Share This:
https://ntp.niehs.nih.gov/go/imm91019abs

Abstract for IMM91019

Immunotoxicity of Glycidol in Female B6C3F1 Mice

CASRN: 556-52-5
Chemical Formula: C3H6O2
Molecular Weight: 74.0784
Report Date: October 1993

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 The findings have not been peer reviewed and were not evaluated in accordance with the levels of evidence criteria established by NTP in March 2009.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

Glycidol is a viscous, colorless liquid which is used primarily as a stabilizer in the manufacture of vinyl polymers. It is also used as an intermediate in the production of pharmaceuticals and as an additive for oils and synthetic hydraulic fluids. Over 10 million pounds of glycidol compounds are produced or imported annually.

Glycidol 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 glycidol on the immune system.

The studies were conducted in female B6C3F1 mice. The animals were administered glycidol daily for 14 days at doses of 25, 125 and 250 mg/kg. Glycidol was administered by gavage as a solution in sterile distilled water.

The baseline toxicology studies are summarized in Table ES-1. Mice exposed to glycidol at doses up to and including 250 mg/kg did not have significant decreases in body weight or body weight gain when evaluated over the two-week exposure period. While the brain, thymus, spleen and lungs were unaffected by the glycidol exposure, an increasing trend was observed in liver weights. Additionally, kidney weights were increased (42%) in the glycidol exposure animals dose dependently. No statistically significant effects were observed on leukocyte numbers, leukocyte differentials, reticulocytes, mean corpuscular volume, mean corpuscular hemoglobin or mean corpuscular hemoglobin concentrations. A slight, albeit statistically significant, decrease was observed in the erythroid elements, erythrocytes (4%), hemoglobin (4%), and hematocrit (5%) which was dose related.

Table ES-2 summarizes the immunology studies. Exposure to glycidol decreased the number of B cells (23%) and decreased the number of CD4+CD8- (15%) in the T cell subsets. Total T cells and the other T cell subsets were not affected. Glycidol produced a dose-dependent decrease (41%) in the antibody-forming cell response to sheep erythrocytes. The proliferative response to mitogens, both Con A and LPS, was not affected. However, a decreasing trend in the proliferative response to F(ab)2+BSF-1 was observed. The proliferative response to allogeneic cells as evaluated in the MLR was not affected and overall the CTL response was not affected. A dose-dependent decrease was observed in the natural killer cell activity (29%) when evaluated at the highest (25:1) effector:target ratio. An increase in cytotoxicity of both resident macrophages alone and resident macrophages stimulated with gamma interferon was observed in animals receiving low dose glycidol exposure. No effect was observed on macrophage cytotoxicity at the middle and high dose groups. The peritoneal cell numbers were not affected at any dose level.

In the three host resistance studies conducted, host resistance to Listeria monocytogenes was not affected, while an increase in host resistance to Streptococcus pneumoniae and a decrease in host resistance to the B16F10 Melanoma tumor model was observed.

In summary, while most of the immunosuppressive effects resulting from glycidol exposure were observed at the 125 mg/kg and above dose levels, a true no-effect level for glycidol in the female B6C3F1 mouse could not be established since the lowest dose administered significantly altered several parameters including erythrocyte number, hemoglobin, spleen cell number and macrophage cytotoxicity.

Studies

Table ES-1
Summary Table for Toxicology Studies
GCD-14-1-PO


Parameter Results Maximum
Effect
Dose Comment
Body Weight

        Day 8

No Effect

 

 

 

        Day 15

No Effect

 

 

 

Weight Changes

        Day 8-1

No Effect

 

 

 

        Day 15-1

No Effect

 

 

 

Pathology

        Gross Pathology

No Effect

 

 

 

        Hispathology

Not Done

 

 

 

        Organ Weights

 

 

 

 

           Brain

No Effect

 

 

 

           Liver

Increased

9%

250 mg/kg

% Body Wt Only

           Spleen

No Effect

 

 

 

           Lungs

No Effect

 

 

 

           Thymus

No Effect

 

 

 

           Kidney

Increased

15%

250 mg/kg

Dose Response

Hematology

        RBCs

Increased

6%

25 mg/kg

Mixed Response

           Hemoglobin

Decreased

4%

250 mg/kg

Mixed Response

           Hematocrit

Decreased

5%

250 mg/kg

Dose Response

           MCV

No Effect

 

 

 

           MCH

No Effect

 

 

 

           MCHC

No Effect

 

 

           Reticulocytes

No Effect

 

 

 

           Leukocytes

No Effect

 

 

 

           Leukocyte Diff

 

 

 

 

           Lymphocytes

No Effect

 

 

 

           Neutrophils

No Effect

 

 

 

           Eosinophils

No Effect


Table ES-2
Summary Table for Immunology Studies
GCD-14-1PO

Parameter Results Maximum
Effect
Dose Comment
Surface Markers

Ig+

Decreased

23%

250 mg/kg

Dose Response

Thy 1.2+

No Effect

 

 

 

CD4+CD8-

Decrease

15%

250 mg/kg

Dose Response

CD4-CD8+

No Effect

 

 

 

CD4+CD8+

No Effect

 

 

 

Spleen IgM Antibody-Forming Cell Response to Sheep Erythrocytes

IgM AFC to sRBC Cells

Decreased

41%

250 mg/kg

Dose Response

Proliferation Assays, i.e. Mixed Leukocyte Response

Con A

No Effect

 

 

 

LPS

No Effect

 

 

 

F(ab1)2+BSF-1

Decreased

16%

125 mg/kg

Middle Dose Only

Medium

Increased

45%

25 mg/kg

Mitogen Assay Only

MLR

No Effect

 

 

 

Cytotoxic T Lymphocyte Activity

CTL

No Effect

 

 

 

NK Cell Activity

1:100

Decreased

31%

125 mg/kg

Dose Response

1:50

Decreased

36%

250 mg/kg

Dose Response

1:25

Increased

79%

25 mg/kg

Low Dose Only

Macrophage Activity

Resident

 

 

 

 

     Macrophage %

Increased

151%

25 mg/kg

Low Dose Only

     +Gamma
     Interferon

Increased

68%

25 mg/kg

Low Dose Only

PE Cell Number

No Effect


Table ES-3
Summary Table for Host Resistance Studies
GCD-14-1PO

Parameter Results Maximum
Effect
Dose Comment

 

 

 

 

 

Listeria monocytogenes

No Effect

 

 

 

Streptococcus pneumoniae

Increased Resistance

50%

250
mg/kg

High
Challenge

B16F10 Melanoma

Decreased
Resistance

129% Increase
in Tumor
Burden

250
mg/kg

Dose
Response