CYCLOHEPTADECA-9-EN-1-ONE

CAS: 542-46-1 FLAVORING AGENT OR ADJUVANT

CYCLOHEPTADECA-9-EN-1-ONE, also known as civetone and listed under CAS 542-46-1, is a macrocyclic ketone used as a flavoring agent or adjuvant with a distinctive musk-like aroma and regulatory evaluations by international bodies.

What It Is

CYCLOHEPTADECA-9-EN-1-ONE, commonly referred to as civetone (sometimes spelled civettone), is a large-ring macrocyclic ketone with the reference CAS number 542-46-1. As a chemical species, it belongs to the class of unsaturated cyclic ketones, characterized by a 17-membered carbon ring with a single double bond at the 9 position and a ketone functional group at the 1 position. This structural motif contributes to its potent musky odor, historically derived from natural sources such as the glandular secretions of civet animals, but now more commonly produced synthetically. Civetone has a long history in the flavor and fragrance industries due to its ability to impart warm, animalic, and musk-like notes, often at very low concentrations. Chemically, civetone is represented by the molecular formula C17H30O and exhibits high lipophilicity and limited water solubility. Its sensory properties make it useful in complex flavor formulations where a musk note is desired, or as an adjuvant to modify sensory perception. Despite its common association with perfumery, civetone is also utilized as a flavoring agent or adjuvant in specific food flavor applications under regulated conditions. Because of its strong odor and high potency, only trace amounts are used in formulations. Alternate names for CYCLOHEPTADECA-9-EN-1-ONE reflect its synonyms in chemical nomenclature, including 9-cycloheptadecen-1-one and various cis and (Z) isomer designations. The use of these alternate names underscores its identification across different regulatory, industrial, and scientific contexts, especially in databases tracking flavoring agents and fragrance chemicals like FEMA (Flavor and Extract Manufacturers Association) and scientific registries.

How It Is Made

The production of CYCLOHEPTADECA-9-EN-1-ONE has evolved from traditional extraction methods to modern synthetic strategies due to ethical, sustainability, and consistency concerns. Historically, civetone was isolated from the glandular secretions of civet cats and related species, but the extraction of animal-derived material raised welfare and supply variability issues. As a result, most commercial civetone used today is synthesized through organic chemical processes. In synthetic production, macrocyclic ketones like civetone are typically formed through ring-closing reactions that establish the 17-carbon macrocycle. One approach involves the Dieckmann condensation, a variant of intramolecular ester condensation, where appropriately functionalized linear precursors are cyclized under basic conditions to form the large ring. Starting materials such as dimethyl (Z)-9-octadecendioate or oleic acid derivatives may serve as building blocks for these macrocyclizations. Catalysts and controlled reaction conditions facilitate the formation of the macrocyclic ketone with the desired unsaturation and stereochemistry. Once the macrocyclic ketone is formed, purification steps such as distillation, crystallization, or chromatography are used to isolate the target compound to a high degree of purity. Quality specifications for synthetic civetone ensure that the final material has consistent sensory and physicochemical properties compatible with its intended use in flavor and fragrance formulations. The synthetic route allows for greater control over the isomeric form of the compound, often favoring the cis or (Z) configuration that aligns with sensory and regulatory requirements. Production methods emphasize solvent selection, reaction controls, and waste management practices to align with industrial safety and environmental standards. Overall, modern manufacturing of civetone relies on well-established organic synthesis techniques that deliver a stable and reproducible product suitable for regulated flavoring applications.

Why It Is Used In Food

CYCLOHEPTADECA-9-EN-1-ONE is used in food flavoring and adjuvant applications because of its unique sensory profile and ability to enhance or modify aromatic characteristics when incorporated at low concentrations. Flavoring agents and adjuvants are added to food and beverage formulations to help create complex sensory experiences that align with specific product goals, such as replicating natural flavors or achieving a desired aroma profile. Civetone’s warm, musky, animalic odor can contribute depth and nuance to certain flavor profiles where subtle musk-like notes are desired. In food science and flavor formulation, compounds like civetone serve both as direct contributors to aroma and as modifiers that interact synergistically with other flavor molecules. Their use often centers on enhancing overall complexity or introducing a signature component that elevates a formulation’s sensory appeal. Although civetone itself is potent and distinctive, its application in foods is typically in trace amounts, carefully balanced to avoid overpowering primary flavor components. Furthermore, the use of civetone as an adjuvant is linked to its functional role in blending and harmonizing disparate volatile components within a formulation. By interacting with other aromatic constituents, civetone can help round off sharp edges in a flavor profile or provide a bridge between disparate notes. This functional versatility makes it valuable in specialized flavor applications despite its limited direct taste contribution. Overall, the controlled use of civetone in food processing reflects a combination of sensory science principles and regulatory compliance, where formulation objectives must be balanced with safety evaluations and permissible use levels. The compound’s distinctive aroma and ability to augment flavor complexity support its continued use in niche applications where such characteristics are desired.

Adi Example Calculation

To illustrate how an acceptable daily intake (ADI) might be conceptually applied, consider a hypothetical adult with a body weight of 70 kg. If a flavoring agent had an established ADI of X mg/kg body weight, the total allowable daily intake would be calculated by multiplying the ADI by the person’s body weight. For example, an ADI of 1 mg/kg body weight would translate to a daily threshold of 70 mg for that individual. However, for CYCLOHEPTADECA-9-EN-1-ONE specifically, regulatory evaluations such as those by JECFA have concluded that there is no safety concern at current levels of intake when used as a flavoring agent without establishing a numeric ADI. In practice, this means that typical exposures from flavored foods and products are so low that they are not expected to approach any threshold associated with adverse effects observed in toxicology studies. If a numeric ADI were available, the illustrative calculation would follow the principle described above: multiply the numeric ADI by body weight to derive a daily exposure limit appropriate for that body weight category. This exercise demonstrates how safety margins and consumer exposure assessments are integrated into regulatory frameworks to ensure that use remains well below levels associated with any known risk.

Safety And Health Research

The safety profile of CYCLOHEPTADECA-9-EN-1-ONE has been examined through toxicological evaluations focusing on parameters relevant to flavor and fragrance ingredients. Evaluations by expert committees, such as JECFA, consider available toxicology data, exposure estimates, and potential health endpoints to determine whether use at levels typical in food and fragrance applications poses safety concerns. For civetone, JECFA’s assessment concluded that there is no safety concern at current levels of intake when used as a flavoring agent. Toxicology studies for civetone — often derived from compiled data in fragrance material reviews — include acute oral and dermal toxicity assessments, where high-dose exposures in animal models demonstrated relatively low systemic toxicity at doses orders of magnitude above estimated human exposures. These studies typically show minimal adverse effects at doses far exceeding those encountered through flavor use. Additionally, investigations into skin irritation and sensitization focus on dermal exposure relevant to cosmetic uses rather than ingestion. While such data contribute to a broader picture of safety, interpretations for food application require a holistic analysis of all available evidence. Regulatory and scientific evaluations carefully distinguish between hazard and risk. Hazard refers to the intrinsic potential of a substance to cause adverse effects, whereas risk accounts for both hazard and the likelihood of exposure at realistic use levels. For civetone, the low concentrations used in flavor formulations significantly reduce potential exposure, thereby mitigating risk. Furthermore, safety assessments include conservative assumptions to ensure that typical consumer exposure remains well within margins of safety. Ongoing research and data compilation efforts continue to inform safety assessments of flavoring agents. For civetone, authoritative evaluations reflect a consensus that current use levels do not present a safety concern, but continued vigilance and data updates remain part of regulatory science practice to protect public health.

Regulatory Status Worldwide

International regulatory bodies have evaluated CYCLOHEPTADECA-9-EN-1-ONE, often under the synonym civetone, primarily for safety in flavoring applications. The Joint FAO/WHO Expert Committee on Food Additives (JECFA) conducted evaluations and concluded there is no safety concern at current levels of intake when used as a flavoring agent, as reported in its technical reports and monographs. This evaluation supports its regulated use in food flavoring applications while emphasizing that exposure levels typical in foods are low and managed within safety assessments. The specific JECFA evaluation details are available in official committee reports that outline the basis for this conclusion without establishing a numeric acceptable daily intake. In the United States, substances added to food are cataloged in the FDA’s EAFUS (Everything Added to Food in the United States) database, where CYCLOHEPTADECA-9-EN-1-ONE appears as a listed flavoring substance. However, explicit references to specific regulatory sections in the Code of Federal Regulations for this compound’s use as an approved additive could not be confirmed, leading to uncertainty in directly citing a CFR provision. Consequently, statements about FDA approval must be interpreted with caution and contextualized with appropriate regulatory documentation. Within the European Union, food additives and flavoring agents are regulated through comprehensive frameworks that assess safety, permissible use levels, and labeling requirements. While many flavoring agents undergo evaluation by the European Food Safety Authority (EFSA), specific details on civetone’s status, such as an assigned E-number or explicit EFSA opinion documents with numeric values, were not identified in available authoritative sources at the time of writing. In such cases, national and regional regulatory agencies often rely on international evaluations and harmonized safety assessments to guide permissible use. Global regulation of flavoring agents reflects a balance between sensory utility and consumer safety, with ongoing monitoring and periodic reevaluation as new scientific data emerges. For civetone, its inclusion in authoritative evaluations by bodies like JECFA provides a basis for continued regulated use, while regional frameworks like those in the US and EU integrate these assessments within broader additive control systems.

Taste And Functional Properties

While CYCLOHEPTADECA-9-EN-1-ONE is classified primarily as a flavoring agent or adjuvant, its intrinsic taste and functional properties are closely linked to its strong odor and behavior within complex flavor matrices. Sensory scientists describe civetone as possessing a warm, rich, and animalic musky note that can be perceived at extremely low concentrations. The presence of such a potent aroma component means that its contribution to taste perception is often more about modifying and enhancing overall flavor impressions than imparting a distinct standalone taste. The musky, slightly sweet, and animalic character of civetone originates from its macrocyclic ketone structure, which interacts with olfactory receptors in ways that evoke musk-like sensory impressions. This makes it useful in applications where a depth of aroma or a unique sensory signature is needed, even though the compound itself lacks traditional sweet, bitter, or salty taste properties. In food formulation, these aroma characteristics contribute to perceived flavor complexity and can influence how other taste-active components are experienced. Functionally, civetone is highly lipophilic, meaning it preferentially dissolves in fats and oils rather than water. This property impacts how it is incorporated into food systems, often requiring appropriate carriers or solvents to ensure even distribution within a formulation. Its stability under typical food processing conditions can vary depending on temperature, pH, and interaction with other ingredients, but at the low concentrations used for flavoring, major stability concerns are generally mitigated. From a sensory perspective, civetone’s musk aroma can linger and provide a lasting impression when combined with other volatile compounds. In complex formulations, it may act synergistically with floral or fruity notes to create a balanced overall profile. Due to its potent nature, careful calibration by trained flavorists is essential to avoid overpowering the intended flavor characteristics of the final product.

Acceptable Daily Intake Explained

The concept of an acceptable daily intake (ADI) is central to understanding how regulatory bodies assess the safety of food additives like CYCLOHEPTADECA-9-EN-1-ONE. An ADI represents an estimate of the amount of a substance that can be ingested daily over a lifetime without appreciable health risk, typically expressed in milligrams per kilogram of body weight. ADIs are derived from toxicological data, often using the highest no-observed-adverse-effect level (NOAEL) from animal studies and applying conservative safety factors to account for uncertainties in extrapolating to human populations. For some flavoring agents, regulatory bodies such as JECFA or EFSA establish numeric ADI values when sufficient data exist to support specific thresholds. However, for CYCLOHEPTADECA-9-EN-1-ONE, JECFA’s evaluation concluded there is no safety concern at current levels of intake when used as a flavoring agent, without specifying a numerical ADI range. This type of conclusion indicates that, based on available data and anticipated exposure levels from typical use, the compound does not warrant a formal ADI because the risk at these levels is considered negligible. It is important to note that the absence of a formal numeric ADI does not imply that any amount is safe. Rather, it reflects a regulatory judgment that estimated exposures from authorized uses are far below levels associated with potential adverse effects. Regulatory scientists use conservative modeling to ensure that even high-end consumers remain within safe exposure boundaries. By maintaining use levels well below those that could pose risks in toxicological studies, regulatory agencies help protect public health while allowing industry to utilize flavoring agents effectively. For consumers and professionals alike, understanding the ADI concept clarifies why certain additives are permitted and how safety margins are built into regulatory decisions to minimize risk while supporting innovation in food flavoring.

Comparison With Similar Additives

CYCLOHEPTADECA-9-EN-1-ONE shares functional similarities with other macrocyclic ketones and musk-type compounds used in flavoring and fragrance applications. Examples include muscone and galaxolide, which also provide musky sensory notes and are used at low concentrations to achieve specific aromatic characteristics. While muscone is a natural or synthetic macrocyclic ketone with a distinct musk scent, galaxolide is a synthetic polycyclic musk with broader use in consumer products. Compared to civetone, which imparts a warm, animalic musk, muscone tends to offer a softer and slightly sweeter musk profile, making it suitable in different flavor contexts. Another related compound is ambrettolide, a macrocyclic lactone used primarily in perfumery for its musky and fruity attributes. Unlike civetone, ambrettolide’s chemical structure includes an oxygen-containing lactone ring, which alters its sensory and physicochemical properties. Ambrettolide may be chosen over civetone when a lighter or more floral musk note is desired in a formulation. Additionally, less intensely odorous linear ketones can be used in specific flavor blends where strong musky notes from civetone would be inappropriate or overpowering. In comparing these additives, formulation scientists consider both sensory characteristics and regulatory status. Compounds with well-established safety evaluations and documented exposure profiles may be preferred in applications where regulatory clarity is paramount. Civetone’s unique animalic musk signature distinguishes it functionally but also necessitates careful calibration to avoid overwhelming a product’s intended flavor identity. By contrasting civetone with similar additives, flavorists can tailor sensory outcomes to achieve precise aromatic endpoints while navigating regulatory frameworks that govern permissible use in food and flavor products.

Common Food Applications Narrative

CYCLOHEPTADECA-9-EN-1-ONE finds its place in select food applications where nuanced aroma profiles are a central part of the sensory experience. While not a ubiquitous additive across mainstream processed foods, this compound is used in specialized flavor blends developed for certain beverage categories, confectionery items, and savory applications where a subtle musk or complex aromatic character can contribute to a distinctive sensory identity. In beverage formulations, trace amounts of civetone can impart a background note that enhances overall bouquet and harmonizes with fruity or floral components. Similarly, in confectionery and dairy flavors, it may help round out sweet profiles or provide a signature layer of nuance in artisanal or high-end products. In the realm of savory applications, civetone’s role is typically supportive rather than dominant. It may be included in spice blends or seasoning systems to contribute depth without introducing overtly recognizable musk notes. Because civetone is highly potent, its incorporation is always at very low levels and typically engineered by professional flavorists who understand how it interacts with other compounds. These applications are often tailored to specific product lines where consumers expect a richer and more complex flavor experience. Manufacturers using flavor blends that include civetone must also navigate regulatory frameworks that ensure its use remains within safe and approved levels. In practice, the use of civetone is more common in products marketed with a focus on premium sensory attributes, such as craft beverages, gourmet confections, and bespoke culinary products. Across these categories, the narrative of complexity and sophistication in flavor supports the inclusion of unique aroma compounds like civetone as part of a broader flavor strategy.

Safety & Regulations

FDA

  • Notes: Specific CFR approval could not be confirmed from available authoritative sources.

EFSA

  • Notes: No specific EFSA numeric ADI or E-number was identified in available authoritative sources.

JECFA

  • Notes: JECFA concluded no safety concern at current intake levels without assigning a numeric ADI.

Sources

Comments

No comments yet. Be the first to share!