Cinnamyl Anthranilate--prohibited

Cinnamyl anthranilate, identified by its CAS number 87-29-6, is a synthetic organic compound categorized as a flavoring agent. Chemically, it is an ester formed from cinnamyl alcohol and anthranilic acid. This structure gives it an aromatic profile, often described as having floral, fruity, grape-like, or sometimes slightly spicy nuances, which made it a candidate for use in various food and beverage formulations to impart or enhance specific flavors.

Like many synthetic flavorings, cinnamyl anthranilate was developed as an alternative or supplement to natural extracts, offering consistent flavor profiles and cost-effectiveness. Its potential function in food was as a FLAVORING AGENT OR ADJUVANT, meaning it would be added to food products in small quantities to provide a specific taste or to modify existing flavors. Despite its chemical composition suggesting potential as a flavoring, its journey toward food use was halted due to safety concerns.

Historically, cinnamyl anthranilate was considered for use as a flavoring agent in a variety of food products, including baked goods, candies, beverages, and desserts, where its unique aromatic notes could contribute to desired taste profiles. Flavoring agents play a crucial role in the food industry by making products more appealing and consistent in taste. However, it is critical to state that cinnamyl anthranilate is *not* currently used in food. Its intended application as a food additive was never fully realized due to regulatory actions based on safety assessments.

Prior to its prohibition, industry bodies like the Flavor and Extract Manufacturers Association (FEMA) had initially evaluated cinnamyl anthranilate. However, these initial evaluations were later superseded by governmental regulatory scrutiny. Therefore, while it was designed for food use, it does not have any established common uses in the food supply today, either in the United States or internationally, due to its prohibited status.

The safety assessment of cinnamyl anthranilate led to its prohibition for use in food. The primary concern arose from animal studies, specifically carcinogenicity studies conducted on rodents. These studies indicated that exposure to cinnamyl anthranilate resulted in an increased incidence of tumors in the tested animals, raising significant questions about its potential to cause cancer in humans. The findings from these animal tests were deemed sufficiently concerning by regulatory authorities to classify it as unsafe for human consumption.

The U.S. Food and Drug Administration (FDA) reviewed the toxicological data and, based on the evidence of carcinogenicity in animal models, concluded that cinnamyl anthranilate could not be considered safe for use in food. As a result, its use as a food additive has been explicitly prohibited. It is important to note that the FDA has recorded 0 adverse events and 0 recalls associated with cinnamyl anthranilate, which is expected given that the substance was prohibited before it could be widely used in food products, thus preventing any public exposure or subsequent adverse reports.

In the **United States**, cinnamyl anthranilate is prohibited for use as a food additive. The U.S. Food and Drug Administration (FDA) had initially allowed its use based on early GRAS (Generally Recognized As Safe) notifications from industry, but subsequent scientific studies, particularly those identifying carcinogenic potential, led to a reversal of this stance. In 1982, the FDA published a notice proposing to affirm cinnamyl anthranilate as a food additive for interim use, but then proposed to prohibit its use in food due to the new safety data. This prohibition was finalized, ensuring it is not permitted in the U.S. food supply. It is explicitly not on the FDA's GRAS list, nor is it an approved food additive.

In the **European Union**, cinnamyl anthranilate is also not approved for use in food. The European Food Safety Authority (EFSA) has evaluated numerous flavoring substances, but cinnamyl anthranilate is not listed among authorized flavorings for food use. While it has been considered in group evaluations of flavoring substances (e.g., Flavouring Group Evaluation 20), the absence of approval reflects a similar caution regarding its safety profile, aligning with the U.S. prohibition. Consequently, it has no regulatory approval for food use in major global markets.

The pivotal studies that led to the prohibition of cinnamyl anthranilate were long-term toxicology and carcinogenicity studies conducted in rodents. These studies, often performed by programs such as the National Toxicology Program (NTP), aimed to evaluate the potential health effects of prolonged exposure to the substance.

Specifically, studies in both rats and mice showed that cinnamyl anthranilate induced tumors at various sites, including the liver, lungs, and skin. For instance, increased incidences of hepatocellular neoplasms (liver tumors) were observed in mice, and skin tumors (squamous cell papillomas and carcinomas) were noted in rats. These findings of carcinogenicity across different animal species and at multiple organ sites were the basis for regulatory bodies, particularly the FDA, to conclude that cinnamyl anthranilate posed an unacceptable risk to human health if used in food. Given its prohibited status, there have been no subsequent human studies or further extensive research into its food safety, as regulatory focus shifted to preventing exposure rather than re-evaluating its safety for food use.