Dosis sola facit venenum or “The dose makes the poison.” Everything is toxic: toxicity depends on the dose. We all know that… don’t we? And yet, we all feel a deep sense of frustration, when legislators refuse to speak clearly about the safety and the efficacy of ingredients! Even more so when working with cosmetic ingredients. 

On the topic of safety, the first rule for the legislator to follow, when promulgating some sort of guidelines, is to avoid absolute, unnuanced, definitive statements. Should the legislator state that product X is safe without further explanation, it would trigger a gigantic number of lawsuits by lawyers claiming that their clients experienced undesirable effects when using product X, perhaps even at ridiculous concentrations or in nonsensical ways. To steer clear of this, and to avoid spending millions of dollars to compensate consumers who used product X “at their disadvantage,” the legislator created the concept of “generally recognized as safe…when administered within the normally used amounts and concentrations, for the intended use.”

What Is GRAS?

In the June 15, 2015 newsletter published by Crisis Control, it is stated verbatim that “GRAS” is an acronym for the phrase “Generally Recognized As Safe.” Under sections 201(s) and 409 of the Federal Food, Drug, and Cosmetic Act (the Act), any substance that is intentionally added to food is a food additive, that is subject to premarket review and approval by FDA, unless the substance is generally recognized, among qualified experts, as having been adequately shown to be safe under the conditions of its intended use, or unless the use of the substance is otherwise excluded from the definition of a food additive. 

There are several categories regarding GRAS substances, each serves a specific purpose: food additives, pharmaceutical excipients and cosmetic ingredients. 

The certification that an ingredient is GRAS does not happen because of supernatural interventions! The person interested in certifying that ingredient Y is GRAS must undertake a complex process consisting of the following steps:

Analysis of the existing scientific literature relative to ingredient Y. 

Gathering of an Expert Panel formed by people with expertise in pertinent fields and willing to comment and conclude on the safety of the ingredient of interest. 

If the review of the literature and the opinion of the Expert Panel are favorable, a GRAS notification can be prepared and submitted to the regulatory authorities, such as the FDA in the US. 

The authorities will examine the GRAS notification and may require further documentations. If they conclude that the ingredient is safe for consumption, GRAS certification will be granted. One should keep in mind, though, that an ingredient may be considered GRAS for one use but may not necessarily be GRAS for all uses. 

What Is GRASE?

GRASE is a term used by the US Food and Drug Administration to mean “Generally Recognized As Safe and Effective.” The acronym GRASE is often employed when discussing well-known over-the-counter (OTC) drugs. In a sense, the GRASE label facilitates the process of putting OTC drugs on the American market. For instance, sunscreens produced abroad that meet certain requirements are considered GRASE and are no longer considered as new drugs. This means that certain drugs that have been in the market abroad for quite a while, can be sold in the United States without undergoing the lengthy and very expensive process to obtain the “new drug approval” by the FDA. 

NDAs and Sunscreens

This opens a new chapter in the never-ending discussion about sunscreens, the most striking aspects of which is that it never reached a conclusion, that the guidelines have been perpetually updated without ever be finalized, let alone enforced, and that the positive list of UV filters has been trimmed down to just two molecules, while granting a long time to be used and… to provide evidence of safety all the UV filters that were on the previous positive lists! 

Needless to say, if I am allowed a positive criticism, this is the oxymoron of the week! As a matter of fact, while one can provide evidence that something happens, let’s say, a toxic effect, one cannot provide evidence that a toxic effect does not occur, correct? How can one prove that some effect does not occur? The only reasonable thing to do, after years of utilization of a UV filter for which no toxic effects have been observed, is to tentatively formulate the hypothesis that the sunscreen is safe…until experimental evidence is provided, that it is indeed toxic. This is the approach of the regulatory authorities. The question remains, though, about how many years of utilization need to pass before such hypothesis be accepted by the regulatory authorities?

What are GRASE Ingredients?

Ingredients labelled as GRASE can be found in products regulated as OTC drugs such as sunscreens, pain relievers, anti-acne lotions, antiperspirants and more. These products may contain active ingredients like zinc oxide, titanium dioxide, calamine, salicylic acid, potassium alum KAl(SO­4)2, etc. The process for an ingredient or a product to be considered GRASE requires that the manufacturer provides scientific evidence and/or clinical data that the OTC drug or product of interest is safe and effective for its intended use. Over-the-counter drugs and therapeutic ingredients must fulfill the requirements of sets of directions called monographs that are established by the FDA. There are many monographs, giving guidelines for antiperspirants, sunscreens, dandruff products, cold remedies, acne, etc. 

For OTC active ingredients, the monographs will include information on dosages, labeling requirements, and other standards for a particular category. If an ingredient meets and complies with the protocols and standards outlined in the monograph, it’s considered GRASE. 

Paolo Giacomoni, PhD

Insight Analysis Consulting

paologiac@gmail.com
516-769-6904

Paolo Giacomoni acts as an independent consultant to the skin care industry. He served as Executive Director of Research at Estée Lauder and was Head of the Department of Biology with L’Oréal. He has built a record of achievements through research on DNA damage and metabolic impairment induced by UV radiation as well as on the positive effects of vitamins and antioxidants. He has authored more than 100 peer-reviewed publications and has more than 20 patents. He is presently Head of R&D with L.RAPHAEL—The science of beauty—Geneva, Switzerland.