Toxin and Antitoxin Testing
Acute toxicity testing for toxins, alkaloids and immunotoxins
Who needs it?
Manufacturers of toxins, alkaloids and immunotoxins for use in human and veterinary medicines.
Why do they need it?
International regulations relating to human health require that all new pharmaceutical drugs are tested for safety prior to use in human volunteers and patients.
A key stage in ensuring the safety of drugs is to conduct toxicity tests in appropriate animal models and acute toxicity studies are just one of a battery of toxicity tests that are used.
These studies are usually conducted in rodents and this test is particularly contentious as it is the only test in pharmaceutical development where lethality is a key endpoint.
The use of natural products as novel therapeutics in medical indications has increased in recent years. This group includes toxins produced by a bacterial protein, or plant-based alkaloids, as well as their derived immunotoxins.
One such product is botulinum neurotoxin, a protein produced by the bacterium Clostridium botulinum that is used to treat muscle spasms, chronic pain, hyperactive nerves, eye muscle disorders and other emerging therapeutic indications.
Because of the toxicity of botulinum toxin, it is crucial that the potency of the product is very accurately determined. Each preparation must be tested for potency before being released for use.
How is it done?
Hoeford supports acute toxicity testing of both the active pharmaceutical ingredient (Drug Substance) and the final formulated product (Drug Product) for potency using the LD50 test - a procedure to determine the dose of a substance that will cause death in 50% of the test animals. Here is a general overview of the test:
- Select the test substance and obtain regulatory approval
- Choose the appropriate animal species and number required
- Prepare different doses of the test substance in a way that allows determination of the dose-response relationship
- Administer the test to animals, usually via oral gavage, inhalation or injection
- Observe the animals, typically 14 days. Record any adverse effects and monitor for mortality
- Report results to customer and regulatory agencies