Are food preservatives bad for you?

What are Food Preservatives

Foods deteriorate in quality due to a wide range of reactions including some that are physical, some that are chemical, some enzymic and some microbiological.  Preservation of foodstuffs has always been a necessity for a number of reasons: the durability of food is limited, numerous foodstuffs are only available during a short harvesting season, the transport routes of food or raw materials from the production site to the consumers are continuously increasing in length and the consumers in modern society characterized by division of labor and changed shopping habits increasingly insist on buying durable products.

Food preservatives main function is to prevent food spoilage from bacteria, molds, fungi, or yeast (antimicrobials); slow or prevent changes in color, flavor, or texture and delay rancidity (antioxidants); maintain freshness ⁵⁾.

Oxidation causes food rancidity or spoilage and leads to discoloration, change in the food’s taste and/or texture as well as formation of off-flavors and odors. Antioxidant food preservatives like ascorbic acid, BHA, BHT and citric acid help to protect foods against oxidation reactions that accelerate aging, which may be due to the oxygen in the air, certain enzymes or trace metals.

Anti-microbial food preservatives are type of food preservatives that work by preventing the growth of bacteria, fungi, molds or yeasts in foods. Examples of anitmicrobial food preservatives are benzoates, nitrates and sulfites.

Food preservatives can be classified as Natural Food preservatives or Artificial / Chemical Food preservatives.

The use of food chemical preservatives is often combined with physical methods. The application of preservatives has a long history, such as the use of common salt, smoke or sulfur dioxide. For example, sulphur dioxide – preservative (220) is added to some meat products such as sausage meat to limit microbial growth ⁶⁾. Some of these agents, such as benzoic acid, are achievements of the last century. Others, such as propionic acid and sorbic acid, result from research during the last few decades. The preservatives now in use have been thoroughly tested for their toxicological properties. Their use in the food industry is subject to stringent legal regulations.

Chemical Food Preservatives

The use of food preservatives, such as benzoic acid, nitrites, and sulphites, as antimicrobials, and butylated hydroxyanisole (BHA), butylated hydroxytoluene (BHT), ascorbic acid and tocopherols, as antioxidants, has probably changed food production patterns and eating habits more than has the use of any other class of food additive ⁷⁾. These food preservative chemicals confer substantial benefits on man, not only by the preservation and increased palatability of food, but also by affording protection against the pathological effects of reactive oxygen species (ROS) which are associated with cancer, cardiovascular disease and aging. Nevertheless, although most preservatives are now considered to be without potential adverse effects and are classified as GRAS, there have been problems concerning the safety of some of these chemicals, including the possibility of allergies from benzoic acid and sulphites, the formation of carcinogenic nitrosamines from nitrites, and the possible rodent carcinogenicity of Butylated hydroxyanisole (BHA) and butylated hydroxytoluene (BHT) widely used antioxidant food additives.

Most of the preservatives that are used in foods are acids, such as the weak lipophilic organic acids (sorbate, benzoate, propionate) or the inorganic ones (sulphite, nitrite). All are more effective at low rather than at high pH. Indeed, with the possible exceptions of the alkyl esters of p-hydroxybenzoate (‘parabens’), there are no wide-spectrum antimicrobial food preservatives that are effective at near-neutral pH. There is a well-established rationale for the effectiveness of the weak acids and for their synergy with hydrogen ions, i.e. with low pH. This derives from the fact that in their unionized forms, which are favoured at low pH, they
are able to readily equilibrate across the microbial cell membrane and access the cytoplasm of the cell.

List of Commonly Used Food Preservatives in the US ⁸⁾:

• Ascorbic acid,
• sorbic acid,
• lactic acid,
• citric acid,
• sodium benzoate,
• sodium nitrite and sodium nitrate
• calcium propionate,
• sodium erythorbate,
• sodium nitrite,
• calcium sorbate,
• potassium sorbate,
• BHA (Butylated hydroxyanisole),
• BHT (Butylated hydroxytoluene),
• EDTA (Ethylenediaminetetraacetic acid),
• sulphur dioxide and sulphites,
• carbon dioxide,
• lecithin,
• propyl gallate,
• tocopherols (Vitamin E)

Food Preservatives can be found in fruit sauces and jellies, beverages, baked goods, cured meats, oils and margarines, cereals, dressings, snack foods, fruits and vegetables.

Bread

Calcium propionate (282) prevents mould growth on bread and is often heavily used in humid, tropical areas. It’s been linked to migraines and behavioural and learning problems, but these reports lack scientific credibility.

Wine and dried fruit

Preservatives that contain sulphur (220-228), including sulphur dioxide (220), which is used in wine and dried fruit, can trigger asthma attacks. The 2005 national diet survey found that young children who eat lots of foods that contain sulphites, such as dried apricots, sausages and cordial, could be exceeding the ADI for sulphites.

Sulphur dioxide should be avoided by people who have asthma.

Sodium nitrite and sodium nitrate

Sodium nitrite

There is limited evidence in humans for the carcinogenicity of nitrite in food ⁹⁾. Nitrite in food is associated with an increased incidence of stomach cancer. …There is sufficient evidence in experimental animals for the carcinogenicity of nitrite in combination with amines or amides. There is limited evidence in experimental animals for the carcinogenicity of nitrite per se.

Overall evaluation: Ingested nitrate or nitrite under conditions that result in endogenous nitrosation is probably carcinogenic to humans ¹⁰⁾.

Processed meats

The food preservatives sodium nitrite (250) and sodium nitrate (251) – typically found in processed cured meats like ham and bacon – are both listed as “carcinogenic to humans” by WHO’s International Agency for Research on Cancer (IARC), because they can be converted into nitrosamines in the stomach and nitrosamines increase the risk of cancer ¹¹⁾. The IARC Working Group assessed more than 800 epidemiological studies that investigated the association of cancer with consumption of red meat or processed meat in many countries, from several continents, with diverse ethnicities and diets. The found there is now, in the case of processed meat, convincing evidence of carcinogenicity in humans. This classification is based on sufficient evidence from epidemiological studies that eating processed meat causes colorectal cancer ¹²⁾.

The report differentiates the two meats as follows:

• Processed meat – meat that has been transformed through salting, curing, fermentation, smoking, or other processes to enhance flavor or improve preservation (Group 1 – carcinogenic to humans),
• Red meat – unprocessed mammalian muscle meat such as beef, veal, pork, lamb, mutton, horse and goat meat (Group 2A – probably carcinogenic to humans).

Consumption of processed meat was classified as carcinogenic and red meat as probably carcinogenic after the IARC Working Group – comprised of 22 scientists from ten countries – evaluated over 800 studies. Conclusions were primarily based on the evidence for colorectal cancer. Data also showed positive associations between processed meat consumption and stomach cancer, and between red meat consumption and pancreatic and prostate cancer.

The Cancer Council now recommends limiting or avoiding processed meats such as sausages, frankfurts, salami, bacon and ham. But also keep in mind that the cancer risk is relatively small and that sodium nitrite prevents the growth of bacteria that cause botulism poisoning – which can be more immediately deadly.

Meat processing such as curing (e.g. by adding nitrates or nitrites) or smoking can lead to the formation of potentially cancer-causing (carcinogenic) chemicals such as N-nitroso-compounds (NOC) and polycyclic aromatic hydrocarbons (PAH) ¹³⁾. Meat also contains heme iron, which can facilitate production of carcinogenic NOCs. Cooking – especially high-temperature cooking including cooking meats over a flame (e.g., pan-frying, grilling, barbecuing) – can also produce carcinogenic chemicals, including heterocyclic aromatic amines (HAA) and PAHs.

Even though smoking is in the same category as processed meat (Group 1 carcinogen), however, the magnitude or level of risk associated with smoking is considerably higher (e.g., for lung cancer about 20 fold or 2000% increased risk) from those associated with processed meat – an analysis of data from 10 studies, cited in the IARC report showed an 18 percent increased risk in colorectal cancer per 50g processed meat increase per day ¹⁴⁾.

Are processed meats made from so-called “organic” meats safer ?

Processed meats made from so-called “organic meats” are generally treated with natural nitrate such as celery juice or smoked as well. At this point there is insufficient data to conclude whether those meats are safer than the “non-organic” meats.

Are there any specific types of processed meats that should be avoided more than others ?

IARC evaluated consumption of total processed meat, not one specific type of meat, because data relating specific subtypes of processed and red meat to risk of cancers are currently limited. Therefore, it is not yet possible to draw a conclusion on whether specific types of meats are safer. Overall, it is best to limit consumption of any processed meat.

Some people purchase “nitrate-free” processed meats, a fairly new food trend. Could that help make processed meat less carcinogenic ?

So-called “nitrate-free” processed meats are often preserved with celery juice, a plant rich in nitrate. The source of nitrate added for meat preservation will likely not matter. Furthermore, processed meats can also contain other carcinogenic compounds such as PAHs which can be formed during smoking of meat (e.g. salami). Processed meats, particularly those containing red meat also contain heme iron, which can enhance the formation of carcinogenic compounds (NOCs) in the body. Until we know more about the exact mechanisms underlying the relationship between processed meat and cancers, it is best to treat those nitrate-free processed meats the same as any other processed meats and limit intake.

How about chicken or turkey hot dogs, or turkey bacon – are those safer to eat than bacon or hot dogs containing red meats such as beef or pork ?

Chicken and turkey hot dogs and turkey bacon may also contain preservatives such as nitrates. However, those meats contain less heme iron than processed meats made from red meats. A good alternative is to replace red or processed meat with unprocessed, fresh chicken or turkey, which is a good source of protein, vitamins and minerals. Also to be considered are nuts, peanuts, soy, and legumes, such as hummus.

 

Benzoic acid and sodium benzoate

Benzyl Alcohol is an aromatic alcohol used in a wide variety of cosmetic formulations as a fragrance component, preservative, solvent, and viscosity-decreasing agent ¹⁵⁾. Benzoic Acid is an aromatic acid used in a wide variety of cosmetics as a pH adjuster and preservative ¹⁶⁾. Sodium Benzoate is the sodium salt of Benzoic Acid used as a preservative, also in a wide range of cosmetic product types ¹⁷⁾. Benzyl Alcohol is metabolized to Benzoic Acid, which reacts with glycine and excreted as hippuric acid in the human body. Acceptable daily intakes were established by the World Health Organization at 5 mg/kg for Benzyl Alcohol, Benzoic Acid, and Sodium Benzoate. Benzoic Acid and Sodium Benzoate are generally recognized as safe (GRAS) in foods according to the U.S. Food and Drug Administration ¹⁸⁾. No adverse effects of Benzyl Alcohol were seen in chronic exposure animal studies using rats and mice. Effects of Benzoic Acid and Sodium Benzoate in chronic exposure animal studies were limited to reduced feed intake and reduced growth. Some differences between control and Benzyl Alcohol-treated populations were noted in one reproductive toxicity study using mice, but these were limited to lower maternal body weights and decreased mean litter weights. Another study also noted that fetal weight was decreased compared to controls, but a third study showed no differences between control and Benzyl Alcohol-treated groups. Benzoic Acid was associated with an increased number of resorptions and malformations in hamsters, but there were no reproductive or developmental toxicty findings in studies using mice and rats exposed to Sodium Benzoate, and, likewise, Benzoic Acid was negative in two rat studies ¹⁹⁾. Genotoxicity tests for these ingredients were mostly negative, but there were some assays that were positive. Carcinogenicity studies, however, were negative ²⁰⁾. Clinical data indicated that these ingredients can produce nonimmunologic contact urticaria and nonimmunologic immediate contact reactions, characterized by the appearance of wheals, erythema, and pruritus. In one study, 5% Benzyl Alcohol elicited a reaction, and in another study, 2% Benzoic Acid did likewise. Benzyl Alcohol, however, was not a sensitizer at 10%, nor was Benzoic Acid a sensitizer at 2%. Recognizing that the nonimmunologic reactions are strictly cutaneous, likely involving a cholinergic mechanism, it was concluded that these ingredients could be used safely at concentrations up to 5%, but that manufacturers should consider the nonimmunologic phenomena when using these ingredients in cosmetic formulations designed for infants and children. Additionally, Benzyl Alcohol was considered safe up to 10% for use in hair dyes ²¹⁾. The limited body exposure, the duration of use, and the frequency of use were considered in concluding that the nonimmunologic reactions would not be a concern ²²⁾. Because of the wide variety of product types in which these ingredients may be used, it is likely that inhalation may be a route of exposure ²³⁾. The available safety tests are not considered sufficient to support the safety of these ingredients in formulations where inhalation is a route of exposure ²⁴⁾. Inhalation toxicity data are needed to complete the safety assessment of these ingredients where inhalation can occur ²⁵⁾.

Benzoic acid (E210) or its sodium benzoate (E211) is a common ingredient added as preservative in many foodstuffs, toothpastes and cosmetics creams, and values ranging in 226 to 1776 mg kg-1 have been reported, in beverages, processed fruits and vegetable products ²⁶⁾. However, benzoic acid may also occur naturaly in plant and animal products at levels not exceeding 40 mg/kg ²⁷⁾.

Sodium benzoate is a colorless crystalline powder. It is used as food preservative, antiseptic, medicine, in tobacco, in pharmaceutical preparations, as an intermediate for manufacture of dyes, and as a rust and mildew inhibitor ²⁸⁾.

HUMAN EXPOSURE AND TOXICITY ²⁹⁾

ANIMAL STUDIES: An acute dermal irritation/corrosion study gave no indication for skin irritating effect in rabbits. Sodium benzoate was only slightly irritating to the eye. In a 90-day study with rats dosed with 0, 1, 2, 4, or 8% sodium benzoate via diet, the mortality in the highest dose group (approx. 6290 mg/kg body weight per day) was about 50% ³⁰⁾. Other effects in this group included a reduced weight gain, increased relative weights of liver and kidneys, and pathological changes in these organs. Sodium benzoate was given in drinking water to 50 female and 50 male mice from weeks 5 on for lifespan. The average daily intake of sodium benzoate was 119.2 mg for a female and 124.0 mg for a male (approx. 5.95 – 6.2 g/kg bw/d). There was no effect on the survival of the treated mice when compared with the untreated control. There were no significant differences between the tumor distribution in sodium benzoate-treated and untreated control mice. In a developmental study rats were injected intraperitoneally with 100, 315, or 1000 mg/kg sodium benzoate on gestation days 9 to 11 or 12 to 14. Reduced fetal body weight, increased in utero deaths (by 12%), and gross anomalies were noted at the highest dose. No evidence of teratogenicity was noted in rats administered 510 mg/kg of sodium benzoate by gavage on gestation days 9 to 11. Sodium benzoate (up to 3.0 mg/plate) was tested in the Salmonella/microsome test using S. typhimurium TA 92, TA 94, TA 98, TA 100, TA 1535 and TA 1537. No significant increases in the numbers of revertant colonies were detected in any S. typhimurium strains at the maximum dose. Sodium benzoate tested negative in a cytogenetic assay (bone marrow) in rats after single or multiple oral application of doses up to 5000 mg/kg body weight. In a study with mice, there was also no indication of mutagenic activity in a host-mediated assay ³¹⁾.

In a study with 2045 patients of dermatological clinics, only 5 persons (approximately 0.2%) showed a positive reaction in patch tests, while 34 of 5202 patients (approximately 0.7%) with contact urticaria reacted positively ³²⁾. Cases of urticaria, asthma, rhinitis, or anaphylactic shock have been reported following oral, dermal, or inhalation exposure to sodium benzoate ³³⁾. The symptoms appear shortly after exposure and disappear within a few hours. Chromosome aberration test was carried out on sodium benzoate using human embryonic lung culture cells. Sodium benzoate produced no significant increase in the aberration frequency in the anaphase chromosomes when tested at the dosage levels 0, 2.0 ug/mL, 20 ug/mL and 200 g/mL. In human embryonic lung cells (WI-38) treated with sodium benzoate both chromosome abnormalities and mitotic indices were within normal values ³⁴⁾. Sodium benzoate was mutagenic and cytotoxic in lymphocytes, where it caused micronucleus formation and chromosome break ³⁵⁾.

After oral uptake, both additives are rapidly absorbed from the gastrointestinal tract and metabolized in the liver, resulting in the formation of hippuric acid, which, in general, is rapidly excreted via the urine ³⁶⁾ thus, its toxicity to humans is considered to be very low ³⁷⁾. However, they may cause non-immunological contact reactions exacerbated in patients with frequent urticaria or asthma, while there are also carcinogenic concerns ³⁸⁾. Benzoic acid itself is only slightly soluble in water, thus sodium benzoate — which, under acid conditions, converts to undissociated benzoic acid – is often used instead. The European Commission Regulation states in its Article 27 that “Member States shall maintain systems to monitor the consumption and use of food additives on a risk-based approach and report their findings with appropriate frequency” ³⁹⁾, while responsible authorities are strongly encouraged to characterize risk on the basis of locally measured or predicted exposure scenarios.

In many products a trend of increasing formation of benzene has been associated to the presence of sodium benzoate and ascorbic acid, after exposure to heat and or light and low pH ⁴⁰⁾. Benzene is confirmed as a carcinogenic substance, however, most people are exposed to benzene primarily by breathing air that contains the chemical ⁴¹⁾. Benzene is produced by both natural and man-made processes. It is a natural component of crude oil, which is the main source of benzene produced today. Other natural sources include gas emissions from volcanoes and forest fires ⁴²⁾. Exposure to benzene may increase the risk of developing leukemia and other blood disorders ⁴³⁾.

The primary use of benzene today is in the manufacture of organic chemicals (e.g. to manufacture rubbers, lubricants, dyes, detergents, pesticides), and as an additive to unleaded gasoline. In Europe, benzene is mainly used to make styrene, phenol, cyclohexane, aniline, maleic anhydride, alkyl-benzenes and chlorobenzenes. It is an intermediate in the production of anthraquinone, hydroquinone, benzene hexachloride, benzene sulfonic acid and other products used in drugs,  dyes, insecticides and plastic ⁴⁴⁾.

U.S. Food and Drug Administration Select Committee on GRAS Substances Opinion on Benzoic acid and sodium benzoate ⁴⁵⁾

There are extensive metabolic data on benzoic acid and sodium benzoate in experimental animals and man ⁴⁶⁾. It appears that the rat and human have similar metabolic pathways. Short- and long-term feeding studies, as well as teratological investigations, have also been reported in the rat. Interpolation of the rat data and consumer exposure data indicates that the highest no effect level reported in the long-term laboratory feeding study of sodim benzoate is approximately 180 fold the amount usually present in man’s daily diet. The highest no effect level reported in laboratoy animal feeding is approximately 90 fold the amount that would be consumed if an individual’s diet were to consist only of those foods containng the greatest amoutns of sodium benzoate in current usage ⁴⁷⁾.

In the light of the foregoing the Select Committee concludes that:

“There is no evidence in the available information to show that benzoic acid and sodium benzoate as food ingredients constitute a hazard to the general public when used at levels that are now current or that might reasonably be expected in future” ⁴⁸⁾.

Soft drinks

In drinks, the combination of sodium benzoate or potassium benzoate (212) and ascorbic acid (vitamin C, both naturally occurring and the additive 300) can result in the formation of benzene, a known carcinogen. Exposing the bottle to heat or light during transport or storage can boost the amount of benzene formed.

FSANZ tested 68 flavoured drinks, including flavoured mineral waters, cordial, fruit juice and fruit drinks, and found 38 of the samples contained trace levels of benzene. While the majority had benzene levels below WHO guidelines for drinking water – 10 parts per billion (ppb) – some contained levels up to 40 ppb – 1 ppb is the reference level for benzene in Australia’s more stringent drinking water guidelines ⁴⁹⁾.

On top of that, an Australian national diet survey in 2005 found that young children who consume lots of drinks that contain a form of benzoate (non-cola soft drinks, orange juice and cordial, for example) could be exceeding the acceptable daily intake (ADI) for benzoates ⁵⁰⁾.

Exposure to benzene in food and drink products may be small when compared with breathing air that contains benzene from traffic pollution or tobacco smoke, but it’s unnecessary. So it makes sense to avoid drinks that contain benzoates and ascorbic acid.

BHT Preservative

BHT (butylated hydroxytoluene) is the recognized name in the cosmetics industry ⁵¹⁾. Known uses of BHT (butylated hydroxytoluene) are as antioxidant for petroleum and food products; animal feed; food packaging ⁵²⁾. BHT (butylated hydroxytoluene) is also associated with tobacco: reported either as a natural component of tobacco, pyrolysis product (in tobacco smoke), or additive for one or more types of tobacco products ⁵³⁾.

BHT (butylated hydroxytoluene) Uses ⁵⁴⁾

• EMPLOYED TO RETARD OXIDATIVE DEGRADATION OF OILS & FATS IN VARIOUS COSMETICS & PHARMACEUTICALS.
• ANTIOXIDANT FOR SYNTHETIC RUBBERS, PLASTICS, SOAPS, ANIMAL & VEGETABLE OILS; ANTISKINNING AGENT IN PAINTS & INKS
• Antioxidant for petroleum products, jet fuels, food products, food packaging, animal feeds.
• BHT is used as an antioxidant in pyrethrum extract, an insecticide product.
• FOOD ADDITIVE
• IN CHEWING GUM BASE, PACKAGING MATERIALS, BUTTER, CANDY, PARAFFIN & MINERAL OILS
• Satisfies ASTM D910-64T for use in aviation gasoline.
• Stabilizer in motor and aviation gasoline.
• Used by Shell Chemical Company as a stabilizer for monomers.

BHT (butylated hydroxytoluene) is also used in a wide range of cosmetic formulations as an antioxidant at concentrations from 0.0002% to 0.5%. BHT does penetrate the skin, but the relatively low amount absorbed remains primarily in the skin. Oral studies demonstrate that BHT is metabolized. The major metabolites appear as the carboxylic acid of BHT and its glucuronide in urine. At acute doses of 0.5 to 1.0 g/kg, some renal and hepatic damage was seen in male rats. Short-term repeated exposure to comparable doses produced hepatic toxic effects in male and female rats. Subchronic feeding and intraperitoneal studies in rats with BHT at lower doses produced increased liver weight, and decreased activity of several hepatic enzymes.

In addition to liver and kidney effects, BHT applied to the skin was associated with toxic effects in lung tissue. BHT was not a reproductive or developmental toxin in animals. BHT has been found to enhance and to inhibit the humoral immune response in animals. BHT itself was not generally considered genotoxic, although it did modify the genotoxicity of other agents. BHT has been associated with hepatocellular and pulmonary adenomas in animals, but was not considered carcinogenic and actually was associated with a decreased incidence of neoplasms.

BHT has been shown to have tumor promotion effects, to be anticarcinogenic, and to have no effect on other carcinogenic agents, depending on the target organ, exposure parameters, the carcinogen, and the animal tested. Various mechanism studies suggested that BHT toxicity is related to an electrophillic metabolite. In a predictive clinical test, 100% BHT was a mild irritant and a moderate sensitizer. In provocative skin tests, BHT (in the 1% to 2% concentration range) produced positive reactions in a small number of patients. Clinical testing did not find any depigmentation associated with dermal exposure to BHT, although a few case reports of depigmentation were found. The Cosmetic Ingredient Review Expert Panel recognized that oral exposure to BHT was associated with toxic effects in some studies and was negative in others. BHT applied to the skin, however, appears to remain in the skin or pass through only slowly and does not produce systemic exposures to BHT or its metabolites seen with oral exposures.

Although there were only limited studies that evaluated the effect of BHT on the skin, the available studies, along with the case literature, demonstrate no significant irritation, sensitization, or photosensitization. Recognizing the low concentration at which this ingredient is currently used in cosmetic formulations, it was concluded that BHT is safe as used in cosmetic formulations ⁵⁵⁾.

U.S. Food and Drug Administration Select Committee on GRAS Substances Opinion on Butylated Hydroxytoluene (BHT) ⁵⁶⁾

The information on the metabolism and toxicology of BHT (butylated hydroxytoluene) is extensive. There is ample evidence of efficacy of this compound as an antioxidant. It has been suggested that BHT in fatty tissue may even have some effect similar to that of vitamin E. There are some data to indicate that BHT (butylated hydroxytoluene) in diets reduces the incidence of certain tumors and the rate of absorption in the rat.

The available evidence does not support the view that BHT (butylated hydroxytoluene) interferes in any specific way with cellular metabolism. There is no evidence that demonstrates that BHT causes frank biochemical lesions in the liver; moreover, it is obvious that high doses of BHT are needed to induce biochemical alterations. With 0.1% BHT in the diet in rats there are differening data in the literature concerning the effect of such treatment on liver growth and liver enzymes. At 0.05 % in the dit, no toxic effects are discernible. This “no-effect level” is equivalent to 50 mg per kg per day.

However, BHT (butylated hydroxytoluene) increases the level of microsomal enzymes in the liver. The significance of this increase raises certain questions. The liver weight of animals fed BHT is increased and some interpret this enlargement as hypertrophy which is fully reversible and without apparent toxicological significance. But a point could occur at which adaptation fails, a new condition is created, and injury commences. It does not appear that “fully adapted” livers have been challenged by additional doses of BHT or, more importantly, other chemicals. In view of the widespread use, for example, of oral contraceptives, it is felt that informatoin should be available on the effect of challenging fully adapted livers with compounds which are themselves metabolized by microsomal hydroxylases. Therefore, there is the need to determine the effects of BHT at levels now present in foods under conditions where steroid hormones or oral contraceptives are being ingested.

Other tissues such as lung and the gastrointestinal mucosa, in addition to liver, can respond to enzyme inducing agents. More information is required on the inducing properties of BHT (butylated hydroxytoluene) on extra hepatic organs. If induction should be found to occur, it would be necessary to determine the effect of such enzymes on the conversion of other ingeted materials into toxic substances or carcinogens.

The Select Committee has weighed the foregoring and concludes that:

“While no evidence in the available information on BHT (butylated hydroxytoluene) demonstrates a hazard to the public when it is used at levels that are now current and in the manner now practiced, uncertainties exist requiring that additional studies should be conducted” ⁵⁷⁾.

BHA Preservative

BHA (butylated hydroxyanisole) is a white or slightly yellow waxy solid. It has a faint odor. BHA (butylated hydroxyanisole) is not soluble in water ⁵⁸⁾. BHA (butylated hydroxyanisole) is an important commercial chemical that is used as a preservative in food, cosmetics, animal feeds as well as in rubber and petroleum products. It prevents fat-containing foods and edible fats and oils from becoming rancid and developing odors ⁵⁹⁾. Workers that use BHA may breathe in vapors or have direct skin contact. The general population may be exposed by consumption of food and use of cosmetics. If BHA is released to the environment, it will be broken down in air. It is not expected to be broken down by sunlight. It will move into air from moist soil and water surfaces. It is expected to move slowly through soil. It will not be broken down by microorganisms, and is expected to build up in fish.

Data on the potential for BHA (butylated hydroxyanisole) to cause adverse effects in humans are limited to reports of allergic skin reactions, irritation, and whitening of skin in some people ⁶⁰⁾. Damage to the lining of the stomach and enlargement of the liver have been reported in laboratory animals fed very high oral doses of BHA (butylated hydroxyanisole) ⁶¹⁾. BHA (butylated hydroxyanisole) has also led to changes in certain enzymes, which could potentially change how the body breaks down other chemicals or drugs. However, since the effects occur at doses much higher than expected human exposure, the U.S. Food and Drug Administration considers BHA (butylated hydroxyanisole) a “GRAS” (generally recognized as safe) food additive ⁶²⁾. However the FDA’s Select Committee on GRAS substances added a precautionary statement regarding the use of BHA : “While no evidence in the available information on butylated hydroxyanisole (BHA) demonstrates a hazard to the public when it is used at levels that are now current and in the manner now practiced, uncertaintied exist requiring that additional studies be conducted” ⁶³⁾.

The evidence indicates that BHA (butylated hydroxyanisole) is not mutagenic ⁶⁴⁾. While there are teratogenic effects of BHA in the avian embryo test system, several investigations using three mammalian species have failed to establish any teratogenic or embryotoxic potential when BHA (butylated hydroxyanisole) is fed to young or adult and pregnant animals at dosages that greatly exceed estimates of human consumption. Data from several studies indicate that BHA is not a carcinogenic substance. There is evidence that BHA (butylated hydroxyanisole) may interfere with synthesis of natural carcinogens and suppress or retard growth of tumors induced by known chemical carcinogens ⁶⁵⁾.

Stomach tumors developed in laboratory animals fed high-to-very-high dietary levels of BHA over time. No skin tumors were observed in mice following repeated skin application of BHA (butylated hydroxyanisole). No evidence of infertility, abortion, or birth defects were observed in laboratory animals exposed before and/or during pregnancy. The International Agency for Research on Cancer determined that BHA (butylated hydroxyanisole) is possibly carcinogenic to humans based on no evidence of cancer in humans and sufficient evidence of cancer in laboratory animals ⁶⁶⁾. The potential for BHA (butylated hydroxyanisole) to cause cancer in humans has not been assessed by the U.S. EPA IRIS program or the U.S. National Toxicology Program 14th Report on Carcinogens ⁶⁷⁾.

Natural Food Preservation Techniques

The various forms of spoilage and food poisoning caused by micro-organisms are preventable to a large degree by a number of preservation techniques, most of which act by preventing or slowing microbial growth. These include:

• Freezing to slow or prevent the growth of micro-organisms,
• Chilling to slow or prevent the growth of micro-organisms,
• Heating (pasteurization and sterilization) to kill micro-organisms,
• Drying,
• Curing,
• Conserving via control of microstructure e.g. in water-in-oil emulsion foods,
• Vacuum Packing by removing Oxygen O2,
• Modified Atmosphere Packing by replacement of air with CO2, Oxygen and Nitrogen mixtures,
• Acidifying lowers the pH by using acetic, citric acids, etc.,
• Fermenting lowers the pH,
• adding Chemical Preservatives inorganic (e.g. inorganic – sulphite & nitrite; organic – propionate, sorbate, benzoate, parabens; bactenocin – nisin; antimycotic – natamycin).

A smaller number complementary techniques restrict access of micro-organisms to food products, e.g. aseptic processing and packaging.

New and ’emerging’ preservation techniques ⁶⁸⁾ include more that act by inactivation. They include:

• the application of ionizing radiation,
• high hydrostatic pressure,
• high voltage electric discharges,
• high intensity light,
• ultrasonication in combination with heat and slightly raised pressure (‘manothermosonication’), and
• the addition to foods of bacteriolytic enzymes, bacteriocins, and other naturally-occurring antimicrobials.

Major trends, reacting to consumers’ needs, are towards the use of procedures that deliver food products that are less ‘heavily’ preserved, higher quality, more convenient, more ‘natural’, freer from additives, nutritionally healthier, and still with high assurance of microbiological safety ⁶⁹⁾. The food industry reactions to these changes have been to develop ‘minimal’ preservation and processing technologies.

The greater proportion of foodstuffs is rendered durable by physical procedures: drying, cooling, deep-freezing and heating ⁷⁰⁾. But chemical preservation also plays a prominent role. Chemical preservatives are biocidal chemicals added to cosmetics, topical medicaments, consumer goods, foods, and industrial products to protect them against microbial spoilage and to protect the consumer against infection ⁷¹⁾. The ideal preservative, both effective and devoid of irritant or sensitizing potential, is still to be discovered. Food chemical preservatives are food additives that are used to preserve food when this is the most practical way of extending its storage life.

Low temperature Freezing

Many types of spoilage micro-organisms may continue to grow at sub-zero temperatures, multiplying slowly at temperatures down to about -7°C (minus 7 degrees Celsius). Badly stored frozen foods may, therefore, slowly spoil through the activities of micro-organisms, but not become dangerous if thawing has
not occurred. At the temperature of properly stored frozen foods, nominally -18°C in many countries, microbial growth is completely prevented, although slow loss of quality may still occur through the activities of enzymes and through chemical reactions and physical changes  ⁷²⁾.

Reduction in water activity

Water activity values (a _w) are widely used to predict the stability of foods with respect to the growth of micro-organisms and the chemical, enzymic and physical changes that lead to quality deterioration ⁷³⁾. Values range from 1 (pure water) to zero (no water), equivalent to equilibrium relative humidities (ERH) on a scale from 100% to 0%. The water activity of foods is reduced by drying or by adding solutes such as salt, as in cured products, or sugars, as in conserves, or by combinations of these treatments. Small reductions, e.g. to about 0.97, are sufficient to prevent the growth of some important spoilage micro-organisms, e.g. Pseudomonas species that grow at high a _ws, and rapidly spoil foods such as fresh meat stored in air. Cured meats generally have a _ws sufficiently reduced to ensure longer Pseudomonas-free shelf-lives. Slow souring, caused by lactic acid bacteria occurs instead. If the a _w is lower still, below about 0.95, as in some salamis and dry-cured meat products, even these are inhibited, and slow spoilage by low a _w -tolerant micrococci takes over. These and similar relationships are widely used to explain and predict the storage stability and safety of foods. Of the food poisoning micro-organisms,
Staphylococcus aureus is the most tolerant, with a low a _w limit for growth of about 0.86 in air, but only 0.91 anaerobically, so that it may grow and produce enterotoxin in relatively low a _w foods if other conditions are conducive, e.g. temperature and time of storage. At a _w values below 0.86, few bacteria, and no bacteria  of public health concern, can grow, and food is spoiled by yeasts or moulds, some of which can multiply slowly at a _w as low as 0.6. Below this a _w, no micro-organisms are able to grow. Shelf-stable dried foods are generally formulated around a _w 0.3, where lipid oxidation and other chemical changes are minimal.

Vacuum and modified atmosphere packaging (MAP)

The effectiveness of vacuum and MAP derive firstly from the removal of oxygen, with the consequent inhibition of strictly oxidative micro-organisms. Fermentative organisms continue to multiply but they do so more slowly and, for some types of foods, they have less unpleasant consequences for food quality. Special attention is always given to the possibility of encouraging the growth of strictly anaerobic food poisoning micro-organisms, such as C. botultnum, so that for foods such as ‘sous vide’ products, which are vacuum packed and pasteurized rather than sterilized, minimal heat treatments and tight temperature control in distribution are recommended ⁷⁴⁾. Carbon dioxide is widely used in MAP foods because it has a specific antimicrobial activity, acting as a preservative that uniquely dissipates when the food pack is opened ⁷⁵⁾. For example, much supermarket meat is packed in gas mixtures containing about 70% Oxygen (O2) and 30% CO2. The Oxygen maintains the meat in the bright red oxymyoglobin colour that consumers prefer, while the CO2 slows down the growth of Gram-negative spoilage bacteria so as to about double the useful shelf-life.

Acidification

Many yeasts and moulds are able to multiply at very low pH values, i.e. well below pH 2, so that they predominate in the flora of spoiling acidified foods. Few bacteria grow below about pH 3.5 or so. Those that do are adapted to acid environments, e.g. the lactic acid bacteria, and indeed are employed in numerous acid generating food fermentations such as those for yoghurts, cheeses and salamis. A particularly important pH for food safety is pH 4.5, because it is the pH below which C.botulinum is unable to multiply. Consequently, in thermal processing, it is not necessary to heat foods that are more acid than this to the same extent
as higher pH ‘low acid’ foods. Below about pH 4.2, other food poisoning and spoilage bacteria are mostly controlled. However, recently the spore-forming bacterium Alicyclobacillus acidoterrestris, capable of growth at pH values as low as 2, has caused spoilage problems (‘disinfectant taints’) in some low pH foods.

Survival of micro-organisms at low pH may be important, even if they are unable to multiply. For example, Eschenchia coli 0157 has an acid tolerance that may have contributed to some food poisoning outbreaks in which the vehicle was a low pH food, e.g. American (non-alcoholic) apple cider. Furthermore, acid tolerance may aid passage of such organisms through the stomach. Food processors are aware that acid tolerance may be increased by prior exposure to mild acidification, or even by seemingly unrelated stresses, such as mild heating ⁷⁶⁾.

Natural Food Preservatives

Natural food preservatives are things that can be easily found in the kitchen amongst the everyday cooking ingredients.

Commonly available natural food preservatives at home:

• Salt
• Sugar
• Vinegar
• Basil oil is used in post harvest protection of mango fruits and table grapes
• Honey
• Syrup
• Onion – good source of bio-active compounds such as organo-sulphurs, thiosulfinates and flavanoids
• Cardamon oil
• Sage and Rosemary oils
• Alcohol

Food processors have also explored novel food preservation systems. An ideal food preservative would come from a natural source and preserve food without being labeled a synthetic chemical preservative. Such preservatives include bacteriocins, dimethyl dicarbonate (Velcorin), competitive microbial inhibition, controlled and modified atmospheres, and irradiation ⁷⁷⁾. Bacteriocins are not new; however, like nisin, they are now being used to extend shelf life and enhance the safety of a variety of food products. The use of bacteriocins is likely to be expanded in the future. Dimethyl dicarbonate, a relatively new preservative used in beverages such as wine, tea, and juices, is particularly effective in preventing spoilage caused by yeasts ⁷⁸⁾. Competitive microbial inhibition relies on the fact that many harmless bacteria, notably lactic acid bacteria, can inhibit the growth of both spoilage bacteria and pathogens. Inhibitory strains of lactic acid bacteria can be selected for use in dairy cultures or be added to refrigerated foods to extend shelf life and enhance safety.

Nisin

Nisin is produced as a fermentation product of a food-grade bacterium (Lactococcus lactis) and the safety and efficacy of nisin as a food preservative have resulted in its widespread use throughout the world, including the U.S. ⁷⁹⁾. Both nisin variants A and Z, with a difference of an amino acid ⁸⁰⁾, are approved for use in foodstuffs by food additive legislating bodies in the United States (Food and Drug Administration) ⁸¹⁾, the United Kingdom, and the European Union ⁸²⁾.

Nisin is a member of the class of antimicrobial substances known as lantibiotics, so called because they contain the unusual amino acid lanthionine. Lantibiotics, in general, have considerable promise as food preservatives, although only nisin has been sufficiently well characterized to be used for this purpose.

Nisin is employed in the dairy industry to inhibit Clostridium botulinum and Bacillus cereus, due to its capacity to prevent spore germination. Nisin was first identified in fermented cow milk. Since then, it has been isolated from various milk and dairy products as well as from plant material and river water.

Approximately 30% of human milk contains nisin-producing bacteria suggests that humans may have a long history of consuming nisin-producing bacteria ⁸³⁾. However, little is known about the potential effects of ingesting nisin-producing bacteria. Nisin-producing L. lactis may protect mothers (mastitis) and infants (toxication) from pathogenic skin flora, such as Staphylococcus aureus. The effect of nisin producers on the human gastrointestinal tract and its microbiota remains unclear. Nisin producers survive passage through the intestine, but it is not known if nisin is produced in the intestine.

Natamycin

Natamycin is a polyene macrolide antimycotic with a molecular weight of 665.7; the CAS Registry Number is 7681-93-8. FDA approved natamycin as GRAS for use as an antimycotic to prevent the growth of molds and yeasts in yogurt at use levels not to exceed 5 milligrams per kilogram (mg/kg) ⁸⁴⁾.

Pediocin

Pediocin is a broad-spectrum lactic acid bacteria bacteriocin that shows a particularly strong activity against Listeria monocytogenes, a foodborne pathogen of special concern among the food industries ⁸⁵⁾. This antimicrobial peptide is the most extensively studied class Ila (or pediocin family) bacteriocin, and it has been sufficiently well characterized to be used as a food biopreservative. Pediocin was approved by the FDA for use in reduced nitrtite bacon to aid in the prevention of botulinum toxin production.

Lactoperoxidase

Lactoperoxidase is a glycoprotein with one iron (Fe) group that occurs naturally in tears, milk and saliva of many mammals. Lactoperoxidase exerts a bacteriostatic (stops bacteria from reproducing, while not necessarily killing them) on Listeria and Staphylococcus. The addition of Lactoperoxidase to starter culture for yogurt production inhibited the acid production and the new yogurt produced with extended shelf life. Lactoperoxidase is also used in toothpaste and ground beef products.

Chitosan

Chitosan is a polysaccharide derived from the partial deacetylation of chitin, primarily from crustacean and insect shells. There is some evidence that chitosan is more effective than placebo in the short-term treatment of overweight and obesity. However, many trials to date have been of poor quality and results have been variable. Results obtained from high quality trials indicate that the effect of chitosan on body weight is minimal and unlikely to be of clinical significance ⁸⁶⁾.

Antimicrobial, antifungal, and wound-healing properties have also been reported ⁸⁷⁾. Chitosan and its blends with other natural polymers such as starch and other ingredients for example essential oils, and clay in the field of edible films for food protection such as a coating on fruit and vegetables ⁸⁸⁾. Chitosan-Starch-Based Edible Coating To Improve the Shelf Life of Bod Ljong Cheese. ⁸⁹⁾. Chitosan coating combined with acetic acid could be a promising antimicrobial method to prevent the proliferation of Listeria monocytogenes in refrigerated ready-to-eat shrimps ⁹⁰⁾.

Defensins

Defensins are antimicrobial peptides produced at a variety of epithelial surfaces. In the intestinal tract, they contribute to host immunity and assist in maintaining the balance between protection from pathogens and tolerance to normal flora ⁹¹⁾.

Reuterin

Lactobacillus reuteri converts glycerol into a potent cell growth inhibitor. This substance, termed reuterin, inhibits the growth of gram-positive and gram-negative bacteria as well as yeasts, fungi, and protozoa ⁹²⁾.

Reuterin has a high potential as a food preservative due to both its chemical characteristics and its antimicrobial activity against food-borne pathogens and spoilage bacteria ⁹³⁾. Reuterin can be considered a promising food biopreservative, although additional toxicology research is needed before permission for use can be granted.

Pleurocidin

Pleurocidin is a peptide derived from the winter flounder. Previous study has reported the antifungal effect of Pleurocidin ⁹⁴⁾.

Olive Pulp Extract

FDA GRAS approval for olive pulp extract polyphenols compounds as food grade ingredients with antioxidant properties. Antioxidant helps protect foods against oxidation reactions that accelerate aging.

What are food additives ?

Food additives can be used for various purposes. The European Union legislation defines 26 “technological purposes”.

Food additives are substances used for a variety of reasons – such as preservation, coloring, sweetening, etc.- during the preparation of food. The European Union legislation defines them as “any substance not normally consumed as a food in itself and not normally used as a characteristic ingredient of food, whether or not it has nutritive value” ⁹⁵⁾.

Food additives are added to food for technological purposes in its manufacture, processing, preparation, treatment, packaging, transport or storage, food additives become a component of the food ⁹⁶⁾.

Some food additives have more than one use. Food additives are food ingredients and are listed in the statement of ingredients according to the most appropriate class name for the purpose of the food additive in that food. For example, the additives must be designated by the name of their functional class, followed by their specific name or  number. For instance: “colour – curcumin” or “colour: E 100”. This E-number can be used in order to simplify the labelling of substances with sometimes complicated chemical names.

Food additives are commonly used, among other things, as:

• Acids/Acidity regulators/Alkalis help to maintain a constant acid level in food. This is important for taste, as well as to influence how other substances in the food function. For example, an acidified food can retard the growth of some micro-organisms.

• Anti-caking agents reduce the tendency of individual food particles to adhere and improve flow characteristics. For example, seasoning with an added anti-caking agent flows freely and doesn’t clump together.

• Antioxidants retard or prevent the oxidative deterioration of foods. For example, in fats and oils, rancid flavours can develop when they are exposed to oxygen. Antioxidants prevent this from happening.

• Bulking agents contribute to the volume of the food, without contributing significantly to its available energy. For example, sugar often contributes to the volume of lollies, while some low-joule foods need bulking agents added to them to replace the bulk normally provided by sugar.

• Colors add or restore color to foods, e.g. icing mixture is colored to make it more attractive on cakes.

• Emulsifiers facilitate or maintain oil and water from separating into layers, e.g. emulsifiers may be used in margarine to prevent oil forming a layer on top of the margarine.

• Firming agents/stabilisers maintain the uniform dispersion of substances in solid and semi-solid foods.

• Flavor enhancers enhance the existing taste and/or odor of a food.

• Flour treatment agents – added to flour or to dough to improve its baking quality.

• Foaming agents maintain the uniform dispersion of gases in aerated foods.

• Gelling agents modify the texture of the food through gel formation.

• Glazing agents impart a coating to the external surface of the food, e.g. a wax coating on fruit to improve its appearance.

• Humectants reduce moisture loss in foods, e.g. glycerine may be added to icing to prevent it from drying out.

• Preservatives retard or prevent the deterioration of food by micro-organisms, and thus prevent spoilage of foods.

• Raising agents liberate gases, thereby increasing the volume of a food and are often used in baked goods.

• Sweeteners replace the sweetness normal provided by sugars in foods without contributing significantly to their available energy.

• Thickeners increase the viscosity of a food, e.g. a sauce might contain a thickener to give it the desired consistency.

Is it possible to prepare food without additives ?

It is indeed possible to prepare food without the use of any additives. Additives are normally not added to food prepared at home. However at home, food is usually consumed directly. In addition home preparation may also have less influence on the appearance compared to industrially processed food.

Not all industrially prepared foodstuffs need additives. Examples include certain types of bread, some kinds of prepared meals, certain breakfast cereals, etc. Whether additives are needed or not, depends on the production process, the ingredients used, the final appearance, the required preservation, the need to protect against possible development of harmful bacteria, the kind of packaging, etc.

On the other hand, it is worth mentioning that many foodstuffs contain naturally occurring substances, which are at the same time authorized as food additives. For example, in apples you can find riboflavins (E 101), carotenes (E 160a), anthocyanins (E 163), acetic acid (E 260), ascorbic acid (E 300), citric acid (E 330), tartaric acid (E 334), succinic acid (E 363), glutamic acid (E 620) and L-cysteine (E 920).

Are food additives safe ?

The safety of all food additives that are currently authorised has been assessed by the Scientific Committee on Food (SCF) and/or the European Food Safety Authority (EFSA). Only additives for which the proposed uses were considered safe are on the EU list.

As most of the evaluations date back to the 80’s and 90’s, some even to the 70’s, it is only appropriate to re-evaluate all authorised additives by EFSA. The re-evaluation will be completed by 2020 . Based on the advice of EFSA the Commission may propose a revision of the current conditions of use of the additives and if needed remove an additive from the list.

As a result of the re-evaluation program, so far the use of three food colours has been revised because EFSA decreased their Acceptable Daily Intake (ADI) and considered that human exposure to these colours is likely to be too high. Therefore, the maximum levels of these colours that can be used in food will be lowered in early 2012. This reference concerns E 104 Quinoline yellow, E 110 Sunset Yellow and E 124 Ponceau 4R ⁹⁷⁾.

FD&C Yellow No. 5, is used to color beverages, dessert powders, candy, ice cream, custards and other foods. FDA’s Committee on Hypersensitivity to Food Constituents concluded in 1986 that FD&C Yellow No. 5 might cause hives in fewer than one out of 10,000 people. It also concluded that there was no evidence the color additive in food provokes asthma attacks. The law now requires Yellow No. 5 to be identified on the ingredient line. This allows the few who may be sensitive to the color to avoid it ⁹⁸⁾.

How is the safety of food additives evaluated in the US ?

The U.S. Food and Drug Administration (FDA) regulates approximately 80% of the U.S. food supply and is involved with many facets of food safety ⁹⁹⁾. Within FDA, the Center for Food Safety and Applied Nutrition’s (CFSAN) Office of Food Additive Safety is responsible for reviewing safety information for food ingredients and food packaging.

The FDA has defined “safe” as “a reasonable certainty in the minds of competent scientists that the substance is not harmful under the intended conditions of use” ¹⁰⁰⁾.

In 1958, Congress enacted the Food Additives Amendment to the Federal Food, Drug, and Cosmetic Act (FD&C Act). The amendment and/or supporting legislative documents defined the term ‘food additive’; required premarket approval for new uses of food additives; and established the standard of review (‘fair evaluation of the data…’), the standard of safety, and formal rule making procedures for food additives. Congress broadly defined ‘food additive’ to include any substance the intended use of which results or may reasonably be expected to result, directly or indirectly, in its becoming a component or otherwise affecting the component of food. Congress further stated that ‘substances that are generally recognized, among experts qualified by scientific training and experience to evaluate their safety as having been adequately shown . . . to be safe under the conditions of their intended use,’ are excluded from the definition. Put simply, substances that are Generally Recognized As Safe (GRAS) under conditions of their intended use are not food additives and do not require premarket approval by FDA ¹⁰¹⁾.

For a substance to be GRAS (Generally Recognized As Safe), the scientific data and information about the use of a substance must be widely known and there must be a consensus among qualified experts that those data and information establish that the substance is safe under the conditions of its intended use ¹⁰²⁾. GRAS determinations made in this manner are said to be made through scientific procedures. For a food additive, privately held data and information about the use of a substance are sent by the sponsor to FDA, which evaluates those data and information to determine whether they establish that the substance is safe under the conditions of its intended use (21 CFR 171.1). Thus, for a food additive, FDA determines the safety of the ingredient; whereas a determination that an ingredient is GRAS can be made by qualified experts outside of government.

There is, however, an additional way that a GRAS determination can be made. For a substance used in food before 1958, a GRAS determination can be made through experience based on common use in food. It should be noted that determinations based on common use in food require a substantial history of consumption in food by a significant number of consumers (21 CFR 170.30(c) and 170.3(f)), and that this basis for GRAS determination is seldom relied on today ¹⁰³⁾.

Lastly, the FDA concluded by saying that “Irrespective of whether a substance is deemed to be GRAS or if its safety is established through a premarket approval process, the safety determination is always limited to the substance’s intended conditions of use” ¹⁰⁴⁾.

How is the safety of food additives evaluated in European Union ?

EFSA assesses the safety of the food additives. The substances are evaluated based on a dossier, usually provided by an applicant (normally the producer or a potential user of the food additive). This dossier must contain the chemical identifications of the additive, its manufacturing process, methods of analyses and reaction and fate in food, the case of need, the proposed uses and toxicological data.

The toxicological data must contain information on metabolism, sub-chronic and chronic toxicity, carcinogenicity; genotoxicity, reproduction and developmental toxicity and, if required, other studies.

Based on this data, EFSA determines the level below which the intake of the substance can be considered safe – the so-called Acceptable Daily Intake (ADI). At the same time, EFSA also estimates, based on the proposed uses in the different foodstuffs requested, whether this Acceptable Daily Intake (ADI) can be exceeded.

In case the Acceptable Daily Intake (ADI) will not be exceeded, the use of the food additive is considered safe.

What are some major concerns with food additives ?

Most concerns about food additives have to do with man-made ingredients that are added to foods. Some of these are:

• Antibiotics given to food-producing animals, such as chickens and cows
• Antioxidants in oily or fatty foods
• Artificial sweeteners, such as aspartame, saccharin, sodium cyclamate, and sucralose
• Benzoic acid in fruit juices
• Lecithin, gelatins, cornstarch, waxes, gums, and propylene glycol in food stabilizers and emulsifiers
• Many different dyes and coloring substances
• Monosodium glutamate (MSG)
• Nitrates and nitrites in hot dogs and other processed meat products
• Sulfites in beer, wine, and packaged vegetables.

The United States Food and Drug Administration (FDA) has a list of food additives that are thought to be safe.

• International Food Information Council (IFIC) and U.S. Food and Drug Administration – Overview of Food Ingredients, Additives & Colors database, is available on the internet: at ¹⁰⁵⁾ https://www.fda.gov/Food/IngredientsPackagingLabeling/FoodAdditivesIngredients/ucm091048.htm

Many have not been tested, but most scientists consider them safe. These substances are put on the “generally recognized as safe (GRAS)” list. This list contains about 700 items.

• U.S. Food and Drug Administration GRAS Notices Database is available on the internet: at ¹⁰⁶⁾ https://www.accessdata.fda.gov/scripts/fdcc/?set=GRASNotices

Congress defines safe as “reasonable certainty that no harm will result from use” of an additive. Examples of items on this list are: guar gum, sugar, salt, and vinegar. The list is reviewed regularly.

Some substances that are found to be harmful to people or animals may still be allowed, but only at the level of 1/100th of the amount that is considered harmful ¹⁰⁷⁾. For their own protection, people with any allergies or food intolerances should always check the ingredient list on the label. Reactions to any additive can be mild or severe. For example, some people with asthma have worsening of their asthma after eating foods or drinks that contain sulfites ¹⁰⁸⁾.

What are the benefits of food additives for the consumer ?

The EU legislation provides that food additives must have advantages and benefits for the consumer ¹⁰⁹⁾. Therefore, they have to serve one or more of the following purposes:

• preserve the nutritional quality of the food;
• provide necessary ingredients or constituents for foods manufactured for groups of consumers with special dietary needs;
• enhance the keeping quality or stability of a food or improving its organoleptic properties, provided that the consumer is not misled;
• aid the manufacture, processing, preparation, treatment, packing, transport or storage of food, including food additives, food enzymes and food flavourings, provided that the food additive is not used to disguise faulty raw materials or cover up unhygienic practices.

Food colors may mislead the consumer – why are they authorized ?

The use of food colors is considered acceptable for the following purposes:

• to restore the original appearance of food of which the color has been affected by processing, storage, packaging and distribution;
• to make food more visually appealing;
• to give colour to food otherwise colourless.

The use of food colors must always comply with the general condition that they do not mislead the consumer. For example, the use of colours should not give the impression that it contains ingredients that have never been added.

Is it possible to consume food additives at dangerously high levels ?

When EFSA estimates the possible exposure to a food additive, it considers the maximum level requested to be added in the different foodstuffs. In addition, EFSA assumes that the largest quantities of these foodstuffs are eaten on a daily basis. Only when this estimated exposure via the different foodstuffs remains below the Acceptable Daily Intake (ADI), EFSA will consider that the proposed use of the substances is safe. If the Acceptable Daily Intake (ADI) is exceeded, the Commission can decide to restrict the use of the additive or not to authorise it at all.

The presence of food additives should therefore be considered safe even for consumers that eat large quantities of foodstuffs to which the additives have been used at the maximum permitted level.

Do food additives cause childhood hyperactivity or ADHD?

Although this hypothesis was popularized in the 1970’s, results from studies on this issue either have been inconclusive, inconsistent, or difficult to interpret due to inadequacies in study design ¹¹⁰⁾. A Consensus Development Panel of the National Institutes of Health concluded in 1982 that for some children with attention deficit hyperactivity disorder (ADHD) and confirmed food allergy, dietary modification has produced some improvement in behavior. Although the panel said that elimination diets should not be used universally to treat childhood hyperactivity, since there is no scientific evidence to predict which children may benefit, the panel recognized that initiation of a trial of dietary treatment or continuation of a diet in patients whose families and physicians perceive benefits may be warranted. However, a 1997 review published in the Journal of the American Academy of Child & Adolescent Psychiatry noted there is minimal evidence of efficacy and extreme difficulty inducing children and adolescents to comply with restricted diets. Thus, dietary treatment should not be recommended, except possibly with a small number of preschool children who may be sensitive to tartrazine, known commonly as FD&C Yellow No.5. In 2007, synthetic certified color additives again came under scrutiny following publication of a study commissioned by the UK Food Standards Agency to investigate whether certain color additives cause hyperactivity in children. Both the FDA and the European Food Safety Authority independently reviewed the results from this study and each has concluded that the study does not substantiate a link between the color additives that were tested and behavioral effects ¹¹¹⁾.

In the meantime, if your child shows signs of hyperactivity, cutting out foods that contain these colours (tartrazine (102), quinoline yellow (104), sunset yellow FCF (110), carmoisine (122), ponceau 4R (124) and allura red AC (129)) from their diet could help. However, if you think you or your child has an intolerance or allergy to any food or food additive, seek advice from your medical practitioner or dietitian – just cutting out certain foods may not be the answer.

Can any substance be used as food additive ?

Only food additives that are listed in the EU legislation can be added to food and this can be done only under specific conditions.

Additives causing minimum toxicological concerns may be added in almost all processed foodstuffs. Examples include calcium carbonate (E 170), lactic acid (E 270), citric acid (E 330), pectins (E 440), fatty acids (E 570) and nitrogen (E 941).

For other additives the use is more restricted, for example:

• Natamycin (E 235) can only be used as preservative for the surface treatment of cheese and dried sausages
• Erythorbic acid (E 315) can only be used as antioxidant in certain meat and fish products
• Sodium ferrocyanide (E 535) can only be used as anti-caking agent in salt and its substitutes

Can food additives be used in all foodstuffs ?

In some foodstuffs the use of additives is very limited. For unprocessed foodstuffs such as milk, fresh fruit and vegetables, fresh meat and water only a few additives are authorised.

The more a foodstuff is processed, the more additives are authorised and used. Confectionary, savoury snacks, flavoured beverages and desserts are some products falling under this category of highly processed foodstuffs, where a lot of additives are authorised for use.

List of Generally Recognized as Safe (GRAS) in the US

“GRAS” is an acronym for the phrase Generally Recognized As Safe. Under sections 201(s) and 409 of the Federal Food, Drug, and Cosmetic Act (the Act), any substance that is intentionally added to food is a food additive, that is subject to premarket review and approval by FDA, unless the substance is generally recognized, among qualified experts, as having been adequately shown to be safe under the conditions of its intended use, or unless the use of the substance is otherwise excepted from the definition of a food additive ¹¹²⁾.

U.S. Food and Drug Administration GRAS Notices Database is available on the internet: at ¹¹³⁾ https://www.accessdata.fda.gov/scripts/fdcc/?set=GRASNotices

List of Authorized Food Additives in the US

International Food Information Council (IFIC) and U.S. Food and Drug Administration – Overview of Food Ingredients, Additives & Colors database, is available on the internet: at ¹¹⁴⁾ https://www.fda.gov/Food/IngredientsPackagingLabeling/FoodAdditivesIngredients/ucm091048.htm

List of Authorized Food Additives in the European Union

The additives that are authorised in foodstuffs and their conditions of use are listed Annex II of Regulation (EC) No 1333/2008 on food additives. Only additives that are in that list are authorised under specific conditions. The additives are listed on the basis of the categories of food to which they may be added.

The Commission’s food additive database, is available on the internet: at ¹¹⁵⁾  https://webgate.ec.europa.eu/foods_system/main/?event=substances.search&substances.pagination=1

Through this database the consumer or business operator can find out what additives are authorised in a particular food.

List of food preservatives and food additives with permissions in the US and Europe

The table below provides information on the most often cited examples of additives banned in the United States or Europe.

All the food additives listed in the tables below have been allocated a Codex Alimentarius food additive name and number (INS stands for International Numbering System).

In cases where manufacturers have never sought permission to use an additive this is noted as “no permission sought”.

Colours
INS Number	Name (Food Standards Code)	US name	US permission1	EU permission2
102	Tartrazine	FD+C Yellow No 5	, CFR §74.705	, Regulation (EC) No 1333/2008
104	Quinoline yellow FCF	D+C Yellow No 10	food	, Regulation (EC) No 1333/2008
110	Sunset yellow	FD+C Yellow No 6	, CFR §74.706	, Regulation (EC) No 1333/2008
122	Azorubine/Carmoisine		No permission sought	, Regulation (EC) No 1333/2008
123	Amaranth	FD+C Red No 2	, Banned CFR §81.10, §81.30 (see earlier discussion and explanation)	, Regulation (EC) No 1333/2008
124	Ponceau 4R		No permission sought	, Regulation (EC) No 1333/2008
127	Erythrosine	FD+C Red No 3	, CFR §74.303	, Regulation (EC) No 1333/2008
129	Allura red AC	FD+C Red No 40	, CFR §74.340	, Regulation (EC) No 1333/2008
132	Indigotine	FD+C Blue No 2	, CFR §74.102	, Regulation (EC) No 1333/2008
133	Brilliant blue FCF	FD+C Blue No 1	, CFR §74.101	, Regulation (EC) No 1333/2008
142	Green S		No permission sought	, Regulation (EC) No 1333/2008
151	Brilliant black BN		No permission sought	, Regulation (EC) No 1333/2008
153	Vegetable carbon	Carbon black	, Banned CFR §81.10 (see earlier discussion and explanation)	, Regulation (EC) No 1333/2008
155	Brown HT		No permission sought	, Regulation (EC) No 1333/2008
Other food additives
INS Number	Name (Food Standards Code)	US name	US permission1	EU permission2
320	Butylated hydroxyanisole	Butylated hydroxyanisole	, CFR §172.110	, Regulation (EC) No 1333/2008
342	Ammonium phosphates	Ammonium phosphate, monobasic Ammonium phosphate, dibasic	GRAS (generally recognised as safe), §184.1141a §184.1141b	No permission sought
349	Ammonium malate			No permission sought
952	Cyclamate or calcium cyclamate or sodium cyclamate	Cyclamate and its derivatives	, Banned §189.135 (see earlier discussion and explanation)	, Regulation (EC) No 1333/2008

1. Colors and food additive permissions have been checked against the requirements of the US Code of Federal Regulations (CFR) Title 21 – Food and Drugs which is written, amended and enforced by the US Food and Drug Administration (US FDA). The individual standards from the CFR relevant to the food additive is provided; § stands for section of the CFR.

2. The European permissions have been checked against the European food additive legislation – i.e. Regulation (EC) No 1333/2008 of the European Parliament and of the Council of 16 December 2008 on food additives. The legislation lists the permitted food additives as well as their conditions of use.

Note: Last updated December 2012

[Source ¹¹⁶⁾]

Food colors and food additives reported as banned

Sometimes food colors and other food additives are reported as “banned” in some countries but permitted in others.

A lack of permission in a country is not the same thing as a ban. It may mean manufacturers have never sought permission to use the additive, usually because alternatives are approved.

Sometimes additives are not approved because of circumstances unique to a country (e.g. different dietary exposure).

Different countries also have their own food regulatory systems and legislation. This can mean an additive may have been banned many years ago, however scientific evidence since then has proven it is safe. For example, there is legislation in the US that prevents permission of additives if there is any evidence (in animal studies) that the additive is carcinogenic. Because of this legislation, some additives were banned in the 1970s – 1980s due to animal studies indicating the chemicals were carcinogenic. Subsequent studies by other agencies (e.g. the Joint Food and Agricultural Organization/World Health Organization Expert Committee on Food Additives (JECFA) and the European Food Safety Authority (EFSA) have not supported these earlier conclusions. While there have been changes in science and new evidence, the US legislation remains in place.

All additives undergo a thorough safety assessment before being approved for use in humans.

Examples of food additives cited as “banned”

These additives are often cited as banned in the US but permitted in Europe, Australia and New Zealand.

• Amaranth (INS 123)

The US terminated the provisional listing for the colour Amaranth for use in food in 1977.

Since that time the European Food Safety Authority (EFSA) and the Joint Food and Agricultural Organization/World Health Organization Expert Committee on Food Additives (JECFA) have both assessed more recent studies and have both concluded that Amaranth is not carcinogenic.

Read more about EFSA’s assessment of Amaranth here ¹¹⁷⁾.

• Vegetable carbon (carbon black), INS 153

This color is not permitted in the US if it is produced by certain production processes. This decision was made because of the possible presence of polycyclic aromatic hydrocarbons.

However EFSA’s recent 2012 review of the safety of carbon black (vegetable carbon) came to a different conclusion due to the very large margins of exposure of dietary exposure to the color. Margin of exposure values indicate the differences between levels that people may consume in their diet and the levels shown to induce cancer.

Read more about EFSA’s review here ¹¹⁸⁾.

• Cyclamate, INS 952

Cyclamate was banned as an intense sweeter in the US in 1970 due to a 1969 rat study implicating the additive as a rat bladder carcinogen. However other studies since this time could not replicate these results. Other US agencies (the Cancer Assessment Committee of the FDA and the National Academy of Sciences) later concluded it is not a carcinogen.

Food Standards Australia New Zealand (FSANZ) assessed the safety of cyclamate and concluded that it is a safe food additive. Food Standards Australia New Zealand reduced the maximum permitted level for cyclamates in water-based flavoured drinks to ensure exposure to cyclamates for all consumers is safe.

Food Standards Australia New Zealand (FSAN) reviewed permission for cyclamate in 2007 ¹¹⁹⁾.

• Butylated hydroxyanisole (BHA), INS 320

Butylated hydroxyanisole (BHA) is authorized alone, or in combination with other antioxidants such as gallates, tertiary butylhydroquinone and butylated hydroxytoluene, for a wide range of different food categories in Europe.

Butylated hydroxyanisole (BHA) is also permitted for a variety of foods in the United States, as well as by many other food regulators around the world. It is also permitted in a variety of food categories in the Codex General Standard for Food Additives (GSFA).

• Ammonium phosphates, INS 342

These food additives are generally recognised as safe (GRAS) in the US. They are not listed as permitted in the European food additive legislation. It is possible that no request for permission of the food additives has been sought.

• Ammonium malate, INS 349

This food additive does not appear to have a permission in the US or Europe. Again it is possible that no request has been sought for its permission. It is permitted in the Australia New Zealand Food Standards Code.

Animal studies

From time to time there are media reports about additives causing cancer in animals. It’s important to note substances that cause cancer or illness is animals don’t always cause cancer in humans because these substances act in very different ways in people. A good example of this is chocolate, which can be deadly to dogs but doesn’t affect humans.

Some chemicals can cause adverse effects at high doses, as used in animal safety studies, but are innocuous at low doses. This may occur because the body is unable to detoxify the chemical above certain levels – a type of overload situation. Effects seen at such high levels may not be relevant to the much lower levels in food as consumed. Therefore when adverse effects are reported in animal studies this does not mean that the same effects will be caused when people eat the substance.

Table 1. Numeric Food Additives List (Symbols used in this list: A or α = alpha; β = beta; δ = delta; γ = gamma)

NUMBER	ADDITIVE
–	Sodium hydrosulphite
100	Curcumin or turmeric
101	Riboflavin
101	Riboflavin-5′-phosphate sodium
102	Tartrazine
103	Alkanet or Alkannin
104	Quinoline yellow
110	Sunset yellow FCF
120	Cochineal or carmines or carminic acid
122	Azorubine or Carmoisine
123	Amaranth
124	Ponceau 4R
127	Erythrosine
129	Allura red AC
132	Indigotine
133	Brilliant Blue FCF
140	Chlorophyll
141	Chlorophyll-copper complex
141	Chlorophyllin copper complex, sodium and potassium salts
142	Green S
143	Fast green FCF
150a	Caramel I
150b	Caramel II
150c	Caramel III
150d	Caramel IV
151	Brilliant black BN or Brilliant Black PN
153	Carbon blacks or Vegetable carbon
155	Brown HT

160a	Carotene
160b	Annatto extracts
160c	Paprika oleoresins

160d	Lycopene
160e	b-apo-8′-Carotenal
160f	b-apo-8′-Carotenoic acid methyl or ethyl ester
161a	Flavoxanthin
161b	Lutein
161c	Kryptoxanthin
161d	Rubixanthin
161e	Violoxanthin
161f	Rhodoxanthin
162	Beet red
163	Anthocyanins or Grape skin extract or Blackcurrant extract
164	Saffron or crocetin or crocin
170	Calcium carbonate
171	Titanium dioxide
172	Iron oxide
173	Aluminium
174	Silver
175	Gold
181	Tannic acid or tannins
200	Sorbic acid
201	Sodium sorbate
202	Potassium sorbate
203	Calcium sorbate
210	Benzoic acid
211	Sodium benzoate
212	Potassium benzoate
213	Calcium benzoate
216	Propylparaben or Propyl-p-hydroxy-benzoate

218	Methylparaben or Methyl-p-hydroxy-benzoate
220	Sulphur dioxide
221	Sodium sulphite
222	Sodium bisulphite
223	Sodium metabisulphite
224	Potassium metabisulphite
225	Potassium sulphite
228	Potassium bisulphite
234	Nisin
235	Natamycin or pimaricin
243	Ethyl lauroyl arginate
249	Potassium nitrite
250	Sodium nitrite
251	Sodium nitrate
252	Potassium nitrate
260	Acetic acid, glacial
261	Potassium acetate or Potassium diacetate
262	Sodium acetate
262	Sodium diacetate
263	Calcium acetate
264	Ammonium acetate
270	Lactic acid
280	Propionic acid
281	Sodium propionate
282	Calcium propionate
283	Potassium propionate
290	Carbon dioxide
296	Malic acid
297	Fumaric acid
300	Ascorbic acid
301	Sodium ascorbate
302	Calcium ascorbate

303	Potassium ascorbate
304	Ascorbyl palmitate
307b	Tocopherols concentrate, mixed
307	α-Tocopherol
308	δ-Tocopherol
309	γ-Tocopherol
310	Propyl gallate
311	Octyl gallate
312	Dodecyl gallate
315	Erythorbic acid
316	Sodium erythorbate
319	tert-Butylhydroquinone
320	Butylated hydroxyanisole
321	Butylated hydroxytoluene
322	Lecithin
325	Sodium lactate
326	Potassium lactate
327	Calcium lactate
328	Ammonium lactate
329	Magnesium lactate
330	Citric acid
331	Sodium citrate
331	Sodium dihydrogen citrate
332	Potassium citrate
332	Potassium dihydrogen citrate
333	Calcium citrate
334	Tartaric acid
335	Sodium tartrate
336	Potassium tartrate or Potassium acid tartrate
337	Potassium sodium tartrate
338	Phosphoric acid
339	Sodium phosphate, dibasic

339	Sodium phosphate, monobasic
339	Sodium phosphate, tribasic
340	Potassium phosphate, dibasic
340	Potassium phosphate, monobasic
340	Potassium phosphate, tribasic
341	Calcium phosphate, dibasic or calcium hydrogen phosphate
341	Calcium phosphate, monobasic or calcium dihydrogen phosphate
341	Calcium phosphate, tribasic
342	Ammonium phosphate, dibasic
342	Ammonium phosphate, monobasic or Ammonium dihydrogen phosphates
343	Magnesium phosphate, dibasic
343	Magnesium phosphate, monobasic
343	Magnesium phosphate, tribasic
349	Ammonium malate
350	Sodium hydrogen malate
350	Sodium malate
351	Potassium malate
352	Calcium malate
353	Metatartaric acid
354	Calcium tartrate
355	Adipic acid
357	Potassium adipate
359	Ammonium adipates
363	Succinic acid
365	Sodium fumarate
366	Potassium fumarate
367	Calcium fumarate
368	Ammonium fumarate
380	Ammonium citrate
380	Triammonium citrate
381	Ferric ammonium citrate

385	Calcium disodium ethylenediaminetetraacetate or calcium disodium EDTA
400	Alginic acid
401	Sodium alginate
402	Potassium alginate
403	Ammonium alginate
404	Calcium alginate
405	Propylene glycol alginate
406	Agar
407	Carrageenan
407a	Processed eucheuma seaweed
409	Arabinogalactan or larch gum
410	Locust bean gum or carob bean gum
412	Guar gum
413	Tragacanth gum
414	Acacia or gum arabic
415	Xanthan gum
416	Karaya gum
417	Tara gum
418	Gellan gum
420	Sorbitol or sorbitol syrup
421	Mannitol
422	Glycerin or glycerol
431	Polyoxyethylene (40) stearate
433	Polysorbate 80 or Polyoxyethylene (20) sorbitan monooleate
435	Polysorbate 60 or Polyoxyethylene (20) sorbitan monostearate
436	Polysorbate 65 or Polyoxyethylene (20) sorbitan tristearate
440	Pectin
442	Ammonium salts of phosphatidic acid
444	Sucrose acetate isobutyrate

445	Glycerol esters of wood rosins
450	Potassium pyrophosphate
450	Sodium acid pyrophosphate
450	Sodium pyrophosphate
451	Potassium tripolyphosphate
451	Sodium tripolyphosphate
452	Potassium polymetaphosphate
452	Sodium metaphosphate, insoluble
452	Sodium polyphosphates, glassy
455	Yeast mannoproteins
460	Cellulose microcrystalline
460	Cellulose, powdered
461	Methyl cellulose
463	Hydroxypropyl cellulose
464	Hydroxypropyl methylcellulose
465	Methyl ethyl cellulose
466	Sodium carboxymethylcellulose
470	Fatty acid salts of aluminium, ammonia, calcium, magnesium, potassium and sodium
471	Mono- and di-glycerides of fatty acids
472a	Acetic and fatty acid esters of glycerol
472b	Lactic and fatty acid esters of glycerol
472c	Citric and fatty acid esters of glycerol
472e	Diacetyltartaric and fatty acid esters of glycerol
472f	Mixed tartaric, acetic and fatty acid esters of glycerol or tartaric, acetic and fatty acid esters of glycerol (mixed)
473	Sucrose esters of fatty acids
475	Polyglycerol esters of fatty acids
476	Polyglycerol esters of interesterified ricinoleic acid
477	Propylene glycol mono- and di-esters or Propylene glycol esters of fatty acids
480	Dioctyl sodium sulphosuccinate
481	Sodium lactylate

481	Sodium oleyl lactylate
481	Sodium stearoyl lactylate
482	Calcium lactylate
482	Calcium oleyl lactylate
482	Calcium stearoyl lactylate
491	Sorbitan monostearate
492	Sorbitan tristearate
500	Sodium bicarbonate
500	Sodium carbonate
501	Potassium bicarbonate
501	Potassium carbonate
503	Ammonium carbonate
503	Ammonium hydrogen carbonate
504	Magnesium carbonate
507	Hydrochloric acid
508	Potassium chloride
509	Calcium chloride
510	Ammonium chloride
511	Magnesium chloride
512	Stannous chloride
514	Sodium sulphate
515	Potassium sulphate
516	Calcium sulphate
518	Magnesium sulphate
519	Cupric sulphate
526	Calcium hydroxide
529	Calcium oxide
530	Magnesium oxide
535	Sodium ferrocyanide
536	Potassium ferrocyanide
541	Sodium aluminium phosphate

542	Bone phosphate
551	Silicon dioxide, amorphous
552	Calcium silicate
553	Magnesium silicate or Talc
554	Sodium aluminosilicate
555	Potassium aluminium silicate
556	Calcium aluminium silicate
558	Bentonite
559	Aluminium silicate
560	Potassium silicate
570	Stearic acid or fatty acid
575	Glucono δ-lactone or Glucono delta-lactone
576	Sodium gluconate
577	Potassium gluconate
578	Calcium gluconate
579	Ferrous gluconate
580	Magnesium gluconate
586	4-hexylresorcinol
620	L-glutamic acid
621	Monosodium L-glutamate or MSG
622	Monopotassium L-glutamate
623	Calcium glutamate
624	Monoammonium L-glutamate
625	Magnesium glutamate
627	Disodium-5′-guanylate
631	Disodium-5′-inosinate
635	Disodium-5′-ribonucleotides
636	Maltol
637	Ethyl maltol
640	Glycine
641	L-Leucine

900a	Polydimethylsiloxane or Dimethylpolysiloxane
901	Beeswax, white and yellow
903	Carnauba wax
904	Shellac
905b	Petrolatum or petroleum jelly
914	Oxidised polyethylene
920	L-cysteine monohydrochloride
941	Nitrogen
942	Nitrous oxide
943a	Butane
943b	Isobutane
944	Propane
946	Octafluorocyclobutane
950	Acesulphame potassium
951	Aspartame
952	Cyclamate or calcium cyclamate or sodium cyclamate
953	Isomalt
954	Saccharin
955	Sucralose
956	Alitame
957	Thaumatin
961	Neotame
960	Steviol glycosides
962	Aspartame-acesulphame salt
965	Maltitol and maltitol syrup or hydrogenated glucose syrup
966	Lactitol
967	Xylitol
968	Erythritol
969	Advantame
999(i)	Quillaia extract (type 1)

999(ii)	Quillaia extract (type 2)
1001	Choline salts
1100	α-Amylase
1101	Proteases (papain, bromelain, ficin)
1102	Glucose oxidase
1104	Lipases
1105	Lysozyme
1200	Polydextrose
1201	Polyvinylpyrrolidone
1400	Dextrin roasted starch
1401	Acid treated starch
1402	Alkaline treated starch
1403	Bleached starch
1404	Oxidised starch
1405	Enzyme treated starches
1410	Monostarch phosphate
1412	Distarch phosphate
1413	Phosphated distarch phosphate
1414	Acetylated distarch phosphate
1420	Starch acetate
1422	Acetylated distarch adipate
1440	Hydroxypropyl starch
1442	Hydroxypropyl distarch phosphate
1450	Starch sodium octenylsuccinate
1451	Acetylated oxidised starch

1505	Triethyl citrate
1518	Triacetin
1520	Propylene glycol
1521	Polyethylene glycol 8000
1522	Calcium lignosulphonate (40-65)

Note: Last Updated June 2016

[Source ¹²⁰⁾