Butylated hydroxyanisole: Carcinogenic food additive to be avoided or harmless antioxidant important to protect food supply?

Tumor data from rodent bioassays are used for cancer hazard classification with wide-ranging consequences. This paper presents a case study of the synthetic antioxidant butylated hydroxyanisole (BHA), which IARC classified as Group 2B ("possibly carcinogenic to humans") on the basis of forestomach tumors in rodents following chronic dietary exposure to high levels. IARC later determined that the mechanism by which BHA induces forestomach tumors is not relevant to humans; however, the classification has not been revoked. BHA was listed on California Proposition 65 as a direct consequence of the IARC classification, and there is widespread concern among consumers regarding the safety of BHA driven by the perception that it is a carcinogen. While many regulatory agencies have established safe exposure limits for BHA, the IARC classification and Proposition 65 listing resulted in the addition of BHA to lists of substances banned from children's products and products seeking credentials such as EPA's Safer Choice program, as well as mandatory product labeling. Classifications have consequences that many times pre-empt the ability to conduct an exposure-based risk-based assessment., It is imperative to consider human relevance of both the endpoint and exposure conditions as fundamental to hazard identification.

[Classic and new-generation commercial thickeners. Organoleptic qualities and usefulness in the diagnostic tests of dysphagia]. / Espesantes comerciales clásicos y de nueva generación. Cualidades organolépticas y utilidad en las pruebas diagnósticas de la disfagia.

INTRODUCTION: Introduction: thickeners are widely used in swallowing disorders, both for diagnosis and to achieve a safe and effective diet. Recently, products composed of gums have been commercialized in the Spanish market in order to improve the organoleptic and physical qualities of thickened foods. Objective: to compare thickening agents of clinical scope marketed in Spain, and to verify their organoleptic and physical characteristics, to be used in the diagnostic procedures and the feeding of patients with dysphagia. Method: the organoleptic (appearance, colour, smell, taste, aftertaste) and physical (solubility, stability) properties of eight thickeners (4 classic starch-based and 4 new gum-based) were assessed in a sample of 44 healthy subjects. In addition, their usefulness in diagnostic tests was studied by mixing them with dyes and water-soluble contrasts. Results and conclusions: new-generation thickeners, based on gums, generally obtain better scores for their physical and organoleptic qualities than conventional thickeners. Starch thickeners are more suitable for diagnostic tests, as gum thickeners present some peculiarities in their mixtures with dyes and contrasts that must be taken into account in diagnostic tests.

INTRODUCCIÓN: Introducción: los espesantes son muy utilizados en los trastornos de la deglución, tanto para su diagnóstico como para conseguir una alimentación segura y eficaz. Recientemente se han comercializado en el mercado español productos compuestos por gomas con el fin de mejorar las cualidades organolépticas y físicas de los alimentos espesados. Objetivo: comparar agentes espesantes de ámbito clínico comercializados en España y verificar sus características organolépticas y físicas para ser utilizados en los procedimientos diagnósticos y en la alimentación del paciente con disfagia. Método: se valoraron las propiedades organolépticas (apariencia, color, olor, sabor y regusto) y físicas (solubilidad y estabilidad) de ocho espesantes (4 clásicos con almidón y 4 nuevos a base de gomas) en una muestra de 44 sujetos sanos. Además, se estudió su utilidad en las pruebas diagnósticas al mezclarlos con colorantes y contrastes hidrosolubles. Resultados y conclusiones: los espesantes de nueva generación, a base de gomas, obtienen en general mejores puntuaciones en sus cualidades físicas y organolépticas con respecto a los espesantes convencionales. Los espesantes con almidón son más adecuados en las pruebas diagnósticas, ya que los espesantes con gomas presentan algunas peculiaridades en las mezclas con colorantes y contrastes que deben ser tenidas en cuenta en dichas pruebas.

How the 62-year old Delaney Clause continues to thwart science: Case study of the flavor substance ß-myrcene.

The Delaney Clause is a provision of the 1958 Food Additive Amendment to the Food, Drug and Cosmetic Act of 1938 which stipulates that if a substance is found by the Food and Drug Administration to be carcinogenic in any species of animal or in humans, then it cannot be used as a food additive. This paper presents a case study of ß-myrcene, one of seven synthetic substances that was challenged under the Delaney Clause, ultimately resulting in revocation of its regulatory approval as a food additive despite a lack of safety concern. While it is listed as a synthetic flavor in 21 CFR 172.515, ß-myrcene is also a substance naturally occurring in a number of dietary plants. The exposure level to naturally-occurring ß-myrcene is orders of magnitude higher (estimated to be 16,500 times greater) than the exposure via ß-myrcene added to food as a flavoring substance. The National Toxicology Program conducted genotoxicity testing (negative), a 13-week range-finding study, and a two-year cancer bioassay in B6C3F1 mice and F344/N rats. An increase in liver tumors was seen in male mice and kidney tumors in male rats, ultimately resulting in ß-myrcene being classified by IARC as a Class 2B carcinogen and being listed on California Proposition 65; in contrast, ß-myrcene is not classified as a carcinogen by any other regulatory authority. The doses administered in the NTP bioassay were five-six orders of magnitude higher than human exposures, and the FDA concluded after a thorough evaluation that there was no safety concern associated with the use of ß-myrcene as a flavor substance at the current use level. The Delaney Clause, however, does not consider the exposure potential or the human health relevance of effects observed in animals. The lack of options available to the US FDA led to the 2018 decision to remove ß-myrcene from the list of approved food additives. This revocation has contributed to the ongoing erosion of trust in regulatory agencies (and industry), which has both economic implications for food manufacturers and consumers alike, and implications for consumer perception of safety of the US food supply. It is time for us to reconsider the rationale behind any legislation that relies on classification alone, and whether there is, in fact, a reason to still classify nongenotoxic carcinogens at all.

[Hypersensitivity reactions to food additives]. / Reacciones de hipersensibilidad a aditivos alimentarios.

Food additives are ingredients that are intentionally added to food in order to modify its physical, chemical, biological, or sensorial characteristics. Food additives may act as allergens and generate IgE-mediated immune reactions, or they may act as pseudo allergens and generate non-IgE-mediated immune reactions. Such reactions can generate diverse clinical pictures or they may exacerbate diseases as diverse as eosinophilic esophagitis, bronchial asthma, atopic dermatitis, contact dermatitis, chronic urticaria, or anaphylaxis. Thousands of food additives are being used daily in industrialized countries and, although their use has been globalized, there is not much science information about their adverse effects; especially about their hypersensitivity reactions that, despite being reported in literature as rare, it is probably because they are under-diagnosed due to the fact that they require a high level of clinical suspicion by the physician, and the proof of a causal connection between the symptomatology and the food additive. Hypersensitivity reactions to food additives must be suspected in patients who report symptoms with the intake of multiple commercially prepared foods or to a commercially prepared food without presenting symptoms with the intake of the natural or homemade version of the same food or with the presence of idiopathic reactions. The diagnostic role of the in vivo or in vitro test against IgE (Skin Tests or RAST) is limited to some natural food additives. The gold standard diagnosis that shows causality between the additive and the symptoms is the oral food challenge. The treatment shall always be the elimination of the food additive from the patient's diet.

Los aditivos alimentarios son ingredientes agregados intencionalmente para modificar las características físicas, químicas, biológicas o sensoriales de los alimentos; pueden actuar como alérgenos y generar reacciones inmunológicas mediadas por IgE o como pseudoalérgenos y generar reacciones inmunológicas no mediadas por IgE. Dichas reacciones pueden provocar diversos cuadros clínicos o exacerbar diferentes enfermedades: esofagitis eosinofílica, asma bronquial, dermatitis atópica, dermatitis de contacto, urticaria crónica o anafilaxia. Diariamente, miles de aditivos alimentarios son utilizados en países industrializados y aunque su uso se ha globalizado, se dispone de poca información científica sobre sus efectos adversos, particularmente sobre las reacciones de hipersensibilidad, las cuales son raras en la literatura, muy probablemente porque son infradiagnosticadas debido a que requieren un alto grado de sospecha clínica por parte del médico y la demostración de una relación de causalidad entre la sintomatología y el aditivo alimentario. Las reacciones de hipersensibilidad a aditivos alimentarios deben ser sospechadas en paciente con reporten síntomas a múltiples alimentos o a un alimento de preparación comercial sin sintomatología ante la ingesta natural o casera del mismo o ante reacciones idiopáticas. El papel diagnóstico de la prueba in vivo o in vitro contra IgE (pruebas cutáneas o RAST) está limitado a algunos aditivos alimentarios naturales. La prueba diagnóstica que demuestra causalidad entre el aditivo y la sintomatología es el reto oral alimentario. El tratamiento deberá ser siempre la eliminación del aditivo de la dieta.

Hypersensitivity reactions to food and drug additives: problem or myth?

BACKGROUND AND AIM OF THE WORK: The possibility of an allergic reaction or an intolerance to additives is frequently suspected by parents, especially for chronic illness with frequent exacerbations such as atopic dermatitis or chronic urticaria. For more than 50 years, potential adverse reactions to additives have been suggested, but to date data are conflicting. The purpose of this article is to provide the clinicians with general information about additives and adverse reactions to them and to suggest a practical approach to children suspected to have reactions to food additives. METHODS: We performed an extensive research on all English-language Medline articles, case reports and reviews published online until December 2018. Used search terms were: food additives, food dye, adverse reactions, food allergy, food hypersensitivity, intolerance, drugs, children. RESULTS: There are only few case reports of adverse reactions in childhood with a clear involvement of additives. In this review article we reported the associations between additives and adverse reactions described in literature, in order to inform the pediatrician about the potential clinical manifestations. CONCLUSIONS: Prior to suspect an adverse reaction to additives, it is important to rule out other possible causes: the diagnostic process is complicated and rarely conclusive. The gold standard is the double-blind placebo controlled oral challenge after an exclusion diet.

Analytical methods in food additives determination: Compounds with functional applications.

This work describes the 25 classes of food additives that contain about 230 compounds with technological, sensorial and/or microbiological functionalities. These compounds are added to foods at the processing, packaging and transport steps, to improve the standard of quality, durability and stability of the product and adjust the colour, smell and flavour attributes. Food industries need to follow national and international quality standards that establish the conditions under which food additives may be used, and the food safety is guaranteed by strict quality control. This review describes the analytical techniques used in identification and quantification of food additives in foodstuffs, highlighting the main characteristics of each method (spectroscopy, chromatography and electroanalysis), and indicating the advantages and disadvantages typical of the methods used. Perspectives of the chemical analysis in the food industries are also discussed.

Children with Crohn's Disease Frequently Consume Select Food Additives.

OBJECTIVE: Certain food additives may promote the pathogenesis of Crohn's disease (CD), but thus far the evaluation of food additive exposures in humans has been limited. The objective of this study was to quantify food additive exposures in children with CD. METHODS: In a trial for bone health in CD, children were followed over 24 months with evaluation of disease characteristics, dietary intake, and body composition. At baseline, participants completed three 24-h dietary recalls. Foods were categorized, and the ingredient list for each item was evaluated for the presence of select food additives: polysorbate-80, carboxymethylcellulose, xanthan gum, soy lecithin, titanium dioxide, carrageenan, maltodextrin, and aluminosilicates. The frequency of exposures to these food additives was described for study participants and for food categories. RESULTS: At study baseline, 138 participants, mean age 14.2 ± 2.8 years, 95% having inactive or mild disease, were enrolled and dietary recalls were collected. A total of 1325 unique foods were recorded. Mean exposures per day for xanthan gum was 0.96 ± 0.72, carrageenan 0.58 ± 0.63, maltodextrin 0.95 ± 0.77, and soy lecithin 0.90 ± 0.74. The other additives had less than 0.1 exposures per day. For the 8 examined food additives, participants were exposed to a mean (SD) of 3.6 ± 2.1 total additives per recall day and a mean (SD) of 2.4 ± 1.0 different additives per day. CONCLUSION: Children with CD frequently consume food additives, and the impact on disease course needs further study.

A review of the work of the EU Reference Laboratory supporting the authorisation process of feed additives in the EU. [corrected].

This paper describes the operation of the European Union Reference Laboratory for Feed Additives (EURL) and its role in the authorisation procedure of feed additives in the European Union. Feed additives are authorised according to Regulation (EC) No. 1831/2003, which introduced a completely revised authorisation procedure and also established the EURL. The regulations authorising feed additives contain conditions of use such as legal limits of the feed additives, which require the availability of a suitable method of analysis for official control purposes under real world conditions. It is the task of the EURL to evaluate the suitability of analytical methods as proposed by the industry for this purpose. Moreover, the paper shows that one of the major challenges is the huge variety of the methodology applied in feed additive analysis, thus requiring expertise in quite different analytical areas. In order to cope with this challenge, the EURL is supported by a network of national reference laboratories (NRLs) and only the merged knowledge of all NRLs allows for a scientifically sound assessment of the analytical methods.

Comparação entre suplementos homólogos do leite humano e um suplemento comercial para recém-nascidos de muito baixo peso / Comparison between homologous human milk supplements and a commercial supplement for very low birth weight infants

OBJETIVOS: Descrever a metodologia de preparo de dois aditivos, líquido e em pó, derivados do leite humano e comparar a constituição com aditivo comercial FM85®. MÉTODOS: Foram utilizadas 40 amostras de leite humano para o preparo dos suplementos líquido e em pó. Ambos passaram por três fases de preparo: desnate, evaporação e retirada da lactose. Após essas fases, o suplemento líquido está pronto, e o em pó necessita da quarta fase - a liofilização. Em cada amostra dos suplementos líquido e em pó, foram adicionados, respectivamente, 80 mL (grupo I) e 100 mL (grupo II) de pool de leite humano de banco. Para comparação, 20 amostras de 100 mL do pool foram acrescidas de 5 g do suplemento FM85® (Nestlé) (grupo III). Realizaram-se análises de hidratos de carbono, proteína, lipídios, cálcio, fósforo, sódio, osmolalidade e conteúdo calórico, considerando diferença significativa p < 0,05. RESULTADOS: Os grupos I, II e III mostraram, respectivamente, os seguintes resultados: proteínas = 1,81, 2,38 e 1,96 g/dL (p < 0,001); hidratos de carbono = 6,70, 7,25 e 10,06 g/dL (p = 0,006); gordura = 3,75, 3,75 e 3,73 g/dL (p = 0,96); cálcio = 36,92, 44,75 e 79,37 mg/dL (p = 0,001); fósforo = 20,02, 23,28 e 56,30 mg/dL (p = 0,02); sódio = 14,32, 14,40 e 20,33 mEq/L (p = 0,143); osmolalidade = 391,45, 412,47 e 431, 00 mOsmol/kgH2O (p = 0,074); e conteúdo calórico = 67,78, 72,27 e 81,65 kcal (p = 0,001). CONCLUSÃO: Os aditivos estudados diferem significativamente do aditivo comercial FM85® em alguns de seus constituintes, e a sua constituição pode ou não atender às quantidades de nutrientes propostas pelas recomendações mais recentes.

OBJECTIVES: To describe the methodology for the preparation of two additives derived from human milk, liquid and powdered, and to compare this composition with the commercial additive FM85®. METHODS: For the preparation of the liquid and powdered supplements, 40 samples of human milk were used. Both supplements have been through three preparation phases: skimming, evaporation and lactose removal. After these phases, the liquid supplement is ready, and the powdered requires a fourth phase - lyophilization. To each sample of the liquid and powdered supplements were added, respectively, 80 mL (group I) and 100 mL (group II) of pooled banked human milk. For comparison, 20 samples of 100 mL of the pool were added to 5 g of the FM85® supplement (Nestlé) (group III). Analyses of carbohydrates, protein, lipids, calcium, phosphorus, sodium, osmolality and caloric content were performed, considering a significant difference p < 0.05. RESULTS: Groups I, II, and III showed, respectively, the following results: protein = 1.81, 2.38 and 1.96 g/dL (p < 0.001); carbohydrates = 6.70, 7.25 and 10.06 g/dL (p = 0.006); fat = 3.75, 3.75 and 3.73 g/dL (p = 0.96); calcium = 36.92, 44.75 and 79.37 mg/dL (p = 0.001); phosphorus = 20.02, 23.28 and 56.30 mg/dL (p = 0.02); sodium = 14.32, 14.40 and 20.33 mEq/L (p = 0.143); osmolality = 391.45, 412.47 and 431.00 mOsmol/kgH2O (p = 0.074); and caloric content = 67.78, 72.27 and 81.65 kcal (p = 0.001). CONCLUSION: The studied additives differ significantly from the commercial additive FM85® in some of its components, and its composition may or may not meet the quantity of nutrients suggested by the most recent recommendations.

Comparison between homologous human milk supplements and a commercial supplement for very low birth weight infants.

OBJECTIVES: To describe the methodology for the preparation of two additives derived from human milk, liquid and powdered, and to compare this composition with the commercial additive FM85®. METHODS: For the preparation of the liquid and powdered supplements, 40 samples of human milk were used. Both supplements have been through three preparation phases: skimming, evaporation and lactose removal. After these phases, the liquid supplement is ready, and the powdered requires a fourth phase - lyophilization. To each sample of the liquid and powdered supplements were added, respectively, 80 mL (group I) and 100 mL (group II) of pooled banked human milk. For comparison, 20 samples of 100 mL of the pool were added to 5 g of the FM85® supplement (Nestlé) (group III). Analyses of carbohydrates, protein, lipids, calcium, phosphorus, sodium, osmolality and caloric content were performed, considering a significant difference p < 0.05. RESULTS: Groups I, II, and III showed, respectively, the following results: protein = 1.81, 2.38 and 1.96 g/dL (p < 0.001); carbohydrates = 6.70, 7.25 and 10.06 g/dL (p = 0.006); fat = 3.75, 3.75 and 3.73 g/dL (p = 0.96); calcium = 36.92, 44.75 and 79.37 mg/dL (p = 0.001); phosphorus = 20.02, 23.28 and 56.30 mg/dL (p = 0.02); sodium = 14.32, 14.40 and 20.33 mEq/L (p = 0.143); osmolality = 391.45, 412.47 and 431.00 mOsmol/kgH(2)O (p = 0.074); and caloric content = 67.78, 72.27 and 81.65 kcal (p = 0.001). CONCLUSION: The studied additives differ significantly from the commercial additive FM85® in some of its components, and its composition may or may not meet the quantity of nutrients suggested by the most recent recommendations.

Toxicology and carcinogenesis studies of pulegone (CAS No. 89-82-7) in F344/N rats and B6C3F1 mice (gavage studies).

Several essential oils contain pulegone and are used for flavoring foods, drinks, and dental products, as fragrance agents, and in herbal medicines. Pulegone was nominated for study by the National Institute of Environmental Health Sciences based on the potential for human exposure and the absence of carcinogenicity data. Male and female F344/N rats and B6C3F1 mice received pulegone (approximately 96% pure) by gavage for 2 weeks, 3 months, or 2 years. Genetic toxicology studies were conducted in Salmonella typhimurium, Escherichia coli, and mouse peripheral blood erythrocytes. 2-WEEK STUDY IN RATS: Groups of five male and five female rats were administered 0, 37.5, 75, 150, 300, or 600 mg pulegone/kg body weight in corn oil by gavage, 5 days per week for 16 days. All male rats and nearly all female rats in the 300 and 600 mg/kg groups died prior to the end of the study. All moribund sacrifices and early deaths were attributed to liver toxicity. Mean body weight gains of males administered 37.5 or 150 mg/kg were significantly less than that of the vehicle controls. Clinical findings in 300 and 600 mg/kg rats included nasal/eye discharge, thinness, lethargy, and ruffled fur. Liver and kidney weights of dosed groups of females were generally significantly greater than those of the vehicle control group. The incidences of necrosis and cytoplasmic vacuolization of the liver in 300 and 600 mg/kg males and females were significantly greater than those in the vehicle control groups. 2-WEEK STUDY IN MICE: Groups of five male and five female mice were administered 0, 18.75, 37.5, 75, 150, or 300 mg pulegone/kg body weight in corn oil by gavage, 5 days per week for 16 days. Four females and one male in the 300 mg/kg groups died by study day 5. All early deaths were attributed to liver toxicity. Mean body weights of the dosed groups were similar to those of the vehicle controls. Clinical findings were observed only in 300 mg/kg mice and included thinness, lethargy, and ruffled fur. Liver weights of 300 mg/kg males were significantly greater than those of the vehicle controls. The incidences of cytoplasmic vacuolization and diffuse fatty change in 300 mg/kg females and necrosis in 300 mg/kg males were significantly greater than those in the vehicle controls. 3-MONTH STUDY IN RATS: Groups of 10 male and 10 female rats were administered 0, 9.375, 18.75, 37.5, 75, or 150 mg pulegone/kg body weight in corn oil by gavage, 5 days per week for 14 weeks. All rats survived until the end of the study except for one female in the 150 mg/kg group that died on day 9. Mean body weights of 75 and 150 mg/kg males and 150 mg/kg females were significantly less than those of the vehicle controls. At the end of the study, there was a small dose-related decrease in the erythron, evidenced by decreases in the hematocrit and hemoglobin values and the erythrocyte counts. An apparent erythroid response to the decreased erythron was evidenced by increased reticulocyte counts. Reduced and oxidized glutathione levels were generally increased in 75 and 150 mg/kg males and in 37.5 mg/kg or greater females. Absolute and relative liver weights of 75 and 150 mg/kg females and relative liver weights of males administered 18.75 mg/kg or greater were significantly greater than those of the vehicle controls. The absolute kidney weight of 150 mg/kg females and the relative kidney weights of all dosed groups, except 9.375 mg/kg males, were significantly greater than those of the vehicle controls. Absolute and relative thymus weights of 150 mg/kg males and females and the absolute thymus weight of 75 mg/kg males were significantly less than those of the vehicle controls. In the kidney, there was hyaline glomerulopathy in 75 mg/kg males and 150 mg/kg males and females. The incidence of renal tubule protein casts was significantly increased in the 150 mg/kg females. In the liver, incidences of bile duct hyperplasia and hepatocyte hypertrophy in 75 and 150 mg/kg males and 150 mg/kg females, hepatocyte focal necrosis in 150 mg/kg males, and oval cell hyperplasia and periportal fibrosis in 150 mg/kg males and females were increased. Incidences of bone marrow hyperplasia in 37.5 mg/kg males and 75 and 150 mg/kg males and females, heart mineralization in 150 mg/kg males, glandular stomach mineralization in 75 and 150 mg/kg females, and cellular histiocytic infiltration in the lung and ovarian cyst in 150 mg/kg females were significantly increased. 3-MONTH STUDY IN MICE: Groups of 10 male and 10 female mice were administered 0, 9.375, 18.75, 37.5, 75, or 150 mg pulegone/kg body weight in corn oil by gavage, 5 days per week for 14 weeks. All mice survived to the end of the study. Mean body weights of dosed mice were similar to those of the vehicle controls. Reduced and oxidized glutathione levels were generally greater than vehicle control levels in 150 mg/kg males and in 75 and 150 mg/kg females. Liver weights of 150 mg/kg males and 75 and 150 mg/kg females were significantly greater than those of the vehicle controls. No histopathologic lesions were observed that could be attributed to the administration of pulegone. 2-YEAR STUDY IN RATS: Groups of 50 male and 50 female rats were administered 0, 18.75 (males only), 37.5, 75, or 150 (females only) mg pulegone/kg body weight in corn oil by gavage, 5 days per week for up to 104 weeks. Due to excessive morbidity and mortality, 75 mg/kg males and 150 mg/kg females were not administered pulegone after week 60 (stop-exposure); these groups were administered the corn oil vehicle until the end of the study. Survival of 37.5 mg/kg males was significantly less than that of the vehicle controls; only two 75 mg/kg stop-exposure males survived, and no 150 mg/kg stop-exposure females survived to the end of the study. Compared to those of the vehicle controls, mean body weights were less in 75 mg/kg stop-exposure males after week 13 and in 75 mg/kg and 150 mg/kg stop-exposure females after weeks 21 and 9, respectively. Clinical findings included thinness, lethargy, and ruffled fur in the 75 mg/kg stop-exposure males and 150 mg/kg stop-exposure females. The incidences of urinary bladder papilloma and of papilloma or carcinoma (combined) were significantly increased in 150 mg/kg stop-exposure females. In the kidney, incidences of hyaline glomerulopathy were significantly increased in 37.5 mg/kg and 75 mg/kg stop-exposure males and in all dosed groups of females. The severity of chronic progressive nephropathy was increased in 37.5 mg/kg and 75 mg/kg stop-exposure males and in 75 mg/kg and 150 mg/kg stop-exposure females; the incidences of nephropathy were significantly increased in 75 mg/kg and 150 mg/kg stop-exposure females. The incidence of renal cyst was significantly increased in 75 mg/kg stop-exposure males. In the liver, incidences of diffuse hepatocyte cellular alteration were significantly increased in 37.5 mg/kg and 75 mg/kg stop-exposure males and 75 mg/kg and 150 mg/kg stop-exposure females. There were significant increases in the incidences of other liver lesions including fatty change, bile duct cyst, hepatocyte necrosis, oval cell hyperplasia, bile duct hyperplasia, and portal fibrosis. In the nose, 37.5 mg/kg and 75 mg/kg stop-exposure males and all dosed groups of females had significantly increased incidences of olfactory epithelium degeneration. All dosed groups of females had significantly increased incidences of respiratory metaplasia of the olfactory epithelium and nasal inflammation. In the forestomach, incidences of inflammation and ulcer were significantly increased in 37.5 mg/kg and 75 mg/kg stop-exposure males, and incidences of epithelial hyperplasia and perforation were increased in 75 mg/kg stop-exposure males. In the glandular stomach, the incidence of inflammation was significantly increased in 75 mg/kg stop-exposure males. 2-YEAR STUDY IN MICE: Groups of 50 male and 50 female mice were administered 0, 37.5, 75, or 150 mg pulegone/kg body weight in corn oil by gavage, 5 days per week for 105 weeks. Survival of all dosed groups was similar to that of the vehicle controls. Mean body weights of 150 mg/kg males and females were less than those of the vehicle controls after weeks 25 and 33, respectively. The incidences of multiple hepatocellular adenoma were significantly increased in all dosed groups of males, and the incidences of hepatocellular adenoma (includes multiple) and hepatoblastoma (includes multiple) were significantly increased in the 75 mg/kg males. The combined incidences of hepatocellular adenoma, hepatocellular carcinoma, or hepatoblastoma occurred with positive trends and were significantly increased in 75 mg/kg males and 150 mg/kg females. The incidence of hepatocellular adenoma was significantly increased in 150 mg/kg females. The incidences of several nonneoplastic liver lesions were significantly increased, primarily in the 75 and 150 mg/kg groups. These nonneoplastic lesions included clear cell, eosinophilic, and mixed cell foci; focal fatty change; centrilobular hepatocyte hypertrophy; intravascular hepatocyte; necrosis; pigmentation; bile duct cyst and hyperplasia; and oval cell hyperplasia. In the kidney, incidences of hyaline glomerulopathy were significantly increased in all dosed groups of males and 75 and 150 mg/kg females. The incidence of mineralization was significantly increased in 150 mg/kg females, and the incidence of nephropathy in 150 mg/kg females and severity of nephropathy in 150 mg/kg males were increased. Incidences of congestion of the glomerulus were increased in 150 mg/kg males and females. The incidence of osteoma or osteosarcoma (combined) in all organs of 75 mg/kg females exceeded the historical control ranges. One 150 mg/kg male and one 75 mg/kg female had nasal osteoma; no nasal osteomas have been observed in historical control mice. (ABSTRACT TRUNCATED)

Estudo de Rótulos Coletados pela VISA do Estado do Rio de Janeiro em Indústria de Alimentos para Praticantes de Atividades Física / Study of Labels Collected by VISA in the State of Rio de Janeiro in the Food Industry for Physical Activity Practitioners

O presente trabalho avaliou a rotulagem de alimentos para praticantes de atividades físicas coletados em uma indústria de alimentos no Rio de Janeiro, no ano de 2008. De acordo com os resultados obtidos, constatou-se que 81 % dos rótulos avaliados apresentavam não conformidades de acordo com as especificações legais, sendo comumente observado a não declaração no painel principal que o produto em questão é aromatizado artificialmente.

Hypersensitivity reactions to food additives.

PURPOSE OF REVIEW: To provide an updated concise review on food additives adverse reactions, diagnosis, and management. RECENT FINDINGS: Despite the common use of food additives, their adverse reactions seem to be very rare in the general population (0.01-0.23%) but higher in atopic individuals (2-7%). Probably because of the difficulty in diagnosis, most of the available information is based on case reports or small series. Reported reactions are mostly mild and may affect the skin, the gastrointestinal tract, or the airways, and rarely anaphylaxis. SUMMARY: Food additives should be suspected as the culprit in patients who report a history of reactions to a number of unrelated foods or to a certain food when commercially prepared but not when prepared at home. The major problem in dealing with reactions to additives is the identification of the offending agent(s). Apart from a careful history taking, allergy skin testing or in-vitro testing are rarely useful. Trials of elimination and reintroduction may be more helpful. If the anticipated reaction is severe, a well designed challenge testing should be carried out. Once the offending additive(s) is confirmed, treatment is avoidance. Because accidental exposure often happens, patients with a history of severe reactions should have self-injectable epinephrine and wear MedicAlert (Turlock, California, USA) identification.

Compendio de normas técnicas obligatorias de alimentos / Compendium of mandatory technical standards for food

El documento proporciona una herramienta para el desarrollo del trabajo técnico de los inspectores sanitarios del Ministerio de Salud, a fin de hacer cumplir las normas en los establecimientos de alimentos

Adverse reactions to food additives.

OBJECTIVES: To summarize the literature related to the classification of food additives and their reported adverse reactions and to provide a practical approach for evaluation of patients suspected of having such reactions. DATA SOURCES: Information was derived from selected reviews and original articles published in peer-reviewed journals and from authoritative textbook chapters, supplemented by the clinical experience of the authors. STUDY SELECTION: Priority was given to studies that used blinded, placebo-controlled oral challenges to confirm adverse reactions to food additives. In addition, selected, appropriately evaluated case reports are included. RESULTS: A large number of food additives are widely used in the food industry. Adverse reactions to additives seem to be rare but are likely underdiagnosed in part due to a low index of suspicion. Numerous symptoms have been attributed to food additive exposure, but the cause-and-effect relationship has not been well demonstrated in all. CONCLUSIONS: Reactions to food additives should be suspected in patients who report symptoms to multiple unrelated foods or to a certain food when commercially prepared but not when homemade and the allergy evaluation rules out a role for food protein. It is also prudent to investigate food additives in patients considered to have idiopathic reactions. There is a minor role for skin testing or in vitro testing. Oral challenge testing with common additives, preferably preceded by a trial of an additive-free diet, is the definitive procedure for detecting the offending agent. Once the specific additive is identified, management is basically avoidance of all its forms.

Transición en el consumo alimentario de preescolares en la ciudad de São Paulo, Brasil (1984/85 - 1995/96) / Transition in food consumption in preschool children in Sao Paulo, Brasil (1984/85 - 1995/96)

Fundamentos: Evaluar el consumo medio de energía ymicronutrientes de 9 grupos alimentarios, en dos averiguacionesdietéticas; la contribución de energía ymicronutrientes y la frecuencia del consumo de los gruposalimentarios.Métodos: Recordatorio 24h, de muestra representativade la población de niños de 0 a 59 meses, de 1984/85(n=299) y 1995/96 (n=721). Fueron estudiados elconsumo medio, contribución y frecuencia de la leche enpolvo y fluido, espesantes, polvo achocolatado, azúcar,panes, galletas, embutidos, frutas, dulces y “snacks”. Seaplicó el test t (p=0,05), test de la frecuencia y proporcionesde los grupos.Resultados: Aumentó el consumo medio de la leche enpolvo (31,23%), espesantes (32,53%), polvoachocolatado (74,24%), galletas (52,49%), azúcar(76,75%) y disminuyeron los panes (21,29%). Aumentóla contribución de energía por las galletas, polvoachocolatado y azúcar. Los alimentos más frecuentes de1984/85 fueron azúcar, panes y leche fluido y en 1995/96 panes, frutas y leche fluido. Los menos frecuentesfueron los “snacks”, embutidos y polvo achocolatado.Conclusiones: Hubo cambio en la dieta de los niños conaumento en el consumo medio de espesantes, leche enpolvo, azúcar, polvo achocolatado y galletas, contribuyendocon más energía. Los panes contribuyeron menos paratodos los nutrientes y los “snacks”, embutidos y polvoachocolatado permanecieron con menor frecuencia

Objectives: to evaluate the medium food intake in energyand micronutrients of 9 food groups, in the 2 nutritionsurveys; to evaluate the percentage contribution of energyand micronutrients; to verify the frequency of each foodgroup's intake.Methods: A single 24-hour dietary recall (Rec24h) ofrepresentative sample of the children's population from 0to 59 months of age, of 1984/1985 (n=299) and 1995/96 (n=721). The studied aspects were the medium foodintake, the contribution and frequency of powdered milkand fluid, thickener, chocolate powder, sugar, breads,cookies, sausages, fruits, sweets and salty snacks. Afterthe variance tests it was applied the “t” test (p=0,05), thefrequency test and the proportions of the food groups.Results: There was an increase in medium food intake ofpowdered milk (31,23%), thickeners (32,53%), chocolatepowdered (74,24%), cookies (52,49%), sugar(76,75%), and a reduction of bread intake (21,29%).The energy contribution from cookies, chocolate powdersand sugar has increased. The most frequent ingested foodof 1984/1985 were sugar, breads and milk and in 1995/1996 breads, fruits and fluid milk. In both periods theless frequent were salty snacks, sausages and chocolatepowders.Conclusions: there was a significant change in the childrendiet with expressive increase of the medium food intakeof thickeners, powdered milk, sugar, chocolate powderand cookies. These three last ones gave significantcontribution of energy in children diet. Breads decreasedthe percentage contribution for all the nutrients. Saltysnacks, sausages and chocolate powder, in both periods,have continued as the less frequency food

Position of the American Dietetic Association: use of nutritive and nonnutritive sweeteners.

Sweeteners elicit pleasurable sensations with (nutritive) or without (nonnutritive) energy. Nutritive sweeteners (eg, sucrose, fructose) are generally recognized as safe (GRAS) by the Food and Drug Administration (FDA), yet concern exists about increasing sweetener intakes relative to optimal nutrition and health. Dietary quality suffers at intakes above 25% of total energy (the Institutes of Medicine's suggested maximal intake level). In the United States, estimated intakes of nutritive sweeteners fall below this, although one in four children (ages 9 to 18 years) can surpass this level. Polyols (sugar alcohols), GRAS-affirmed or petitions filed for GRAS, add sweetness with reduced energy and functional properties to foods/beverages and promote dental health. Five nonnutritive sweeteners with intense sweetening power have FDA approval (acesulfame-K, aspartame, neotame, saccharin, sucralose) and estimated intakes below the Acceptable Daily Intake (level that a person can safely consume everyday over a lifetime without risk). By increasing palatability of nutrient-dense foods/beverages, sweeteners can promote diet healthfulness. Scientific evidence supports neither that intakes of nutritive sweeteners by themselves increase the risk of obesity nor that nutritive or nonnutritive sweeteners cause behavioral disorders. However, nutritive sweeteners increase risk of dental caries. High fructose intakes may cause hypertriglyceridemia and gastrointestinal symptoms in susceptible individuals. Thus, it is the position of The American Dietetic Association that consumers can safely enjoy a range of nutritive and nonnutritive sweeteners when consumed in a diet that is guided by current federal nutrition recommendations, such as the Dietary Guidelines for Americans and the Dietary References Intakes, as well as individual health goals. Dietetics professionals should provide consumers with science-based information about sweeteners and support research on the use of sweeteners to promote eating enjoyment, optimal nutrition, and health.

Toxicological review of inorganic phosphates.

Inorganic phosphate salts are widely used as food ingredients and in a variety of commercial applications. The United States Food and Drug Administration (FDA) considers inorganic phosphates "Generally Recognized As Safe" (GRAS) (FDA, 1973a, 1979) [FDA: Food and Drug Administration 1973a. GRAS (Generally Recognized as Safe) food ingredients-phosphates. NTIS PB-221-224, FDA, Food and Drug Administration, 1979. Phosphates; Proposed Affirmation of and Deletion From GRAS Status as Direct and Human Food Ingredients. Federal Register 44 (244). 74845-74857, 18 December (1979)] and the European Union (EU) allows inorganic phosphates to be added directly to food (EU Directive 95/2/EC as amended by 98/72/EC). In this review, data on the acute, subchronic and chronic toxicity, genotoxicity, teratogenicity and reproductive toxicity from the published literature and from unpublished studies by the manufacturers are reviewed. Based on the toxicity data and similar chemistry, the inorganic phosphates can be separated into four major classes, consisting of monovalent salts, divalent salts, ammonium salts and aluminum salts. The proposed classification scheme supports the use of toxicity data from one compound to assess the toxicity of another compound in the same class. However, in the case of eye and skin irritation, the proposed classification scheme cannot be used because a wide range of responses exists within each class. Therefore, the eye and skin hazards associated with an individual inorganic phosphate should be assessed on a chemical-by-chemical basis. A large amount of toxicity data exists for all four classes of inorganic phosphates. The large and comprehensive database allows an accurate assessment of the toxicity of each class of inorganic phosphate. Overall, all four classes of inorganic phosphates exhibit low oral, inhalation and dermal toxicities. Based on these data, humans are unlikely to experience adverse effects when the daily phosphorus consumption remains below 70 mg/kg/day (JECFA, 1964, 1982a) [JECFA (Joint FAO/WHO Expert Committee on Food Additives 1964. Specifications for the Identity and Purity of Food Additives and their Toxicological Evaluation) Emulsifiers, Stabilizers, Bleaching, and Maturing Agents. Technical Report Series of the World Health Organization 281; ECFA (Joint FAO/WHO Expert Committee on Food Additives 1982a. Phosphoric Acid and Phosphate Salts. ICS/FA/82)].

What are additives?

Historical development of the concern exercised by the public institutions of a country for the food taken by their citizens, through care for its safety and proper testing by authorized governmental institutions, is presented. In the USA, FDA was established for this purpose, whereas European Union agencies are in charge in Europe. Additives are listed and classified according to E-number groups introduced in the European Union in 1990. Difference between the additives and supplements is explained. Special reference is given to an anonymous leaflet that appeared in Zagreb in the autumn 2000, in which some additives were described as harmful, detrimental, carcinogenic and highly hazardous, providing no valid arguments for such a statement. The author considers it merely an unargumented propaganda attack on particular European food manufactures.