Data gaps in toxicity testing of chemicals allowed in food in the United States

Reprod Toxicol. 2013 Dec;42:85-94. doi: 10.1016/j.reprotox.2013.07.023. Epub 2013 Aug 13.


In the United States, chemical additives cannot be used in food without an affirmative determination that their use is safe by FDA or additive manufacturer. Feeding toxicology studies designed to estimate the amount of a chemical additive that can be eaten safely provide the most relevant information. We analyze how many chemical additives allowed in human food have feeding toxicology studies in three toxicological information sources including the U.S. Food and Drug Administration's (FDA) database. Less than 38% of FDA-regulated additives have a published feeding study. For chemicals directly added to food, 21.6% have feeding studies necessary to estimate a safe level of exposure and 6.7% have reproductive or developmental toxicity data in FDA's database. A program is needed to fill these significant knowledge gaps by using in vitro and in silico methods complemented with targeted in vivo studies to ensure public health is protected.

Keywords: CASRN; Chemical Abstract Service Registry Number; EAFUS; EPA; Everything Added to Food in the United States; FCS; FDA; FEMA; Flavor and Extract Manufacturers Association; Food Contact Substances; Food chemicals, Food additives, FDA, GRAS, Safe, Toxicology, Food contact substances, Flavors; GRAS; Generally Recognized as Safe; PAFA; Priority-based Assessment of Food Additives.; TOR; Threshold of Regulation; U.S. Environmental Protection Agency; U.S. Food and Drug Administration.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Databases, Factual
  • Food Additives / toxicity*
  • Humans
  • Research Design
  • Toxicity Tests*
  • United States
  • United States Food and Drug Administration


  • Food Additives