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Abstract for IMM89025 - Aldicarb Oxime (CASRN 1646-75-9)

Abstract

The following abstract presents results of a study conducted by a contract laboratory for the National Toxicology Program (NTP). The findings have not been peer reviewed and were not evaluated in accordance with the levels of evidence criteria established by the NTP on March 2009 (see http://ntp.niehs.nih.gov/ntp/htdocs/levels/09-3566%20NTP-ITOX-R1.pdf). The findings and conclusions for this study should not be construed to represent the views of the NTP or the US Government.

The Immunotoxicity of Aldicarb Oxime
(CAS No. 1646-75-9)

in Female B6C3F1 Mice
NTP Report Number IMM89025

Summary

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.


Table ES-1

SUMMARY TABLE FOR TOXICOLOGYSTUDIES

Aldicarb Oxime

Parameter Results Maximum Effect Dose (mg/kg) Comments
Body Weight No effect   
     
Gross PathologyNo changes   
HistopathologyNo changes   
Organ Weights
     LiverNo effect   
     SpleenNo effect   
     LungsNo effect   
     ThymusNo effect   
     KidneyNo effect   
     Brain No effect   
Hematology
     RBCsNo effect   
     HemoglobinNo effect   
     HematocritNo effect   
     MCVNo effect   
     Leukocyte No.No effect   
     Leukocyte Diff    
        Lymphocytes%No effect   
        Neutrophils%No effect   
Serum Chemistries
     SGPTNo effect   
     AlbuminDecreased
16%
15
Dose Dependent
     BUNDecreased
12%
15
Dose Dependent
     GlucoseNo effect   
     Total ProteinIncreased
63%
15
Dose Dependent
Bone Marrow
     CellularityIncreased
26%
15
Dose Dependent
     DNA SynthesisNo effect   
     Stem Cells    
          CFU-MIncreased  Dose Dependent*
          CFU-GMIncreased  Dose Dependent*
__________________________________________________________
* = Does not reach statistical significance for a given treatment group


Table ES-2

SUMMARY TABLE FOR IMMUNOLOGYSTUDIES

Aldicarb Oxime

ParameterResultsMaximum EffectDose (mg/kg)Comments
T lymphocytesNo effect   
     L3T4No effect   
     LyT2No effect   
B lymphocytesDecreased
8%
1.0
Dose dependent
IgM AFC Response to sRBC No effect   
Cytolytic T Cell ResponseDecreased
7%
15
Dose Dependent
Response to Mitogens
     Concanavalin ANo effect   
     PhytohemagglutininNo effect   
     LipopolysaccharideNo effect   
     MediumNo effect   
F(ab')2 + BSF-1No effect   
Mixed Leukocyte ResponseNo effect   
Natural Killer Cell ActivityNo effect   
Macrophage ActivityNo effect   
     Without MAFNo effect   
     With MAFNo effect   


Table ES-3

SUMMARY TABLE FOR HOST RESISTANCESTUDIES

Aldicarb Oxime

ParameterResultsMaximum EffectDose (mg/kg) Comments
Listeria Monocytogenes No effect   
Streptococcus pneumoniae No effect   
B16F10 MelanomaNo effect   


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