Radioisotopes; D002800:Cholinesterase Inhibitors / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004784:Environmental Monitoring; D004912:Erythrocytes / Q000187:drug effects / Q000378:metabolism*; D006454:Hemoglobins / Q000187:drug effects / Q000378:metabolism*; D007306:Insecticides / Q000378:metabolism*; D008297:Male; D008954:Models, Biological; D051381:Rats; D017207:Rats, Sprague-Dawley
D015415:Biomarkers; D002250:Carbon Radioisotopes; D002800:Cholinesterase Inhibitors; D006454:Hemoglobins; D007306:Insecticides; D001387:Azinphosmethyl; D000110:Acetylcholinesterase