National Toxicology Program

National Toxicology Program

Abstract for IMM96006 - Thalidomide (CASRN 50-35-1)

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 The findings have not been peer reviewed and were not evaluated in accordance with the levels of evidence criteria established by the NTP on March 2009 (see The findings and conclusions for this study should not be construed to represent the views of the NTP or the US Government.

28-day Dose Range-Finding Study for the Immunotoxicity Evaluation of Thalidomide (CAS No. 50-35-1) in Female B6C3F1 Mice

NTP Report Number IMM96006


Thalidomide (TLM) is presently being suggested in the treatment of immune-related diseases, in particular, the treatment of AIDS patients. In the 1960's TLM was used in Europe as a sedative and taken off the market when fetal abnormalities were discovered.

The purpose of these studies was to establish the potential effects of TLM on the immune system. These studies were conducted in female B6C3F1 mice. The animals were treated with TLM for 28 days by the intraperitoneal route. TLM was prepared daily at doses of 30, 100 and 150 mg/kg in sterile distilled water.

The baseline toxicology studies are summarized in Table ES-1. Mice treated with TLM at doses of 30, 100 and 150 mg/kg had no significant changes in body weight when evaluated over the four week treatment period. No significant effects were seen in body weight change with the exception of a statistically significant decrease in body weight gain of 23% for Day 22-1. No statistically significant effects were observed on organ weights - liver, spleen, lungs, thymus and kidneys, nor the hematology parameters - erythrocytes, hemoglobin, hematocrit, leukocyte numbers, leukocyte differentials, reticulocytes, mean corpuscular volume, mean corpuscular hemoglobin, mean corpuscular hemoglobin concentrations and platelets.

Table ES-2 summarizes the immunology studies. When the data were expressed as absolute values, there was no statistically significant difference in B cells, T cells or CD4 cells with treatment of TLM. TLM treatment increased by 23% the number of CD4-CD8+ cells in the T cell subsets and decreased by 11% the number of NK1.1+CD3- cells at the highest dosage (150 mg/kg/day). The AFC response was increased by 37% and 42% for AFC/106 spleen cells (specific activity) and AFC/spleen (total spleen activity), respectively, at the highest dose (150 mg/kg/day) tested. TLM treatment had no effect on serum IgM titers. A significant increase was seen in the CTL response at 1.5:1, 3:1 and 6:1 E:T ratios. No biologically significant effects were seen in either the NK cell activity or the MLR response.

The results of the host resistance study are summarized in Table ES-3. Host resistance to Listeria monocytogenes was not affected.

In summary, thalidomide in doses of 30, 100 and 150 mg/kg, administered for 28 days by the intraperitoneal route, produced a slight increase in humoral and cellular immune indicators.

Table ES-1
Summary Table for Toxicology Studies


Parameter Result Maximum Effect Dose Comment



Body Weight

Day 8 No Effect

Day 15 No Effect

Day 22 No Effect

Day 29 No Effect

Weight Changes

Day 8-1 No Effect

Day 15-1 No Effect

Day 22-1 Decreased -23% 100 mg/kg

Day 29-1 No Effect



Gross Pathology No Effect

Histopathology Not Done

Organ Weights

Brain No Effect

Liver No Effect

Spleen No Effect

Lungs No Effect

Thymus No Effect

Kidneys No Effect



RBCs No Effect

Hemoglobin No Effect

Hematocrit No Effect

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


Parameter Results Maximum Effect Dose Comment


Surface Markers/Absolute Values
Ig+ No Effect

CD3+ No Effect

CD4+CD8- No Effect

CD4-CD8+ Increased 23%
Dose Dependent
CD4+CD8+ No Effect

NK1.1+CD3- Decreased 11% 150 mg/kg Dose Dependent
MAC-3+ No Effect


IgM Humoral Immune Response to Sheep Erythrocytes
IgM AFC to sRBC Increased 42% 150 mg/kg Total Spleen Activity
Serum Titers to


No Effect


Mixed Leukocyte Response
MLR No Effect


Cytotoxic T Lymphocyte Activity
CTL Increased 121% 150 mg/kg 1.5:1 Ratio


NK Cell Activity
100:1 No Effect



Table ES-3
Summary Table for Host Resistance Studies


Parameter Results Maximum Effect Dose Comment


Listeria monocytogenes No Effect



Report Date: August 1989

NTIS # PB92-140383


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