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

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 The findings have not been peer reviewed and were not evaluated in accordance with the levels of evidence criteria established by the NTP on March 2009 (see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

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

Summary

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
TLM-28-1M-IP

 


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



 

Pathology




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



 

Hematology




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
TLM-28-1M-PO

 

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

sRBC

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
TLM-28-IM-PO

 

Parameter Results Maximum Effect Dose Comment

 

Listeria monocytogenes No Effect



 

 


Report Date: August 1989

NTIS # PB92-140383

 

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