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Abstract for IMM89025

Immunotoxicity of Aldicarb Oxime in Female B6C3F1 Mice

CASRN: 1646-75-9
Chemical Formula: C5H11NOS
Molecular Weight: 133.2139

Abstract

The following abstract presents results of a study conducted by a contract laboratory for the National Toxicology Program. The findings have not been peer reviewed and were not evaluated in accordance with the levels of evidence criteria established by NTP in March 2009. The findings and conclusions for this study should not be construed to represent the views of the NTP or the U.S. Government.

Aldicarb oxime [2-Methyl-2-(methyl-thio)-propanal,oxime] is produced primarily as an intermediate in the synthesisof aldicarb [2-methyl-2-(methylthio)-prioionaldehyde)-(methylcarbamoyl)oxime] which is used as a pesticide. Aldicarb oxime is also anintermediate in the metabolism of aldicarb.

Aldicarb oxime was nominated to theNTP for toxicological evaluation with moderate priority becauseof the production volume and lack of a toxicological data base.It was recommended for immunotoxicological evaluation by the chemicalmanager. The pesticide aldicarb has been studied for possibleactions on the immune system and there is no clear evidence thatit affects the immune system. In well-conducted studies by Thomas et al., FAAT 1988, aldicarb was found not to affect theimmune system.

Aldicarb oxime was administered bygavage at doses of 1, 7.5 or 15 mg/kg daily for 14 consecutivedays. The highest dose was the maximum tolerated dose. Doses of20 mg/kg or higher produced major central nervous system effectsand lethality.

The baseline toxicology data are summarizedin Table ES-1. Aldicarb oxime produced no overt pharmacotoxicologicalsigns. There was no alteration in body weight or body weight gain,and no change in weight, gross or histopathology of the liver,spleen, lungs, thymus, kidneys or brain. The hematological parametersmeasured were not affected. The changes observed in the serumchemistries were minimal and not considered biologically meaningful.There was a slight increase in bone marrow cellularity. This increasewas accompanied by an increase in the CFU-GM stem cells, basedon a trend analysis, but no exposure group reached statisticalsignificance. In summary, aldicarb oxime, administered in dosesbetween 1 and 15 mg/kg by gavage, produced no detectable adverseeffects on basic toxicological parameters.

Table ES-II summarizes the immunologystudies. Aldicarb oxime produced no changes in the number or functionof T cells which are considered biologically meaningful. T cellresponses to mitogens (Con A and PHA) and allogeneic cells (MLR)were all unaffected by exposure to aldicarb oxime. The slightchange (7%) in the CTL response is not considered a biologicallymeaningful change. The slight decrease in B cells (7%) does nottranslate into functional changes as measured by proliferativeresponse to mitogen stimulation or F(ab') receptor driven proliferationor in the spleen antibody-forming cell response to the T-dependentantigen sheep erythrocytes. With respect to innate immunity, naturalkiller cell function and peritoneal macrophage number and functionswere unaffected by aldicarb oxime exposure.

Table ES-3 summarizes the three hostresistance studies that were conducted. Streptococcus pneumoniae,Listeria monocytogenes, and the B16F10 pulmonary metastaticmelanoma models were all unaffected by exposure to aldicarb oxime.

In summary, aldicarb oxime, in dosesbelow those that produced major central nervous system action,administered daily for 14 days, did not alter any of the toxicological,immunological or host resistance parameters measured.

Studies

Table ES-1

Summary Table for Toxicology Studies

Aldicarb Oxime

Parameter Results Maximum Effect Dose (mg/kg) Comments
Body Weight No effect      
         
Gross Pathology No changes      
Histopathology No changes      
Organ Weights
     Liver No effect      
     Spleen No effect      
     Lungs No effect      
     Thymus No effect      
     Kidney No effect      
     Brain No effect      
Hematology
     RBCs No effect      
     Hemoglobin No effect      
     Hematocrit No effect      
     MCV No effect      
     Leukocyte No. No effect      
     Leukocyte Diff        
        Lymphocytes% No effect      
        Neutrophils% No effect      
Serum Chemistries
     SGPT No effect      
     Albumin Decreased
16%
15
Dose Dependent
     BUN Decreased
12%
15
Dose Dependent
     Glucose No effect      
     Total Protein Increased
63%
15
Dose Dependent
Bone Marrow
     Cellularity Increased
26%
15
Dose Dependent
     DNA Synthesis No effect      
     Stem Cells        
          CFU-M Increased     Dose Dependent*
          CFU-GM Increased     Dose Dependent*
__________________________________________________________
* = Does not reach statistical significance for a given treatment group

Table ES-2

Summary Table for Immunology Studies

Aldicarb Oxime

Parameter Results Maximum Effect Dose (mg/kg) Comments
T lymphocytes No effect      
     L3T4 No effect      
     LyT2 No effect      
B lymphocytes Decreased
8%
1.0
Dose dependent
IgM AFC Response to sRBC No effect      
Cytolytic T Cell Response Decreased
7%
15
Dose Dependent
Response to Mitogens
     Concanavalin A No effect      
     Phytohemagglutinin No effect      
     Lipopolysaccharide No effect      
     Medium No effect      
F(ab')2 + BSF-1 No effect      
Mixed Leukocyte Response No effect      
Natural Killer Cell Activity No effect      
Macrophage Activity No effect      
     Without MAF No effect      
     With MAF No effect      



Table ES-3

Summary Table for Host Resistance Studies

Aldicarb Oxime

Parameter Results Maximum Effect Dose (mg/kg) Comments
Listeria Monocytogenes No effect      
Streptococcus pneumoniae No effect      
B16F10 Melanoma No effect