Disappearing Evidence of Harm

One 1994 internal Allergan report conducted by Pharmaco LSR offers critical insights into how high-dose, repeated intramuscular injections of Botox behave.

Important Note for Readers: This internal document previously surfaced as part of a KFOR news investigation into Botox (INVESTIGATION: What many don’t know about popular wrinkle drug | KFOR.com Oklahoma City), but it has mysteriously disappeared from the web. This happened at some unknown point between January 2025 and July of 2026. Because primary source documents like this are vital for transparent medical education and safety research, we strongly encourage readers to download this PDF at the end of the post and save a copy directly to your computer or local drive for future reference.

Keep in Mind before reading:

• This study was done in 1994, after Allergan purchased Botox from Dr. Alan Scott in 1989 

• This was an internal proprietary study not available to the public or industry until it was used as evidence in a lawsuit in 2010

• All fatalities were female

• All surviving monkeys met the clinical definition of non-lethal botulism

  
  
  
  

  1. Study Overview: What Did They Test?

The study evaluated the long-term toxicity, local tissue response, and reversibility of Botox when injected into cynomolgus monkeys.

• Dosing Schedule: Seven total injections administered once every two months over a 1-year period into the left calf muscle. The right leg was left untreated as a control.  

• Dosages:

  • Control (Saline)  

  • Low Dose: 4 units per kg

  • Mid Dose: 8 units per kg

  • High Dose: 16 units per kg

• Recovery Phase: A 3-month (14-week) post-dosing period to see if affected muscles and nerves recovered.  

  
  

2. Key Findings: Local vs. Systemic Effects

Local Muscle Atrophy and Morphological Changes

The primary local effect was dramatic muscle reduction in the injected leg:  

• Severe Weight & Volume Loss: At 12 months, mean weights of the treated gastrocnemius muscle were 65-80% lower than vehicle-treated control legs across all dose groups.  

• Microscopic & Ultrastructural Damage: Pathologists noted focal muscle degeneration, severe muscle fiber atrophy, an increase in extracellular collagen fibers (fibrosis), and a loss of normal banding structure in skeletal muscle fibers.  

• Contralateral Spread: Mild reductions in muscle size were occasionally noted in adjacent or opposite-leg muscles (the untreated right leg or left quadriceps), indicating localized diffuse spreading.  

  
  

Motor End Plate Damage & Limited 3-Month Recovery

• Destruction of Junctions: Silver cholinesterase staining revealed severe destruction/absence of functional neuromuscular motor end plates in the injected muscle.  

• Incomplete Recovery: Following the 3-month recovery window, muscle mass and structure showed minimal recovery. While some axonal nerve sprouting was observed, full motor end plate regeneration and functional architecture had not returned by the 14-week mark.  

  
  

Systemic Toxicity and "NOEL"

• Body Weight Suppression: Animals receiving 8 and 16 units/kg exhibited lower body weight gains during treatment compared to controls.  

• NOEL Established: The No Observed Effect Level (NOEL) for systemic toxicity was determined to be 4 units per kg (note that according to Botoxone.com, "The recommended dose for treating Pediatric ULS is 3 Units/kg to 6 Units/kg divided among the affected muscles"; 6 units per kg is ABOVE the established NOEL of 4 units per kg)

• Mortality: Three high-dose females were euthanized moribund. Two of these deaths were attributed to foreign body/aspiration pneumonia a known botulism complication.

3. Why Is This Study Important?

This 1994 report is a key piece of preclinical safety data for several reasons:

1. It Defines the Structural Recovery Timeline

While botulinum toxin’s clinical paralytic effects generally wear off within 3–6 months in humans as new nerve sprouts form, this study demonstrates that structural recovery (rebuilding muscle volume and fully functioning motor end plates) takes significantly longer than 3 months following repetitive exposure to high doses.  

2. Highlights the Potential for Local Spread (Distant Effects)

The occurrence of aspiration pneumonia in high-dose females underscored the risk of local diffusion into swallowing muscles (dysphagia)- a well-known black-box warning Botox today

3. Establishes Clear Preclinical Safety Margins

By establishing a NOEL 4 units/kg, Allergan was able to define safe clinical human dosing thresholds. However, today, they recommend injecting as many as 6 units per kg for children with muscle spasticity.

Download the study below and SAVE it to your computer!!

Study-No.-91-3708.pdf

Download PDF • 4.49MB