Regulatory toxicology and pharmacology : RTP
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Regul. Toxicol. Pharmacol. · Oct 1999
Review Comparative StudyThe significance of excursions above the ADI. Case study: monosodium glutamate.
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. ⋯ 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.
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Regul. Toxicol. Pharmacol. · Apr 1999
Developmental toxicity study of vegetable oil-derived stanol fatty acid esters.
In a standard developmental toxicity study, a mixture of vegetable oil-derived stanol fatty acid esters was administered in the diet to groups of 28 mated female HsdCpb:WU Wistar rats at concentrations that provided 0, 1, 2.5, and 5% total stanols (equivalent to 0, 1.75, 4.38, and 8.76% plant stanol esters). Test diets were adjusted with rapeseed oil to maintain an equivalent caloric content of fatty acids at each of the treatment levels. The treatment period extended from day 0 to 21 of gestation. ⋯ In addition, there was no biologically meaningful effect on fetal sex ratio. Visceral and skeletal examinations did not show any significant increases in the incidence of malformations, anomalies, or variations that were considered to be treatment related. Dietary plant (8.76% plant stanol esters) stanol esters at concentrations up to 5% total stanols were concluded to have no adverse effects on reproduction or development.
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Regul. Toxicol. Pharmacol. · Aug 1998
Review Comparative StudyA qualitative and quantitative risk assessment of snuff dipping.
The presence of highly carcinogenic tobacco-specific nitrosamines (TSNA) in snuff has been a matter of serious concern. However, the levels of TSNA in such products may differ by orders of magnitude depending on origin and manner of processing, and the mere presence of such agents at low levels does hardly constitute a meaningful prerequisite for classifying all types of snuff as human carcinogens. Reviewing available epidemiological evidence, a wide discrepancy is found for estimated cancer risk associated with snuff dipping derived from on one hand previous investigations conducted in the United States and on the other from recent extensive Swedish epidemiological studies. ⋯ Bioassays using pure TSNA in rodents appear to give exaggerated risk estimates for humans, a discrepancy that could be ascribed to species-related differences in the relation between exposure and DNA target dose and/or adduct repair rates, as well as to the presence of anticarcinogens in snuff. Although a small risk cannot be excluded, the use of smokeless tobacco products low in TSNA which now are available on the market entails a risk that at any rate is more than 10 times lower than that associated with active smoking. Nevertheless, due to the decisive role of potent TSNA in determining possible cancer risks in users of smokeless tobacco, and due to the fact that large variations in the concentrations may occur, adequate control measures should be taken to keep the levels of these nitrosamines in smokeless tobacco products as low as is technically feasible.
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Regul. Toxicol. Pharmacol. · Apr 1998
Comparative StudySubchronic intravenous toxicity studies with gamma-cyclodextrin in rats.
The toxicity of gamma-cyclodextrin (gamma-CD), a cyclic polymer of 8 alpha-1,4-linked glucopyranosyl units with potential applications in food and pharmaceutical preparations, was examined in two toxicity studies in rats with intravenous administration of gamma-CD for 1 and 3 months, respectively. Each study comprised four groups of 15 rats/sex each. In the 1-month study, gamma-CD was administered to the four groups at daily doses of 0 (controls), 200, 630, or 2000 mg/kg body wt, respectively. ⋯ However, degenerative changes (fibrosis) were not seen, and at the end of the recovery period only some small residual changes were noted in the lungs of a few animals. In conclusion, daily intravenous gamma-CD doses of 120-200 mg/kg body wt were tolerated without adverse effects. The changes observed at higher dose levels (>/=600-630 mg/kg body wt) were reversible on cessation of the treatment and are considered to be biochemical responses, without toxicological relevance, to the presence of transiently high concentrations of gamma-CD in the circulating blood.
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Regul. Toxicol. Pharmacol. · Apr 1998
Comparative StudySubchronic oral toxicity studies with gamma-cyclodextrin in rats.
The toxicity of gamma-cyclodextrin (gamma-CD), a cyclic polymer of eight alpha-1,4-linked glucopyranosyl units with potential applications as a food ingredient, was examined in a 2-week pilot study followed by a 13-week oral toxicity study in Wistar rats. In the 2-week study, the test substance was administered to groups of 5 male rats at dietary levels of 0, 5, 10, 15, and 20%. In the 13-week study, groups of 20 rats/sex received diets with 0, 1.5, 5, or 20% gamma-CD. ⋯ Except for a slight cecal enlargement, which is commonly observed in rodents upon ingestion of incompletely absorbed carbohydrates, organ weights did not exhibit relevant changes as a result of gamma-CD treatment. On histopathological examination (13-week study), no treatment-related abnormalities were found. In conclusion, the ingestion of gamma-CD for 13 weeks at dietary levels of up to 20% (corresponding to intakes of 11.4 and 12.7 g/kg body wt/day for male and female rats, respectively) was well tolerated and did not produce any signs of toxicity.