Range-Finding Report on the Immunotoxicity of 2',3'-Dideoxyinosine in Female B6C3F1 Mice (CAS No. 69655-05-6)
Report Date: October 1995
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 The findings have not been peer reviewed and were not evaluated in accordance with the levels of evidence criteria established by NTP in March 2009.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.
2',3'-Dideoxyinosine is presently being used for the treatment of human immunodeficiency virus positive individuals and for the treatment of acquired immune deficiency syndrome patients. Previous studies by Luster et al. showed that some of the anti-HIV drugs had adverse effects on the immune system . Cao et al. showed the B lymphocyte was a target for 2,3-dideoxyadenosine. ddA is metabolized to ddI.
Studies were conducted using 2, 4, and 26 weeks of exposure. The 26 week (6 month) study is provided in a separate report.
These studies were conducted in female B6C3F1 mice. The animals were treated with ddl twice daily for either a 14 or 28 day period by-oral gavage. ddI was prepared as a suspension in Maalox Therapeutic Concentrate. The purpose of these studies was to determine the period of treatment time required to produce the suppression of humoral immunity. As shown in the 6 months study (see the Immunotoxicity of 2',3'-Dideoxyinosine in Female B6C3F1 Mice report), ddI produced a profound suppression of humoral immunity as expressed in a decrease in ability of mice to make immunoglobulin M antibody to sheep red blood cells.
ddI produced a minor suppression of the antibody-forming cell response with 14 days of treatment but a marked response after 28 days of treatment. The no observable adverse effect level for 14 days of treatment is 500 mg/kg and < 100 mg/kg for 28 days of treatment.
The results of these studies show that ddI, administered by oral gavage, requires at least 28 days to produce immunosuppression in female B6C3F1 mice.