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Defining Safety: How Safe is Safe?

As a neuroscientist with a research focus in toxicology, I am often asked by friends and family about the safety of household items and beauty products. Safety as a scientific concept is widely misunderstood. In this post, we’ll explore the concept of safety, provide an overview of the categories FDA and EPA use to define safety and how those categories affect regulation.

What is safety?

Safety: the condition of being protected from or unlikely to cause danger, risk, or injury.

This seems like a straightforward concept when we use the word in everyday conversation. However, safety is quite complex because it is not an absolute. Note the word “unlikely” in the definitely above; this is a probability.

Safety is always relative (much like risk, discussed in depth in our Risk in Perspective series). There is nothing in the world that is 100% safe, 100% of the time. Even a kiss from our child isn’t 100% safe, because kids are little germ-mobiles. Here are a few important things to keep in mind when we talk about safety:

  • Safety is examined within a specific context. Scientists cannot examine the safety of a substance or action in every single condition, so they examine safety within the context of intended use. For example, Tide Pods are safe to have in the house when used as intended. Safety is contingent upon hazards staying in their zone.
  • Safety is relative. For example, from crash tests, we may be able to conclude that a car seat makes a car crash less dangerous. Using a car seat is safer than not using a car seat. Yet, even with the best, most highly rated car seat, driving is not and will never be 100% safe or without risk.
  • Absolute safety (or zero risk) is an impossible dream. Instead, regulatory agencies, public health agencies and scientists aim to minimize risk. The FDA and EPA have created categories of substances that they have deemed to have minimal risks. This helps to prioritize resources towards the regulation of materials that are more dangerous (or riskier).

Minimal Risk Categories

GRAS

GRAS stands for “generally recognized as safe.” This is a regulatory classification used by the FDA in the regulation of food and drugs. At the FDA, this term applies in the regulation of food additives.

Food additives were legally defined in 1958 in the Food Additives Amendment to the Food, Drug and Cosmetic Act as “any substance the intended use of which results or may reasonably be expected to result, directly or indirectly, in its becoming a component or otherwise affecting the component of food.” Translated from legalese, this means that a food additive is any substance that becomes part of our food. New food additives require premarket testing and FDA approval before they can be used. In contrast, substances that are categorized as GRAS are not subject to this premarket approval process. FDA must certify that the information submitted to classify a substance as GRAS is sufficient to earn that classification.

A food additive is categorized as GRAS only when it is generally recognized to be safe when used as intended. The “generally” here does not mean recognized by the general public; rather, it means it is recognized by the relevant experts with appropriate scientific training and experience.

GRAS-E

“Generally recognized as safe and effective” is a minimal risk regulatory category used by the FDA in the regulation of over the counter (OTC) drugs. The FDA is responsible for premarket approval of all drugs. In the US, premarket approval requires demonstration of both safety and efficacy of all drugs prior to approval for use. (Note: Under The Dietary and Supplemental Health and Education Act of 1994, dietary supplements are exempted from this premarket requirement to demonstrate safety and efficacy.)

Similar to the exemption of GRAS food additives from premarket approval processes, OTC drugs that are considered GRAS-E can also skip the approval process. The FDA has three criteria that it uses to specify drugs as GRASE, found at this link.

  1. There must be sufficient studies to establish that the drug is both safe and effective.
  2. Those studies must have been published in the scientific literature and be available to qualified experts.
  3. The relevant experts must generally agree, based on those published studies, that the product is safe and effective for its intended uses.

Importantly, a GRAS-E classification requires the same quality and quantity of data required for any new drug undergoing FDA approval. This is not a way to bypass testing. GRAS-E does not imply that drugs have not been tested.

Minimal Risk Pesticides

GRAS and GRAS-E are not used by the EPA, which is the US federal agency that regulates pesticides. Instead, EPA uses a regulatory category called “minimal risk pesticides.”

The concept behind this category is similar to the FDA’s GRAS and GRAS-E categories. Minimal risk pesticides are pesticides that the EPA has determined pose little to no risk to human health and the environment when used according to the label. (Note: “The label is the law” and it is a violation of Federal law to not follow the instructions a pesticide label.) Thus, pesticides in this category are exempted from the registration process required for all other pesticides by the Federal Insecticide, Fungicide and Rodenticide Act.

For a product to be classified as a minimal risk pesticide, all of the active and inactive ingredients must have a minimal risk classification. EPA maintains a list of both active and inert ingredients that are allowed to be used in minimum risk pesticides (See Table 1 and Table 2 in the link). This list (cinnamon, cloves, garlic, peppermint, rosemary, sesame, salt, spearmint, thyme, white pepper, and the oils derived from these and other plants) looks like my spice drawer (shown in the picture)!

Does GRAS or minimal risk mean that a substance is 100% safe in all conditions?

No. There is nothing in the world that is 100% safe, 100% of the time. This is an impossible standard to aim for. These minimal risk categories are designed to set a lower threshold for where we use our limited public resources to maintain and enforce regulations. It is impossible to regulate to a level of zero risk because zero risk is impossible.

Personally, I think the “minimal risk” name is more scientifically accurate than GRAS. To me, it more accurately represents what scientists and regulators are defining: that safety is always relative and substances in these categories pose risks below some threshold requiring regulation. But “generally recognized as minimally risky” (GRAMR) doesn’t have the same ring to it.

Resources

Risk In Perspective Series Introduction

Risk In Perspective: Zero Risk is an Impossible Dream

Are GMOs 100% safe?