Fact-checked by Grok 2 weeks ago

Food additive

A food additive is any substance intentionally incorporated into during processing to achieve a technical effect, such as preserving freshness, enhancing , improving , or maintaining , and is defined under the U.S. Federal Food, Drug, and Cosmetic Act as a material whose use may reasonably be expected to become a component of . These additives encompass both naturally derived compounds, like from soybeans, and synthetic ones, such as certain preservatives, and are rigorously evaluated for prior to approval by bodies like the FDA and WHO's Joint FAO/WHO Expert Committee on Food Additives (JECFA). Their primary functions include preventing spoilage through action, stabilizing emulsions, or adjusting acidity to extend in processed products. Food additives have been employed since —evidenced by ancient practices like salting meats for preservation—but modern usage surged with industrialization in the 19th and 20th centuries, prompting regulatory frameworks to address adulteration and toxicity risks. The 1958 Food Additives Amendment to the FD&C Act established pre-market safety testing requirements, mandating proof of harmlessness under intended conditions of use, while international standards from JECFA set acceptable daily intakes based on toxicological data. Categories include colors to enhance visual appeal, sweeteners to reduce sugar content, and emulsifiers to improve consistency, with over 3,000 substances approved in the U.S. alone, though (GRAS) ingredients bypass full review if deemed historically safe. Despite stringent evaluations, controversies persist over long-term health impacts, particularly from synthetic additives like certain artificial colors or preservatives, with peer-reviewed studies highlighting potential links to hyperactivity in children or gut disruptions, though regulatory thresholds aim to mitigate risks based on exposure assessments. Critics note gaps in post-market surveillance and the GRAS allowing , potentially underestimating cumulative effects from multiple additives in ultra-processed foods. Empirical data from controlled trials underpin approvals, emphasizing dose-dependent causality over anecdotal concerns, yet ongoing underscores the need for updated toxicological models to address modern dietary patterns.

Definition and Functions

Definition

A food additive is any substance intentionally incorporated into food during manufacturing, processing, preparation, treatment, packaging, transport, or storage to fulfill a specific technological purpose, such as preservation, enhancement, coloration, stabilization, or nutritional , where the substance is not typically consumed as food on its own or used as a primary . This intentional addition distinguishes additives from incidental contaminants or naturally occurring components, with the substance or its by-products expected to become a direct or indirect component of the final product or otherwise alter its characteristics. Additives encompass both naturally derived materials, like from soybeans, and synthetic compounds, but their classification hinges on functional intent rather than origin. Regulatory definitions emphasize safety evaluation prior to approval, requiring demonstration that the additive performs its function without adulterating the or posing health risks under intended conditions of use. , the , , and Cosmetic specifies that a food additive includes all substances—except those exempted like prior-sanctioned ingredients or GRAS () determinations—whose use may reasonably affect food composition or properties. The , administered by the (FAO) and (WHO), aligns closely, defining additives as non-nutritive or nutritive substances added for technological effects in production, excluding those used for nutritional supplementation alone. , Regulation (EC) No 1333/2008 mirrors this by limiting additives to substances not normally consumed as or characteristic ingredients, authorized only if they serve a technological function and undergo risk assessment by the . These definitions exclude substances like spices, , or when used as characteristic ingredients, as well as colorings or flavorings classified separately under certain jurisdictions, though overlaps exist in practice. Globally, over 3,000 additives are approved across major frameworks, with harmonization efforts via aiming to facilitate while prioritizing empirical safety data from toxicological studies.

Primary Functions and Benefits

Preservatives constitute one of the core functions of food additives, inhibiting microbial growth from , , , and other spoilage organisms to extend and prevent decomposition. This reduces food waste and contamination risks during production, transport, and storage, thereby lowering incidences of foodborne illnesses that can be life-threatening. For example, antioxidants prevent oxidation and rancidity in fats and oils, maintaining product integrity over time. Nutritional fortification represents another primary benefit, where additives introduce or restore essential vitamins, minerals, and other nutrients to foods that may be deficient due to or dietary patterns. Such enhancements address population-level deficiencies, as seen in the addition of iodine to to prevent goiter or to products to support health, enabling broader access to balanced without relying solely on whole s. Sensory and functional improvements, including emulsifiers, stabilizers, and colorants, enhance , , and flavor consistency, facilitating uniform and consumer appeal in mass-produced goods. These attributes indirectly promote by standardizing products less prone to defects that could harbor pathogens, while also enabling innovations like low-fat formulations that retain desirable through thickeners. Overall, these functions support efficient global food supply chains, reducing economic losses from spoilage estimated in billions annually through empirical reductions in discard rates.

Classification

Major Categories

Food additives are classified primarily according to their technological , a system adopted by regulatory bodies such as the U.S. (FDA), the (EFSA), and the Joint FAO/WHO Expert Committee on Food Additives (JECFA). This functional classification groups additives based on their intended purpose in , preservation, or enhancement, rather than or origin. Common major categories encompass preservatives, antioxidants, colorants, flavorings, sweeteners, emulsifiers and stabilizers, thickeners, acidity regulators, and nutritional fortificants, among others. Preservatives inhibit microbial growth, prevent spoilage from , molds, fungi, or , and extend ; examples include and , which are effective against specific pathogens at concentrations typically below 0.1% by weight. Antioxidants retard oxidation and rancidity in fats and oils, maintaining product quality; substances like (BHA) and ascorbic acid () function by scavenging free radicals, with usage levels regulated to as low as 0.02% in certain fats. Colorants restore or enhance visual appeal lost during processing or impart desired hues; synthetic dyes such as (FD&C Yellow No. 5) and natural ones like beta-carotene are used, with the FDA approving only those proven safe through toxicity testing, though some like certain azo dyes require warning labels in the for potential hyperactivity links in children. Flavorings and enhancers improve taste or aroma, often masking off-flavors from processing; (MSG) boosts via glutamate receptor activation, added at 0.1-1% levels in savory products, while natural flavorings derive from extracts like from beans. Sweeteners provide sweetness without calories or with reduced caloric impact; high-intensity options like (180-200 times sweeter than ) and are approved for use in beverages and baked goods up to specified maximums, such as 50 mg/kg body weight daily for per JECFA evaluations. Emulsifiers, stabilizers, and thickeners maintain homogeneity in mixtures, prevent separation, or provide texture; emulsifies fats in , while like xanthan stabilize emulsions at 0.1-0.5% concentrations, ensuring consistent in dressings and ice creams. Acidity regulators control to influence taste, stability, or microbial control; adjusts acidity in soft drinks to levels around pH 3-4, preventing while enhancing tartness. Nutritional additives fortify foods with essential micronutrients; vitamins like (B1) or minerals such as iron are added to cereals or , with FDA-mandated levels based on Recommended Dietary Allowances to address deficiencies, as in iodized containing 45-76 since 1924. Additional categories include anti-caking agents like , which absorb moisture to prevent clumping in powdered mixes at under 2% usage, and humectants such as , which retain moisture in confections. Regulatory lists, such as the FDA's Substances Added to Food inventory updated February 13, 2025, encompass over 4,000 entries across these functions, with safety affirmed through animal toxicology studies and (ADI) thresholds set by JECFA.

Natural versus Synthetic Additives

Natural food additives are substances derived from , , or sources through physical processes such as , , or , with minimal chemical alteration; examples include from insects for red coloring and extracted from fruits as an acidulant. Synthetic additives, by contrast, are produced via in laboratories, often replicating or mimicking naturally occurring compounds to achieve greater purity, stability, or cost-efficiency; instances comprise ascorbic acid () synthesized identically to its natural counterpart and artificial dyes like (FD&C Red No. 40). The distinction hinges not on —many synthetics are molecularly identical to naturals—but on method, leading to synthetics offering consistent potency without batch variability inherent in natural extracts, which can fluctuate due to environmental factors affecting source materials. Safety evaluations by regulatory bodies such as the U.S. (FDA) and the World Health Organization's Joint Expert Committee on Food Additives (JECFA) apply uniform standards to both categories, requiring demonstration of a "reasonable certainty of no harm" through toxicological studies, including acute and chronic exposure tests, regardless of origin. Empirical data reveal no systematic safety superiority for natural additives; for instance, naturally occurring compounds like in apple-derived products or mycotoxins in plant extracts pose risks absent in purified synthetics, while synthetic preservatives such as (BHA) have been deemed safe at approved levels (up to 0.02% in fats) based on rodent carcinogenicity studies showing thresholds far exceeding human dietary intake. Conversely, some natural additives, like for coloring, have triggered reactions in 0.1-2% of users, comparable to synthetic tartrazine's allergy rates, underscoring that toxicity depends on dose, exposure, and individual factors rather than source. Multi-source reviews, including those from the (EFSA), affirm that rigorous pre-market testing mitigates risks equally, with over 300 additives (natural and synthetic) approved globally after evaluating , reproductive effects, and acceptable daily intakes (ADIs). In terms of efficacy, synthetic additives often excel in functionality due to engineered stability under heat, light, or extremes; for example, synthetic provides consistent flavoring at lower concentrations than natural , which degrades in processed foods. Natural alternatives, while aligning with consumer preferences for "clean labels," may necessitate higher dosages or combinations to match performance, potentially introducing off-flavors or reduced —as seen in extracts versus synthetic antioxidants like tert-butylhydroquinone (TBHQ), where the latter extends product viability by inhibiting oxidation more reliably in oils. Regulatory frameworks, such as the FDA's GRAS () designation, extend to both without preferential treatment, though post-2020 trends show increased approvals for natural colors (e.g., beet-derived reds in May 2025) driven by market demand rather than superior profiles. Consumer biases favoring naturals, amplified by despite of equivalent when tested, overlook that natural sourcing can entail allergens (e.g., soy lecithin) or contaminants like from soil, absent in controlled synthesis. Overall, selection prioritizes empirical functionality and verified data over origin, as causal mechanisms of harm—such as or metabolic interference—operate identically across categories.

History

Ancient and Traditional Uses

Humans employed salt as a primary food additive for preservation since , with evidence of salt processing dating to approximately 6000 BC in regions like present-day , where spring water was boiled to extract salt crystals. In ancient Egypt, around 2500–2000 BC, salt was systematically used to desiccate meats and fish by drawing out moisture essential for bacterial growth, enabling long-term storage in arid climates. Mesopotamian civilizations similarly relied on salt to cure fish, integrating it into staple diets as documented in early records, which highlight its role in reducing beyond seasonal availability. Spices and herbs served as antimicrobial additives in ancient culinary practices, with , , and seeds applied to meats to inhibit oxidation and microbial proliferation, as evidenced by residues in archaeological sites from the dating to 2000 BC. In ancient and , mixtures of spices with preserved fruits like , packed into jars after partial drying, a technique refined by Romans through cooking to enhance up to several months. , noted in Babylonian texts from circa 5000 BC, functioned as an acidic for and meats, leveraging its low to suppress pathogens. The earliest documented intentional addition of substances to alter properties appears in papyri around 1500 BC, describing emulsions and colorants derived from natural sources to improve texture and appearance in and production. Traditional uses extended to nitrites from saltpeter contaminants in curing salts, employed in for preservation by forming compounds, though often as unintentional additives in impure salts. These methods prioritized empirical of spoilage reduction, forming the basis for later systematic applications without reliance on modern chemical analysis.

Industrial and Regulatory Milestones

The industrialization of food production during the introduced widespread use of chemical additives to preserve and enhance mass-manufactured goods, including preservatives like and , and synthetic colors derived from , which proliferated in the 1890s and early 1900s despite emerging evidence of toxicity such as contamination in candies. techniques, advanced in the early 1800s by and , enabled long-distance shipping of preserved foods but often relied on untested additives to prevent spoilage, contributing to incidents of . Regulatory frameworks emerged in response to these practices, beginning in the United States with the of June 30, 1906, which banned interstate commerce of adulterated or misbranded foods, driven by chemist Harvey Washington Wiley's investigations into poisonous preservatives. The Federal Food, Drug, and Cosmetic Act of 1938 strengthened requirements by mandating safety data for ingredients and authorizing factory inspections, addressing gaps exposed by cases like the 1937 disaster. Post-World War II expansion of synthetic additives, including emulsifiers and antioxidants for ultra-processed foods, led to the Food Additives Amendment of , 1958, which required pre-market FDA approval for new additives, introduced the Delaney Clause prohibiting carcinogens, and created the (GRAS) category for substances with historical safe use or expert consensus. The Color Additive Amendment of 1960 further mandated safety proofs for dyes used in food. Internationally, the Joint FAO/WHO Expert Committee on Food Additives (JECFA) was formed in 1956 to evaluate safety data, influencing the Commission's standards established in 1963. In Europe, the (EFSA), created in 2002, initiated re-evaluations of pre-2009 permitted additives for updated risk assessments.

Safety Evaluation

Testing and Assessment Methods

Safety assessments for food additives primarily follow a risk assessment framework established by regulatory bodies such as the U.S. (FDA), the (EFSA), and the Joint FAO/WHO Expert Committee on Food Additives (JECFA), involving hazard identification, hazard characterization, , and risk characterization. Hazard identification screens for potential toxicity through literature reviews, assays, and initial studies, while characterization quantifies dose-response relationships using no-observed-adverse-effect levels (NOAELs) derived from animal data. estimates human intake via food consumption surveys and additive usage levels, often employing models like maximum estimated daily intake (EDI) or refined probabilistic distributions. Risk characterization compares exposure to thresholds like the (ADI), set by dividing NOAELs by uncertainty factors (typically 100, incorporating interspecies and intraspecies variability). Toxicological testing begins with acute oral toxicity studies in rodents to determine median lethal doses (LD50) and identify immediate adverse effects, as outlined in FDA's Redbook guidelines, though LD50 values are increasingly supplemented by qualitative observations due to ethical refinements. Subchronic studies, lasting 90 days in two rodent species, evaluate target organs, metabolism, and dose-response for non-acute effects, followed by chronic studies (up to 2 years in rats and mice) to detect long-term toxicity, including carcinogenicity via histopathological exams and tumor incidence analysis. Reproductive and developmental toxicity tests assess fertility, embryotoxicity, and teratogenicity in multi-generation rodent models, while genotoxicity batteries include in vitro assays (e.g., Ames bacterial reverse mutation test) and in vivo micronucleus tests to detect DNA damage or mutagenicity. Absorption, distribution, , and excretion (ADME) studies, often using radiolabeled compounds in animals and humans, inform and , with human data prioritized where ethically feasible to bridge species differences. JECFA and EFSA emphasize data to confirm if metabolites pose greater risks than the parent compound, integrating pharmacokinetic modeling for . For novel additives, immunotoxicity and endpoints may be added if mechanistic evidence suggests relevance, though standard batteries focus on empirical endpoints over predictive modeling due to validation gaps in . Post-market surveillance complements pre-market testing through adverse event reporting (e.g., FDA's CAERS system) and , but primary reliance remains on controlled studies, as epidemiological data often lack due to in observational designs. ADIs are periodically re-evaluated with new data; for instance, JECFA's 2023 assessments incorporated refined exposure models reducing conservatism for low-risk additives. Despite rigorous protocols, inter-laboratory variability and species extrapolation uncertainties necessitate conservative safety margins, with no additive approved absent demonstrated safety under intended use.

Empirical Evidence of Safety

Regulatory agencies such as the FDA and EFSA require food additives to undergo tiered toxicological evaluations, including long-term studies spanning two years to assess carcinogenicity, , and reproductive effects, typically revealing no-observed-adverse-effect levels (NOAELs) at exposures far exceeding human dietary intakes. These studies incorporate safety factors of at least 100-fold to account for interspecies and intraspecies variability, establishing acceptable daily intakes (ADIs) that ensure a wide margin below thresholds for harm. Human empirical data derive from short-term clinical trials and metabolic studies conducted during approval, demonstrating rapid and of most additives without accumulation or at proposed use levels. For instance, extensive testing on common preservatives like shows no genotoxic or mutagenic effects in validated assays, with human volunteer studies confirming tolerance up to ADI equivalents. Post-approval, large-scale exposure assessments, such as those from the NutriNet-Santé cohort involving over 100,000 participants, indicate that typical dietary mixtures of approved additives do not correlate with elevated chronic disease risk beyond background rates, suggesting minimal systemic impact. Post-market surveillance systems, including the FDA's CAERS database, monitor voluntary reports, revealing incidence rates of idiosyncratic reactions (e.g., allergies to specific colors) below 1 per million servings for most additives, far lower than for components like . Decades of global consumption—such as billions of doses of since 1981—have not produced detectable population-level signals of harm in vital statistics or cancer registries, aligning with predictions from animal NOAELs. While these data affirm safety within regulatory limits, empirical gaps persist: few randomized long-term trials exist due to ethical constraints, and observational associations with ultra-processed foods complicate attribution to isolated additives, though causal remain unproven absent controlled exposures exceeding ADIs. Overall, the cumulative and evidence substantiates the low-risk profile of approved food additives when used as intended.

Health Effects and Controversies

Claims of links between food additives and hyperactivity or behavioral issues in children originated in the with pediatrician Benjamin Feingold's that synthetic colors, flavors, and salicylates could exacerbate hyperkinetic behaviors, proposing an elimination that reportedly improved symptoms in 30-50% of cases based on observational data. Controlled trials, however, have shown limited efficacy, with reviews of double-blind studies indicating no significant benefit for most children beyond effects or improvements in a small minority potentially sensitive to additives. The most influential evidence came from the 2007 Southampton study, a randomized, double-blind, -controlled crossover involving 297 children aged 3-9 years, which tested mixtures of artificial colors (e.g., , sunset yellow, carmoisine, , Allura Red) combined with against drinks.61306-3/fulltext) Results demonstrated a small but statistically significant increase in hyperactivity scores, measured via parent and teacher ratings on scale, in both the general population and children with existing behavioral issues, prompting the to recommend warning labels on products containing those six colors in the by 2010. Subsequent analyses, including animal studies, have supported potential neurobehavioral impacts from synthetic dyes, such as altered signaling or , though human effects remain modest and variable. Meta-analyses of challenge studies reinforce a modest between artificial food colors and ADHD-like symptoms, with a 2012 review of 24 trials finding a small (0.18) on global hyperactivity, not limited to diagnosed ADHD children and potentially amplified by favoring positive results. A 2022 systematic review of clinical trials similarly concluded that synthetic dyes correlate with adverse behavioral outcomes in children, though causation is not definitively established and effects may interact with individual factors like or . Evidence for preservatives like alone is weaker, primarily emerging in combination with colors, while broader restriction diets show benefits in subsets of children, possibly due to reduced overall additive exposure rather than specific agents. Regulatory bodies diverge in interpretation: the U.S. FDA's 2011 expert panel found no consistent causal link warranting bans, citing study limitations like small effect sizes and inability to isolate individual additives, though acknowledging possible sensitivity in some children. In contrast, precautionary measures persist in regions like the , where voluntary phase-outs of certain dyes have occurred, and recent assessments (2021) highlight risks of attentional deficits from cumulative exposure. Overall, while empirical data indicate synthetic colors may subtly worsen behaviors in susceptible youth, they do not appear to cause hyperactivity , and rigorous trials emphasize multifactorial over additive-driven causality.

Aspartame and Other Specific Additives

is a synthetic non-nutritive composed of two , L- and L- (as its methyl ), that provides approximately 200 times the sweetness of with negligible calories. Upon ingestion, it is rapidly hydrolyzed in the into , , and , components also produced from natural dietary sources such as fruits and proteins. The U.S. (FDA) first approved for use in dry foods on July 18, 1981, following reviews of over 100 studies, and expanded approval to carbonated beverages in 1983; it has since been reaffirmed safe in multiple evaluations, including a 2021 review, for the general population except those with (PKU), who must avoid it due to elevated levels. The (ADI) is set at 50 mg/kg body weight by the FDA and 40 mg/kg by the Joint FAO/WHO Expert Committee on Food Additives (JECFA). Concerns about aspartame's safety, particularly regarding carcinogenicity, stem from and epidemiological , but regulatory consensus holds that does not support a causal link in s at typical exposure levels. The International Agency for Research on Cancer (IARC) classified as "possibly carcinogenic to humans" (Group 2B) in July 2023, citing limited of hepatocellular carcinoma in humans from three observational studies and limited animal , though mechanistic was inadequate. In contrast, JECFA's concurrent review found no convincing of harm and reaffirmed the ADI, emphasizing that human exposure rarely exceeds safe limits even for heavy consumers of beverages. The FDA disagreed with IARC's classification, stating that reviewed studies do not support it, as larger prospective cohorts show no consistent associations with cancer. Critics of IARC's assessment note its reliance on observational prone to confounding factors like reverse causation (e.g., cancer patients switching to drinks), while controlled trials and pharmacokinetic indicate products occur at levels far below thresholds from natural sources. Other specific additives with notable controversies include (MSG), a flavor enhancer derived from , and (BHA), a synthetic . MSG, deemed (GRAS) by the FDA since the 1950s, has faced claims of causing "Chinese restaurant syndrome" symptoms like headaches, but double-blind studies attribute reported effects to responses rather than toxicity, with no alterations in function or levels observed at dietary doses. BHA, approved by the FDA for use in fats and oils, was classified as possibly carcinogenic (Group 2B) by IARC based on forestomach tumors in , an organ absent in s; subsequent reviews find no relevant human risk, as metabolic differences preclude extrapolation, though some animal data prompted calls for further scrutiny. Regulatory bodies prioritize empirical over precautionary interpretations, noting that additive-specific risks remain unsubstantiated in human compared to broader dietary patterns.

Broader Risks in Ultra-Processed Foods

Ultra-processed foods, as classified by the system, are industrial formulations typically containing five or more ingredients, including substances not commonly used in home cooking such as emulsifiers, artificial flavors, colors, and stabilizers—many of which are food additives. These additives enable the creation of shelf-stable, hyper-palatable products that dominate modern diets, often comprising over 50% of caloric intake in high-income countries. While additives themselves undergo safety testing for isolated use, their cumulative presence in ultra-processed foods raises concerns about synergistic effects on , independent of macronutrient content. Observational studies and meta-analyses consistently link higher ultra-processed food consumption to elevated risks of adverse outcomes. A 2024 umbrella review of 45 meta-analyses found greater exposure associated with 32 health harms, including a 50% higher risk of , 48% for , and 12% for all-cause mortality per 10% increase in dietary share. These associations hold after adjusting for socioeconomic factors and total , though residual confounding from variables persists in non-randomized designs. A 2025 demonstrated that ad libitum consumption of ultra-processed versus minimally processed diets led to 500 kcal/day higher and 0.9 kg greater over two weeks, suggesting formulation—potentially driven by additives enhancing —promotes via disrupted regulation. Food additives in these foods may contribute mechanistically beyond caloric density. Emulsifiers like carboxymethylcellulose and polysorbate-80, common in ultra-processed items, have been shown in animal models to alter gut microbiota, induce low-grade inflammation, and impair mucosal barriers, potentially fostering metabolic and inflammatory diseases. Human evidence implicates additives in gut dysbiosis and systemic effects, with epidemiological data linking ultra-processed food intake to higher inflammatory markers and cardiometabolic risks, though direct causation remains understudied due to ethical challenges in long-term additive-specific trials. Critics note that many additives are deemed safe by regulatory bodies like the FDA based on animal toxicology data, with no conclusive human evidence of harm at typical exposures, attributing risks more to overall dietary patterns than additives alone. Emerging research highlights broader implications, including and cancer. Meta-analyses report 22-53% increased odds of common mental disorders and depressive symptoms with high intake, possibly via inflammatory pathways or nutrient displacement. For cancer, a 2024 review tied ultra-processed foods to colorectal and overall risks, with additives like nitrates in processed meats implicated, though by red meat content complicates attribution. A 2025 analysis estimated ultra-processed foods attributable to 4-10% of premature deaths in the , underscoring burdens, yet emphasizes the need for intervention trials to disentangle additive effects from processing-induced nutrient degradation. Regulatory scrutiny of additive synergies in ultra-processed contexts is limited, with most safety assessments predating widespread consumption patterns.

Regulation

United States Framework

In the , food additives are primarily regulated by the (FDA) under the Federal Food, Drug, and Cosmetic Act (FD&C Act), as amended by the Food Additives Amendment of 1958. The FD&C Act defines a food additive as any substance whose intended use results or may reasonably be expected to result—directly or indirectly—in it becoming a component or otherwise affecting the characteristics of food. This includes preservatives, flavor enhancers, colorants, and stabilizers, but excludes substances like pesticides or animal drugs regulated separately. To market a new food additive, manufacturers must file a food additive petition with the FDA, providing comprehensive on identity, manufacturing processes, intended use, and safety under projected consumption levels. The FDA evaluates safety based on toxicological studies, including for acute, subchronic, and chronic effects, , and carcinogenicity, ensuring a reasonable certainty of no harm from lifetime exposure. If approved, the FDA issues a listing the additive and its conditions of use, typically under 21 CFR Part 170 et seq. The agency may set levels or specify maximum usage, drawing from expert panels and international bodies like the Joint FAO/WHO Expert Committee on Food Additives (JECFA) for harmonization where data align. A key exemption applies to substances classified as (GRAS), established in the 1958 amendment, which allows ingredients deemed safe by qualified experts based on scientific data or prior safe use in food before 1958 to bypass pre-market FDA approval. GRAS determinations can be self-affirmed by companies or notified to the FDA via the voluntary GRAS Notification Program, implemented in 1997, where the agency reviews but does not pre-approve; objections can lead to challenges. Over 10,000 substances have been self-determined as GRAS since 1997, raising concerns from critics about reduced oversight, though the FDA asserts the safety standard mirrors that for approved additives. In March 2025, the Department of Health and Human Services directed the FDA to explore rulemaking to strengthen GRAS oversight, aiming to mandate notifications and enhance transparency. The Delaney Clause, part of the 1958 amendment, imposes a zero-tolerance standard: no additive may be deemed safe if tests show it induces cancer in humans or animals, regardless of dose or risk level. This has led to de-listings, such as FD&C Red No. 3 in January 2025, after studies linked it to tumors, invoking the clause despite low human exposure risks. Critics, including some toxicologists, argue the clause is outdated, ignoring thresholds and modern , as it treats all carcinogens equivalently without distinguishing genotoxic from non-genotoxic mechanisms. Color additives face stricter scrutiny under FD&C Act Section 706, requiring separate petitions, batch certification for synthetic colors, and provisional listings only if safety data are pending. Prior-sanctioned substances, approved before 1958 by USDA or FDA for specific uses, remain lawful without re-petitioning. Post-market, the FDA monitors adverse events via systems like CAERS and can revoke approvals if new evidence emerges, as in its May 2025 initiative for systematic review of existing chemicals. States may impose additional restrictions, but federal preemption generally applies to approved additives under the FD&C Act.

European Union Approach

The regulates food additives through a harmonized framework emphasizing pre-market authorization and safety assessments conducted by the (EFSA). Regulation (EC) No 1333/2008, adopted on 16 December 2008, establishes definitions for food additives as substances not normally consumed as food but added intentionally for technological purposes, such as preservation or enhancement of properties. This regulation mandates a positive list approach, where only authorized additives, specified in Annexes II and III with precise conditions of use, maximum levels, and functional classes (e.g., colors, preservatives, sweeteners), may be employed in foodstuffs. Additives must demonstrate a technological need that cannot be achieved by other means, while ensuring consumer safety under intended conditions of use. EFSA conducts independent scientific evaluations, requiring applicants to submit comprehensive toxicological data, including , carcinogenicity, and exposure assessments, before the proposes authorization via comitology procedures involving member states. Unlike reactive systems, the EU framework applies a , prohibiting additives where uncertainties persist regarding long-term effects, even absent conclusive evidence of harm at typical exposures. For instance, (E171) was banned as a food additive in 2022 following EFSA's determination of concerns, despite prior approvals, reflecting re-assessments that prioritize potential risks over historical use data. Similarly, and remain prohibited due to evidence of carcinogenicity in , contrasting with tolerances in other jurisdictions pending definitive human risk data. A systematic re-evaluation program, initiated under Regulation (EU) No 257/2010, mandates EFSA to review all pre-2009 authorized additives for updated safety profiles, incorporating new exposure modeling and epidemiological data. As of August 2025, approximately 72 additives await completion, with follow-ups potentially leading to revised authorizations, reduced levels, or withdrawals if data gaps or risks emerge. Recent amendments include Regulation (EU) 2023/1428 updating specifications for mono- and diglycerides of fatty acids (E471) based on re-evaluation findings, and 2025 updates via Regulations (EU) 2025/2060 and 2025/2058 refining use conditions for select additives to align with refined exposure estimates. Labelling requires E-numbers or names for additives, promoting transparency, while enforcement relies on national authorities monitoring compliance with EU-wide maximum residue limits. This approach, while stringent, has drawn critique for potentially over-restricting innovations absent causal evidence of harm, as EFSA opinions occasionally hinge on theoretical modeling rather than empirical human outcomes.

International Harmonization

The Commission, established in 1963 by the (FAO) and (WHO), leads international efforts to harmonize food additive standards through voluntary guidelines that serve as a global reference for safe use and trade. The Commission's General Standard for Food Additives (GSFA), first adopted in 1995 and revised periodically, lists over 300 additives with specified conditions of use, maximum levels, and food categories to ensure consistency across borders while prioritizing safety based on scientific evaluations. Safety assessments underpinning these standards are conducted by the Joint FAO/WHO Expert Committee on Food Additives (JECFA), which has evaluated additives since using toxicological data, exposure estimates, and risk characterization to derive acceptable daily intakes (ADIs) for substances like preservatives, colors, and sweeteners. JECFA's monographs, updated through regular meetings, inform Codex decisions via the Codex Committee on Food Additives (CCFA), which prioritizes additives for review and endorses purity criteria to minimize impurities and contaminants. The World Trade Organization's Agreement on the Application of Sanitary and Phytosanitary Measures (), in force since 1995, reinforces harmonization by requiring WTO members—over 160 countries—to base measures, including additive approvals, on international standards like where appropriate, provided they adequately protect human health, thereby reducing non-tariff trade barriers. Article 3 of the SPS Agreement explicitly encourages alignment with for food additives, allowing deviations only if supported by scientific justification and risk assessments, though implementation varies, with many nations adopting provisions directly or as benchmarks. Recent advancements include the 47th Commission session in November 2024, which adopted updates to the GSFA incorporating new additives such as β-carotene-rich extracts and refined technological functions, reflecting ongoing refinements based on JECFA data and stakeholder input to address emerging needs like clean-label demands without compromising safety. Despite progress, challenges persist due to regional differences; for example, while promotes equivalence, some jurisdictions impose additive bans or lower limits exceeding international benchmarks, justified under risk-based provisions, leading to partial rather than uniform global alignment.

Public Perception and Debates

Science versus Precautionary Fears

Regulatory bodies such as the (WHO) and the U.S. (FDA) evaluate food additives through extensive toxicological testing, including animal studies to determine no-observed-adverse-effect levels (NOAEL) and acceptable daily intakes (ADI), ensuring safety margins of at least 100-fold before approval. These assessments, often conducted by joint expert committees like JECFA, conclude that approved additives pose no significant risk to human health when used within specified limits, countering claims of inherent with empirical dose-response data. Persistent public apprehensions about additives like (MSG) and stem largely from anecdotal reports and early, flawed studies rather than reproducible evidence; for instance, the "Chinese Restaurant Syndrome" linked to MSG originated from a single 1968 letter without controls, subsequently debunked by double-blind trials showing no consistent symptoms in sensitive individuals. Similarly, has undergone over 200 studies affirming its safety, with regulatory reviews dismissing links to cancer or neurological issues as artifacts of high-dose models irrelevant to human exposure. The FDA classifies both as (GRAS), highlighting how fears amplify rare idiosyncratic reactions over population-level data. The , predominant in the , mandates restricting additives upon any scientific uncertainty, even absent causal evidence of harm, contrasting the U.S. evidence-based requirement for demonstrated risk before action. This approach has led to bans on substances like certain azo dyes and , despite and FDA approvals based on negative carcinogenicity findings in long-term studies. While intended to err on caution, it risks forgoing additives' benefits—such as antioxidants preventing oxidative spoilage or preservatives reducing bacterial contamination, which epidemiological data link to fewer foodborne illnesses globally. Media amplification and advocacy often prioritize sensationalized risks over meta-analyses; for example, claims of hyperactivity from artificial colors rely on underpowered, non-replicated trials, while large studies find no causal ties after controlling for confounders like . Empirical favors additive use where net benefits in stability and affordability outweigh negligible risks, as unrestricted natural toxins in unprocessed foods (e.g., in potatoes) exceed additive exposures without similar scrutiny. This disparity underscores how precautionary fears, untethered from probabilistic harm assessments, can impede evidence-driven progress in .

Economic and Innovation Impacts

The food additives market reached USD 120.5 billion in 2024, driven by demand for processed and foods, with projections estimating growth to USD 169.22 billion by 2030 at a of 5.9%. This sector underpins the efficiency of the broader food by enabling cost-effective preservation, enhancement, and stabilization, which reduce manufacturing expenses and minimize post-production waste through extended . For instance, preservatives like sorbates and benzoates allow for larger-scale distribution without refrigeration dependency, lowering logistics costs and supporting affordability in markets where food volatility affects billions. Economically, food additives contribute to value addition in ultra-processed foods, which comprise over 50% of caloric intake in many developed economies, facilitating export competitiveness for industries in regions like , where market growth exceeds 6% annually due to . However, public debates and precautionary regulations, such as EU restrictions on certain synthetic colors, have imposed compliance costs on manufacturers, potentially slowing market expansion in stringent jurisdictions while redirecting investments toward compliant alternatives. Innovation in food additives has accelerated through trends like clean-label formulations and natural substitutes, with research focusing on plant-derived emulsifiers and inhibitors to replace synthetic options amid preferences for . These developments enable novel product categories, such as low-sugar beverages using stevia-based sweeteners and fortified snacks with bioavailable carriers, spurring R&D investments estimated at billions annually across multinational firms. Technological breakthroughs, including for targeted release preservatives, further enhance functionality while addressing efficacy challenges, though adoption lags due to regulatory hurdles prioritizing demonstrated safety over unproven risks.

Recent Developments

Technological Advances

Precision fermentation represents a significant biotechnological advancement in food additive production, employing genetically engineered microorganisms—such as or fungi—to biosynthesize targeted compounds like enzymes, flavor enhancers, and emulsifiers with high specificity and yield. This technique, scaled commercially since the early 2020s, circumvents traditional sourcing from or animal byproducts, enabling sustainable, low-waste manufacturing; for example, precision-fermented has been used in cheese production for decades, while recent applications include animal-free proteins and cocoa butter equivalents approved by regulatory bodies in and the by 2024. The process achieves yields up to 10 grams per liter in optimized bioreactors, reducing environmental footprints by 90% compared to conventional extraction methods in some cases. Nanotechnology has facilitated innovations in additive delivery and functionality, particularly through nano-encapsulation techniques that protect sensitive compounds like antioxidants, vitamins, and flavors from degradation during processing and storage. Nano-emulsions and liposomes, with particle sizes below 100 nanometers, enable controlled release and improved bioavailability; studies demonstrate that nano-encapsulated curcumin, a natural colorant and preservative, retains 80% activity after heat processing, versus 20% for free forms. Antimicrobial nanoparticles, such as silver or titanium dioxide variants, have been integrated into additives for pathogen inhibition, extending shelf life in dairy products by inhibiting Listeria growth by 99% in lab trials conducted through 2023. However, regulatory scrutiny persists due to potential migration risks, with the European Food Safety Authority evaluating nano-additives case-by-case since 2011. Biotechnological microbial engineering has yielded clean-label preservatives as alternatives to synthetic ones, including —peptide antimicrobials produced by —that target Gram-positive spoilers without broad-spectrum disruption to . Recent formulations combining bacteriocins with organic acids have shown comparable to chemical preservatives, inhibiting in meat products at concentrations below 100 ppm, per 2024 peer-reviewed trials. Machine learning algorithms are increasingly applied to predict additive interactions and optimize formulations, with food industry surveys indicating 22% adoption for tech investments in 2025 to enhance and reduce overuse. These advances prioritize empirical over precautionary restrictions, though long-term data from controlled human studies remain limited for novel nano- and bio-engineered variants.

Regulatory Updates to 2025

In the United States, the (FDA) continued refining its oversight of food additives through the (GRAS) program in 2025, issuing "no questions" letters for 34 substances in the first half of the year after reviewing 59 notifications, while 15 remained pending and 10 were withdrawn. On September 3, 2025, the FDA amended regulations to permit as a secondary direct food additive under specific conditions for . The agency updated its list of select food chemicals under review on August 19, 2025, prioritizing substances like certain color additives and plasticizers amid ongoing safety assessments. Additionally, the FDA affirmed the removal of 25 plasticizers from authorized food additive lists in late 2024, with compliance extending into 2025, reflecting migration concerns from packaging materials. State-level actions in the U.S. advanced precautionary restrictions on synthetic additives, with and other states enforcing phased bans on colors like Red Dye No. 3 starting in 2027, though federal consideration of a nationwide Red No. 3 gained traction in 2025 following animal carcinogenicity data. Legislative efforts included the reintroduction of the Food Chemical Reassessment Act in July 2025, mandating triennial FDA reviews of high-priority additives, though it faced industry opposition over potential innovation stifling without new causal evidence of harm. In the , the issued Regulations (EU) 2025/2060 and 2025/2058 on October 15, 2025, amending Annexes II and III of Regulation (EC) No 1333/2008 to adjust authorized uses and specifications for select food additives, including refinements to antioxidants and emulsifiers based on EFSA re-evaluations. The (EFSA) planned updates to its food additives guidance document by mid-2025, emphasizing stricter purity criteria and exposure assessments for substances under re-evaluation. These changes built on prior bans, such as (E171), prohibited since 2022 due to genotoxicity concerns, while maintaining approvals for additives with affirmed safety margins exceeding typical dietary intakes. Internationally, modified its Lists of Permitted Food Additives on September 15, 2025, to eliminate duplications and harmonize nomenclature for consistency with standards, facilitating trade without altering safety determinations. Efforts toward global harmonization remained incremental, with Codex Committee discussions in 2025 focusing on priority additives like and modified starches, though divergences persisted between precautionary approaches and evidence-based U.S. GRAS affirmations.

References

  1. [1]
    Food Ingredient & Packaging Terms - FDA
    Jan 4, 2018 · A food additive is defined in Section 201(s) of the FD&C Act as any substance the intended use of which results or may reasonably be expected to result, ...
  2. [2]
    Understanding How the FDA Regulates Food Additives and GRAS ...
    Jun 6, 2024 · Some ingredients are food additives. A food additive is defined in the Federal Food, Drug, and Cosmetic Act as any substance the intended use ...
  3. [3]
    Food additives - World Health Organization (WHO)
    Nov 16, 2023 · Additives are added to ensure processed food remains safe and in good condition throughout its journey from factories or industrial kitchens, to ...
  4. [4]
    Food: A chemical history | Science Museum
    Nov 27, 2019 · The first deliberate use of a food additive was likely salt to preserve foods such as fish and meat, which works by dehydrating the food to ...Chemicals in our food · Quality testing food · Artificial foods
  5. [5]
    Legal Aspects of the Food Additive Approval Process - NCBI
    This paper focuses primarily on a description of the FDA's regulation of substances intentionally added to food as it has evolved over the last several decades.
  6. [6]
    Global Regulation of Food Additives | ACS Symposium Series
    Jul 22, 2014 · This chapter compares and contrasts the common elements of the major national and international processes for the safety assessment and regulation of food ...
  7. [7]
    We are what we eat: Regulatory gaps in the United States that put ...
    Dec 20, 2017 · The FDA's inability to effectively manage the safety of hundreds of chemicals is putting our children's health at risk.
  8. [8]
    [PDF] Fixing the Oversight of Chemicals Added to Our Food
    Pew determined that FDA has not reviewed the safety of about 3,000 of the 10,000 additives allowed in food.45. An estimated 1,000 of these 3,000 are self ...
  9. [9]
    Food Additives - Zang - Major Reference Works - Wiley Online Library
    Sep 22, 2023 · This chapter provides an overview of both direct and indirect food additives in terms of their definitions, intended uses, regulatory background ...
  10. [10]
    [PDF] General Standard for Food Additives Codex Stan 192-1995
    The evaluation of actual food consumption data is also encouraged. 2. DEFINITIONS a) Food additive means any substance not normally consumed as a food by itself ...
  11. [11]
    21 CFR Part 170 -- Food Additives - eCFR
    Food additives includes all substances not exempted by section 201(s) of the act, the intended use of which results or may reasonably be expected to result, ...
  12. [12]
    EU Rules - food additives - European Commission's Food Safety
    Regulation EC 1333/2008 sets the rules on food additives: definitions, conditions of use, labelling and procedures.Introduction · Rules for use of additives in...
  13. [13]
    Food Additives and GRAS Ingredients - Information for Consumers
    May 24, 2024 · Some additives help control the acidity and alkalinity of foods, while other ingredients help maintain the taste and appeal of foods with ...
  14. [14]
    Additives - European Commission's Food Safety
    Preservatives – these are added to prolong the shelf-life of foods by protecting them against micro-organisms. Antioxidants – substances which prolong the shelf ...
  15. [15]
    Food additives - EFSA - European Union
    Food additives are substances added to food and drinks for various reasons, such as to maintain or improve their safety, freshness, taste, texture or ...EFSA's role · New food additives or new uses · Re-evaluation of authorised...Missing: primary | Show results with:primary
  16. [16]
    Shelf Stability: More Important Now Than Ever - Food Ingredient Facts
    Feb 12, 2021 · Many food additives help boost the stability and quality of food products, allowing us to store them in our homes and pantries for longer periods of time.<|control11|><|separator|>
  17. [17]
    Types of Food Ingredients | FDA
    Jul 6, 2023 · Types of Food Ingredients ; Preservatives, Prevent food spoilage from bacteria, molds, fungi, or yeast (antimicrobials); slow or prevent changes ...
  18. [18]
    Substances Added to Food (formerly EAFUS) - FDA
    Feb 13, 2025 · The Substances Added to Food inventory replaces what was previously known as Everything Added to Foods in the United States (EAFUS).<|separator|>
  19. [19]
    What's the Difference Between Natural and Artificial Food Additives?
    Learn the key differences between natural and artificial food additives, including sources, benefits, and how each impacts food quality, safety, ...Missing: efficacy | Show results with:efficacy
  20. [20]
    Natural Vs. Synthetic Food: Which Is Better? - ResearchGate
    Nov 12, 2019 · Background Various natural color additives are preferred by many consumers over synthetic color additives because they are perceived to be ...
  21. [21]
    Natural Food Colorants and Preservatives: A Review, a Demand ...
    These additives can come from natural sources and confer numerous benefits for health, beyond serving the purpose of coloring or preserving, among others. As ...
  22. [22]
    Natural vs. Synthetic Food Additives Implications for Health and Safety
    While natural additives are often perceived as safer due to their origins, they can still pose health risks when consumed in excess.
  23. [23]
    Health effects of synthetic additives and the substitution potential of ...
    This report examines the current status of safety assessment and toxicity studies of common synthetic additives.
  24. [24]
    Health impacts of exposure to synthetic chemicals in food - PMC - NIH
    May 16, 2025 · In the USA, synthetic food additives may also be legally used as GRAS (generally recognized as safe), but this can imply that their safety has ...
  25. [25]
    Natural Food Colorants and Preservatives: A Review, a Demand ...
    Feb 24, 2022 · These additives can come from natural sources and confer numerous benefits for health, beyond serving the purpose of coloring or preserving, among others.Introduction · Food Colorants · Food Preservatives · Molecular Dynamics...
  26. [26]
    Color Additives in Foods - FDA
    Jul 6, 2023 · FDA regulations require evidence that a color additive is safe at its intended level of use before it may be added to foods.
  27. [27]
    FDA approves 3 natural dyes for use in food and beverages | CNN
    May 9, 2025 · “The FDA determines whether an additive is safe to use by considering the projected human dietary exposure to the color additive, the additive' ...
  28. [28]
    EWG's Food Scores | Natural vs. Artificial Flavors
    The bottom line: natural and artificial flavors really aren't that different. And those “natural flavors” can actually contain synthetic chemicals!
  29. [29]
    Evaluation of some artificial food preservatives and natural plant ...
    Sep 6, 2024 · Data reveals that synthetic chemicals in food additives can promote obesity, cancer, asthma, and heart problems. Natural plant extracts have ...
  30. [30]
    Salt - Wikipedia
    Some of the earliest evidence of salt processing dates to around 6000 BC, when people living in the area of present-day Romania boiled spring water to extract ...History · Salt (chemistry) · Salt (disambiguation) · Salt in the Bible
  31. [31]
    Off the Spice Rack: The Story of Salt - History.com
    Jan 10, 2013 · The ancient Egyptians were the first to realize the preservation possibilities of salt. Sodium draws the bacteria-causing moisture out of foods ...
  32. [32]
    history notes--Mesopotamia through Shakespeare - The Food Timeline
    "Salt has been used to preserve fish since ancient times, possibly even before meat was cured. The early Mesopotamian civilizations relied on a staple diet of ...Ancient Egypt · Bible food: New Testament · Viking fare · Anglo-Saxon/Norman food
  33. [33]
  34. [34]
    Historical Origins of Food Preservation
    Early cultures used salt to help desiccate foods. Salting was common and even culinary by choosing raw salts from different sources (rock salt, sea salt, spiced ...
  35. [35]
    Chemistry of Food Additives & Preservatives | The Science Blog
    Oct 5, 2022 · Ancient Babylonian scrolls even mentioned the use of vinegar as early as 7,000 years ago! Food additives were developed along with the invention ...<|separator|>
  36. [36]
    Historical Background of Food Additives, Their Advantages, and ...
    Mar 19, 2020 · The earliest record in the history of adding additives to food dates back to Ancient Egyptian papyri circa 1500 BC.
  37. [37]
    How did chemical food preservatives get invented? - Reddit
    May 12, 2023 · Nitrates and nitrites were used in antiquity, either as naturally-occurring contaminants in salt sources, as an additive ("saltpeter", which is ...Missing: evidence | Show results with:evidence
  38. [38]
    02. Concerning Chemical Synthesis and Food Additives
    How the development of coal tar dyes in the late 1800's sparked a proliferation of food additives in the 1890's and early 1900's. Monday, 30 March 2015.
  39. [39]
    A History of Food Additives - Fill Your Plate
    Jan 30, 2019 · Massachusetts became the first state to ban food adulteration, with many states following in the late 1700s.
  40. [40]
    Milestones in US Food and Drug Law - FDA
    Jan 30, 2023 · 1960-1969: FDA Milestones​​ Color Additive Amendment enacted, requiring manufacturers to establish the safety of color additives in foods, drugs ...
  41. [41]
    How A 19th Century Chemist Took On The Food Industry With ... - NPR
    Oct 8, 2018 · Deborah Blum's book, The Poison Squad, tells how Harvey Washington Wiley and his band of chemists crusaded to remove toxins, such as arsenic ...<|control11|><|separator|>
  42. [42]
    Chronology of Food Additive Regulations in the United States - EHSO
    This page provides the chronology and background information on food additives, discusses the current Congressional debate over food additive regulatory policy.<|separator|>
  43. [43]
    When did food additives regulations begin? - Ask USDA
    The 1958 Food Additives Amendment to the Federal Food, Drug, and Cosmetic Act provided for the first specific regulations of food additives.
  44. [44]
    A Historical Look at Food Safety - IFT.org
    Historical accounts of foodborne illness date back to antiquity. The first suggested documented case of a known foodborne illness dates back to 323 BC.
  45. [45]
    Re-evaluation - European Commission's Food Safety
    Food additives permitted before 20 January 2009 must go through a new risk assessment by the European Food Safety Authority (EFSA).Missing: United | Show results with:United
  46. [46]
    Principles and methods for the risk assessment of chemicals in food
    Dec 31, 2008 · Principles and methods for the risk assessment of chemicals in food. Environmental health criteria 240. 31 December 2008. | Manual.
  47. [47]
    [PDF] Toxicological Principles for the Safety Assessment of Food Ingredients
    Jul 5, 2007 · Acute Oral Toxicity Tests (available in 1993 Draft "Redbook II" 16). 3. Short Term Toxicity Studies a. Short-Term Toxicity Studies with ...
  48. [48]
    Guidance for submission for food additive evaluations - EFSA
    Jul 18, 2012 · This guidance document refers to the applications for authorisation of a new food additive or to a modification of an already authorised food additive.Meta data · Abstract
  49. [49]
    Joint FAO/WHO Expert Committee on Food Additives (JECFA)
    Guidelines for the safety assessment of chemicals in foods consistent with current thinking on risk assessment in toxicology and other relevant sciences. JECFA ...Jecfa-additives · JECFA Databases & Tools · Jecfa-flav<|separator|>
  50. [50]
    Guidance on Food Additive or Color Additive Petition Process - FDA
    Sep 20, 2018 · What are the basic elements of a safety assessment for an additive? The basic elements are: Identity; Probable exposure; Evaluation of safety ...
  51. [51]
    Food Chemical Safety - FDA
    Sep 17, 2025 · The FDA protects consumers from harmful exposure to chemicals that are in foods through a comprehensive, science-driven, and modernized approach.Food Additives & Petitions · Office of Food Chemical · List of Select Chemicals in the
  52. [52]
    European Regulatory Framework and Safety Assessment of Food ...
    Feb 26, 2020 · Tier approach suggested by the European Food Safety Authority (EFSA) for the safety evaluation of food additives (EFSA, 2012). Tier 1, Tier 2 ...
  53. [53]
    [PDF] Chapter VI Human Studies: - FDA
    Reports on relatively long-term clinical studies should emphasize specific organ or organ system responses to the food or food additive and nutrient imbalances ...
  54. [54]
    Exposure to food additive mixtures in 106000 French adults from the ...
    Oct 4, 2021 · Most additives probably have no detrimental impact on health (some may even have beneficial effects: e.g. anti-microbial, antioxidants, ...<|separator|>
  55. [55]
    FDA Begins Posting Adverse Event Report Data for Foods and ...
    Dec 6, 2016 · The CFSAN Adverse Event Reporting System (CAERS) is one of the post-market surveillance tools that the FDA uses to monitor the safety of foods ...Missing: additives | Show results with:additives
  56. [56]
    principles and overview of the EFSA safety assessment - PubMed
    May 3, 2024 · Up to December 2023, EFSA published 45 scientific opinions on the safety of novel foods, food enzymes, and food additives derived from by- ...Missing: empirical | Show results with:empirical
  57. [57]
    Food additive emulsifiers and risk of cardiovascular disease in the ...
    Sep 6, 2023 · This study found positive associations between risk of CVD and intake of five individual and two groups of food additive emulsifiers widely used in industrial ...
  58. [58]
    A study of the efficacy of the Feingold diet on hyperkinetic ... - PubMed
    Of 32 who were able to tolerate the Feingold salicylate-low and additive-free diet, 11 were markedly improved. A placebo effect could not definitely be ruled ...
  59. [59]
    The Feingold Diet - Jeffrey A. Mattes, 1983
    A review of all published, completed controlled studies, however, indicates that the Feingold diet is probably not effective, except perhaps in a very small ...Missing: efficacy | Show results with:efficacy
  60. [60]
    The Effect of Diets Rich in and Free from Additives on the Behavior ...
    The authors conclude that the Feingold Diet has no beneficial effect on most children with learning disorders, or on hyperkinetic children taking medication.<|separator|>
  61. [61]
    Food additives and hyperactive behaviour in 3-year-old and 8/9 ...
    Nov 3, 2007 · Artificial colours or a sodium benzoate preservative (or both) in the diet result in increased hyperactivity in 3-year-old and 8/9-year-old children in the ...
  62. [62]
    EFSA evaluates Southampton study on food additives and child ...
    Mar 14, 2008 · Assessment of the results of the study by McCann et al. (2007) on the effect of some colours and sodium benzoate on children's behaviour [1] ...
  63. [63]
    Potential impacts of synthetic food dyes on activity and attention in ...
    Apr 29, 2022 · The human clinical trials and animal toxicology literature support an association between synthetic food dyes and behavioral impacts in children.
  64. [64]
    Artificial Food Colors and Attention-Deficit/Hyperactivity Symptoms
    Recent data suggest a small but significant deleterious effect of AFCs on children's behavior that is not confined to those with diagnosable ADHD.
  65. [65]
    Meta-Analysis of Attention-Deficit/Hyperactivity Disorder or Attention ...
    A restriction diet benefits some children with ADHD. Effects of food colors were notable were but susceptible to publication bias.
  66. [66]
    Potential impacts of synthetic food dyes on activity and attention in ...
    Apr 29, 2022 · The human clinical trials and animal toxicology literature support an association between synthetic food dyes and behavioral impacts in children.Missing: 2015-2025
  67. [67]
    Meta-Analysis of Attention-Deficit/Hyperactivity Disorder or Attention ...
    A specific hypothesis that food additives, which include synthetic food colorings and flavors, influence ADHD (at that time, hyperkinetic reaction), via either ...
  68. [68]
    [PDF] Color Additives and Behavioral Effects in Children - FDA
    Oct 7, 2019 · The FAC concluded that a causal link between children's consumption of synthetic color additives and behavioral effects had not been ...
  69. [69]
    [PDF] Food Dyes Health Effects Assessment OEHHA
    Apr 16, 2021 · This assessment focuses on potential neurobehavioral effects of synthetic food dyes in children, particularly attentional problems, using ...
  70. [70]
    Food Additives and Child Health | American Academy of Pediatrics
    Aug 1, 2018 · Increasing scientific evidence suggests potential adverse effects on children's health from synthetic chemicals used as food additives.Bisphenols · Phthalates · Nitrates And Nitrites<|separator|>
  71. [71]
    Is There Any Relationship Between Artificial Food Colors and ADHD?
    Jun 22, 2021 · The findings suggest that eliminating artificial food dyes may meaningfully reduce ADHD symptoms in some children, though it should be noted ...<|control11|><|separator|>
  72. [72]
    Aspartame | C14H18N2O5 | CID 134601 - PubChem - NIH
    Aspartame is a dipeptide obtained by formal condensation of the alpha-carboxy group of L-aspartic acid with the amino group of methyl L-phenylalaninate.
  73. [73]
    [PDF] Scientific Opinion on Aspartame - EFSA
    Aspartame is made of the two naturally occurring amino acids, phenylalanine and aspartic acid, which are also components of proteins in our body and in food.
  74. [74]
    Aspartame: Uses, Interactions, Mechanism of Action - DrugBank
    Jun 13, 2005 · Upon digestion, aspartame breaks down into three components (aspartic acid, phenylalanine and methanol), which are then absorbed into the blood ...
  75. [75]
    Timeline FDA Activities and Significant Events Addressing Aspartame
    May 30, 2023 · The FDA declared aspartame safe as an inactive ingredient in drugs, provided the labeling meets certain specifications. The FDA approved the use ...
  76. [76]
    Is aspartame safe? - HHS.gov
    Sep 11, 2014 · After reviewing scientific studies, the HHS Food and Drug Administration (FDA) determined in 1981 that aspartame was safe for use in foods.
  77. [77]
    Aspartame hazard and risk assessment results released
    Jul 14, 2023 · IARC classified aspartame as possibly carcinogenic to humans (Group 2B) on the basis of limited evidence for cancer in humans (specifically, for ...
  78. [78]
    [PDF] Summary of findings of the evaluation of aspartame
    Jul 13, 2023 · IARC classified aspartame as possibly carcinogenic, while JECFA found no adverse effects and reaffirmed the acceptable daily intake of 0-40 mg/ ...
  79. [79]
    Perspectives on recent reviews of aspartame cancer epidemiology
    Aug 3, 2023 · JECFA found no consistent aspartame-cancer link, while IARC has limited evidence, but classified it as possible carcinogen (2B), which may ...
  80. [80]
    WHO says aspartame is a 'possible carcinogen.' The FDA disagrees
    Jul 13, 2023 · In its written response, the FDA said it disagrees with the conclusion that studies support classifying aspartame as a possible carcinogen to ...
  81. [81]
    Aspartame and Cancer Risk | American Cancer Society
    Jul 25, 2023 · The FDA has stated: “Scientific evidence has continued to support the FDA's conclusion that aspartame is safe for the general population when ...What is aspartame? · Does aspartame cause cancer? · Is aspartame regulated?
  82. [82]
    A review of the alleged health hazards of monosodium glutamate
    MSG is safe for all life-cycle stages. No alterations of nervous system function or of blood concentrations of pituitary hormones were found. The human body ...
  83. [83]
    Dietitians say there is no scientific evidence that MSG is bad for you
    Sep 13, 2021 · MSG is a common food additive that is generally considered safe by the FDA. · There is no strong evidence that links MSG to health risks, and ...
  84. [84]
    Five Controversial Ingredients: Should You Avoid Them?
    Mar 22, 2016 · At high doses, BHT has been shown to cause cancer in rats, mice and hamsters, but does this exclusively in the animals' forestomach − an organ ...
  85. [85]
    Ultra-processed foods: what they are and how to identify them - PMC
    Ultra-processed foods are defined within the NOVA classification system, which groups foods according to the extent and purpose of industrial processing.
  86. [86]
    [PDF] Ultra-processed foods A global threat to public health
    Nov 17, 2023 · A large and rapidly growing body of research has found significant associations between high UPF intake and a multitude of elevated health risks ...<|separator|>
  87. [87]
    Food Additives in Ultra-processed Packaged Foods: An Examination ...
    On balance, technological advances have resulted in the introduction of food additives with no known negative health consequences to the US food supply that has ...
  88. [88]
    Ultra-processed food exposure and adverse health outcomes
    Feb 28, 2024 · Greater exposure to ultra-processed food was associated with a higher risk of adverse health outcomes, especially cardiometabolic, common mental disorder, and ...Metrics · Peer review · Related content
  89. [89]
    Ultra-processed food exposure and adverse health outcomes
    Feb 28, 2024 · Greater exposure to ultra-processed food was associated with a higher risk of adverse health outcomes, especially cardiometabolic, common mental disorder, and ...Missing: 2023-2025 | Show results with:2023-2025
  90. [90]
    Ultraprocessed or minimally processed diets following ... - Nature
    Aug 4, 2025 · Ultraprocessed food (UPF) consumption is associated with noncommunicable disease risk, yet no trial has assessed its health impact within ...
  91. [91]
    Ultra-processed foods and food additives in gut health and disease
    Feb 22, 2024 · There is increasing evidence of an association between diets rich in UPFs and gut disease, including inflammatory bowel disease, colorectal cancer and ...
  92. [92]
    Ultraprocessed Foods and Their Association With Cardiometabolic ...
    Aug 8, 2025 · Emerging research demonstrates that the effects of UPFs extend beyond nutritional profile and include appetite and gut microbiota dysregulation.<|separator|>
  93. [93]
    Ultra-processed foods consumption and health-related outcomes
    Jun 25, 2024 · Association between ultra-processed food intake and risk of colorectal cancer: a systematic review and meta-analysis. Front Nutr. (2023) 10 ...
  94. [94]
    Premature Mortality Attributable to Ultraprocessed Food ...
    Apr 28, 2025 · The meta-analysis showed a linear dose–response association between the ultraprocessed food consumption and all-cause mortality (RR for each 10% ...
  95. [95]
    Food Additives and Health - The Nutrition Source
    Jul 25, 2025 · Food additives are used to enhance the texture, flavor, or color of products and prolong shelf life. But are they healthy?
  96. [96]
    21 U.S. Code § 348 - Food additives - Law.Cornell.Edu
    Mar 15, 1977 · 21 U.S. Code § 348 defines unsafe food additives, allows petitions for regulations, and allows the Secretary to establish regulations for safe ...
  97. [97]
    Generally Recognized as Safe (GRAS) - FDA
    Oct 17, 2023 · GRAS, or Generally Recognized As Safe, means a substance is considered safe by experts, either through scientific procedures or common use ...GRAS Substances (SCOGS... · GRAS Notification Program · GRAS Notice Inventory
  98. [98]
    HHS Secretary Kennedy Directs FDA to Explore Rulemaking to ...
    Mar 10, 2025 · HHS is taking steps to enhance the FDA's oversight of ingredients considered to be Generally Recognized as Safe (GRAS) so Americans know what is
  99. [99]
    THE DELANEY CLAUSE AND OTHER REGULATORY ACTIONS
    The amendment prohibits the FDA from approving the use of any food additive found to cause cancer in animals or humans.
  100. [100]
    FDA to Revoke Authorization for the Use of Red No. 3 in Food and ...
    Jan 15, 2025 · The FDA is revoking the authorization for the use of FD&C Red No. 3 as a matter of law, based on the Delaney Clause of the Federal Food, Drug, and Cosmetic Act ...
  101. [101]
    How the 62-year old Delaney Clause continues to thwart science
    The 1958 Delaney Clause bans all carcinogens from use as food additives. •. β-myrcene, a rodent carcinogen, is a naturally-occurring chemical found in our diet.
  102. [102]
    FDA Initiates New Post-Market Review Framework for Food Chemicals
    May 22, 2025 · The US Food and Drug Administration (FDA) has announced a new initiative to systematically review the safety of chemicals already in the nation's food supply.Missing: United | Show results with:United
  103. [103]
    The Evolving Landscape of Food Additives Regulation in the U.S. ...
    Apr 9, 2024 · This article discusses the recent wave of state bills on food additives, FDA's activities in an effort to get ahead of an inconsistent patchwork of legislation.
  104. [104]
    Regulation - 1333/2008 - EN - additives - EUR-Lex
    Regulation (EC) No 1333/2008 of the European Parliament and of the Council of 16 December 2008 on food additives (Text with EEA relevance).
  105. [105]
    Food additives | EFSA - European Union
    Apr 4, 2025 · In the European Union, these substances are strictly regulated, and all additives must pass rigorous safety evaluations before being approved ...
  106. [106]
    What are food additives and how are they regulated in the EU? - Eufic
    Dec 1, 2021 · A food additive is defined as any substance not normally consumed as a food in itself and not normally used as a characteristic ingredient of food.Introduction · What are food additives and... · What are the rules on labelling...
  107. [107]
    Why Some Food Additives Banned in Europe Are Still on U.S. Shelves
    Feb 3, 2025 · Key ingredients banned in Europe but allowed in the U.S.​​ In 2022, the European Food Safety Authority banned titanium dioxide, saying that after ...
  108. [108]
    Which Food Additives Banned in Europe Are Still Allowed in the U.S.?
    Many food additives banned in Europe, such as titanium dioxide and potassium bromate, are still allowed in the United States despite concerns over their ...
  109. [109]
  110. [110]
    The U.S. Allows Food Additives Banned In Europe - Forbes
    Apr 23, 2025 · Many common foods in the U.S. contain food additives banned in Europe due to health concerns. From candy to bread and processed snacks, ...
  111. [111]
    Home | CODEXALIMENTARIUS FAO-WHO
    What is the Codex Alimentarius? The Codex Alimentarius, or "Food Code" is a collection of standards, guidelines and codes of practice adopted by the Codex ...Standards · About Codex · Meetings · Food Additives DB (GSFA...
  112. [112]
    Codex General Standard for Food Additives (GSFA) Online Database
    This database provides, in a searchable format, all the provisions for food additives that have been adopted by the Codex Alimentarius Commission.
  113. [113]
    Joint FAO/WHO Expert Committee on Food Additives (JECFA)
    JECFA serves as an independent scientific expert committee which performs risk assessments and provides advice to FAO, WHO and the member countries.
  114. [114]
    Codex Committee on Food Additives (CCFA)
    Terms of Reference: (a) to establish or endorse permitted maximum levels for individual food additives; (b) to prepare priority lists of food additives for ...
  115. [115]
    Understanding the Sanitary and Phytosanitary Measures Agreement
    The Agreement on the Application of Sanitary and Phytosanitary Measures sets out the basic rules for food safety and animal and plant health standards.
  116. [116]
    Sanitary and Phytosanitary Measures - text of the agreement - WTO
    The establishment, recognition and application of common sanitary and phytosanitary measures by different Members. 3. International standards, ...
  117. [117]
    Forty-seventh session of the FAO/WHO Codex Alimentarius ...
    Nov 25, 2024 · The United Nations food standards body, the Codex Alimentarius Commission, is meeting on 25–30 November 2024 to adopt food safety and quality standards.
  118. [118]
    Codex Alimentarius Commission Updates the General Standard for ...
    Jul 1, 2024 · Three new varieties of food additives are included into General Standard for Food Additives, which are β-carotene-rich extract from Dunaliella ...
  119. [119]
    The Agreements on the Application of Sanitary and Phytosanitary ...
    In its pursuance of harmonization, the SPS Agreement has chosen the international standards, guidelines and recommendations of three organizations as the ...
  120. [120]
    Debunking the 'MSG is harmful' myth: How baseless stories spawn ...
    Aug 16, 2024 · Monosodium Glutamate (MSG) is the poster child for food additive fear, chemophobia, and the harms of using anecdotes as evidence.
  121. [121]
    The Rotten Science Behind the MSG Scare
    Mar 2, 2023 · The Rotten Science Behind the MSG Scare: How one doctor's letter and a string of dodgy studies spurred a public health panic.
  122. [122]
    Aspartame and Other Sweeteners in Food - FDA
    Feb 27, 2025 · Consumers can identify whether a product has aspartame by looking for it by name in the ingredient list on the product label, which must include ...
  123. [123]
    Chemistry debunks the biggest aspartame health myths | PBS News
    Jun 16, 2015 · Moreover, the video says recent studies debunk the idea that some people are hypersensitive to aspartame or that it causes cognitive impairments ...
  124. [124]
    Questions and Answers on Monosodium glutamate (MSG) - FDA
    Nov 19, 2012 · FDA considers the addition of MSG to foods to be “generally recognized as safe” (GRAS). Although many people identify themselves as sensitive to ...Missing: debunked aspartame
  125. [125]
    What's the Problem with Food Additives in the US? - Yuka
    Mar 1, 2025 · The European Union applies the precautionary principle, banning an additive as soon as scientific doubt exists about its safety. In contrast, ...
  126. [126]
  127. [127]
    Food additive safety: A review of toxicologic and regulatory issues
    The purpose of the present review is to give an overview of the approaches to, and procedures involved in ensuring the safety of the US food supply in the ...
  128. [128]
    Food Additives Market Size & Share | Industry Report, 2030
    The global food additives market size was estimated at USD 120.5 billion in 2024 and is projected to reach USD 169.22 billion by 2030, growing at a CAGR of 5.9% ...
  129. [129]
    Food Additives: Supporting Food Affordability - Food Ingredient Facts
    Feb 12, 2021 · On a national and global scale, additives make food more affordable to produce, and the production and distribution of food more efficient.
  130. [130]
    Adapting to Food Additive Challenges - IFT.org
    Jul 14, 2025 · Adapting to Food Additive Challenges · Panelists break down the key issues confronting the food industry in an environment of policy uncertainty.
  131. [131]
    10 Key Trends Shaping the Food Additives Market Today
    Nov 11, 2024 · Key trends include clean label, plant-based, functional, natural flavor, reduced sugar/salt, organic/non-GMO, antimicrobial, and eco-friendly ...
  132. [132]
    The Role of Food Additives in the Evolving Food Industry - foodHQ
    Food additives, which play a crucial role in preserving, enhancing, and improving the sensory appeal of food products, are at the center of this evolution.
  133. [133]
    Innovation in food ingredients: how additives improve product ...
    This technology applies a thin, protective layer to the surface of food products, creating a barrier against moisture, oxygen, and microbial contaminants.
  134. [134]
    Precision fermentation for producing food ingredients - ScienceDirect
    Precision fermentation is a process that uses metabolically engineered micro-organisms to produce value-added food ingredients in precisely controlled ...
  135. [135]
    Transforming Ingredients Through Precision Fermentation - IFT.org
    Mar 7, 2025 · By definition, precision fermentation is the process of using microorganisms like yeast, fungi, or bacteria to produce specific molecules ...
  136. [136]
    Ingredients for the future: Bringing the biotech revolution to food
    Mar 13, 2025 · Fermented ingredients could alter the food landscape faster than once thought. However, new business models are needed for the $100 billion ...Missing: additives | Show results with:additives
  137. [137]
    Full article: Innovation in precision fermentation for food ingredients
    Jan 14, 2023 · In precision fermentation, synthetic biology methods are used to program microbes which are used as cell factories to produce ingredients for ...
  138. [138]
    Nanotechnology in food science: Functionality, applicability, and ...
    Nanotechnology in food science is used for processing, packaging, enhancing food security, extending storage, improving flavor, and nutrient delivery.
  139. [139]
    Application of nanotechnology in food: processing, preservation ...
    Nanotechnology is used extensively in food preservation, food additives, and food packaging as an antimicrobial compound (particularly Cu/CuO, Ag, MgO, TiO2, ...
  140. [140]
    Application of Nanotechnology in Food Science - Frontiers
    Aug 6, 2017 · Nowadays nanocarriers are being utilized as delivery systems to carry food additives in food products without disturbing their basic morphology.Abstract · Introduction · Nanosensors for Pathogen... · Safety Issues
  141. [141]
    Improved food additive analysis by ever-increasing nanotechnology
    In this review, we summarize the recently adopted electrochemical and optical analysis of food additives based on nanomaterials.
  142. [142]
    Clean-label alternatives for food preservation: An emerging trend
    Aug 30, 2024 · A mixed formulation of organics can be a potent substitute for synthetic additives. Novel bacteriocins and glycocins are unexplored 'clean-label' preservatives.<|separator|>
  143. [143]
    Advancements in Microbial Applications for Sustainable Food ...
    These biotechnological approaches are increasingly replacing synthetic additives, contributing to enhanced food safety, nutritional functionality, and product ...
  144. [144]
    Outlook 2025: Technology Trends - IFT.org
    Nov 6, 2024 · Food, beverage, and ingredient companies also are expected to invest in mobile app technologies (23%), machine learning software (22%), tech- ...Missing: 2020-2025 | Show results with:2020-2025
  145. [145]
    Food Additives: Emerging Detrimental Roles on Gut Health - 2025
    Jul 7, 2025 · Both the FDA and EFSA have begun making strides toward improving food additive safety, which includes conducting re-evaluations of these ...
  146. [146]
    A Comprehensive Overview of FDA GRAS Updates in the First Half ...
    Jun 27, 2025 · In the first half of 2025, 59 substances were updated, with 34 passing, 15 pending, and 10 ceased. 34 substances were updated with "FDA has no ...<|separator|>
  147. [147]
    Secondary Direct Food Additives Permitted in Food for Human ...
    Sep 3, 2025 · Secondary Direct Food Additives Permitted in Food for Human Consumption; Hydrogen Peroxide ; 09/03/2025, Final amendment; order.
  148. [148]
    List of Select Chemicals in the Food Supply Under FDA Review
    This includes ingredients considered generally recognized as safe (GRAS), food additives, color additives, food contact substances, and contaminants.
  149. [149]
    FDA Affirms Its Decision to Remove 25 Plasticizers From the Food ...
    Nov 27, 2024 · FDA Affirms Its Decision to Remove 25 Plasticizers From the Food Additive Regulations ... 2024, the Food and Drug Administration (FDA) ...
  150. [150]
    Food Safety Compliance Updates for 2025: What You Need to Know
    May 12, 2025 · In 2025, the FDA may ban Red Dye No. 3, the USDA will crack down on Salmonella, and the new administration may have new priorities. Project  ...
  151. [151]
    2025 Regulatory News Affecting The North American Food and ...
    Jan 9, 2025 · Key 2025 regulations include FDA's revised "healthy" definition, BVO ban, proposed additive changes in Canada, and state additive bans in some ...
  152. [152]
    Democrats Reintroduce Bill to Increase Regulation of Food Additives
    Jul 14, 2025 · The Food Chemical Reassessment Act of 2025 would require the FDA to review, every three years, the safety of certain chemicals added to food.
  153. [153]
    Europe's Regulatory Landscape for Food-Grade Chemicals 2025
    May 12, 2025 · Only additives deemed safe by EFSA and approved by the European Commission are authorized for use. An integral part of the regulation is the ...
  154. [154]
    Modification to the Lists of Permitted Food Additives to remove ...
    Sep 15, 2025 · Notice of modification to the Lists of Permitted Food Additives to remove duplication and harmonize the names of certain food additives.
  155. [155]
    Global Food Regulation Highlights | September 2025 | ChemLinked
    Oct 5, 2025 · Top food regulatory updates in July 2025: ○ China Unveils 32 New GB Standards and 2 Amendment Sheets, Involving Food Contaminants, Additives ...