title: The significance of excursions above the ADI. Case study: monosodium glutamate.
abstract: Monosodium glutamate (MSG) has been allocated an "ADI not specified" by the JECFA, which indicates that no toxicological concerns arise associated with its use as a food additive in accordance with good manufacturing practice (GMP) and for that reason it is not necessary to allocate a numerical ADI. The question in this case, then, is not whether excursions above a numerical ADI might occur but whether high peak intakes might arise which could invalidate the assumption of absence of hazard. Two major issues have arisen in relation to high intakes of MSG: (1) What is the significance of neural damage (focal necrosis in the hypothalamus) seen following high parenteral or intragastric doses of MSG to neonatal animals and is this a particular risk for children? (2) What is the role of MSG in "Chinese Restaurant Syndrome" (flushing, tightness of the chest, difficulty in breathing, etc.) following consumption of Chinese foods? In relation to the first issue, human studies have been crucial in resolving the question. The threshold blood levels associated with neuronal damage in the mouse (most sensitive species) are 100-130 mumol/dl in neonates rising to > 630 mumol/dl in adult animals. In humans, plasma levels of this magnitude have not been recorded even after bolus doses of 150 mg/kg body wt (ca. 10 g for an adult). Additionally, studies in infants have confirmed that the human baby can metabolize glutamate as effectively as adults. It is concluded that blood levels of glutamate + aspartate do not rise significantly even after abuse doses and babies are no more at risk than adults. Intake levels associated with the use of MSG as a food additive and natural levels of glutamic acid in foods therefore do not raise toxicological concerns even at high peak levels of intake. It is not envisaged that use of MSG according to GMP requires the allocation of a numerical ADI. With regard to the second issue, controlled double-blind crossover studies have failed to establish a relationship between Chinese Restaurant Syndrome and ingestion of MSG, even in individuals reportedly sensitive to Chinese meals, and MSG did not provoke bronchoconstriction in asthmatics. Thus, high usage of MSG in ethnic cuisines does not represent a situation in which intakes might achieve unsafe levels, even among individuals claiming idiosyncratic intolerance of such foods. In the light of the toxicological studies, the human metabolic studies in neonates and adults, and the physiological and nutritional role of glutamic acid and the fact that food additive use does not markedly increase the total dietary burden, no foreseeable circumstances arise in which intakes would be such as to invalidate the appropriateness of allocating an ADI not specified to MSG.
authors.affiliation: University of Surrey, School of Biological Sciences, Guildford, Surrey, United Kingdom. r.walker@surrey.ac.uk
authors.forename: R
authors.initials: R
authors.lastname: Walker
mesh_terms: D000328:Adult; D000818:Animals; D000831:Animals, Newborn; D000833:Animals, Suckling; D002637:Chest Pain / Q000139:chemically induced; D018849:Controlled Clinical Trials as Topic; D004311:Double-Blind Method; D005260:Female; D005503:Food Additives / Q000378:metabolism / Q000633:toxicity*; D006261:Headache / Q000139:chemically induced; D019584:Hot Flashes / Q000139:chemically induced; D006801:Humans; D007031:Hypothalamus / Q000187:drug effects / Q000473:pathology; D007231:Infant, Newborn; D008452:Maximum Allowable Concentration; D008895:Milk, Human / Q000737:chemistry; D011247:Pregnancy; D018570:Risk Assessment / Q000379:methods; D012970:Sodium Glutamate / Q000097:blood / Q000633:toxicity*; D013045:Species Specificity; D013577:Syndrome
chemical_list: D005503:Food Additives; D012970:Sodium Glutamate