Rat studies showing no adverse effects from colloidal silver ingredients fail to demonstrate safety in humans, FDA says in a final rule declaring silver constituents in OTC drugs for internal or external use not generally recognized as safe and effective and misbranded.

Comments submitted in response to FDA's proposed rule on OTC products containing colloidal silver ingredients or silver salts failed to provide necessary human data on "absorption, metabolism, tissue distribution, accumulation, excretion and phamacodynamics of silver in the body, both when taken internally and applied externally, and of the effect of the particle size of the silver on these systemic effects," the agency states.

There are no approved NDAs for OTC products containing colloidal silver ingredients or silver salts. FDA's final rule does not affect silver-containing products marketed as dietary supplements. The final rule, published in the Aug. 17 Federal Register, takes effect in 30 days.

Colloidal silver is a suspension of silver particles in a colloidal, or gelatinous, base. FDA says colloidal silver preparations appearing on store shelves have carried labels indicating treatment in adults and children for various diseases, including HIV, AIDS, cancer, tuberculosis, malaria, lupus, syphilis, scarlet fever, shingles, herpes, pneumonia, typhoid and tetanus.

The dosage form for these products is usually oral, but some are indicated for topical and intravenous use.

In its October 1996 proposed rule, FDA invited interested parties to submit any existing data and information supporting the safety and effectiveness of colloidal silver ingredients or silver salts for any uses not already evaluated under the OTC drug review (¹ Also see "Colloidal silver "cure-all" OTC products not safe and effective -- FDA proposed rule." - Pink Sheet, 21 October, 1996.).

The agency received 251 comments, many of which concurred with the proposed rule. Some comments submitted information purporting to support the safety of colloidal silver and other silver ingredients.

Several comments stated that argyria, a blue discoloration of the skin resulting from prolonged administration of silver compounds and accumulation in the body, is the most common side effect. There are no toxic effects associated with the skin discoloration and colloidal silver is the only known form of the substance not deposited under the skin, one response said.

Another response said most reported cases of argyria result from use of silver nitrate, various ionic silver salts or highly concentrated mild silver protein. The dilute, mild silver products marketed today are similar to pre-1938 colloidal silver solutions and do not cause argyria, the comment concluded.

One respondent presented results of several rat studies involving acute or chronic administration of various amounts of colloidal silver by intravenous injection and drinking water.

The I.V. studies included an initial acute dose finding study, followed by a chronic study. No abnormal clinical or behavioral signs were observed after 12 days of treatment.

Another followup chronic I.V. administration study found no differences in body weight and no clinical signs or gross pathologic changes between rats that received colloidal silver injections three times a week for four weeks and a control group.

A drinking water study found no clinical signs of gross pathological changes at the end of a 40-day treatment period. The study investigator said the data do not provide information about silver's metabolic fate but do support safety if extrapolated to humans based upon the dosage required to equal the rats' highest dose.

"The agency does not consider this information adequate to establish general recognition of the safety of silver salts or colloidal silver ingredients for OTC drug use," FDA says. "The comments themselves indicate that ionic silver salts and highly concentrated mild silver protein clearly are not safe for OTC use."

"The animal data indicate that mild silver protein in colloidal suspension at low concentrations may be safe in rats when administered in specific concentrations for up to 40 days," the rule states. "The agency concludes that a full pharmacologic profile that is relevant to human use is needed."

Comments purporting to show efficacy included human studies and case reports that were inadequate, methodologically flawed and insufficient to establish general recognition of effectiveness for any specific OTC condition, the agency adds.

Colloidal Silver Ingredients Not Safe, Effective In OTCs - FDA Final Rule

More from Archive

More from Pink Sheet