Prevention of spontaneous and cyclophosphamide-induced diabetes in non-obese diabetic (NOD) mice with oral 2-acetyl-4-tetrahydroxybutyIimidazole (THI), a component of caramel colouring III

Mandel, T. E.; Koulmanda, Maria; Mackay, Ian R.

doi:10.1111/j.1365-2249.1992.tb06464.x

Cited by 17 publications

(3 citation statements)

References 20 publications

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“…The effect of oral administration of THI was studied in spontaneous and induced murine diabetes mellitus (Mandel et al, 1992). Continuous administration of THI at 400 mg/kg in drinking water reduced the prevalence of spontaneous diabetes in female NOD/Lt mice from 63% in untreated controls to 8% in treated animals.…”

Section: Annex Bmentioning

confidence: 99%

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Scientific Opinion on the re‐evaluation of caramel colours (E 150 a,b,c,d) as food additives

2011

EFS2

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The ANS Panel provides a scientific opinion re-evaluating the safety of the caramel colours (E150a (Class I), E150b (Class II), E150c (Class III), E150d (Class IV)) used as food additives. The caramel colours are a complex mixture of compounds produced by heating carbohydrates under controlled heat and chemical processing conditions; they are divided into four classes according to the manufacturing reactants used. The caramel colours were previously evaluated by the SCF and by JECFA, which concluded that a numerical ADI was not necessary for Class I, but established ADIs for the other classes of caramels, ranging from160-200 mg/kg bw/day. Given the consistency in the toxicological database, the Panel establishes a group ADI of 300 mg/kg bw/day for the caramel colours, by applying an uncertainty factor of 100 to a NOAEL of 30 g/kg bw/day (highest dose tested) identified in 13-week rat studies with Class IV and a similar NOAEL identified in a rat reproductive toxicity study, also with Class IV. Comparable NOAELS for Classes II, III and IV were reported in the SCF and JECFA evaluations. Within this group ADI, the Panel establishes an individual ADI of 100 mg/kg bw/day for Class III due to new information regarding the immunotoxicity of THI. The Panel concludes that the anticipated dietary exposure of child and adult populations may exceed the ADIs for Classes I, III and IV caramels, but exposure estimates to Class II were below the ADI. Exposure estimates for the caramel constituents THI, 4-MEI and SO 2 are not of concern, but the Panel welcomes additional studies to clarify remaining uncertainties regarding effects of THI on the immune system. The Panel notes that other constituents of caramel colours including 5-HMF and furan may be present at levels that may be of concern, and considers that the specifications should include maximum levels for these constituents. © European Food Safety Authority, 2011 KEY WORDSPlain Caramel, Caustic Caramel, caramel colour I, E 150a, Caustic Sulphite Caramel, caramel colour II, E 150b, Ammonia Caramel, caramel colour III, E 150c, Sulphite Ammonia Caramel, caramel colour IV, E 150d, CAS Registry Number 8028-89-5, food colouring substance. Re-evaluation of caramel colours (E 150 a,b,c,d) SUMMARYFollowing a request from the European Commission, the Panel on Food Additives and Nutrient Sources added to Food (ANS) was asked to deliver a scientific opinion re-evaluating the safety of caramel colours (E 150a,b,c,d) when used as food colouring substances.Caramel colours are colouring substances authorised as food additives in the EU, and are classified according to the reactants used in their manufacture as follows: Class I Plain Caramel or Caustic Caramel (E 150a); Class II Caustic Sulphite Caramel (E 150b); Class III Ammonia Caramel (E 150c) and Class IV Sulphite Ammonia Caramel (E 150d).The four classes of caramel colours have been previously evaluated by the EU Scientific Committee for Food (SCF), by the Joint FAO/WHO Expert Committee on Food Additives (JECFA) and by the ...

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Section: Annex Bmentioning

confidence: 99%

“…However, there was moderate atrophy of the thymus cortex. The authors concluded that THI could be a useful immunosuppressive agent (Mandel et al, 1992).…”

Section: Annex Bmentioning

confidence: 99%

Scientific Opinion on the re‐evaluation of caramel colours (E 150 a,b,c,d) as food additives

2011

EFS2

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“…THI produces lymphopenia, apparently without toxic effects, in rats and mice and is able to affect the immune competence in the rat in quite small quantities (e.g., 1−50 ppm in drinking water) . THI has also been reported to prevent spontaneous and cyclophosphamide-induced diabetes in non-obese diabetic mice . To investigate the structure−activity relationships of this structurally simple but biologically intriguing molecule, we desired a general and flexible synthesis of THI analogues.…”

Section: Introductionmentioning

confidence: 99%

Asymmetric Synthesis of 2-Acetyl-4(5)-(1,2,3,4-tetrahydroxybutyl)imidazoles

and

Pyne

1997

J. Org. Chem.

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A method for preparing the eight stereoisomers of the biologically active compound (1R,2S,3R)-2-acetyl-4(5)-(1,2,3,4-tetrahydroxybutyl)imidazole (THI, 1) is reported. This method employs a palladium(0)-catalyzed coupling of 1-(ethoxymethyl)-4-iodoimidazole (7) to functionalized vinylstannanes (R)- or (S)-12a,b or 13a,b or 1-alkynylstannanes (R)- or (S)-6a,b to introduce the C-4 imidazole four-carbon side chain. The 1,2-dihydroxy functionality of the butyl side chain was introduced by Sharpless catalytic asymmetric dihydroxylation reactions.

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