Are food additives safe to eat?
By
Dr Juliana Davies de Oliveira (PhD)
| Reviewed by
Dr Anny Manrich (PhD)
The contents of this article are fact-based except otherwise stated within the article.
Author bio
Dr Juliana Davies de Oliveira graduated in Biological Sciences with an emphasis on microbiology and immunology. She is PhD in Biochemical Process Engineering. With more than 15 years of experience, she has expertise in Bioprocess, Fermentation, Industrial Microbiology, Biotechnology, Bioinputs, Biopolymer and Bioinsecticide production and Biosecurity.
Dr Juliana Davies de Oliveira’s Highlights
- Researcher Consultant at the SENAI Innovation Institute (ISI – SENAI CETIQT) and member of the Internal Biosafety Commission (CIBio) of SENAI CETIQT
- Postdoctoral fellowship at the Catholic University of Brasilia/Brazil in the Postgraduate Program in Genomic Sciences and Biotechnology
- International Experience in Barcelona/Spain – Department of Chemical, Biological and Environmental Engineering at the Autonomous University of Barcelona/Spain.
- Coordinator and technical-scientific responsible for the Laboratory -Platform of Fermentation in Scale Pilot up to 125 L (Catholic University of Brasilia/Brazil)
- Collaborating researcher at the University of Brasilia/Brazil
- PhD and master’s degree in Chemical and Biochemical Process Engineering at the Federal at the University of Rio de Janeiro/Brazil
- Undergraduate professor at Catholic University of Brasilia/Brazil
- Bachelor’s degree in Biological Sciences: Microbiology and Immunology at the Federal University of Rio de Janeiro/Brazil
Professional profile:
Dr Juliana Davies de Oliveira was a Researcher Consultant for the Biotechnology platform of SENAI CETIQT/SENAI Institute of Innovation in Biosynthetic and Fibers, linked to the fermentation area. In addition, she was a member of the Internal Biosafety Commission (CIBio) of SENAI CETIQT
She played a role in leading the fermentation laboratory, including operational training of equipment; installation of a pilot fermenter at the Catholic University of Brasilia/Brazil.
She additionally was an undergraduate Professor in the Biological Sciences, Pharmacy and General Training courses in Postgraduate Courses (Catholic University of Brasilia/Brazil)
She was a researcher at the University of Brasilia/Brazil.
Besides that, Dr Juliana Davies de Oliveira has done a technical visit to the Autonomous University of Barcelona/Spain
Furthermore, she has experience in reviewing scientific articles at the Brazilian Journal of Microbiology and the Microbial Cell Factories.
Education:
- 2020 – Postdoctoral in Genomic Sciences and Biotechnology at the Catholic University of Brasilia/Brazil
- 2014 – PhD in Chemical and Biochemical Process Engineering at the Federal University of Rio de Janeiro/Brazil
- 2010 – Master’s degree in Chemical and Biochemical Process Engineering at the Federal University of Rio de Janeiro/Brazil
- 2008 – Bachelor in Biological Sciences (Microbiology and Immunology) at the Federal University of Rio de Janeiro/Brazil
Relevant Published work & citations of Dr Juliana Davies de Oliveira
Articles
De Oliveira, Juliana Davies; Carvalho, Lucas Silva; Gomes, Antônio Milton Vieira; Queiroz, Lúcio Rezende; Magalhães, Beatriz Simas; Parachin, Nádia Skorupa. Genetic basis for hyper production of hyaluronic acid in natural and engineered microorganisms. Microbial Cell Factories, v. 15, p. 119-126, 2016.
Oliveira, Juliana D.; Lopes, L. M. A.; Pimenta, Flávia D.; Sérvulo, Eliana F. C. Low Cost Production of Pullulan Obtained From Granulated Sugar and Different Nitrogen Sources. International Journal of Engineering and Technology, v. 15, p. 11-17, 2015.
Oliveira, Juliana D.; Pimenta, Flávia D.; Lopes, Lea M. A.; Sérvulo, Eliana F. C. Rheological Analysis of Biopolymer Produced by Aureobasidium pullulans in Different Sources of Nitrogen. Macromolecular Symposia (Online), v. 319, p. 143-149, 2012.
Patents
De Oliveira, Juliana Davies; Parachin, N. S.; Gomes, A. M. V.; Carvalho, Lucas Silva; Magalhães, B. S. Levedura recombinante da espécie Kluyveromyces lactis para a produção de grandes cadeias de ácido hialurônico. 2016, Brasil. Register number: BR10201602018; Registration institution: INPI – National Institute of Industrial Property. Deposit: 08/31/2016
De oliveira, juliana davies; parachin, nádia skorupa; gomes, a. M. V.; magalhães, b. S.; carvalho, lucas silva. Levedura recombinante da espécie Hansenula polymorpha para a produção de grandes cadeias de ácido hialurônico. 2016, Brasil. Register number: BR10201602019; Registration institution: INPI – National Institute of Industrial Property. Deposit: 08/31/2016.
Book Chapters
Silva, O. B.; Carvalho, Lucas Silva; Almeida, G. C.; Oliveira, Juliana D.; Carmo, T. S.; Parachin, N. S. Biogas – Turning Waste into Clean Energy. In: Angela Faustino Jozala. (Org.). Fermentation Processes. 1ed.Rijeka, Croatia: Intech, 2017, v., p. 161-180.
Carvalho, L.; Silva, O. B.; Almeida, G. C.; Oliveira, Juliana D.; Parachin, N. S.; Carmo, T. S. Production Processes for Monoclonal Antibodies. In: Angela Faustino Jozala. (Org.). Fermentation Processes. 1ed.Rijeka, Croatia: Intech, 2017, v., p. 181-198.
Conference Papers
Oliveira, J. D.; Lopes, L. M. A.; Pimenta, Flávia D.; De Paula, R. C. M.; Sérvulo, Eliana F. C. Avaliação de metodologia para recuperação de pululana livre de melanina. In: 12º Congresso Brasileiro de Polímeros, 2013, Florianópolis. 12º Congresso Brasileiro de Polímeros, 2013.
Oliveira, J. D.; Lopes, L. M. A.; Pimenta, Flávia D.; Sérvulo, Eliana F. C. Produção de pululana em função das concentrações de carbono e nitrogênio. In: XIX Simpósio Nacional de Bioprocessos, 2013, Foz do Iguaçu. XIX Simpósio Nacional de Bioprocessos, 2013.
Oliveira, J. D.; Pimenta, F. D.; Servulo, E. F. C. Produção de pululana a partir de matéria-prima de baixo custo. In: 11º Congresso Brasileiro de Polímeros, 2011, Campos do Jordão/SP. 11º Congresso Brasileiro de Polímeros, 2011. p. 68.
Oliveira, J. D.; Pimenta, F. D.; Servulo, E. F. C. Avaliação reológica do biopolímero produzido por Aureobasidium pullulans em diferentes fontes de nitrogênio. In: 11º Congresso Brasileiro de Polímeros, 2011, Campos do Jordão/SP. 11º Congresso Brasileiro de Polímeros, 2011. p. 19.
Oliveira, J. D.; Pimenta, F. D.; Lopes, L. M. A.; Sarquis, M. I. M.; Servulo, E. F. C. Seleção de estirpe e fonte de nitrogênio para produção de biopolímero a partir de matéria-prima de baixo custo. In: XVII Congresso Brasileiro de Engenharia Química, 2008, Recife. XVII Congresso Brasileiro de Engenharia Química, 2008.
Oliveira, J. D.; Servulo, E. F. C.; Pimenta, F. D.; Lopes, L. M. A. Utilização de matéria prima de baixo custo para produção de biopolímero. In: IV Simpósio de Microbiologia Aplicada, 2009, Rio Claro/SP. Holos Environment – Suplemento 1 – IV Simpósio de Microbiologia Aplicada, 2009. v. 9.
You can view some of Dr Juliana’s work below and links to her professional profile:
Research Gate: https://www.researchgate.net/profile/Juliana-Oliveira-2/research
Google Scholar: https://scholar.google.com/citations?user=G3ZLG84AAAAJ&hl=pt-BR
Linkedin: linkedin.com/in/juliana-davies-de-oliveira-285749197
Reviewer bio
Dr Anny Manrich PhD is a food Engineer with expertise in Food Technology, Natural Polymers, Edible Films, Enzymes, and Nanotechnology. She writes and reviews content on these topics.
Dr Anny Manrich’s Highlights:
- Research and Technology at the Brazilian Agricultural Research Corporation
- PhD in Chemical Engineering with a focus on Biochemistry at the Federal University of Sao Carlos/ Brazil and a one-year scholarship at the Technical University of Munich/ Germany
- Bachelor of Food Engineering at the University of Campinas/ Brazil and a one-year scholarship at the Technical University of Munich/ Germany
“To solve a problem, global vision and multifactorial understanding are necessary. Therefore, in addition to expertise, one should seek multidisciplinary thinking connected with science and reality” – Dr Anny Manrich, PhD.
Professional Experience:
Dr Anny Manrich’s Experience Joining the Brazilian Agricultural Research Corporation, as soon as she completed her doctorate,
Dr Anny Manrich has worked on several projects, including the more than three-year partnership project with BRF, a major food producer in Brazil. As a postdoctoral fellow.
Dr Anny Manrich has also contributed to several business consultancies and research projects of the National Nanotechnology Laboratory System in areas such as food technology, fibres, films and coatings and Nanotechnology; in a very determined way, having a great team relationship, being creative and committed.
Growing concerns about the safe introduction of nanomaterials into today’s life emphasises the need to create regulatory documentation in front of characterising, using and testing them. Dr Anny Manrich worked for two years on a characterization project for nanoscale materials, with the aim of exploring their possible health effects.
Despite not having specific academic training in packaging or polymeric films, Dr Anny Manrich works at the Brazilian Agricultural Research Corporation in areas of edible and biodegradable films produced from agricultural waste and in the development of films with greater resistance to water, having articles published in renowned scientific journals, which demonstrates her multidisciplinary understanding and creativity.
In addition, she worked for four years as a consultant to a food company to develop a line of snacks that are healthy and that add functional ingredients, physiologically active compounds that bring health benefits, made from fruits and vegetables, enabling diet improvement, disease prevention and reduction of nutritional deficiencies.
Dr Anny Manrich participated as a member of the examination board for two Master’s exams and one PhD exam at the Department of Chemical Engineering of the Federal University of São Carlos.
Education:
- 2001 Bachelor in Food Engineering at the State University of Campinas, Brazil
- 1999 One year scholarship at the Technical University of Munich
- 2004 Master in Chemical Engineering at the Federal University of São Carlos, Brazil
- 2012 PhD in Chemical Engineering at the Federal University of São Carlos, Brazil
- 2010 One year scholarship at the Technical University of Munich
The main publications of Dr. Anny Manrich are:
Articles
Manrich, A., Moreira, F. K., Otoni, C. G., Lorevice, M. V., Martins, M. A., & Mattoso, L. H. (2017). Hydrophobic edible films made up of tomato cutin and pectin. Carbohydrate Polymers, 164, 83-91.
Mendes, J. F., Norcino, L. B., Martins, H. H. A., Manrich, A., Otoni, C. G., Carvalho, E. E. N., … & Mattoso, L. H. C. (2020). Correlating emulsion characteristics with the properties of active starch films loaded with lemongrass essential oil. Food Hydrocolloids, 100, 105428.
Norcino, L. B., Mendes, J. F., Natarelli, C. V. L., Manrich, A., Oliveira, J. E., & Mattoso, L. H. C. (2020). Pectin films loaded with copaiba oil nanoemulsions for potential use as bio-based active packaging. Food Hydrocolloids, 106, 105862.
Manrich, Anny, et al. Immobilization of trypsin on chitosan gels: Use of different activation protocols and comparison with other supports. International Journal of Biological Macromolecules 43.1 (2008): 54-61.
Manrich, Anny; Komesu, Andrea ; Adriano, Wellington Sabino; Tardioli, Paulo Waldir ; Giordano, Raquel Lima Camargo . Immobilization and Stabilization of Xylanase by Multipoint Covalent Attachment on Agarose and on Chitosan Supports. Applied Biochemistry and Biotechnology, v. 161, p. 455-467, 2010.
Mendes, J. F., Martins, J. T., Manrich, A., Neto, A. S., Pinheiro, A. C. M., Mattoso, L. H. C., & Martins, M. A. (2019). Development and physical-chemical properties of pectin film reinforced with spent coffee grounds by continuous casting. Carbohydrate polymers, 210, 92-99..
Milessi, T. S., Kopp, W., Rojas, M. J., Manrich, A., Baptista-Neto, A., Tardioli, P. W., … & Giordano, R. L. (2016). Immobilization and stabilization of an endoxylanase from Bacillus subtilis (XynA) for xylooligosaccharides (XOs) production. Catalysis Today, 259, 130-139.
Mendes, J. F., Norcino, L. B., Manrich, A., Pinheiro, A. C. M., Oliveira, J. E., & Mattoso, L. H. C. (2020). Development, physical‐chemical properties, and photodegradation of pectin film reinforced with malt bagasse fibers by continuous casting. Journal of Applied Polymer Science, 137(39), 49178.
Mendes, J. F., Martins, J. T., Manrich, A., Luchesi, B. R., Dantas, A. P. S., Vanderlei, R. M., … & Martins, M. A. (2021). Thermo-physical and mechanical characteristics of composites based on high-density polyethylene (HDPE) e spent coffee grounds (SCG). Journal of Polymers and the Environment, 29, 2888-2900..
Mendes, J. F., Norcino, L. B., Martins, H. H., Manrich, A., Otoni, C. G., Carvalho, E. E. N., … & Mattoso, L. H. C. (2021). Development of quaternary nanocomposites made up of cassava starch, cocoa butter, lemongrass essential oil nanoemulsion, and brewery spent grain fibers. Journal of Food Science, 86(5), 1979-1996.
Manrich, A., Martins, M. A., & Mattoso, L. H. C. (2021). Manufacture and performance of peanut skin cellulose nanocrystals. Scientia Agricola, 79.
Nascimento, V. M., Manrich, A., Tardioli, P. W., de Campos Giordano, R., de Moraes Rocha, G. J., & Giordano, R. D. L. C. (2016). Alkaline pretreatment for practicable production of ethanol and xylooligosaccharides. Bioethanol, 2(1)..
Manrich, Anny, de Oliveira, J. E., Martins, M. A., & Mattoso, L. H. C. Physicochemical and Thermal Characterization of the Spirulina platensis. J. Agric. Sci. Technol. B, v. 10, p. 298-307, 2020.
Book Chapter
Terra, I. A. A., Aoki, P. H., Delezuk, J. A. D. M., Martins, M. A., Manrich, A., Silva, M. J., … & Miranda, P. B. (2022). Técnicas de Caracterização de Polímeros. Nanotecnologia Aplicada a Polímeros, 614.
Conference Papers
Ferreira, L. F., Luvizaro, L. B., Manrich, A., Martins, M. A., Júnior, M. G., & Dias, M. V. (2017). Comparação da estabilidade de suspensões poliméricas de amido/tocoferol e quitosana/tocoferol. In: CONGRESSO BRASILEIRO DE POLÍMEROS, 14., 2017, Águas de Lindóia, SP.
Manrich, A., Hubinger, S. Z., & Paris, E. C. (2017). Citotoxicidade causada por nanomateriais: avaliação do micronúcleo. In: WORKSHOP DA REDE DE NANOTECNOLOGIA APLICADA AO AGRONEGÓCIO, 9., 2017, São Carlos. Anais… São Carlos: Embrapa Instrumentação, 2017. p. 655-658.
Manrich, Anny, et al. Immobilization and Stabilization of Xylanase by multipoint covalent attachment on Glyoxyl Agarose Support. The 31st Symposium on Biotechnology for Fuels and Chemicals. 2009.
Manrich, Anny, et al. Application of immobilized xylanase on hydrolysis of soluble wood hemicelluloses after using microwave and organosolv pre-treatments. The 32nd Symposium on Biotechnology for Fuels and Chemicals. 2010.
You can view some of Dr Anny’s work below and links to her professional profile.
Research Gate: https://www.researchgate.net/profile/Anny-Manrich-2
Scopus: https://www.scopus.com/authid/detail.uri?authorId=23103497100
Google Scholar: https://scholar.google.com/citations?hl=en&user=Ea9qpr0AAAAJ
Linkedin: https://br.linkedin.com/in/anny-manrich-20693129
In this brief guide, we are going to answer the question, “Are food additives safe to eat?”. We will discuss the use of food additives and the potential risks of eating food additives.
Are food additives safe to eat?
Yes, food additives are safe to consume. This is because the use of food additives is subject to controls, based on scientific studies that demonstrate their safety for human health (1).
Some consumers might regard the use of food additives, especially artificial ones, with suspicion; food additives are considered unnatural, unhealthy or even a public health risk (2). However, food additives are safe and make our life easier, being in our daily lives. They are convenient, portable and stay cool for a long time.
Why are food additives used?
Additives are added to foods to maintain or improve safety by combating microbial degradation, and increasing their shelf-life. Also they guarantee freshness, improve or maintain nutritional value, improve taste, texture and appearance (3).
Among the additives that you will possibly find on food labels are: i) antioxidants (these stop food becoming rancid or changing color by reducing the chance of fats combining with oxygen); ii) colors; iii) emulsifiers, stabilizers, gelling agents and thickeners (these help to mix or thicken ingredients); preservatives (used to keep food safer for longer); sweeteners (including intense sweeteners like stevia and aspartame which are many times sweeter than sugar) (4).
How safe are food additives?
Food additives are safe because they must pass a thorough safety evaluation, which includes determining the real danger to public health based on the quantities at which a food additive is likely to be eaten. The Food and Drug Administration (FDA) is responsible for regulating all additives to ensure that foods containing additives are safe to eat, contain only approved ingredients, and are properly labeled (5).
Unfortunately there are scientific limitations, which fatally prevent the FDA from being absolutely sure of the absence of any type of risk from the use of any substance. Given this, FDA must determine – based on the best available science – whether there is reasonable certainty that there is no harm to consumers when an additive is used as intended (5).
Eventually new evidence may emerge that a product, already on the market, may be unsafe, or that consumption levels have changed. Once this is found, federal authorities can ban its use or conduct further studies to determine its safety (5).
Then, you should feel safe about the foods you eat. In the meantime however consumption should be moderate.
What are the possible adverse effects of eating food additives?
Although consuming small amounts of additives may be safe (10), there are some health risks that are increased if you overindulge in processed foods (which inevitably contain food additives). A diet high in processed foods is linked to chronic diseases such as obesity, high blood pressure, heart disease and cancer (11).
There are some food additives that you must avoid and its risks (11). Below are some examples and the main harmful effects:
– – Sodium nitrites: it may cause smooth muscle relaxation, vasodilation and, consequently, a decrease in blood pressure and methemoglobinemia (17).
– Sulfites: it can induce various respiratory diseases in some individuals, induce cardiovascular diseases and neurological diseases such as abdominal pain, hives, asthma, lung cancer, myocardial ischemia and brain cancer (18).
– Monosodium Glutamate (MSG) it causes cardiac, circulatory, gastrointestinal, muscular, and neurological disorders (19):
– Artificial coloring (FD&C yellow no. 5 and no. 6): allergic reactions such as bronchial asthma and urticaria in susceptible people (20)
– Trans fats: it affects multiple cardiovascular risk factors and contributes significantly to increased risk of coronary heart disease events (21).
Who should avoid food additives?
There are some food additives that everybody must avoid. Though some people can have hypersensitivity reactions to food additives (6). There are many clinical features such as chronic urticaria (also called ‘hives’ or ‘nettle rash’, consists of blanchable, erythematous, oedematous papules or ‘wheals’) or angioedema (characterized by localized swelling of sudden onset affecting the skin and/or mucous membranes), atopic eczema (inflammatory skin disease ), flushing (endocrine disorders), hypotension, abdominal pain, diarrhea and asthmatic reactions (7, 13, 14, 15, 16). Studies have been evaluating the potential of food additives to cause adverse symptoms, but robust research is difficult to conduct (8).
Also people who are diagnosed at birth with phenylketonuria need to avoid foods containing certain sweeteners – i.e. aspartame and aspartame-acesulfame salt. This is because they cannot consume foods containing phenylalanine (9).
How can you avoid unhealthy food additives?
Although food additives are a necessary component in most processed foods, you should avoid harmful food additives whenever possible. For that, you must buy and eat fresh; cook your own meals; read the labels (12).
“Peel more and unpack less” is the basis of healthy eating (12).
Other FAQs about food additives that you may be interested in.
What food additives are harmful?
What are natural food additives?
Conclusion
In this brief guide, we answered the question, “Are food additives safe to eat?”. We discussed how food additives are safe when consumption is moderate.
If you have any questions or comments, please let us know.
References
1. Saltmarsh M. Essential Guide to Food Additives. Royal Society of Chemistry; 2013.
2. Bearth A, Cousin ME, Siegrist M. The consumer’s perception of artificial food additives: Influences on acceptance, risk and benefit perceptions. Food Quality and Preference. 2014 Dec;38:14–23.
3. Center for Food Safety. Overview of Food Ingredients, Additives & Colors [Internet]. U.S. Food and Drug Administration. 2010 [cited 2023 Jun 4]. Available from: https://www.fda.gov/food/food-ingredients-packaging/overview-food-ingredients-additives-colors#why
4. Food Standards Agency. Food additives [Internet]. Food Standards Agency. 2019 [cited 2023 Jun 4].
5. Center for Food Safety, U.S. Food & Drug Administration. Overview of Food Ingredients, Additives & Colors [Internet]. U.S. Food and Drug Administration. 2010 [cited 2023 Jun 4].
6. Witkowski M, Grajeta H, Gomułka K. Hypersensitivity Reactions to Food Additives—Preservatives, Antioxidants, Flavor Enhancers. International Journal of Environmental Research and Public Health. 2022 Sep 13;19(18):11493.
7. Muraro A, Werfel T, Hoffmann-Sommergruber K, Roberts G, Beyer K, Bindslev-Jensen C, et al. EAACI Food Allergy and Anaphylaxis Guidelines: diagnosis and management of food allergy. Allergy. 2014 Jun 9;69(8):1008–25.
8. Skypala IJ, Williams M, Reeves L, Meyer R, Venter C. Sensitivity to food additives, vaso‐active amines and salicylates: a review of the evidence. Clinical and Translational Allergy. 2015 Jan;5(1):34.
9. Food Standards Agency. Food additives [Internet]. Food Standards Agency. 2019 [cited 2023 Jun 4].
10. Han X, Zhu F, Chen L, Wu H, Wang T, Chen K. Mechanism analysis of toxicity of sodium sulfite to human hepatocytes L02. Molecular and Cellular Biochemistry. 2020 Jul 6;473(1–2):25–37.
11. Heart, Team V. 5 Food Additives You Should Avoid [Internet]. Cleveland Clinic. 2020 [cited 2023 Jun 4].
12. Ministério da Educação. “Descascar mais e desembalar menos” é a base da alimentação saudável. Empresa Brasileira de Serviços Hospitalares [Internet]. 2019 Apr 8 [cited 2023 Jun 4].
13. Deacock SJ. An approach to the patient with urticaria. Clinical and Experimental Immunology. 2008 Jul 11;153(2):151–61.
14. Greaves M, Lawlor F. Angioedema: Manifestations and management. Journal of the American Academy of Dermatology. 1991 Jul;25(1):155–65.
15. McAleer M A, Flohr C, Irvine A D. Management of difficult and severe eczema in childhood. The BMJ. 2012 Jul 23;345(jul23 2):e4770–e4770.
16. Hannah-Shmouni F, Stratakis CA, Koch CA. Flushing in (neuro)endocrinology. Reviews in Endocrine and Metabolic Disorders. 2016 Sep;17(3):373–80.
17. Mortensen A, Aguilar F, Crebelli R, Di Domenico A, Dusemund B, Frutos MJ, et al. Re‐evaluation of potassium nitrite (E 249) and sodium nitrite (E 250) as food additives. EFSA Journal. 2017 Jun;15(6).
18. Lv X, Liu Y, Zhou S, Wu M, Jiang Z, Wen G. A stable and sensitive Au metal organic frameworks resonance Rayleigh scattering nanoprobe for detection of SO32– in food based on fuchsin addition reaction. Frontiers in Nutrition. 2022 Nov 10;9.
19. Kazmi Z, Fatima I, Perveen S, Malik SS. Monosodium glutamate: Review on clinical reports. International Journal of Food Properties. 2017 Feb 22;1807–15.
20. Moutinho Ild, Bertges Lc, Assis Rvc. Prolonged use of the food dye tartrazine (FD&C yellow n° 5) and its effects on the gastric mucosa of Wistar rats. Brazilian Journal of Biology. 2007 Feb;67(1):141–5.
21. Mozaffarian D, Aro A, Willett WC. Health effects of trans-fatty acids: experimental and observational evidence. European Journal of Clinical Nutrition. 2009 May;63(S2):S5–21.
