Ask a RIFM Scientist

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What is TTC, and how does it help avoid animal testing?

Kaushal Joshi, PhD

In 2013, with the development of the Safety Assessment Criteria Document, RIFM adopted the Threshold of Toxicological Concern (TTC) approach as part of its Safety Assessment program.

The United States Food and Drug Administration (FDA) first conceived of the TTC method in 1990 in a review of regulatory policy on food additives. (At that time, FDA referred to the TTC as the Threshold of Regulation, or ToR.)

TTC is used explicitly for substances that have limited or no toxicity study data available. Simply put, TTC is a level of exposure to a substance beneath which there are no concerns for adverse effects. As a result of its pioneering use of TTC, RIFM has saved hundreds of thousands of animals.

To define a fragrance ingredient’s TTC, we must first identify its potency based on chemical structure and reactivity: low, medium, or high. Then, we take the aggregate exposure—how much of the ingredient consumers come in contact with from all products used—and compare that exposure to what we know to be a safe-use level of similarly potent ingredients. If a consumer’s total aggregate exposure to an ingredient is below the TTC, we know there is no appreciable risk of toxic effects associated with the ingredient.

After decades of using the TTC method, scientists around the world are confident in its reliability. In 2012, the European Scientific Committees on Consumer Safety (SCCS), Health and Environmental Risks (SCHER), and Emerging and Newly Identified Health Risks (SCENIHR) published a joint opinion paper on TTC. In their report, the Committees verified the TTC approach as scientifically valid for human health risk assessment of systemic toxic effects caused by chemicals present at minimal levels.

Senior Scientist Kaushal Joshi, PhD, leads RIFM’s Repeated Dose and Reproductive Toxicology research and safety assessment programs.