National Toxicology Program

National Toxicology Program
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Abstract from Report IMM98011

ABSTRACT

The Immunotoxicity of Diethanolamine (CAS No.111-42-2) in Female B6C3F1 Mice

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 The findings have not been peer reviewed and were not evaluated in accordance with the levels of evidence criteria established by NTP in March 2009.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.


Abstract

Diethanolamine is a viscous, colorless liquid which is formed by ammonolysis of ethylene oxide. Diethanolamine is extensively used in pharmaceutical ointments and skin cleaners. It has been approved for use in numerous cosmetic formulations.Furthermore, it is permitted as a secondary direct food additive from use in delinting cottonseed. Diethanolamine is also widely used as a dispensing agent in various agriculture chemicals including herbicides. As a direct result of its wide spread consumer and industrial usages, large amounts of diethanolamine are discharged directly into water and sewage.

Diethanolamine (DEA) was nominated to the NTP for toxicological evaluation and was selected for immunotoxicity studies by the chemical manager. Thus, the purpose of these studies was to determine the effect of diethanolamine on the immune system.

Diethanolamine (DEA) was nominated to the NTP for toxicological evaluation and was selected for immunotoxicity studies by the chemical manager. Thus, the purpose of these studies was to determine the effect of diethanolamine on the immune system.

The studies were conducted in two rodent species, the female Fischer 344 rat and the female B6C3F1 mouse. Studies on the mouse are presented in this report and the studies conducted in the rat are provided under a separate report. In the studies reported here, female B6C3F1 mice were administered diethanolamine daily for 14 days at doses of 100, 300 and 600 mg/kg. Diethanolamine was administered by gavage as a solution in sterile distilled water.

The baseline toxicology studies are summarized in Table ES-1. Mice exposed to diethanolamine at doses up to and including 600 mg/kg did not have significant decreases in body weight or body weight changes when evaluated over the two week exposure period. While the thymus, spleen, and kidney were unaffected by the diethanolamine exposure, the liver (42%) weights were dose dependently increased. No effects were observed on leukocyte numbers, leukocyte differentials, mean corpuscular volume, mean corpuscular hemoglobin or mean corpuscular hemoglobin concentrations. However, the erythroid elements, erythrocytes (16%), hemoglobin (17%), hematocrit (18%) and reticulocytes (59%) were all dose dependently decreased. Serum chemistries were unaffected by DEA exposure.

Table ES-2 summarizes the immunology studies. Exposure to diethanolamine increased the number of B-cells (30%), and decreased the number of CD4+CD8- (18%) T-cell subsets. Total T-cells and the other T-cell subsets were not affected. Diethanolamine produced a dose-dependent decrease (58%) in the antibody-forming cell response to sheep erythrocytes at a 800 mg/kg exposure level. The proliferative response to mitogens, both Con A and LPS, were not affected. Furthermore, the proliferative response to F(ab)2 + BSF-1 was not affected nor was the proliferative response to allogeneic cells as evaluated in the MLR. Over all, the natural killer cell response was not affected; however, a dose-dependent decrease was observed in the CTL response (14%) when evaluated at the highest (25:1) effector/target ratio. A dose-dependent decrease in the cytotoxicity (21%) of resident macrophages resulted following diethanolamine exposure. However, the cytotoxicty of resident macrophages stimulated with gamma interferon was not affected nor was the cytotoxicity of peptone-elicited macrophages with or without stimulation. Peritoneal cell differentials were not affected following diethanolamine exposure.

In the three host resistance studies conducted, host resistance to Listeria monocytogenes was not affected, while a decrease in host resistance was observed to Streptococcus pneumoniae and in the B16F10 melanoma tumor model (Table ES-3).

A no-effect level for diethanolamine in the female B6C3F1 mouse could not be established since the lowest dose administered significantly decreased the cytotoxic T lymphocyte (CTL) activity, and produced an increase in tumor burden following challenge with the B16F10 melanoma tumor.

  

Table ES-1

SUMMARY TABLE FOR TOXICOLOGY STUDIES

DEA-14-1-PO
Parameter Result Maximum Effect Dose Comment
Body Weight
Day 8 No Effect      
Day 15 No Effect      
Weight Changes
Day 8-1 Increased 186% 600 mg/kg Dose-Dependent
Day 15-1 No Effect      
Pathology
Gross Pathology No Effect      
Histopathology Not Done      
Organ Weights        
   Liver Increased 42% 600 mg/kg Dose-Dependent
   Spleen No Effect      
   Lungs No Effect      
   Thymus No Effect      
   Kidney No Effect      
Hematology
RBCs Decreased 16% 600 mg/kg Dose-Dependent
   Hemoglobin Decreased 17% 600 mg/kg Dose-Dependent
   Hematocrit Decreased 18% 600 mg/kg Dose-Dependent
   MCV No Effect      
   MCH No Effect      
   MCHC No Effect      
   Reticulocytes Decreased 60% 600 mg/kg Dose-Dependent
Leukocytes No Effect      
   Leukocoyte Diff        
       Lymphocytes No Effect      
       Neutrophils No Effect      
       Eosinophils No Effect      
Serum Chemistries
BUN No Effect      
SGPT No Effect      

 

  

Table ES-2

SUMMARY TABLE FOR IMMUNOLOGY STUDIES

DEA-14-1-PO
Parameter Results Maximum Effect Dose Comment
Surface Markers
Ig+ Increased 30% 600 mg/kg Dose-Dependent
Thy 1.2+ No Effect      
CD4+CD8- Decreased 18% 600 mg/kg Dose-Dependent
CD4-CD8+ No effect      
CD4+CD8+ No Effect      
Spleen IgM Antibody-Forming Cell Response to Sheep Erythrocytes
IgM AFC to sRBC Decreased 58% 800 mg/kg Dose-Dependent
Proliferation Assays, i.e. Mitogens, Mixed Leukocyte Response
Con A No Effect      
LPS No Effect      
F(ab')2 + BSF-1 No Effect      
Medium No Effect      
MLR No Effect      
Cytotoxic T Lymphocyte Activity
CTL Decreased 14% 100 mg/kg Dose-Dependent
NK Cell Activity
1:100 No Effect      
1:50 No Effect      
1:25 Decreased 20% 600 mg/kg Dose-Dependent
Macrophage Activity
Resident        

Macrophage %

Decreased 21% 600 mg/kg Dose-Dependent

Cytotoxicity + Gamma Interferon

No effect      
Peptone-Elicited        

Macrophage %

No effect      

Cytotoxicity + Gamma Interferon

No effect      
PE Cell Differentials        

Lymphocytes

No Effect      

Neutrophils

No Effect      

Monocytes

No Effect      

Eosinophils

No Effect      

Mast Cells

No Effect      

 

  

Table ES-3

SUMMARY TABLE FOR HOST RESISTANCE STUDIES

DEA-14-1-PO
Parameter Result Maximum Effect Dose Comment
Listeria monocytogenes No Effect      
Streptococcus pneumoniae Decreased Resistence 73% increase in mortality 600 mg/kg Dose-Dependent
B16F10 Melanoma Decreased Resistence 161% increase in CPM/lung 300 mg/kg  

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