For those who may not be familiar with LD50 data: 

In toxicology measurements, the median lethal dose, LD50 (“Lethal Dose, 50%”), is a widely used measurement to determine relative acute toxicity of an agent.  

This assay has been used since the late 1920’s and continues as a prerequisite for drug approval. 

It provides information to the investigator(s) as to the therapeutic dose relative safety. 

It contributes to a basic understanding of risk to benefit considerations, i.e., does the benefit of administering a medication outweigh the risk.

Most medications, even water, (e.g.,  “water intoxication”) are toxic if administered in high enough concentrations. Many widely prescribed drugs can only be used within strict limits as to dose and time.

The following LD50 study data demonstrates that the therapeutic dose used in Zetetin administration is insignificant when compared to the lethal range.  

                                          Zetetin® Toxicity
                                                   (Murines)
In the intraperitoneal, subcutaneous and intracerebral studies, mice were divided into 5 groups of 10 each and injected with  1, 10, 100, 1000 and 10,000 ppm dosages respectively. 
All subcutaneous and intraperitoneal injected mice each received 1 cc while intracerebrally injected mice received .04 cc.  All groups were observed 21 - 25 days. Mice weighed 18 - 19 grams.

RESULTS:

1. The LD50 dose varies depending on  the route of injection.
2.  No animals died at drug doses of 1,000  ppm  or less.
    a)  SUBCUTANEOUS:  3 of 10 mice treated with10,000 ppm died within 48 hours.  
         No deaths were observed in  other groups given 1,000 ppm or less  

    b)  INTRAPERITONEAL: 6 of 10 mice died within 30 hours on the 10,000 ppm dosage 
         No deaths were observed in the 40 other  mice given 1,000 ppm or less.
  

   c)  INTRACEREBRAL:  9 of 10 mice administered 10,000 ppm  died within 18 hours. No deaths were observed in the 40 other  mice given 1,000 ppm or less.

CONCLUSIONS:

1. The therapeutic dose in other species administered intravenously,  was non toxic in this murine model.. 
 
The lowest dose of drug producing toxicity in this model was  9 ,000 fold  to 18,000 fold  greater than the therapeutic dose used in other species  by every route including intracerebrally.

This small rodent model was not conducive to administration of drug by intravenous injection. Since this route is most efficacious in humans, toxicity studies in larger animals (such as Beagle dogs) using this route must be evaluated. In addition, gross and microscopic post-mortem examination of treated animals should be performed to localize and quantatate any toxic effects that may produce morbidity without mortality.

BETA 2 MICROGLOBULIN

               Beta 2 Microglobulin Reduction in HIV infected patients

Beta 2 Microglobulin  (normal range: less than 3.0 mg/L),   “is a measurement of Cell Breakdown. It is a surface protein present on nearly all cells. It is released into the blood and urine, usually at a constant  low rate. It is a nonspecific measure. Elevated B2Mg can result from other chronic infections such as HIV, CMV,etc., but it reflects active infection in a range of cells besides Lymphocytes”. SmithKlein-Beecham, 1988 & 89) 

Post treatment  blood draw = one week post treatment,
Zetetin® IV in 1000 ml Ringers Lactate administered in 18 - 24 hours 

The reduced levels of B2 microglobulin  post treatment,  provides  additional documentation and supports  the proposition that  Zetetin® is non-toxic when administered to humans (IV)  at therapeutic dose. 

Additionally, this data also sustains an assertion that Zetetin® administered IV exhibits a therapeutic outcome, diminishing cytopathic effect in these HIV infected individuals.