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Abstract for IMM20303

Assessment of the Immunotoxicity of Diethanolamine in Female Fischer 344 Rats (Gavage Studies)

CASRN: 111-42-2
Chemical Formula: C4H11NO2
Molecular Weight: 105.136
Report Date: June 1992

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 The findings have not been peer reviewed and were not evaluated in accordance with the levels of evidence criteria established by NTP in March 2009.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

Diethanolamine is a viscous, colorless liquid which is formed by ammonolysis of ethylene oxide. Diethanolamine has found extensive use 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 for use in delinting cottonseed. Diethanolamine has also found wide use 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.

The studies were conducted in two rodent species, the female Fischer 344 rat and the female B6C3F1 mouse. Studies on the rat are presented in this report and the studies conducted in the mouse are provided under a separate report. In the studies reported here, female Fischer 344 rats were administered DEA daily for 14 days at doses of 50, 100 and 200 mg/kg. Diethanolamine was administered by gavage as a solution in sterile distilled water.

The baseline toxicology studies are summarized in Table ES-1. Rats exposed to DEA in doses of 100 and 200 mg/kg had significant decreases in body weight (4%) and/or body weight changes (24%). While the thymus, spleen, lung and adrenals were unaffected by the DEA exposure, both the liver (23%) and kidney (21%) weights were dose dependently increased. Additionally, a dose-dependent increase (68%) in BUN was observed. Significant elevation in the BUN was observed in the animals exposed to the lowest dose (50 mg/kg) of DEA. 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 (9%), hematocrit (13%), hemoglobin (14%) and reticulocytes (59%) were all dose dependently decreased. The reticulocytes appeared to be the most sensitive erythroid parameter evaluated. Even the lowest dose tested, 50 mg/kg, significantly decreased the percentage of reticulocytes following 14 days of exposure.

Table ES-2 summarizes the immunology studies. Exposure to DEA did not alter the number of B-cells, T-cells or T-cell subsets. Furthermore, DEA did not decrease the antibody-forming cell response to sheep erythrocytes. The proliferative response to mitogens, both Con A and STM, was not affected. However, the proliferative response to alfogeneic cells, as evaluated in the MLR, was increased (93%) in a dose-dependent manner. Several immune functional assays were decreased in DEA-treated animals. These included the natural killer cell response (39%) and the cytotoxicity (23%) of resident macrophages. Conversely, the cytotoxicity of peptone-elicited macrophages was increased (45%) following DEA exposure.

Based on the results of this protocol study, using doses of 50, 100 and 200 mg/kg, a no effect level could not be established, since a significant decrease in reticulocyte number was observed at all dose levels. However, based on the results from the range finding study (Appendix D - Table 5), the no effect level was determined to be 25 mg/kg. No significant decrease in reticulocyte number was observed at this dose level. The decrease observed in doses greater than 25 mg/kg suggest that DEA has a deleterious effect on erythroporesis.

Studies

Table ES-1


Summary Table for Toxicology Studies

DEA-14-1-PO

Parameter Result Maximum Effect Dose Comment
Body Weight
   Day 8 Decreased 4% 200 mg/kg Dose Dependent
   Day 15 Decreased 4% 200 mg/kg Dose Dependent
Weight Changes
   Day 8-1 Decreased 35% 200 mg/kg Dose Dependent
   Day 15-1 Decreased 24% 200 mg/kg Dose Dependent
Pathology
Gross Pathology No Effect      
Histopathology Not Done      
Organ Weights
   Liver Increased 23% 200 mg/kg Dose Dependent
   Spleen No Effect      
   Lungs No Effect      
   Thymus No Effect      
   Kidney Increased 21% 200 mg/kg Dose Dependent
Hematology
RBCs Decreased 9% 200 mg/kg Dose Dependent
   Hemoglobin Decreased 14% 200 mg/kg Dose Dependent
   Hematocrit Decreased 13% 200 mg/kg Dose Dependent
   MCV No Effect      
   MCH No Effect      
   MCHC No Effect      
   Reticulocytes Decreased 59% 200 mg/kg Dose Dependent
Leukocytes No Effect      
    Leukocyte Diff
      Lymphocytes No Effect      
      Neutrophils No Effect      
      Eosinophils No Effect      
Serum Chemistries
   BUN Increased 68% 200 mg/kg Dose Dependent
   SGPT No Effect      


Table ES-2

Summary Table for Immunology Studies

DEA-14-1-PO

Parameter Results Maximum Effect Dose Comment
Surface Markers
   W3/13 No Effect      
   W33/25 No Effect      
   OX4 No Effect      
   OX8 No Effect      
Spleen IgM Antibody-Forming Cell Response to Sheep Erythrocytes
IgM AFC to sRBC No Effect      
(T-dependent)
Proliferation Assays, i.e. mitogens, Mixed Leukocyte Response
   Con A No Effect      
   STM No Effect      
   Medium No Effect      
   MLR Increased 93% 200 mg/kg Dose Dependent
NK Cell Activity
   1:100 Decreased 39% 200 mg/kg Dose Dependent
   1:50 Decreased 50% 200 mg/kg Dose Dependent
Macrophage Activity
Resident
   Macrophage % Decreased 23% 100 mg/kg Dose Dependent
   Cytotoxicity
   + Gamma Decreased 25% 100 mg/kg Dose Dependent
   Interferon
Peptone-Elicited
   Macrophage % Increased 45% 100 mg/kg Dose Dependent
   Cytotoxicity
   + Gamma No Effect      
   Interferon
PE Cell Differentials
   Lymphocytes Increased 69% 200 mg/kg  
   Neutrophils Decreased 30% 200 mg/kg  
   Monocytes No Effect      
   Eosinophils No Effect      
   Mast Cells No Effect